George A. Poultsides, MD, MS, FACS

All Publications

• Defining and Predicting Early Recurrence after Resection for Gallbladder Cancer. Annals of surgical oncology Sahara, K., Tsilimigras, D. I., Kikuchi, Y., Ethun, C. G., Maithel, S. K., Abbott, D. E., Poultsides, G. A., Hatzaras, I., Fields, R. C., Weiss, M., Scoggins, C., Isom, C. A., Idrees, K., Shen, P., Yabushita, Y., Matsuyama, R., Endo, I., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: The optimal time interval to define early recurrence (ER) among patients who underwent resection of gallbladder cancer (GBC) is not well defined. We soughtto develop and validate a novel GBC recurrence risk (GBRR) score to predict ER among patients undergoing resection for GBC.PATIENTS AND METHODS: Patients who underwent curative-intent resection for GBC between 2000 and 2018 were identified from the US Extrahepatic Biliary Malignancy Consortiumdatabase. A minimum p value approach in the log-rank test was used to define the optimal cutoff forER. A risk stratification model was developed to predict ER based on relevant clinicopathological factors and was externally validated.RESULTS: Among 309 patients, 103 patients (33.3%) had a recurrence at a median follow-up period of 15.1months. The optimal cutoff for ER was defined at 12months (p=3.04*10-18). On multivariable analysis, T3/T4 disease (HR: 2.80; 95% CI 1.58-5.11) and poor tumordifferentiation (HR: 1.91; 95% CI 1.11-3.25) were associated with greater hazards of ER. The GBRR score was developed using beta-coefficients of variables in the final model, and patients were classified into three distinct groups relative to the risk forER (12-month RFS; low risk: 88.4%, intermediate risk: 77.9%, high risk: 37.0%, p<0.001). The external validation demonstrated good model generalizability with good calibration (n=102: 12-month RFS; low risk: 94.2%, intermediate risk: 59.8%, high risk: 42.0%, p<0.001). The GBRR score is available online at https://ktsahara.shinyapps.io/GBC_earlyrec/ .CONCLUSIONS: A novel online calculator was developed to help clinicians predict the probability of ER after curative-intent resection for GBC. The proposed web-based tool may help in the optimization of surveillance intervals and the counselling of patients about their prognosis.

  View details for DOI 10.1245/s10434-020-09108-y

  View details for PubMedID 32892270

• Islet Tumors: Resect or Follow? Advances in surgery Sinclair, T. J., Poultsides, G. A. 2020; 54: 69–88

  View details for DOI 10.1016/j.yasu.2020.04.004

  View details for PubMedID 32713440

• A closer look at the natural history and recurrence patterns of high-grade truncal/extremity leiomyosarcomas: A multi-institutional analysis from the US Sarcoma Collaborative. Surgical oncology Lee, R. M., Ethun, C. G., Zaidi, M. Y., Tran, T. B., Poultsides, G. A., Grignol, V. P., Howard, J. H., Bedi, M., Gamblin, T. C., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Oskouei, S. V., Monson, D. K., Reimer, N. B., Maithel, S. K., Cardona, K. 2020; 34: 292–97

  Abstract

  BACKGROUND/OBJECTIVE: Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS).METHODS: Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS).RESULTS: Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6cm. In non-LMS patients, median age was 58 and median tumor size was 8cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5cm and high-grade, n=49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p=0.39), D-RFS (53vs63%, p=0.27), and DSS (67vs91%, p=0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p=0.030) and DSS (77vs65%,p=0.007) in non-LMS patients who received radiation.CONCLUSIONS: In our cohort, patients with LMS have a low local recurrence rate (12-15%) and modest distant recurrence rate (29-35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.

  View details for DOI 10.1016/j.suronc.2020.06.003

  View details for PubMedID 32891345

• A Novel Machine-Learning Approach to Predict Recurrence After Resection of Colorectal Liver Metastases. Annals of surgical oncology Paredes, A. Z., Hyer, J. M., Tsilimigras, D. I., Moro, A., Bagante, F., Guglielmi, A., Ruzzenente, A., Alexandrescu, S., Makris, E. A., Poultsides, G. A., Sasaki, K., Aucejo, F. N., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: Surgical resection of hepatic metastases remains the only potentially curative treatment option for patients with colorectal liver metastases (CRLM). Widely adopted prognostic tools may oversimplify the impact of model parameters relative to long-term outcomes.METHODS: Patients with CRLM who underwent a hepatectomy between 2001 and 2018 were identified in an international, multi-institutional database. Bootstrap resampling methodology used in tandem with multivariable mixed-effects logistic regression analysis was applied to construct a prediction model that was validated and compared with scores proposed by Fong and Vauthey.RESULTS: Among 1406 patients who underwent hepatic resection of CRLM, 842 (59.9%) had recurrence. The full model (based on age, sex, primary tumor location, T stage, receipt of chemotherapy before hepatectomy, lymph node metastases, number of metastatic lesions in the liver, size of the largest hepatic metastases, carcinoembryonic antigen [CEA] level and KRAS status) had good discriminative ability to predict 1-year (area under the receiver operating curve [AUC], 0.693; 95% confidence interval [CI], 0.684-0.704), 3-year (AUC, 0.669; 95% CI, 0.661-0.677), and 5-year (AUC, 0.669; 95% CI, 0.661-0.679) risk of recurrence. Studies analyzing validation cohorts demonstrated similar model performance, with excellent model accuracy. In contrast, the AUCs for the Fong and Vauthey scores to predict 1-year recurrence were only 0.527 (95% CI, 0.514-0.538) and 0.525 (95% CI, 0.514-0.533), respectively. Similar trends were noted for 3- and 5-year recurrence.CONCLUSION: The proposed clinical score, derived via machine learning, which included clinical characteristics and morphologic data, as well as information on KRAS status, accurately predicted recurrence after CRLM resection with good discrimination and prognostic ability.

  View details for DOI 10.1245/s10434-020-08991-9

  View details for PubMedID 32779049

• Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors. HPB : the official journal of the International Hepato Pancreato Biliary Association Heidsma, C. M., Tsilimigras, D. I., van Dieren, S., Rocha, F., Abbott, D. E., Fields, R., Smith, P. M., Poultsides, G. A., Cho, C., Dillhoff, M., Lopez-Aguiar, A. G., Kanji, Z., Fisher, A., Krasnick, B. A., Idrees, K., Makris, E., Beems, M., van Eijck, C. H., Nieveen van Dijkum, E. J., Maithel, S. K., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: Pancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP.METHODS: Patients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP.RESULTS: Among 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5cm, IQR:1.0-1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n=109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p=0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23-71) versus PD/DP (37 months, 95% CI: 33-47, p=0.480).CONCLUSION: Comparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN.

  View details for DOI 10.1016/j.hpb.2020.06.015

  View details for PubMedID 32771338

• High neutrophil-lymphocyte ratio is not independently associated with worse survival or recurrence in patients with extremity soft tissue sarcoma. Surgery Strong, E. A., Park, S. H., Ethun, C. G., Chow, B., King, D., Bedi, M., Charlson, J., Mogal, H., Tsai, S., Christians, K., Tran, T. B., Poultsides, G., Grignol, V., Howard, J. H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Gamblin, T. C., Cardona, K., Clarke, C. N. 2020

  Abstract

  BACKGROUND: Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated.METHODS: We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naive patients using blood counts at or near diagnosis.RESULTS: A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P < .001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P < .001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P= .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P= .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P < .001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P= .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P= .22).CONCLUSION: Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas.

  View details for DOI 10.1016/j.surg.2020.06.017

  View details for PubMedID 32736869

• Analysis of textbook outcomes among patients undergoing resection of retroperitoneal sarcoma: A multi-institutional analysis of the US Sarcoma Collaborative. Journal of surgical oncology Wiseman, J. T., Ethun, C. G., Cloyd, J. M., Shelby, R., Suarez-Kelly, L., Tran, T., Poultsides, G., Mogal, H., Clarke, C., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B., Fields, R., Walle, K. V., Ronnekleiv-Kelly, S., Howard, J. H., Cardona, K., Grignol, V. 2020

  Abstract

  BACKGROUND: The novel composite metric textbook outcome (TO) has increasingly been used as a quality indicator but has not been reported among patients undergoing surgical resection for retroperitoneal sarcoma (RPS) using multi-institutional collaborative data.METHODS: All patients who underwent resection for RPS between 2000 to 2016 from eight academic institutions were included. TO was defined as a patient with R0/R1 resection that discharged to home and was without transfusion, reoperation, grade ≥2 complications, hospital-stay >50th percentile, or 90-day readmission or mortality. Univariate and multivariable analyses were performed.RESULTS: Among 627 patients, 56.1% were female and the median age was 59 years. A minority of patients achieved a TO (34.9%). Factors associated with achieving a TO were tumor size <20cm and low tumor grade, while ASA class ≥3, history of a prior cardiac event, resection of left colon/rectum, distal pancreatic resection, major venous resection and drain placement were associated with not achieving a TO (all P<.05). Achievement of a TO was associated with improved survival (median:12.7 vs 5.9 years, P<.01).CONCLUSIONS: Among patients undergoing resection for RPS, failure to achieve TO is common and associated with significantly worse survival. The use of TO may inform patient expectations and serve as a measure for patient-level hospital performance.

  View details for DOI 10.1002/jso.26136

  View details for PubMedID 32696475

• Predicting Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Tsilimigras, D. I., Sahara, K., Paredes, A. Z., Moro, A., Mehta, R., Moris, D., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: The objective of the current study was to develop a model to predict the likelihood of occult lymph node metastasis (LNM) prior to resection of intrahepatic cholangiocarcinoma (ICC).METHODS: Patients who underwent hepatectomy for ICC between 2000 and 2017 were identified using a multi-institutional database. A novel model incorporating clinical and preoperative imaging data was developed to predict LNM.RESULTS: Among 980 patients who underwent resection of ICC, 190 (19.4%) individuals had at least one LNM identified on final pathology. An enhanced imaging model incorporating clinical and imaging data was developed to predict LNM ( https://k-sahara.shinyapps.io/ICC_imaging/ ). The performance of the enhanced imaging model was very good in the training data set (c-index 0.702), as well as the validation data set with bootstrapping resamples (c-index 0.701) and outperformed the preoperative imaging alone (c-index 0.660). The novel model predicted both 5-year overall survival (OS) (low risk 48.4% vs. high risk 18.4%) and 5-year disease-specific survival (DSS) (low risk 51.9% vs. high risk 25.2%, both p < 0.001). When applied among Nx patients, 5-year OS and DSS of low-risk Nx patients was comparable with that of N0 patients, while high-risk Nx patients had similar outcomes to N1 patients (p > 0.05).CONCLUSION: This tool may represent an opportunity to stratify prognosis of Nx patients and can help inform clinical decision-making prior to resection of ICC.

  View details for DOI 10.1007/s11605-020-04720-5

  View details for PubMedID 32757124

• Prognostic factors differ according to KRAS mutational status: A classification and regression tree model to define prognostic groups after hepatectomy for colorectal liver metastasis. Surgery Moro, A., Mehta, R., Tsilimigras, D. I., Sahara, K., Paredes, A. Z., Bagante, F., Guglielmi, A., Alexandrescu, S., Poultsides, G. A., Sasaki, K., Aucejo, F. N., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: Although KRAS mutation status is known to affect the prognosis of patients with colorectal liver metastasis, the hierarchical association between other prognostic factors and KRAS status is not fully understood.METHODS: Patients who underwent a hepatectomy for colorectal liver metastasis were identified in a multi-institutional international database. A classification and regression tree model was constructed to investigate the hierarchical association between prognostic factors and overall survival relative to KRAS status.RESULTS: Among 1,123 patients, 29.9% (n= 336) had a KRAS mutation. Among wtKRAS patients, the classification and regression tree model identified presence of metastatic lymph nodes as the most important prognostic factor, whereas among mtKRAS patients, carcinoembryonic antigen level was identified as the most important prognostic factor. Among patients with wtKRAS, the highest 5-year overall survival (68.5%) was noted among patients with node negative primary colorectal cancer, solitary colorectal liver metastases, size <4.3 cm. In contrast, among patients with mtKRAS colorectal liver metastases, the highest 5-year overall survival (57.5%) was observed among patients with carcinoembryonic antigen <6 mg/mL. The classification and regression tree model had higher prognostic accuracy than the Fong score (wtKRAS [Akaike's Information Criterion]: classification and regression tree model 3334 vs Fong score 3341; mtKRAS [Akaike's Information Criterion]: classification and regression tree model 1356 vs Fong score 1396).CONCLUSION: Machine learning methodology outperformed the traditional Fong clinical risk score and identified different factors, based on KRAS mutational status, as predictors of long-term prognosis.

  View details for DOI 10.1016/j.surg.2020.05.019

  View details for PubMedID 32675031

• Pancreatic Cancer Prognostication: From Trousseau to Thrombelastography. Annals of surgery Poultsides, G. A. 2020

  View details for DOI 10.1097/SLA.0000000000004139

  View details for PubMedID 32773630

• Recurrence beyond the Milan criteria after curative-intent resection of hepatocellular carcinoma: A novel tumor-burden based prediction model. Journal of surgical oncology Tsilimigras, D. I., Mehta, R., Guglielmi, A., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: Accurate prediction of recurrence patterns of hepatocellular carcinoma (HCC) may allow for prioritization of patients for resection or transplantation as well as guide post-resection surveillance strategies.METHODS: Patients who underwent curative-intent R0 resection for HCC between 2000 and 2017 were identified using a multi-institutional database. A prognostic model that incorporated HCC tumor burden score (TBS) to predict recurrence beyond the Milan criteria (MC) was developed and validated.RESULTS: Among 718 patients who underwent R0 resection for HCC, 185 (25.8%) recurred within and 110 (15.3%) beyond the MC. On multivariable analysis, AFP more than 400ng/mL (hazard ratio [HR]=2.26; 95% confidence interval [CI]: 1.27-4.02), lymphovascular invasion (HR=2.00; 95% CI: 1.14-3.50), and TBS (HR=1.08; 95% CI: 1.03-1.12) were associated with recurrence beyond the MC. A weighted TBS-based score was constructed: [0.074*TBS+0.692*lymphovascular invasion (yes: 1, no: 0)+0.816*AFP>400 (yes:1, no:0)]. Patients with a low, medium, and high TBS-based risk score had a 5-year incidence of recurring beyond the MC of 16.2%, 28.6%, and 47.2%, respectively (P<.001). The predictive accuracy of the model was very good in the training (C-index: 0.761) and validation (C-index: 0.706) datasets and outperformed the previously reported clinical risk score (CRS; C-index: 0.680).CONCLUSION: A TBS-based model accurately predicted recurrence beyond MC after curative-intent resection of HCC and outperformed the CRS. Incorporating TBS allows for better risk stratification and identifies patients in need of closer surveillance.

  View details for DOI 10.1002/jso.26091

  View details for PubMedID 32602143

• Predicting Pancreatic Cancer Resectability and Outcomes Based on an Objective Quantitative Scoring System. Pancreas Toesca, D. A., Jeffrey, R. B., von Eyben, R., Pollom, E. L., Poullos, P. D., Poultsides, G. A., Fisher, G. A., Visser, B. C., Koong, A. C., Chang, D. T. ; 48 (5): 622–28

  Abstract

  To quantitatively assess the probability of tumor resection based on measurements of tumor contact with the major peripancreatic vessels.This is a retrospective cohort study of pancreatic cancer patients treated between January 2001 and December 2015 in a single academic comprehensive cancer center. Radiographic measurements of the circumferential degree and length of solid tumor contact with major peripancreatic vessels were obtained from diagnostic pancreatic protocol computed tomography images and tested for correlation with tumor resection and margin status.Of 294 patients analyzed, 113 (38%) were resected, with 71 (63%) with negative margins. Based on the individual measurements of vascular involvement, a resectability scoring system (RSS) was created. The RSS correlated strongly with resection (P < 0.0001) and R0 resection (P < 0.0001) probabilities. Moreover, the RSS correlated with overall survival (P < 0.0001) and metastasis-free survival (P < 0.0001), being able to substratify resectable (P = 0.022) and unresectable patients (P = 0.014) into subgroups with different prognosis based on RSS scores.Based on a comprehensive and systematic quantitative approach, we developed a scoring system that demonstrated excellent accuracy to predict tumor resection, surgical margin status, and prognosis.

  View details for PubMedID 31091207

• Multi-institutional Development and External Validation of a Nomogram Predicting Recurrence After Curative Liver Resection for Neuroendocrine Liver Metastasis. Annals of surgical oncology Xiang, J., Zhang, X., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Pawlik, T. M. 2020

  Abstract

  OBJECTIVES: To establish and externally validate a novel nomogram to predict recurrence of patients undergoing curative liver resection for neuroendocrine liver metastasis (NELM).METHODS: A total of 279 patients who underwent curative liver resection for NELM identified from an international multicenter database were utilized to develop a nomogram to predict recurrence; 98 cases from two different institutions were used to externally validate the nomogram.RESULTS: Among 279 patients in the development cohort, median age was 57years, and 50.5% were male. On multivariate analysis, primary tumor location (pancreatic vs nonpancreatic, HR 2.1, p=0.004), tumor grade (Ref. well, moderate HR 1.9, p=0.022; poor HR 1.6, p=0.238), lymph node metastasis (positive vs negative, HR 2.6, p=0.002), and extent of resection (major vs parenchymal-sparing resection, HR 0.3, p=0.001) were independently associated with recurrence-free survival. The beta coefficients from the final multivariable model were utilized to develop a nomogram. The nomogram demonstrated good ability to predict risk of recurrence (training cohort, C-index 0.754; validation cohort, C-index 0.748). The calibrated nomogram predicted recurrence-free survival that closely corresponded to actual recurrence. Decision curve analysis demonstrated that the nomogram had a good net benefit for most of the threshold probabilities, especially between 20 and 60%, in both development and validation cohorts.CONCLUSIONS: The externally validated novel nomogram predicted 3- and 5-year recurrence-free survival among patients with NELM. Prediction of individual recurrence risk may help guide personalized estimates of prognosis, as well as surveillance protocols and consideration of adjuvant therapies.

  View details for DOI 10.1245/s10434-020-08620-5

  View details for PubMedID 32436187

• Tumour-specific fluorescence-guided surgery for pancreatic cancer using panitumumab-IRDye800CW: a phase 1 single-centre, open-label, single-arm, dose-escalation study. The lancet. Gastroenterology & hepatology Lu, G., van den Berg, N. S., Martin, B. A., Nishio, N., Hart, Z. P., van Keulen, S., Fakurnejad, S., Chirita, S. U., Raymundo, R. C., Yi, G., Zhou, Q., Fisher, G. A., Rosenthal, E. L., Poultsides, G. A. 2020

  Abstract

  BACKGROUND: Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma, with positive margins in 30-70% of patients. In this study, we aimed to evaluate the use of intraoperative tumour-specific imaging to enhance a surgeon's ability to detect visually occult cancer in real time.METHODS: In this single-centre, open-label, single-arm study, done in the USA, we enrolled patients who had clinically suspicious or biopsy-confirmed pancreatic ductal adenocarcinomas and were scheduled for curative surgery. Eligible patients were 19 years of age or older with a life expectancy of more than 12 weeks and a Karnofsky performance status of at least 70% or an Eastern Cooperative Oncology Group or Zubrod level of one or lower, who were scheduled to undergo curative surgery. Patients were sequentially enrolled into each dosing group and 2-5 days before surgery, patients were intravenously infused with 100 mg of unlabelled panitumumab followed by 25 mg, 50 mg, or 75 mg of the near-infrared fluorescently labelled antibody (panitumumab-IRDye800CW). The primary endpoint was to determine the optimal dose of panitumumab-IRDye800CW in identifying pancreatic ductal adenocarcinomas as measured by tumour-to-background ratio in all patients. The tumour-to-background ratio was defined as the fluorescence signal of the tumour divided by the fluorescence signal of the surrounding healthy tissue. The dose-finding part of this study has been completed. This study is registered with ClinicalTrials.gov, NCT03384238.FINDINGS: Between April, 2018, and July, 2019, 16 patients were screened for enrolment onto the study. Of the 16 screened patients, two (12%) patients withdrew from the study and three (19%) were not eligible; 11 (69%) patients completed the trial, all of whom were clinically diagnosed with pancreatic ductal adenocarcinoma. The mean tumour-to-background ratio of primary tumours was 3·0 (SD 0·5) in the 25 mg group, 4·0 (SD 0·6) in the 50 mg group, and 3·7 (SD 0·4) in the 75 mg group; the optimal dose was identified as 50 mg. Intraoperatively, near-infrared fluorescence imaging provided enhanced visualisation of the primary tumours, metastatic lymph nodes, and small (<2 mm) peritoneal metastasis. Intravenous administration of panitumumab-IRDye800CW at the doses of 25 mg, 50 mg, and 75 mg did not result in any grade 3 or higher adverse events. There were no serious adverse events attributed to panitumumab-IRDye800CW, although four possibly related adverse events (grade 1 and 2) were reported in four patients.INTERPRETATION: To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumour-specific intraoperative imaging might have added value for treatment of patients with pancreatic ductal adenocarcinomas through improved patient selection and enhanced visualisation of surgical margins, metastatic lymph nodes, and distant metastasis.FUNDING: National Institutes of Health and the Netherlands Organization for Scientific Research.

  View details for DOI 10.1016/S2468-1253(20)30088-1

  View details for PubMedID 32416764

• Assessing Textbook Outcomes Following Liver Surgery for Primary Liver Cancer Over a 12-Year Time Period at Major Hepatobiliary Centers. Annals of surgical oncology Tsilimigras, D. I., Sahara, K., Moris, D., Mehta, R., Paredes, A. Z., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Weiss, M., Bauer, T. W., Maithel, S. K., Pulitano, C., Shen, F., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2020

  Abstract

  INTRODUCTION: The objective of the current study was to comprehensively assess the change of practice in hepatobiliary surgery by determining the rates and the trends of textbook outcomes (TO) among patients undergoing surgery for primary liver cancerover time.METHODS: Patients undergoing curative-intent resection for primary liver malignancies, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) between 2005 and 2017 were analyzed using a large, international multi-institutional dataset. Rates of TO were assessed over time. Factors associated with achieving a TO and the impact of TO on long-term survival were examined.RESULTS: Among 1829 patients, 944 (51.6%) and 885 (48.4%) individuals underwent curative-intent resection for HCC and ICC, respectively. Over time, patients were older, more frequently had ASAclass>2, albumin-bilirubin grade 2/3, major vascular invasion and more frequently underwent major liver resection (all p<0.05). Overall, a total of 1126 (62.0%) patients achieved a TO. No increasing trends in TO rates were noted over the years (ptrend=0.90). In addition, there was no increasing trend in the TO rates among patients undergoing either major (ptrend=0.39) or minor liver resection (ptrend=0.63) over the study period. Achieving a TO was independently associated with 26% and 37% decreased hazards of death among ICC (HR 0.74, 95%CI 0.56-0.97) and HCC patients (HR 0.63, 95%CI 0.46-0.85), respectively.CONCLUSION: Approximately 6 in 10 patients undergoing surgery for primary liver tumors achieved a TO. While TO rates did not increase over time, TO was associated with better long-term outcomes following liver resection for both HCC and ICC.

  View details for DOI 10.1245/s10434-020-08548-w

  View details for PubMedID 32388742

• Recurrence Patterns and Outcomes after Resection of Hepatocellular Carcinoma within and beyond the Barcelona Clinic Liver Cancer Criteria. Annals of surgical oncology Tsilimigras, D. I., Bagante, F., Moris, D., Hyer, J. M., Sahara, K., Paredes, A. Z., Mehta, R., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: Several investigators have advocated for extending the Barcelona Clinic Liver Cancer (BCLC) resection criteria to select patients with BCLC-B and even BCLC-C hepatocellular carcinoma (HCC). The objective of the current study wasto define the outcomes and recurrence patterns after resection within and beyond the current resection criteria.PATIENTS AND METHODS: Patients who underwent resection for HCC within (i.e., BCLC 0/A) and beyond (i.e. BCLC B/C) the current resection criteria between 2005 and 2017 were identified from an international multi-institutional database. Overall survival (OS), disease-free survival (DFS), as well as patterns of recurrence of patients undergoing HCC resection within and beyond the BCLC guidelines were examined.RESULTS: Among 756 patients, 602 (79.6%) patients were BCLC 0/A and 154 (20.4%) were BCLC B/C. Recurrences were mostly intrahepatic (within BCLC: 74.3% versus beyond BCLC: 70.8%, p = 0.80), with BCLC B/C patients more often having multiple tumors at relapse (69.6% versus 49.4%, p = 0.001) and higher rates of early (< 2 years) recurrence (88.0% versus 75.5%, p = 0.011). During the first postoperative year, annual recurrence was 38.3% and 21.3% among BCLC B/C and BCLC 0/A patients, respectively; 5-year OS among BCLC 0/A and BCLC B/C patients was 76.9% versus 51.6% (p = 0.003). On multivariable analysis, only a-fetoprotein (AFP) > 400ng/mL(HR = 1.84, 95% CI 1.07-3.15) and R1 resection (HR = 2.36, 95% CI 1.32-4.23) were associated with higher risk of recurrence among BCLC B/C patients.CONCLUSIONS: Surgery can provide acceptable outcomes among select patients with BCLC B/C HCC. The data emphasize the need to further refine the BCLC treatment algorithm as well as highlight the need for surveillance protocols with a particular focus on the liver, especially for patients undergoing resection outside the BCLC criteria.

  View details for DOI 10.1245/s10434-020-08452-3

  View details for PubMedID 32285278

• Neoadjuvant radiation improves margin-negative resection rates in extremity sarcoma but not survival. Journal of surgical oncology Shelby, R. D., Suarez-Kelly, L. P., Yu, P. Y., Hughes, T. M., Ethun, C. G., Tran, T. B., Poultsides, G., King, D. M., Bedi, M., Mogal, H., Clarke, C., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Pollock, R. E., Howard, J. H., Cardona, K., Grignol, V. 2020

  Abstract

  BACKGROUND AND OBJECTIVES: Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas.MATERIALS AND METHODS: A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed.RESULTS: A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P<.001). The radiotherapy groups had more limb-sparing operations (98% AR vs 94% NAR vs 87% surgery; P<.001). NAR resulted in negative margin resections (90% NAR vs 79% surgery vs 75% AR; P<.0001). There were fewer local recurrences in the radiation groups (14% NAR vs 17% AR vs 27% surgery; P=.001). There was no difference in overall or recurrence-free survival between the three groups (OS, P=.132; RFS, P=.227).CONCLUSION: In this large study, radiotherapy improved limb salvage rates and decreased local recurrences. Receipt of NAR achieves more margin-negative resections however this did not improve local recurrence or survival rates over.

  View details for DOI 10.1002/jso.25905

  View details for PubMedID 32232871

• The Impact of Preoperative CA19-9 and CEA on Outcomes of Patients with Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Moro, A., Mehta, R., Sahara, K., Tsilimigras, D. I., Paredes, A. Z., Farooq, A., Hyer, J. M., Endo, I., Shen, F., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Soubrane, O., Koerkamp, B. G., Sasaki, K., Pawlik, T. M. 2020

  Abstract

  BACKGROUND: The objective of the current study was to assess the impact of serum CA19-9 and CEA and their combination on survival among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC).METHODS: Patients who underwent curative-intent resection of ICC between 1990 and 2016 were identified using a multi-institutional database. Patients were categorized into four groups based on combinations of serum CA19-9 and CEA (low vs. high). Factors associated with 1-year mortality after hepatectomy were examined.RESULTS: Among 588 patients, 5-year OS was considerably better among patients with low CA19-9/low CEA (54.5%) compared with low CA19-9/high CEA (14.6%), high CA19-9/low CEA (10.0%), or high CA19-9/high CEA (0%) (P<0.001). No difference in 1-year OS existed between patients who had either high CA19-9 (high CA19-9/low CEA:70.4%) or high CEA levels (low CA19-9/high CEA:72.5%) (P=0.92). Although patients with the most favorable tumor marker profile (low CA19-9/low CEA) had the best 1-year survival (87.9%), 15.1% (n=39) still died within a year of surgery. Among patients with low CA19-9/low CEA, a high neutrophil-to-lymphocyte ratio (NLR) (odds ratio 1.09; 95% confidence interval 1.03-1.64) and large size tumor (odds ratio 3.34; 95% confidence interval 1.40-8.10) were associated with 1-year mortality (P<0.05).CONCLUSIONS: Patients with either a high CA19-9 and/or high CEA had poor 1-year survival. High NLR and large tumor size were associated with a greater risk of 1-year mortality among patients with favorable tumor marker profile.

  View details for DOI 10.1245/s10434-020-08350-8

  View details for PubMedID 32198569

• Incidence and impact of Textbook Outcome among patients undergoing resection of pancreatic neuroendocrine tumors: Results of the US Neuroendocrine Tumor Study Group. Journal of surgical oncology Heidsma, C. M., Hyer, M., Tsilimigras, D. I., Rocha, F., Abbott, D. E., Fields, R., Smith, P. M., Poultsides, G. A., Cho, C., Maithel, S. K., Pawlik, T. M., Other Members of the US Neuroendocrine Tumor Study Group 2020

  Abstract

  BACKGROUND AND OBJECTIVES: We sought to define the incidence and impact of Textbook Outcome (TO) on disease-freesurvival [DFS] among patients undergoing resection of pancreatic neuroendocrine tumors (PNET).METHODS: Patients undergoing resection of a PNET between 2000 and 2016 were identified using a multi-institutional database. TO was defined as no postoperative severe complications (Clavien-Dindo grade≥III), no 90-day mortality, no prolonged length-of-hospital stay (LOS) (ie, >75th percentile), no 90-day readmission after discharge, and R0 resection. The 5-year DFS was calculated and the association with TO was examined.RESULTS: Among 821 patients with a PNET, median tumor size was 2.1cm (IQR 1.4-14.6). Resection consisted of pancreatoduodenectomy (PD) (n=231, 28.1%), distal pancreatectomy (DP) (n=492, 59.9%), and enucleation (EN) (n=98, 11.9%). Overall TO rate was 49.3% (n=405). The incidence of TO varied by procedure type (PD: 32.5% vs DP: 56.7% vs EN: 52.0%; P<.001). After adjusting for all competing factors, achievement of a TO was independently associated with improved DFS (hazard ratio: 0.54, 95% CI, 0.35-0.81; P=.003).CONCLUSIONS: Only one in two patients undergoing resection of a PNET achieved a TO, which varied markedly based on procedure type. Achievement of a TO was associated with improved DFS.

  View details for DOI 10.1002/jso.25900

  View details for PubMedID 32185804

• Outcomes of palliative-intent surgery in retroperitoneal sarcoma-Results from the US Sarcoma Collaborative. Journal of surgical oncology Thalji, S. Z., Tsai, S., Gamblin, T. C., Clarke, C., Christians, K., Charlson, J., Ethun, C. G., Poultsides, G., Grignol, V. P., Roggin, K. K., Votanopoulos, K., Fields, R. C., Abbott, D. E., Cardona, K., Mogal, H., other members of the US Sarcoma Collaborative 2020

  Abstract

  BACKGROUND AND OBJECTIVES: Outcomes of palliative-intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative-intent RPS resection.METHODS: Using a retrospective 8-institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified. Logistic regression and Cox-proportional hazards models were constructed to analyze factors associated with postoperative complications and overall survival (OS).RESULTS: Of 3088 patients, 70 underwent 87 palliative-intent procedures. Most common indications were pain (26%) and bowel obstruction (21%). Dedifferentiated liposarcoma (n=17, 24%), leiomyosarcoma (n=13, 19%) were predominant subtypes. Median OS was 10.69 months (IQR, 3.91-23.23). R2 resection (OR, 8.60; CI, 1.42-52.15; P=.019), larger tumors (OR, 10.87; CI, 1.44-82.11; P=.021) and low preoperative albumin (OR, 0.14; CI, 0.04-0.57; P=.006) were associated with postoperative complications. Postoperative complications (HR, 1.95; CI, 1.02-3.71; P=.043) and high-grade histology (HR, 6.56; CI, 1.72-25.05; P=.006) rather than resection status were associated with reduced OS. However, in R2-resected patients, development of postoperative complications significantly reduced survival (P=.042).CONCLUSIONS: Postoperative complications and high-grade histology rather than resection status impacts survival in palliative-intent RPS resections. Given the higher incidence of postoperative complications which may diminish survival, palliative-intent R2 resection should be offered only after cautious consideration.

  View details for DOI 10.1002/jso.25890

  View details for PubMedID 32167587

• Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit. Journal of surgical oncology Barrett, J. R., Rendell, V., Pokrzywa, C., Lopez-Aguiar, A. G., Cannon, J., Poultsides, G. A., Rocha, F., Crown, A., Beal, E., Michael Pawlik, T., Fields, R., Panni, R. Z., Smith, P., Idrees, K., Cho, C., Beems, M., Maithel, S., Weber, S., Erik Abbott, D. 2020

  Abstract

  BACKGROUND AND OBJECTIVES: Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use.METHODS: Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts.RESULTS: In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P<.01). RFS with somatostatin analog therapy (compared to none) was lower (P<.01), as was OS (P=.01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P<.01).CONCLUSIONS: Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.

  View details for DOI 10.1002/jso.25896

  View details for PubMedID 32153032

• Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors. Pancreas Squires, M. H., Worth, P. J., Konda, B., Shah, M. H., Dillhoff, M. E., Abdel-Misih, S., Norton, J. A., Visser, B. C., Dua, M., Pawlik, T. M., Schmidt, C. R., Poultsides, G., Cloyd, J. M. 2020

  Abstract

  OBJECTIVES: The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established.METHODS: The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed.RESULTS: Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%.CONCLUSIONS: Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

  View details for DOI 10.1097/MPA.0000000000001500

  View details for PubMedID 32132509

• Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors Squires, M., Worth, P., Konda, B., Dillhoff, M., Abdel-Misih, S., Pawlik, T., Schmidt, C., Poultsides, G., Cloyd, J. LIPPINCOTT WILLIAMS & WILKINS. 2020: 488

  View details for Web of Science ID 000526823600120

• Is a Nomogram Able to Predict Postoperative Wound Complications in Localized Soft-tissue Sarcomas of the Extremity? Clinical orthopaedics and related research Bedi, M., Ethun, C. G., Charlson, J., Tran, T. B., Poultsides, G., Grignol, V., Howard, J. H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Cardona, K., King, D. M. 2020; 478 (3): 550–59

  Abstract

  BACKGROUND: Postoperative wound complications are challenging in patients with localized extremity soft-tissue sarcomas. Various factors have been associated with wound complications, but there is no individualized predictive model to allow providers to counsel their patients and thus offer methods to mitigate the risk of complications and implement appropriate measures.QUESTIONS/PURPOSES: We used data from multiple centers to ask: (1) What risk factors are associated with postoperative wound complications in patients with localized soft-tissue sarcomas of the extremity? (2) Can we create a predictive nomogram that will assess the risk of wound complications in individual patients after resection for soft-tissue sarcoma?METHODS: From 2000 to 2016, 1669 patients undergoing limb-salvage resection for a localized primary or recurrent extremity soft-tissue sarcoma with at least 120 days of follow-up at eight participating United States Sarcoma Collaborative institutions were identified. Wound complications included superficial wounds with or without drainage, deep wounds with drainage because of dehiscence, and intentional opening of the wound within 120 days postoperatively. Sixteen variables were selected a priori by clinicians and statisticians as potential risk factors for wound complications. A univariate analysis was performed using Fisher's exact tests for categorical predictors, and Wilcoxon's rank-sum tests were used for continuous predictors. A multiple logistic regression analysis was used to train the prediction model that was used to create the nomogram. The prediction performance of the datasets was evaluated using a receiver operating curve, area under the curve, and calibration plot.RESULTS: After controlling for potential confounding factors such as comorbidities, functional status, albumin level, and chemotherapy use, we found that increasing age (odds ratio 1.02; 95% confidence interval, 1.00-1.03; p = 0.008), BMI (OR 1.05; 95% CI, 1.02-1.09; p = 0.004), lower-extremity location (OR 6; 95% CI, 2.87-12.69; p < 0.001), and neoadjuvant radiation (OR 2; 95% CI, 1.47-3.16; p < 0.001) were associated with postoperative wound complications (area under the curve 69.2% [range 62.8%-75.6%]).CONCLUSIONS: We found that age, BMI, tumor location, and timing of radiation are associated with the risk of wound complications. Based on these factors, a validated nomogram has been established that can provide an individualized prediction of wound complications in patients with a resected soft-tissue sarcoma of the extremity. This may allow for proactive management with nutrition and surgical techniques, and help determine the delivery of radiation in patients with a high risk of having these complications.LEVEL OF EVIDENCE: Level III, therapeutic study.

  View details for DOI 10.1097/CORR.0000000000000959

  View details for PubMedID 32168066

• Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular Carcinoma JOURNAL OF GASTROINTESTINAL SURGERY Sahara, K., Paredes, A. Z., Merath, K., Tsilimigras, D., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Beal, E. W., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Aklile, W., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2020; 24 (3): 551–59

  View details for DOI 10.1007/s11605-019-04174-4

  View details for Web of Science ID 000526452000007

• Survival benefit of lymphadenectomy for gallbladder cancer based on the therapeutic index: An analysis of the US extrahepatic biliary malignancy consortium. Journal of surgical oncology Sahara, K., Tsilimigras, D. I., Maithel, S. K., Abbott, D. E., Poultsides, G. A., Hatzaras, I., Fields, R. C., Weiss, M., Scoggins, C., Isom, C. A., Idrees, K., Shen, P., Endo, I., Pawlik, T. M., and the US Extrahepatic Biliary Malignancy Consortium 2020

  Abstract

  BACKGROUND: The survival benefit of lymphadenectomy among patients with gallbladder cancer (GBC) remains poorly understood.METHODS: Patients who underwent resection for GBC between 2000 and 2015 were identified from a US multi-institutional database. The therapeutic index (LNM rate multiplied by 3-year overall survival [OS]) was determined to assess the survival benefit of lymphadenectomy.RESULTS: Among 449 patients, less than half had LNM (N=183, 40.8%). The median number of evaluated and metastatic lymph nodes (LNs) was 3 (interquartile range [IQR]: 1-6) and 1 (IQR: 0-1), respectively. 3-year OS among patients with LNM in the entire cohort was 26.8%. The therapeutic index was lower among patients with T4 (5.9) or T1 (6.0) tumors as well as carbohydrate antigen (CA19-9) ≥200UI/mL (6.0). Of note, a therapeutic index difference ≥10 was noted relative to CA19-9 (<200: 18.7 vs ≥200: 6.0), American Joint Committee on Cancer T Stage (T1: 6.0 vs T2: 17.8 vs T4: 5.9) and number of LNs examined (1-2: 6.9 vs ≥6: 16.9). Concomitant common bile duct resection was not associated with a higher therapeutic index among patients with either T2 or T3 disease.CONCLUSION: Certain clinicopathological factors including T1 or T4 tumor and CA19-9 ≥200UI/mL were associated with a low therapeutic index. Resection of six or more LNs was associated with a meaningful therapeutic index benefit among patients with LNM.

  View details for DOI 10.1002/jso.25825

  View details for PubMedID 31907941

• Development and Validation of a Laboratory Risk Score (LabScore) to Predict Outcomes after Resection for Intrahepatic Cholangiocarcinoma. Journal of the American College of Surgeons Tsilimigras, D. I., Mehta, R., Aldrighetti, L., Poultsides, G. A., Maithel, S. K., Martel, G., Shen, F., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2020

  Abstract

  Estimating prognosis in the preoperative setting is challenging as most survival risk scores rely exclusively on postoperative factors. We sought to develop a composite score that incorporated preoperative liver, tumor, nutritional and inflammatory markers to predict long-term outcomes following resection of intrahepatic cholangiocarcinoma (ICC).Patients who underwent curative-intent hepatectomy for ICC between 2000-2017 were identified using an international multi-institutional database. Clinico-pathologic factors were assessed using bivariate and multivariable analysis and a prognostic model to estimate overall survival (OS) based only on preoperative laboratory values (LabScore) was developed and validated.Among 660 patients, median and 5-year OS were 43.2 months and 42.4%, respectively. On multivariable analysis, laboratory values associated with OS included carbohydrate antigen (CA) 19-9 (HR=1.16, 95%CI 1.05-1.27), neutrophil-to-lymphocyte ratio (NLR)(HR=1.09, 95%CI 1.05-1.13), platelet count (PLT)(HR=1.01, 95%CI 1.00-1.01) and albumin (HR=0.75, 95%CI 0.62-0.92). A weighted LabScore was constructed based on the formula: (8.2 + 1.45*lnCA19-9 + 0.84*NLR + 0.03*PLT-2.83*Albumin). Patients with a LabScore of 0-9 (n=223), 10-19 (n=353) and >20 (n=88) had an incrementally worse 5-year OS of 54.9%, 38.2% and 21.6%, respectively (p<0.001). The model demonstrated good performance in both the test (c-index: 0.70) and validation cohorts (c-index: 0.67), as well as outperformed individual laboratory markers, the prognostic nutritional index (c-index: 0.58) and 8th edition AJCC staging (c-index: 0.60).A preoperative LabScore was able to predict long-term outcomes of patients following resection for ICC better than AJCC staging system. The LabScore can be used to preoperatively identify patients who will benefit the most from upfront surgery or alternative treatment options including neoadjuvant chemotherapy prior to resection.

  View details for DOI 10.1016/j.jamcollsurg.2019.12.025

  View details for PubMedID 32014569

• PLR and NLR Are Poor Predictors of Survival Outcomes in Sarcomas: A New Perspective From the USSC. The Journal of surgical research Schwartz, P. B., Poultsides, G., Roggin, K., Howard, J. H., Fields, R. C., Clarke, C. N., Votanopoulos, K., Cardona, K., Winslow, E. R. 2020; 251: 228–38

  Abstract

  Elevations in inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), are reportedly associated with decreased overall survival (OS) or recurrence-free survival (RFS) in patients with numerous cancers. A large multicenter sarcoma data set was used to determine if elevated NLR or PLR was associated with worse survival and can guide treatment selection.A total of 409 patients with a primary retroperitoneal sarcoma (n = 268) or truncal (n = 141) sarcoma from 2000 to 2015 were analyzed using the US Sarcoma Collaboration database. Binary NLR and PLR values were developed using receiver operating characteristic curves. Kaplan-Meier model and Cox proportional hazards model identified predictors of decreased OS and RFS. Point biserial analyses were used to correlate binary and continuous data.Neither elevated NLR nor PLR was predictive of decreased OS or RFS. These findings persisted despite exclusion of comorbid inflammatory conditions. Further, NLR and PLR were not correlated with tumor grade. In multivariate models, decreased RFS was associated with tumor factors (e.g., positive margins, tumor grade, tumor size, necrosis, positive nodes); decreased OS was associated with histologic subtype, male gender, and nodal involvement.Although several small studies have suggested that elevated NLR and PLR are associated with decreased survival in patients with abdominal or truncal sarcoma, this large multicenter study demonstrates no association with decreased OS, decreased RFS, or tumor grade. Rather, survival outcomes are best predicted using previously established tumoral factors.

  View details for DOI 10.1016/j.jss.2020.01.008

  View details for PubMedID 32172009

• Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group. Annals of surgical oncology Baechle, J. J., Marincola Smith, P., Tan, M., Solórzano, C. C., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G., Makris, E., Rocha, F. G., Crown, A., Cho, C., Beems, M., Winslow, E. R., Rendell, V. R., Krasnick, B. A., Fields, R., Maithel, S. K., Bailey, C. E., Idrees, K. 2020

  Abstract

  Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs.A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS).High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04).High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

  View details for DOI 10.1245/s10434-020-08497-4

  View details for PubMedID 32328982

• The systemic immune-inflammation index predicts prognosis in intrahepatic cholangiocarcinoma: an international multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Tsilimigras, D. I., Moris, D., Mehta, R., Paredes, A. Z., Sahara, K., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2020

  Abstract

  The objective of this study was to examine whether the systemic immune inflammation index (SII) was associated with prognosis among patients following resection of intrahepatic cholangiocarcinoma (ICC).The impact of SII on overall (OS) and cancer-specific survival (CSS) following resection of ICC was assessed. The performance of the final multivariable models that incorporated inflammatory markers (i.e. neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR] and SII [platelets∗NLR]) was assessed using the Harrell's concordance index.Patients with high SII had worse 5-year OS (37.7% vs 46.6%, p < 0.001) and CSS (46.1% vs 50.1%, p < 0.001) compared with patients with low SII. An elevated SII (HR = 1.70, 95% CI 1.23-2.34) and NLR (HR = 1.58, 95% CI 1.10-2.27) independently predicted worse OS, whereas high PLR (HR = 1.17, 95% CI 0.85-1.60) was no longer associated with prognosis. Only SII remained an independent predictor of CSS (HR = 1.55, 95% CI 1.09-2.21). The SII multivariable model outperformed models that incorporated PLR and NLR relative to OS (c-index; 0.696 vs 0.689 vs 0.692) and CSS (c-index; 0.697 vs 0.689 vs 0.690).SII independently predicted OS and CSS among patients with resectable ICC. SII may be a better predictor of outcomes compared with other markers of inflammatory response among patients with resectable ICC.

  View details for DOI 10.1016/j.hpb.2020.03.011

  View details for PubMedID 32265108

• Correction to: Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis. Annals of surgical oncology Sahara, K., Tsilimigras, D. I., Mehta, R., Moro, A., Paredes, A. Z., Lopez-Aguiar, A. G., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P. M., Poultsides, G. A., Makris, E., Cho, C., Beems, M., Dillhoff, M., Maithel, S. K., Endo, I., Pawlik, T. M. 2020

  Abstract

  In the original article, Ryan C. Fields' middle initial is missing.

  View details for DOI 10.1245/s10434-020-08397-7

  View details for PubMedID 32342296

• Minimally Invasive Versus Open Liver Resection for Hepatocellular Carcinoma in the Setting of Portal Vein Hypertension: Results of an International Multi-institutional Analysis. Annals of surgical oncology Ruzzenente, A., Bagante, F., Ratti, F., Alaimo, L., Marques, H. P., Silva, S., Soubrane, O., Endo, I., Sahara, K., Beal, E. W., Lam, V., Poultsides, G. A., Makris, E. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Hugh, T. J., Guglielmi, A., Aldrighetti, L., Pawlik, T. M. 2020

  Abstract

  Patients with hepatocellular carcinoma (HCC) and portal vein hypertension assessed with platelet count (PVH-PLT; platelet count < 100,000/mL) are often denied surgery even when the disease is technically resectable. Short- and long-term outcomes of patients undergoing minimally invasive surgery (MIS) versus open resection for HCC and PVH-PLT were compared.Propensity score matching (PSM) was used to balance the clinicopathological differences between MIS and non-MIS patents. Univariate comparison and standard survival analyses were utilized.Among 1974 patients who underwent surgery for HCC, 13% had a PVH-PLT and 33% underwent MIS. After 1:1 PSM, 407 MIS and 407 non-MIS patients were analyzed. Incidence of complications and length-of-stay (LoS) were higher among non-MIS versus MIS patients (both p ≤ 0.002). After PSM, among 178 PVH-PLT patients (89 MIS and 89 non-MIS), patients who underwent a non-MIS approach had longer LoS (> 7 days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p <0.001]. In contrast, long-term oncological outcomes were comparable, including 3-year overall survival (non-MIS: 66.2% vs. MIS: 72.9%) and disease-free survival (non-MIS: 47.3% vs. MIS: 50.2%) [both p ≥ 0.08].An MIS approach was associated with improved short-term outcomes, but similar long-term outcomes, compared with open liver resection for patients with HCC and PVH-PLT. An MIS approach for liver resection should be considered for patients with HCC, even those individuals with PVH-PLT.

  View details for DOI 10.1245/s10434-020-08444-3

  View details for PubMedID 32274662

• Overall Tumor Burden Dictates Outcomes for Patients Undergoing Resection of Multinodular Hepatocellular Carcinoma Beyond the Milan Criteria. Annals of surgery Tsilimigras, D. I., Mehta, R., Paredes, A. Z., Moris, D., Sahara, K., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Spolverato, G., Umberto, C., Pawlik, T. M. 2020; 272 (4): 574–81

  Abstract

  The objective of the current study was to define surgical outcomes after resection of multinodular hepatocellular carcinoma (HCC) beyond the Milan criteria, and develop a prediction tool to identify which patients likely benefit the most from resection.Liver resection for multinodular HCC, especially beyond the Milan criteria, remains controversial. Rigorous selection of the best candidates for resection is essential to achieve optimal outcomes after liver resection of advanced tumors.Patients who underwent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Patients were categorized according to Milan criteria status. Pre- and postoperative overall survival (OS) prediction models that included HCC tumor burden score (TBS) among patients with multinodular HCC beyond Milan criteria were developed and validated.Among 1037 patients who underwent resection for HCC, 164 (15.8%) had multinodular HCC beyond the Milan criteria. Among patients with multinodular HCC, 25 (15.2%) patients experienced a serious complication and 90-day mortality was 3.7% (n = 6). Five-year OS after resection of multinodular HCC beyond Milan criteria was 52.8%. A preoperative TBS-based model (5-year OS: low-risk, 73.7% vs intermediate-risk, 45.1% vs high-risk, 13.1%), and postoperative TBS-based model (5-year OS: low-risk, 80.1% vs intermediate-risk, 37.2% vs high-risk, not reached) categorized patients into distinct prognostic groups relative to long-term prognosis (both P < 0.001). Pre- and postoperative models could accurately stratify OS in an external validation cohort (5-year OS; low vs medium vs high risk; pre: 66.3% vs 25.2% vs not reached, P = 0.012; post: 61.4% vs 42.5% vs not reached, P = 0.045) Predictive accuracy of the pre- and postoperative models was good in the training (c-index; pre: 0.68; post: 0.71), internal validation (n = 2000 resamples) (c-index, pre: 0.70; post: 0.72) and external validation (c-index, pre: 0.67; post 0.68) datasets. TBS alone could stratify patients relative to 5-year OS after resection of multinodular HCC beyond Milan criteria (c-index: 0.65; 5-year OS; low TBS: 70.2% vs medium TBS: 54.7% vs high TBS: 16.7%; P < 0.001). The vast majority of patients with low and intermediate TBS were deemed low or medium risk based on both the preoperative (98.4%) and postoperative risk scores (95.3%).Prognosis of patients with multinodular HCC was largely dependent on overall tumor burden. Liver resection should be considered among patients with multinodular HCC beyond the Milan criteria who have a low- or intermediate-TBS.

  View details for DOI 10.1097/SLA.0000000000004346

  View details for PubMedID 32932309

• Development and Validation of a Modified Eighth AJCC Staging System for Primary Pancreatic Neuroendocrine Tumors. Annals of surgery Zhang, X. F., Xue, F., Wu, Z., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Lyu, Y., Maithel, S. K., Pawlik, T. M. 2020

  Abstract

  To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system.Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial.Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification.The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts.A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.

  View details for DOI 10.1097/SLA.0000000000004039

  View details for PubMedID 32511134

• A Novel Classification of Intrahepatic Cholangiocarcinoma Phenotypes Using Machine Learning Techniques: An International Multi-Institutional Analysis. Annals of surgical oncology Tsilimigras, D. I., Hyer, J. M., Paredes, A. Z., Diaz, A., Moris, D., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2020

  Abstract

  Patients with intrahepatic cholangiocarcinoma (ICC) generally have a poor prognosis, yet there can be heterogeneity in the patterns of presentation and associated outcomes. We sought to identify clusters of ICC patients based on preoperative characteristics that may have distinct outcomes based on differing patterns of presentation.Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified using a multi-institutional database. A cluster analysis was performed based on preoperative variables to identify distinct patterns of presentation. A classification tree was built to prospectively assign patients into cluster assignments.Among 826 patients with ICC, three distinct presentation patterns were noted. Specifically, Cluster 1 (common ICC, 58.9%) consisted of individuals who had a small-size ICC (median 4.6 cm) and median carbohydrate antigen (CA) 19-9 and neutrophil-to-lymphocyte ratio (NLR) levels of 40.3 UI/mL and 2.6, respectively; Cluster 2 (proliferative ICC, 34.9%) consisted of patients who had larger-size tumors (median 9.0 cm), higher CA19-9 levels (median 72.0 UI/mL), and similar NLR (median 2.7); Cluster 3 (inflammatory ICC, 6.2%) comprised of patients with a medium-size ICC (median 6.2 cm), the lowest range of CA19-9 (median 26.2 UI/mL), yet the highest NLR (median 13.5) (all p < 0.05). Median OS worsened incrementally among the three different clusters {Cluster 1 vs. 2 vs. 3; 60.4 months (95% confidence interval [CI] 43.0-77.8) vs. 27.2 months (95% CI 19.9-34.4) vs. 13.3 months (95% CI 7.2-19.3); p < 0.001}. The classification tree used to assign patients into different clusters had an excellent agreement with actual cluster assignment (κ = 0.93, 95% CI 0.90-0.96).Machine learning analysis identified three distinct prognostic clusters based solely on preoperative characteristics among patients with ICC. Characterizing preoperative patient heterogeneity with machine learning tools can help physicians with preoperative selection and risk stratification of patients with ICC.

  View details for DOI 10.1245/s10434-020-08696-z

  View details for PubMedID 32495285

• Clinical relevance of performing endoscopic ultrasound-guided fine-needle biopsy for pancreatic neuroendocrine tumors less than 2 cm. Journal of surgical oncology Heidsma, C. M., Tsilimigras, D. I., Rocha, F., Abbott, D. E., Fields, R., Smith, P. M., Poultsides, G. A., Cho, C., van Eijck, C., van Dijkum, E. N., Maithel, S. K., Pawlik, T. M. 2020

  Abstract

  We sought to define the diagnostic yield and concordance rates between endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) and surgical pathology specimen following resection of pancreatic neuroendocrine tumors (pNET) less than 2 cm.Patients with a pNET less than 2 cm who underwent EUS-FNA were identified using a multi-institutional international database. Tumor differentiation, and Ki-67 index, as determined through EUS-FNA were examined and concordance rates between EUS-FNA and the surgical pathology were assessed.Among 628 patients with a pNET less than 2 cm, 57.2% of patients had an EUS-FNA performed. Patients who underwent EUS had slightly smaller size tumors (1.3 vs 1.4 cm), and the pNETs were less likely to be functional (15.3% vs 26.8%) or symptomatic (48.5% vs 56.5%) (both P < .05). Among 314 patients with a pNET less than 2 cm who had an EUS-FNA performed at the time of diagnosis, 243 (73.2%) had the diagnosis confirmed by preoperative EUS-FNA. Tumor differentiation and Ki-67 could be determined by EUS-FNA in only 26.4% and 20.1% of patients, respectively. Concordance rate between EUS-FNA and pathology was high relative to tumor differentiation (92.7%) and Ki-67 (81.0%).Tumor differentiation and Ki-67 index could be determined by EUS-FNA in only 26.4% and 20.1% of cases, respectively. Further studies should focus on EUS techniques to optimize diagnostic yield and cell extraction in the preoperative setting.

  View details for DOI 10.1002/jso.26158

  View details for PubMedID 32783272

• Early Versus Late Recurrence of Hepatocellular Carcinoma After Surgical Resection Based on Post-recurrence Survival: an International Multi-institutional Analysis. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Wei, T., Zhang, X. F., Bagante, F., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Lv, Y., Aldrighetti, L., Pawlik, T. M. 2020

  Abstract

  To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC).Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS.Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early (n = 165, 37.2%) versus late relapse (n = 278, 62.8%) (p = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p < 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- ± intrahepatic (35.5% vs. 19.8%, p = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p < 0.001).Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes.

  View details for DOI 10.1007/s11605-020-04553-2

  View details for PubMedID 32128681

• Single cell genomic characterization reveals the cellular reprogramming of the gastric tumor microenvironment. Clinical cancer research : an official journal of the American Association for Cancer Research Sathe, A., Grimes, S. M., Lau, B. T., Chen, J., Suarez, C., Huang, R. J., Poultsides, G. A., Ji, H. P. 2020

  Abstract

  The tumor microenvironment (TME) consists of a heterogenous cellular milieu that can influence cancer cell behavior. Its characteristics havean impact on treatments such as immunotherapy. These features can be revealed with single-cell RNA sequencing (scRNA-seq). We hypothesized that scRNA-seq analysis ofgastric cancer (GC) together with paired normal tissue and peripheral blood mononuclear cells (PBMCs) would identify critical elements of cellular deregulation not apparent with other approaches.scRNA-seq was conducted on seven patients with GC and one patient with intestinal metaplasia. We sequenced 56,167 cells comprising GC (32,407 cells), paired normal tissue (18,657 cells) and PBMCs (5,103 cells). Protein expression was validated by multiplex immunofluorescence.Tumor epithelium had copy number alterations, a distinct gene expression program from normal, with intra-tumor heterogeneity. GC TME was significantly enriched for stromal cells, macrophages, dendritic cells (DCs) and Tregs. TME-exclusive stromal cells expressed distinct extracellular matrix components than normal. Macrophages were transcriptionally heterogenous and did not conform to a binary M1/M2 paradigm. Tumor-DCs had a unique gene expression program compared to PBMC DCs. TME-specific cytotoxic T cells were exhausted with two heterogenous subsets. Helper, cytotoxic T, Treg and NK cells expressed multiple immune checkpoint or costimulatory molecules. Receptor-ligand analysis revealed TME-exclusive inter-cellular communication.Single-cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the GC TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states and inter-cellular interactions. This characterization facilitates understanding of tumor biology and enables identification of novel targets including for immunotherapy.

  View details for DOI 10.1158/1078-0432.CCR-19-3231

  View details for PubMedID 32060101

• Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. Molecular imaging and biology Pei, J., Juniper, G., van den Berg, N. S., Nisho, N., Broadt, T., Welch, A. R., Yi, G. S., Raymundo, R. C., Chirita, S. U., Lu, G., Krishnan, G., Lee, Y. J., Kapoor, S., Zhou, Q., Colevas, A. D., Lui, N. S., Poultsides, G. A., Li, G., Zinn, K. R., Rosenthal, E. L. 2020

  Abstract

  The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients.Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis.Eighty-one patients underwent infusion of the study drug at a range of doses. Six patients (7.4 %) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7 %). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months while meeting all other stability testing criteria.Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4 %) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.

  View details for DOI 10.1007/s11307-020-01536-2

  View details for PubMedID 32880818

• Retroperitoneal sarcoma perioperative risk stratification: A United States Sarcoma Collaborative evaluation of the ACS-NSQIP risk calculator. Journal of surgical oncology Schwartz, P. B., Stahl, C. C., Ethun, C., Marka, N., Poultsides, G. A., Roggin, K. K., Fields, R. C., Howard, J. H., Clarke, C. N., Votanopoulos, K. I., Cardona, K., Abbott, D. E. 2020

  Abstract

  The ACS-NSQIP risk calculator predicts perioperative risk. This study tested the calculator's ability to predict risk for outcomes following retroperitoneal sarcoma (RPS) resection.The United States Sarcoma Collaborative database was queried for adults who underwent RPS resection. Estimated risk for outcomes was calculated twice in the risk calculator, once using sarcoma-specific CPT codes and once using codes indicative of most comorbid organ resection (eg nephrectomy). ROC curves were generated, with area under the curve (AUC) and Brier scores reported to assess discrimination and calibration. An AUC < 0.6 was considered ineffective discrimination. A negative ▲ Brier indicated improved performance relative to baseline outcome rates.In total, 482 patients were identified with a 42.3% 90-day complication rate. Discrimination was poor for all outcomes except "all complications" and "renal failure." Baseline outcome rates were better predictors than calculator estimates except for "discharge to nursing or rehab facility" and "renal failure." Replacing sarcoma-specific CPT codes with resection-specific codes did not improve performance.The ACS-NSQIP risk calculator poorly predicted outcomes following RPS resection. Changing sarcoma-specific CPT to resection-specific codes did not improve performance. Comorbidities in the calculator may not effectively capture perioperative risk. Future work should evaluate a sarcoma-specific calculator.

  View details for DOI 10.1002/jso.26071

  View details for PubMedID 32557654

• Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors. Annals of surgical oncology Marincola Smith, P., Baechle, J., Tan, M. C., Solórzano, C. C., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G., Cannon, J. G., Rocha, F. G., Crown, A., Cho, C. S., Beems, M., Winslow, E. R., Rendell, V. R., Krasnick, B. A., Fields, R. C., Maithel, S. K., Bailey, C. E., Idrees, K. 2020

  Abstract

  Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear.A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS).The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006].Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

  View details for DOI 10.1245/s10434-020-08359-z

  View details for PubMedID 32219725

• Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma: Considering Alternative Treatment Approaches. JAMA surgery Tsilimigras, D. I., Sahara, K., Wu, L., Moris, D., Bagante, F., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Moro, A., Sasaki, K., Aucejo, F., Zhang, X. F., Matsuyama, R., Endo, I., Pawlik, T. M. 2020

  Abstract

  Although surgery offers the best chance of a potential cure for patients with localized, resectable intrahepatic cholangiocarcinoma (ICC), prognosis of patients remains dismal largely because of a high incidence of recurrence.To predict very early recurrence (VER) (ie, recurrence within 6 months after surgery) following resection for ICC in the pre- and postoperative setting.Patients who underwent curative-intent resection for ICC between May 1990 and July 2016 were identified from an international multi-institutional database. The study was conducted at The Ohio State University in collaboration with all other participating institutions. The data were analyzed in December 2019.Two logistic regression models were constructed to predict VER based on pre- and postoperative variables. The final models were used to develop an online calculator to predict VER and the tool was internally and externally validated.Among 880 patients (median age, 59 years [interquartile range, 51-68 years]; 388 women [44.1%]; 428 [50.2%] white; 377 [44.3%] Asian; 27 [3.2%] black]), 196 (22.3%) developed VER. The 5-year overall survival among patients with and without VER was 8.9% vs 49.8%, respectively (P < .001). A preoperative model was able to stratify patients relative to the risk for VER: low risk (6-month recurrence-free survival [RFS], 87.7%), intermediate risk (6-month RFS, 72.3%), and high risk (6-month RFS, 49.5%) (log-rank P < .001). The postoperative model similarly identified discrete cohorts of patients based on probability for VER: low risk (6-month RFS, 90.0%), intermediate risk (6-month RFS, 73.1%), and high risk (6-month RFS, 48.5%) (log-rank, P < .001). The calibration and predictive accuracy of the pre- and postoperative models were good in the training (C index: preoperative, 0.710; postoperative, 0.722) as well as the internal (C index: preoperative, 0.715; postoperative, 0.728; bootstrapping resamples, n = 5000) and external (C index: postoperative, 0.672) validation data sets.An easy-to-use online calculator was developed to help clinicians predict the chance of VER after curative-intent resection for ICC. The tool performed well on internal and external validation. This tool may help clinicians in the preoperative selection of patients for neoadjuvant therapy as well as during the postoperative period to inform surveillance strategies.

  View details for DOI 10.1001/jamasurg.2020.1973

  View details for PubMedID 32639548

• Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis. Annals of surgery Zhang, X. F., Xue, F., Dong, D. H., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Lv, Y., Pawlik, T. M. 2020

  Abstract

  To determine the prognostic implication of the number and station of LNM, and the minimal number of LNs needed for evaluation to accurately stage patients with intrahepatic cholangiocarcinoma (ICC).Impact of the number and station of LNM on long-term survival, and the minimal number of LNs needed for accurate staging of ICC patients remain poorly defined.Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide. External validation was performed using the SEER registry. Primary outcomes included overall (OS), disease-specific, and recurrence-free survival.Among 603 patients who underwent curative-intent resection, median and 5-year OS were 30.6 months and 30.4%. Patients with 1 or 2 LNM had comparable worse OS versus patients with no nodal disease (median OS, 1 LNM 18.0, 2 LNM 20.0 vs no LNM 45.0 months, both P < 0.001), yet better OS versus patients with 3 or more LNM (median OS, 1-2 LNM 19.8 vs ≥3 LNM 16.0 months, P < 0.01). On multivariable analysis, a proposed new nodal staging with N1 (1-2 LNM) (Ref. N0, HR 2.40, P < 0.001) and N2 (≥3 LNM) [Ref. N0, hazard ratio (HR) 3.85, P < 0.001] categories were independently associated with incrementally worse OS. Patients with no nodal metastasis, 1-2 LNM and ≥3 LNM also had an increasingly worse disease-specific survival, and recurrence-free survival (both P < 0.05). Total number of LNs examined ≥6 had the greatest discriminatory power relative to OS among patients with 1-2 LNM, and patients with ≥3 LNM in both the multi-institutional (area under the curve 0.780) and SEER database (area under the curve 0.820) (n = 1036). Among patients who underwent an adequate regional lymphadenectomy (total number of LNs examined ≥6), LNM beyond the HDL was associated with worse OS versus LNM within the HDL only (median OS, 14.0 vs 24.0 months, HR 2.41, P = 0.003).Standard lymphadenectomy of at least 6 LNs is strongly recommended and should include examination beyond station 12 to have the greatest chance of accurate staging. The proposed new nodal staging of N0, N1, and N2 should be considered to stratify outcomes among patients after curative-intent resection of ICC.

  View details for DOI 10.1097/SLA.0000000000003788

  View details for PubMedID 31972643

• Laparoscopic hepatic lobectomy for symptomatic polycystic liver disease. HPB : the official journal of the International Hepato Pancreato Biliary Association Li, A. Y., Bergquist, J. R., August, A. T., Dua, M. M., Poultsides, G. A., Visser, B. C. 2020

  Abstract

  Laparoscopic fenestration has largely replaced open fenestration of liver cysts. However, most hepatectomies for polycystic liver disease (PCLD) are performed open. Outcomes data on laparoscopic hepatectomy for PCLD are lacking.Patients who underwent surgery for PCLD at a single institution between 2010 and 2019 were reviewed and grouped by operative approach. Pre- and post-operative volumes were calculated for patients who underwent resection. Primary outcomes were: volume reduction, re-admission and postoperative complications.Twenty-six patients were treated for PCLD: 13 laparoscopic fenestration, nine laparoscopic hepatectomy, three open hepatectomy and one liver transplantation. Median length of stay for patients after laparoscopic resection was 3 days (IQR 2-3). The only complication was post-operative atrial fibrillation in one patient. There were no readmissions. Overall volume reduction was 51% (range 22-69) for all resections, 32% (range 22-46) after open resection and 56% (range 39-69) after laparoscopic resection.Volume reduction achieved through laparoscopic approach exceeded open volume reduction at this institution and is comparable to volume reduction in previously published open resection series. Adequate volume reduction can be accomplished by laparoscopic means with acceptable postoperative morbidity.

  View details for DOI 10.1016/j.hpb.2020.04.010

  View details for PubMedID 32451237

• Long-term outcomes after curative resection of HCV-positive versus non-hepatitis related hepatocellular carcinoma: an international multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Wei, T., Zhang, X. F., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Pawlik, T. M. 2020

  Abstract

  To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades.Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias.Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000-2009 55% vs. 2010-2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000-2009 53% vs. 2010-2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients.While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable.

  View details for DOI 10.1016/j.hpb.2020.01.003

  View details for PubMedID 31987739

• Surgical outcomes of patients with duodenal vs pancreatic neuroendocrine tumors following pancreatoduodenectomy. Journal of surgical oncology Dong, D. H., Zhang, X. F., Lopez-Aguiar, A. G., Poultsides, G., Rocha, F., Weber, S., Fields, R., Idrees, K., Cho, C., Spolverato, G., Maithel, S. K., Pawlik, T. M. 2020

  Abstract

  To investigate the short- and long-term outcomes of patients undergoing pancreaticoduodenectomy (PD) for duodenal neuroendocrine tumors (dNETs) vs pancreatic neuroendocrine tumors (pNETs).Patients undergoing PD for dNETs or pNETs between 1997 and 2016 were identified from a multi-institutional database. Overall survival (OS) and recurrence-free survival (RFS) were evaluated.Among 276 patients who underwent PD, 244 (88.4%) patients had a primary pNET, whereas 32 (11.6%) patients had a dNET. Following PD, postoperative morbidity and mortality were comparable. While the total number of lymph nodes examined was similar between the two groups (median, dNETs 15.0 vs pNETs 13.0; P= .648), patients with dNETs had a higher incidence of lymph node metastasis (LNM) (60.0% vs 38.2%; P = .022) and a larger number of metastatic nodes (median, 3.5 vs 2.0; P = .039). No differences in OS or RFS were noted among patients with dNETs vs pNETs in both unadjusted and adjusted analyses. Among patients who recurred after PD, patients with dNETs were more likely to recur early (within 2 years, 100% vs 49.2%; P = .029) and at an extrahepatic site (intrahepatic-only recurrence, 20.0% vs 54.1%; P = 0.142) vs patients with pNETs.Patients with dNETs and pNETs had a similar prognosis following PD. Data on differences in the incidence of LNM, as well as in recurrence time and patterns may help to inform the treatment of these patients.

  View details for DOI 10.1002/jso.25978

  View details for PubMedID 32470159

• Redefining Conditional Overall and Disease-Free Survival After Curative Resection for Intrahepatic Cholangiocarcinoma: a Multi-institutional, International Study of 1221 patients. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Hu, L., Zhang, X., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Lv, Y., Pawlik, T. M. 2019

  Abstract

  OBJECTIVES: To assess conditional survival (CS) according to recurrence status, as well as conditional disease-free survival (cDFS) among patients with intrahepatic cholangiocarcinoma (ICC).METHODS: CS and cDFS were evaluated among ICC patients who underwent curative-intent resection for ICC by using a multi-institutional database. Five-year CS (CS5) at "x" years was calculated separately for patients who did and did not experience recurrence. The cDFS3 at "x" years was defined as the chance to be disease-free for an additional 3 years after not having experienced a recurrence for "x" years postoperatively.RESULTS: Among 1221 patients, median OS was 36.8 months. While estimated actuarial OS decreased over time, CS5 increased as patients survived over longer periods of time and reached 93.9% at 4 years among 139 patients who did not experience a recurrence. Among the 725 (59.4%) patients who did experience a tumor recurrence, CS5 decreased to 17.7% the first postoperative year; however, CS5 subsequently increased to 79.7% for 81 patients who had survived 4 years after surgery. While actuarial DFS decreased from 54.6% at 1 year to 28.2% at 5 years, estimated cDFS3 following liver resection increased over time. Of note, patients with known risk factors for recurrence had even more marked improvements in cDFS3 over subsequent years versus patients without risk factors for recurrence.CONCLUSION: CS and cDFS changed over time according to the presence of disease-specific risk factors, as well as the presence of recurrence.

  View details for DOI 10.1007/s11605-019-04472-x

  View details for PubMedID 31823320

• Tumor burden score predicts tumor recurrence of non-functional pancreatic neuroendocrine tumors after curative resection. HPB : the official journal of the International Hepato Pancreato Biliary Association Dong, D., Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Schmidt, C. R., Dillhoff, M., Maithel, S. K., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: To investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs).METHOD: The TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined.RESULTS: Among 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P<0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p=0.05; TBS vs. number of tumors, p<0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p=0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p=0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p=0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p<0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p<0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p=0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS.CONCLUSIONS: TBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone.

  View details for DOI 10.1016/j.hpb.2019.11.009

  View details for PubMedID 31822386

• Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group AMERICAN SURGEON Armstrong, E. A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Cannon, J. G., Rocha, F., Crown, A., Barrett, J., Ronnkleiv-Kelly, S., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P., Nathan, H., Beems, M., Maithel, S. K., Schmidt, C. R., Pawlik, T. M., Dillhoff, M. 2019; 85 (12): 1334–40

  View details for Web of Science ID 000504743000017

• Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group. The American surgeon Armstrong, E. A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Cannon, J. G., Rocha, F., Crown, A., Barrett, J., Ronnkleiv-Kelly, S., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P. M., Nathan, H., Beems, M. V., Maithel, S. K., Schmidt, C. R., Pawlik, T. M., Dillhoff, M. 2019; 85 (12): 1334–40

  Abstract

  The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality. Our objective was to assess the accuracy of the ACS-NSQIP calculator for estimating risk after curative intent resection for primary GI neuroendocrine tumors (GI-NETs). Adult patients with GI-NET who underwent complete resection from 2000 to 2017 were identified using a multi-institutional database, including data from eight academic medical centers. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using receiver operating characteristic curves and the area under the curve (AUC). Seven hundred three patients were identified who met inclusion criteria. The most commonly performed procedures were resection of the small intestine with anastomosis (N = 193, 26%) and partial colectomy with anastomosis (N = 136, 18%). The majority of patients were younger than 65 years (N = 482, 37%) and ASA Class III (N = 337, 48%). The most common comorbidities were diabetes (N = 128, 18%) and hypertension (N = 395, 56%). Complications among these patients based on ACS NSQIP definitions included any complication (N = 132, 19%), serious complication (N = 118, 17%), pneumonia (N = 7, 1.0%), cardiac complication (N = 1, 0.01%), SSI (N = 80, 11.4%), UTI (N = 17, 2.4%), venous thromboembolism (N = 18, 2.5%), renal failure (N = 16, 2.3%), return to the operating room (N = 27, 3.8%), discharge to nursing/rehabilitation (N = 22, 3.1%), and 30-day mortality (N = 9, 1.3%). The calculator provided reasonable estimates of risk for pneumonia (AUC = 0.721), cardiac complication (AUC = 0.773), UTI (AUC = 0.716), and discharge to nursing/rehabilitation (AUC = 0.779) and performed poorly (AUC < 0.7) for all other complications Fig. 1). The ACS-NSQIP risk calculator estimates a similar proportion of risk to actual events in patients with GI-NET but has low specificity for identifying the correct patients for many types of complications. The risk calculator may require modification for some patient populations.

  View details for PubMedID 31908214

• Appendiceal Neuroendocrine Tumors: Does Colon Resection Improve Outcomes? Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Crown, A., Simianu, V. V., Kennecke, H., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Idrees, K., Smith, P. M., Nathan, H., Beems, M., Abbott, D., Barrett, J., Fields, R. C., Davidson, J., Maithel, S. K., Rocha, F. G. 2019

  Abstract

  BACKGROUND: Appendiceal neuroendocrine tumors (A-NETs) are rare neoplasms of the GI tract. They are typically managed according to tumor size; however, the impact of surgical strategy on the short- and long-term outcomes is unknown.METHODS: All patients who underwent resection of A-NET at 8 institutions from 2000 to 2016 were analyzed retrospectively. Patient clinicopathologic features and outcomes were stratified according to resection type.RESULTS: Of 61 patients identified with A-NET, mean age of presentation was 44.7 ± 16.0 years and patients were predominantly Caucasian (77%) and female (56%). Mean tumor size was 1.2 ± 1.3 cm with a median of 0.8 cm. Thirty-one patients (51%) underwent appendectomy and 30 (49%) underwent colonic resection. The appendectomy group had more T1 tumors (87% vs 42%, p < 0.01) than the colon resection group. Of patients in the colon resection group, 27% had positive lymph nodes and 3% had M1 disease. R0 resections were achieved in 90% of appendectomy patients and 97% of colon resection patients. Complications occurred with a higher frequency in the colon resection group (30%) compared with those in the appendectomy group (6%, p = 0.02). The colon resection group also had a longer length of stay, higher average blood loss, and longer average OR time. Median RFS and OS were similar between groups.CONCLUSION: A-NET RFS and OS are equivalent regardless of surgical strategy. Formal colon resection is associated with increased length of stay, OR time, higher blood loss, and more complications. Further study is warranted to identify patients that are likely to benefit from more aggressive surgery.

  View details for DOI 10.1007/s11605-019-04431-6

  View details for PubMedID 31749094

• Utilizing Machine Learning for Pre- and Postoperative Assessment of Patients Undergoing Resection for BCLC-0, A and B Hepatocellular Carcinoma: Implications for Resection Beyond the BCLC Guidelines. Annals of surgical oncology Tsilimigras, D. I., Mehta, R., Moris, D., Sahara, K., Bagante, F., Paredes, A. Z., Farooq, A., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: There is anongoing debate about expanding the resection criteria for hepatocellular carcinoma (HCC) beyond the Barcelona Clinic Liver Cancer (BCLC) guidelines. We sought to determine the factors that held the most prognostic weight in the pre- and postoperative setting for each BCLC stage by applying a machine learning method.METHODS: Patients who underwent resection for BCLC-0, A and B HCC between 2000 and 2017 were identified from an international multi-institutional database. A Classification and Regression Tree (CART) model was used to generate homogeneous groups of patients relative to overall survival (OS) based on pre- and postoperative factors.RESULTS: Among 976 patients, 63 (6.5%) had BCLC-0, 745 (76.3%) had BCLC-A, and 168 (17.2%) had BCLC-B HCC. Five-year OS among BCLC-0/A and BCLC-B patients was 64.2% versus 50.2%, respectively (p=0.011). The preoperative CART model selected alpha-fetoprotein (AFP) and Charlson comorbidity score (CCS) as the first and second most important preoperative factors of OS among BCLC-0/A patients, whereas radiologic tumor burden score (TBS) was the best predictor of OS among BCLC-B patients. The postoperative CART model revealed lymphovascular invasion as the best postoperative predictor of OS among BCLC-0/A patients, whereas TBS remained the best predictor of long-term outcomes among BCLC-B patients in the postoperative setting. On multivariable analysis, pathologic TBS independently predicted worse OS among BCLC-0/A (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.02-1.07) and BCLC-B patients (HR 1.13, 95% CI 1.06-1.19) undergoing resection.CONCLUSION: Prognostic stratification of patients undergoing resection for HCC within and beyond the BCLC resection criteria should include assessment of AFP and comorbidities for BCLC-0/A patients, as well as tumor burden for BCLC-B patients.

  View details for DOI 10.1245/s10434-019-08025-z

  View details for PubMedID 31696396

• Duodenal neuroendocrine tumors: Impact of tumor size and total number of lymph nodes examined. Journal of surgical oncology Zhang, X., Wu, X., Tsilimigras, D. I., Poultsides, G., Rocha, F., Abbott, D. E., Fields, R., Idrees, K., Cho, C., Maithel, S. K., Pawlik, T. M., other members of the US Neuroendocrine Tumor Study Group 2019

  Abstract

  BACKGROUND: The current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET).METHODS: Patients who underwent curative resection for dNETs between 1997-2016 were identified from 8 high-volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cut-off of TNLE relative to LNM was determined.RESULTS: Among 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51-68) years and median tumor size was 1.2cm (IQR, 0.7-2.0cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (≤1cm:52.2% vs 1-2cm:61.4% vs >2cm:93.8%; P<.05). Similarly, the incidence of LNM increased with dNET size (≤1cm: 40.0% vs 1-2cm:65.7% vs >2cm:80.0%; P<.05). TNLE≥8 had the highest discriminatory power relative to the incidence of LNM (area under the curve=0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR]=0.9; 95% confidence intervals [95%CI], 0.4-2.3), G2/G3 tumor grade was (HR=1.5; 95%CI, 1.0-2.1).CONCLUSIONS: While the incidence of LNM directly correlated with tumor size, patients with dNETs≤1cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.

  View details for DOI 10.1002/jso.25753

  View details for PubMedID 31680243

• Evaluating the ACS NSQIP Risk Calculator in Primary Pancreatic Neuroendocrine Tumor: Results from the US Neuroendocrine Tumor Study Group JOURNAL OF GASTROINTESTINAL SURGERY Dave, A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Kanji, Z., Ronnekleiv-Kelly, S., Rendell, V. R., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P., Nathan, H., Beems, M., Maithel, S. K., Pawlik, T. M., Schmidt, C. R., Dillhoff, M. E. 2019; 23 (11): 2225–31

  View details for DOI 10.1007/s11605-019-04120-4

  View details for Web of Science ID 000494689100008

• KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases Margonis, G. A., Amini, N., Andreatos, N., Sasaki, K., Mcvey, J., Mirza, M. B., Warner, S., Buettner, S., Barbon, C., Wang, J., Pulvirenti, A., Angelou, A., Kamphues, C., Antoniou, E., Pikoulis, E., Pawlik, T. M., Kaczirek, K., Poultsides, G., Wagner, D., Endo, I., Imai, K., Aucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. ELSEVIER SCI LTD. 2019: 1527–34

  View details for DOI 10.1016/j.hpb.2019.03.368

  View details for Web of Science ID 000496805100015

• Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience Melstrom, L. G., Eng, O. S., Raoof, M., Singh, G., Fong, Y., Latorre, K., Choi, G. H., Salem, R., Bentrem, D. J., Lewandowski, R., Makris, E., Poultsides, G., Dhar, V. K., Chadalavada, S., Shah, S. A., Johnson, A. C., Sekhar, A., Kies, D., Maithel, S. K., Rocha, F., Alseidi, A., Hagendoorn, J., Rinkes, I., Fisher, A. V., Ronnekleiv-Kelly, S., Weber, S. M., Winslow, E. R., Abbott, D. E. ELSEVIER SCI LTD. 2019: 1520–26

  View details for DOI 10.1016/j.hpb.2019.03.366

  View details for Web of Science ID 000496805100014

• Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma Buettner, S., ten Cate, D. G., Bagante, F., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T., Maithel, S. K., Pulitano, C., Margonis, G., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J., IJzermans, J. M., Pawlik, T. M., Koerkamp, B. SPRINGER. 2019: 2239–46

  View details for DOI 10.1007/s11605-019-04184-2

  View details for Web of Science ID 000494689100010

• Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nature communications Kimura, R. H., Wang, L., Shen, B., Huo, L., Tummers, W., Filipp, F. V., Guo, H. H., Haywood, T., Abou-Elkacem, L., Baratto, L., Habte, F., Devulapally, R., Witney, T. H., Cheng, Y., Tikole, S., Chakraborti, S., Nix, J., Bonagura, C. A., Hatami, N., Mooney, J. J., Desai, T., Turner, S., Gaster, R. S., Otte, A., Visser, B. C., Poultsides, G. A., Norton, J., Park, W., Stolowitz, M., Lau, K., Yang, E., Natarajan, A., Ilovich, O., Srinivas, S., Srinivasan, A., Paulmurugan, R., Willmann, J., Chin, F. T., Cheng, Z., Iagaru, A., Li, F., Gambhir, S. S. 2019; 10 (1): 4673

  Abstract

  Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin alphavbeta6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin alphavbeta6.

  View details for DOI 10.1038/s41467-019-11863-w

  View details for PubMedID 31611594

• Defining the chance of cure after resection for hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guidelines: A multi-institutional analysis of 1,010 patients. Surgery Tsilimigras, D. I., Bagante, F., Moris, D., Merath, K., Paredes, A. Z., Sahara, K., Ratti, F., Marques, H. P., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: Surgery is considered the only potentially curative treatment option for patients with hepatocellular carcinoma. However, the chance that patients will eventually be "cured" after liver resection for hepatocellular carcinoma remains ill defined.METHODS: Patients who underwent curative-intent hepatectomy for hepatocellular carcinoma between 1998 and 2017 were identified using an international multi-institutional database. A nonmixture cure model was used with disease-free survival as a primary measure to estimate cure fractions after matching patients with the general population by age, race, and sex.RESULTS: Among 1,010 patients, the median and 5-year disease-free survival were 2.8 years and 36.6%, respectively. The probability of being cured after hepatocellular carcinoma resection was 42.2% and the median time to cure was 3.35 years. The multivariable cure model revealed preoperative alpha-fetoprotein level, tumor size, tumor number, and margin status as independent predictors of cure. The cure fraction for patients with an alpha-fetoprotein level ≤ 10 ng/mL, largest tumor size ≤5 cm, ≤3 nodules, and R0 resection was 61.6%. In contrast, patients who had all 4 unfavorable prognostic factors (ie, alpha-fetoprotein >11 ng/mL, nodules ≥4, size >5cm, R1 resection) had a cure fraction of 15.8%. Although the probability of cure was 47.6% among Barcelona Clinic Liver Cancer-A patients, patients undergoing resection for Barcelona Clinic Liver Cancer-B hepatocellular carcinoma had a 37.6% cure fraction. Only alpha-fetoprotein levels predicted the probability of cure among Barcelona Clinic Liver Cancer-B patients.CONCLUSION: Roughly 4 in 10 patients could be considered "cured" after liver resection for hepatocellular carcinoma. Although cure was achieved more often after resection for Barcelona Clinic Liver Cancer-A hepatocellular carcinoma, surgery still provided a reasonable probability of cure among select patients with Barcelona Clinic Liver Cancer-B hepatocellular carcinoma.

  View details for DOI 10.1016/j.surg.2019.08.010

  View details for PubMedID 31606196

• Postoperative Outcomes of Laparoscopic vs Robotic Distal Pancreatectomy: A Propensity-Matched Analysis Jensen, C. W., Baiocchi, M., Dua, M. M., Poultsides, G. A., Norton, J. A., Worth, P. J., Visser, B. C. ELSEVIER SCIENCE INC. 2019: S181–S182

  View details for Web of Science ID 000492740900344

• Prognostic Impact of KRAS Mutational Status in Patients with Colorectal Cancer Liver Metastases Differs According to the Location of the Primary Tumor Amini, N., Margonis, G., Kreis, M. E., Poultsides, G. A., Sasaki, K., Wagner, D., Pikoulis, E., Weiss, M. J., Wolfgang, C. L., Safar, B. ELSEVIER SCIENCE INC. 2019: S69–S70

  View details for Web of Science ID 000492740900114

• Role of Adjuvant Radiation Therapy for Retroperitoneal Sarcomas: An 8-Institution Study from the US Sarcoma Collaborative Chouliaras, K., Cardona, K., Poultsides, G. A., Grignol, V. P., Clarke, C. N., Roggin, K., Fields, R. C., Weber, S. M., Johnson, E., Votanopoulos, K. ELSEVIER SCIENCE INC. 2019: S274

  View details for Web of Science ID 000492740900532

• Impact of tumor size and nodal status on recurrence of nonfunctional pancreatic neuroendocrine tumors ≤2cm after curative resection: A multi-institutional study of 392 cases. Journal of surgical oncology Dong, D., Zhang, X., Poultsides, G., Rocha, F., Weber, S., Fields, R., Idrees, K., Cho, C., Maithel, S. K., Pawlik, T. M., other members of the US Neuroendocrine Tumor Study Group 2019

  Abstract

  BACKGROUND: The current study sought to define the impact of lymph node metastasis (LNM) relative to tumor size on tumor recurrence after curative resection for nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) ≤2cm.METHODS: Patients who underwent curative resection for ≤2-cm NF-pNETs were identified from a multi-institutional database. Risk factors associated with tumor recurrence as well as LNM were identified. Recurrence-free survival (RFS) was compared among patients with or without LNM.RESULTS: A total of 392 ≤2-cm NF-pNETs patients were identified. Among the 328 patients who had lymph node dissection and evaluation, 42 (12.8%) patients had LNM. LNM was associated with tumor recurrence (hazard ratio, 3.06; P=.026) after surgery. RFS was worse among LNM vs no LNM patients (5-year RFS, 81.7% vs 94.1%; P=.019). Patients with tumors measuring 1.5-2cm had a two-fold increase in the incidence of LNM vs patients with tumors <1.5cm (17.9% vs 8.7%, odds ratio, 2.59; P=.022), as well as a higher risk of advanced tumor grade and higher Ki-67 levels (both P<.01). After curative resection, a total of 14 (8.0%) patients with a tumor of 1.5-2cm and 10 (4.5%) patients with tumor <1.5cm developed tumor recurrence.CONCLUSION: Surgical resection with lymphadenectomy should be considered for patients with NF-pNETs ≥1.5-2.0cm.

  View details for DOI 10.1002/jso.25716

  View details for PubMedID 31571225

• Role of radiation therapy for retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative. Journal of surgical oncology Chouliaras, K., Senehi, R., Ethun, C. G., Poultsides, G., Grignol, V., Clarke, C. N., Roggin, K. K., Fields, R. C., Schwartz, P. B., Ronnekleiv-Kelly, S. M., D'Agostino, R. J., Johnson, E. N., Levine, E. A., Cardona, K., Votanopoulos, K. I. 2019

  Abstract

  BACKGROUND: The use of radiation therapy in the treatment of retroperitoneal sarcomas has increased in recent years. Its impact on survival and recurrence is unclear.METHODS: A retrospective propensity score matched (PSM) analysis of patients with primary retroperitoneal soft tissue sarcomas, who underwent resection from 2000 to 2016 at eight institutions of the US Sarcoma Collaborative, was performed. Patients with metastatic disease, desmoid tumors, and palliative resections were excluded.RESULTS: Total 425 patients were included, 56 in the neoadjuvant radiation group (neo-RT), 75 in the adjuvant radiation group (adj-RT), and 294 in the no radiotherapy group (no-RT). Median age was 59.5 years, 186 (43.8%) were male with a median follow up of 31.4 months. R0 and R1 resection was achieved in 253 (61.1%) and 143 (34.5%), respectively. Overall 1:1 match of 46 adj-RT and 59 neo-RT patients was performed using histology, sex, age, race, functional status, tumor size, grade, resection status, and chemotherapy. Unadjusted recurrence-free survival (RFS) was 35.9 months (no-RT) vs 33.5 months (neo-RT) and 27.2 months (adj-RT), P=.43 and P=.84, respectively. In the PSM, RFS was 17.6 months (no-RT) vs 33.9 months (neo-RT), P=.28 and 19 months (no-RT) vs 27.2 months (adj-RT), P=.1.CONCLUSIONS: Use of radiotherapy, both in adjuvent or neoadjuvent setting, was not associated with improved survival or reduced recurrence rate.

  View details for DOI 10.1002/jso.25694

  View details for PubMedID 31486096

• Response to preoperative chemotherapy: impact of change in total burden score and mutational tumor status on prognosis of patients undergoing resection for colorectal liver metastases HPB Ruzzenente, A., Bagante, F., Ratti, F., Beal, E. W., Alexandrescu, S., Merath, K., Makris, E. A., Poultsides, G. A., Margonis, G. A., Weiss, M. J., Popescu, I., Aldrighetti, L., Guglielmi, A., Pawlik, T. M. 2019; 21 (9): 1230–39

  View details for DOI 10.1016/j.hpb.2019.01.014

  View details for Web of Science ID 000485965900015

• Complications after liver surgery: a benchmark analysis HPB Bagante, F., Ruzzenente, A., Beal, E. W., Campagnaro, T., Merath, K., Conci, S., Akgul, O., Alexandrescu, S., Marques, H. P., Lam, V., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Iacono, C., Guglielmi, A., Pawlik, T. M. 2019; 21 (9): 1139–49

  View details for DOI 10.1016/j.hpb.2018.12.013

  View details for Web of Science ID 000485965900005

• Discordance in prediction of prognosis among patients with intrahepatic cholangiocarcinoma: A preoperative vs postoperative perspective JOURNAL OF SURGICAL ONCOLOGY Moro, A., Paredes, A. Z., Farooq, A., Sahara, K., Tsilimigras, D., Mehta, R., Endo, I., Guglielmi, A., Aldrighetti, L., Alexandrescu, S., Marques, H. P., Shen, F., Koerkamp, B. G., Sasaki, K., Pawlik, T. M., Weiss, M., Bauer, T. W., Poultsides, G. A., Maithel, S. K., Martel, G., Pulitano, C., Soubrane, O., Int Intrahepatic Cholangiocarcinom 2019

  Abstract

  The objective of the current study was to characterize patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent surgery with discordant preoperative and postoperative prediction scores and determine factors associated with prediction discrepancy.Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified in a multi-institutional international database. Preoperative and postoperative prognostic models were designed and discordant prognostic scores were identified. A multivariable logistic regression analysis was completed to determined factors associated with score discordance.Among 1149 patients, those who had concordant prediction scores were older (median age, 60 vs 56), and more likely to have a smaller median tumor size (6.0 vs 7.5 cm) (all P < .05). On multivariable logistic analysis, patients with higher neutrophil-lymphocyte ratio (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.09-1.19), higher CEA levels (OR, 1.25; 95% CI, 1.04-1.50), larger tumors (OR, 1.10; 95% CI, 1.04-1.15) and suspicious lymph nodes (OR, 2.05; 95% CI, 1.25-3.36) were more likely to have preoperative and postoperative score discordance. Older patients had decreased odds of having score discordance (OR, 0.98; 95% CI, 0.96-0.99). Patients with score discordance had worse overall survival compared with patients with concordant scores (median:15.9 vs 21.7 months, P < .05).Score discordance may reflect an aggressive variant of ICC that would benefit from early integration of multidisciplinary treatment strategies.

  View details for DOI 10.1002/jso.25671

  View details for Web of Science ID 000481226300001

  View details for PubMedID 31410852

• Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity? Journal of surgical oncology DePalo, D. K., Lee, R. M., Lopez-Aguiar, A. G., Gamboa, A. C., Rocha, F., Poultsides, G., Dillhoff, M., Fields, R. C., Idrees, K., Nathan, H., Abbott, D., Maithel, S. K., Russell, M. C., other members of the United States Neuroendocrine Tumor Study Group 2019

  Abstract

  BACKGROUND AND OBJECTIVES: Although minority race has been associated with worse cancer outcomes, the interaction of race with pathologic variables and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is not known.METHODS: Patients from the US Neuroendocrine Study Group (2000-2016) undergoing curative-intent resection of GEP-NETs were included. Given few patients of other races, only Black and White patients were analyzed.RESULTS: A total of 1143 patients were included. Median age was 58years, 49% were male, 14% Black, and 86% White. Black patients were more likely to be uninsured (7% vs 2%, P=.011), and to have symptomatic bleeding (13% vs 7%, P=.009), emergency surgery (7% vs 3%, P=.006), and positive lymph nodes (LN) (47% vs 36%, P=.021). However, Black patients had improved 5-year recurrence-free survival (RFS) (90% vs 80%, P=.008). Quality of care was comparable between races, seen by similar LN yield, R0 resections, postoperative complications, and need for reoperation/readmission (all P>.05). While both races were more likely to have pancreas-NETs, Black patients had more small bowel-NETs (22% vs 13%, P<.001). LN positivity was prognostic for pancreas-NETs (5-year RFS 67% vs 83%, P=.001) but not for small-bowel NETs.CONCLUSIONS: Black patients with GEP-NETs had more adverse characteristics and higher LN positivity. Despite this, Black patients have improved RFS. This may be attributed to the epidemiologic differences in the primary site of GEP-NETs and variable prognostic value of LN-positive disease.

  View details for DOI 10.1002/jso.25662

  View details for PubMedID 31385621

• The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis. Annals of surgery Margonis, G. A., Amini, N., Buettner, S., Kim, Y., Wang, J., Andreatos, N., Wagner, D., Sasaki, K., Beer, A., Kamphues, C., Morioka, D., Loes, I. M., Imai, K., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P. E., Burkhart, R., Endo, I., Baba, H., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019

  Abstract

  OBJECTIVE: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.BACKGROUND: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.METHODS: Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.RESULTS: 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).CONCLUSIONS: This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.

  View details for DOI 10.1097/SLA.0000000000003504

  View details for PubMedID 31389831

• Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the US neuroendocrine tumor study group JOURNAL OF SURGICAL ONCOLOGY Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Schmidt, C. R., Maithel, S. K., Pawlik, T. M., United States Neuroendocrine Tumor 2019; 120 (2): 231–40

  View details for DOI 10.1002/jso.25481

  View details for Web of Science ID 000475966600018

• Prognostic utility of albumin-bilirubin grade for short- and long-term outcomes following hepatic resection for intrahepatic cholangiocarcinoma: A multi-institutional analysis of 706 patients JOURNAL OF SURGICAL ONCOLOGY Tsilimigras, D. I., Hyer, J., Moris, D., Sahara, K., Bagante, F., Guglielmi, A., Aldrighetti, L., Alexandrescu, S., Marques, H. P., Shen, F., Koerkamp, B., Endo, I., Pawlik, T. M., Merath, K., Paredes, A. Z., Weiss, M., Bauer, T. W., Poultsides, G. A., Maithel, S. K., Martel, G., Pulitano, C., Soubrane, O., Int Intrahepatic 2019; 120 (2): 206–13

  Abstract

  The objective of the current study was to define the impact of albumin-bilirubin (ALBI) grade on short- as well as long-term outcomes among patients with intrahepatic cholangiocarcinoma (ICC).Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified using an international multi-institutional database. Clinicopathologic factors including ALBI score were assessed using bivariate and multivariable analyses, as well as standard survival analyses.Among 706 patients, 453 (64.2%) patients had ALBI grade 1, 231 (32.7%) ALBI grade 2, and 22 (3.1%) had ALBI grade 3. After adjusting for all competing factors, patients with ALBI grade 2/3 had higher odds of a prolonged length-of-stay (>10 days, odds ratio [OR] = 2.37, 95% confidence interval [CI]:1.47-3.80), perioperative transfusion (OR = 2.15, 95% CI:1.45-3.18) and 90-day mortality (OR = 2.50, 95% CI:1.16-5.38). Median and 5-year overall survival (OS) for the entire cohort was 41.5 months (IQR:15.7-107.8) and 39.8%, respectively. Of note, median OS incrementally worsened with increased ALBI grade: grade 1, 49.6 months (IQR:18.3-NR) vs grade 2, 29.6 months (IQR:12.6-98.4) vs grade 3, 16.9 months (IQR:6.5-32.4; P < 0.001). On multivariable analysis, higher ALBI grade remained associated with higher hazards of death (grade 2/3: hazard ratio = 1.36, 95% CI:1.04-1.78).The ALBI score was associated with both short- and long-term outcomes following resection for ICC and could prove a useful surrogate marker to identify patients at risk for adverse outcomes.

  View details for DOI 10.1002/jso.25486

  View details for Web of Science ID 000475966600015

  View details for PubMedID 31025380

• Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma ANNALS OF SURGICAL ONCOLOGY Hu, L., Zhang, X., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Itaru, E., Pawlik, T. M. 2019; 26 (8): 2549–57

  View details for DOI 10.1245/s10434-019-07353-4

  View details for Web of Science ID 000474357200037

• Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group Lopez-Aguiar, A. G., Zaidi, M. Y., Beal, E. W., Dillhoff, M., Cannon, J. D., Poultsides, G. A., Kanji, Z. S., Rocha, F. G., Smith, P., Idrees, K., Beems, M., Cho, C. S., Fisher, A. V., Weber, S. M., Krasnick, B. A., Fields, R. C., Cardona, K., Maithel, S. K. SPRINGER. 2019: 2517–24

  View details for DOI 10.1245/s10434-019-07367-y

  View details for Web of Science ID 000474357200032

• New Nodal Staging for Primary Pancreatic Neuroendocrine Tumors: A Multi-institutional and National Data Analysis. Annals of surgery Zhang, X., Xue, F., Dong, D., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Lv, Y., Maithel, S. K., Pawlik, T. M. 2019

  Abstract

  OBJECTIVE: To determine the prognostic role of metastatic lymph node (LN) number and the minimal number of LNs for optimal staging of patients with pancreatic neuroendocrine tumors (pNETs).BACKGROUND: Prognosis relative to number of LN metastasis (LNM), and minimal number of LNs needed to evaluate for accurate staging, have been poorly defined for pNETs.METHODS: Number of LNM and total number of LN evaluated (TNLE) were assessed relative to recurrence-free survival (RFS) and overall survival (OS) in a multi-institutional database. External validation was performed using Surveillance, Epidemiology and End Results (SEER) registry.RESULTS: Among 854 patients who underwent resection, 233 (27.3%) had at least 1 LNM. Patients with 1, 2, or 3 LNM had a comparable worse RFS versus patients with no nodal metastasis (5-year RFS, 1 LNM 65.6%, 2 LNM 68.2%, 3 LNM 63.2% vs 0 LNM 82.6%; all P < 0.001). In contrast, patients with ≥4 LNM (proposed N2) had a worse RFS versus patients who either had 1 to 3 LNM (proposed N1) or node-negative disease (5-year RFS, ≥4 LNM 43.5% vs 1-3 LNM 66.3%, 0 LNM 82.6%; all P < 0.05) [C-statistics area under the curve (AUC) 0.650]. TNLE ≥8 had the highest discriminatory power relative to RFS (AUC 0.713) and OS (AUC 0.726) among patients who had 1 to 3 LNM, and patients who had ≥4 LNM in the multi-institutional and SEER database (n = 2764).CONCLUSIONS: Regional lymphadenectomy of at least 8 lymph nodes was necessary to stage patients accurately. The proposed nodal staging of N0, N1, and N2 optimally staged patients.

  View details for DOI 10.1097/SLA.0000000000003478

  View details for PubMedID 31356277

• Assessing the Role of Neoadjuvant Chemotherapy in Primary High-Risk Truncal/Extremity Soft Tissue Sarcomas: An Analysis of the Multi-institutional U.S. Sarcoma Collaborative. Annals of surgical oncology Zaidi, M. Y., Ethun, C. G., Tran, T. B., Poultsides, G., Grignol, V. P., Howard, J. H., Bedi, M., Mogal, H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B., Fields, R. C., Oskouei, S., Reimer, N., Monson, D., Maithel, S. K., Cardona, K. 2019

  Abstract

  BACKGROUND: The role of neoadjuvant chemotherapy (NCT) for high-risk soft tissue sarcoma (STS) is questioned. This study aimed to define which patients may experience a survival advantage with NCT.METHODS: All the patients from the U.S. Sarcoma Collaborative database (2000-2016) who underwent curative-intent resection of high-grade, primary truncal/extremity STS size 5cm or larger were included in this study. The primary end points were recurrence-free survival (RFS) and overall survival (OS).RESULTS: Of the 4153 patients, 770 were included in the study. The median tumor size was 10cm, and 669 of the patients (87%) had extremity tumors. The most common histology was undifferentiated pleomorphic sarcoma (UPS), found in 42% of the patients. Of the 770 patients, 216 (28%) received NCT. The patients who received NCT had deeper, larger tumors (p<0.001). Of the patients with tumors 5cm or larger and 8cm or larger, NCT was not associated with improved RFS or OS. However for the patients with tumors 10cm or larger, NCT was associated with improved 5-year RFS (51% vs 40%; p=0.053) and 5-year OS (58% vs 47%; p=0.043). By location, the patients with extremity tumors 10cm or larger but not truncal tumors had improved 5-yearr RFS (54% vs 42%; p=0.042) and 5-year OS (61% vs 47%; p=0.015) with NCT. According to histology, no subtype had improved RFS or OS with NCT, although the patients with UPS had a trend toward improved 5-year RFS (56% vs 42%; p=0.092) and 5-year OS (66% vs 52%; p=0.103) with NCT.CONCLUSION: For the patients with high-grade STS, NCT was associated with improved RFS and OS when tumors were 10cm or larger and located in the extremity. However, no histiotype-specific advantage was identified. Future studies assessing the efficacy of NCT may consider focusing on these patients, with added focus on histology-specific strategies.

  View details for DOI 10.1245/s10434-019-07639-7

  View details for PubMedID 31342400

• Intrahepatic cholangiocarcinoma tumor burden: A classification and regression tree model to define prognostic groups after resection. Surgery Bagante, F., Spolverato, G., Merath, K., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Endo, I., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool.METHODS: Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival.RESULTS: Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n= 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n= 110) and 7.2% (n= 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis.CONCLUSION: Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree-derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.

  View details for DOI 10.1016/j.surg.2019.06.005

  View details for PubMedID 31326191

• A Novel Validated Recurrence Risk Score to Guide a Pragmatic Surveillance Strategy After Resection of Pancreatic Neuroendocrine Tumors: An International Study of 1006 Patients. Annals of surgery Zaidi, M. Y., Lopez-Aguiar, A. G., Switchenko, J. M., Lipscomb, J., Andreasi, V., Partelli, S., Gamboa, A. C., Lee, R. M., Poultsides, G. A., Dillhoff, M., Rocha, F. G., Idrees, K., Cho, C. S., Weber, S. M., Fields, R. C., Staley, C. A., Falconi, M., Maithel, S. K. 2019

  Abstract

  OBJECTIVE: Despite heterogeneous biology, similar surveillance schemas are utilized after resection of all pancreatic neuroendocrine tumors (PanNETs). Given concerns regarding excess radiation exposure and financial burden, our aim was to develop a prognostic score for disease recurrence to guide individually tailored surveillance strategies.METHODS: All patients with primary nonfunctioning, nonmetastatic well/moderately differentiated PanNETs who underwent curative-intent resection at 9-institutions from 2000 to 2016 were included (n = 1006). A Recurrence Risk Score (RRS) was developed from a randomly selected derivation cohort comprised of 67% of patients and verified on the validation-cohort comprised of the remaining 33%.RESULTS: On multivariable analysis, patients within the derivation cohort (n = 681) with symptomatic tumors (jaundice, pain, bleeding), tumors >2 cm, Ki67 >3%, and lymph node (LN) (+) disease had increased recurrence. Each factor was assigned a score based on their weighted odds ratio that formed a RRS of 0 to 10: symptomatic = 1, tumor >2 cm = 2, Ki67 3% to 20% = 1, Ki67 >20% = 6, LN (+) = 1. Patients were grouped into low- (RRS = 0-2; n = 247), intermediate-(RRS = 3-5; n = 204), or high (RRS = 6-10; n = 9)-risk groups. At 24 months, 33% of high RRS recurred, whereas only 2% of low and 14% of intermediate RRS recurred. This persisted in the validation cohort (n = 325).CONCLUSIONS: This international, novel, internally validated RRS accurately stratifies recurrence-free survival for patients with resected PanNETs. Given their unique recurrence patterns, surveillance intervals of 12, 6, and 3 months are proposed for low, intermediate, and high RRS patients, respectively, to minimize radiation exposure and optimize cost/resource utilization.

  View details for DOI 10.1097/SLA.0000000000003461

  View details for PubMedID 31283562

• Prognosis After Resection of Barcelona Clinic Liver Cancer (BCLC) Stage 0, A, and B Hepatocellular Carcinoma: A Comprehensive Assessment of the Current BCLC Classification. Annals of surgical oncology Tsilimigras, D. I., Bagante, F., Sahara, K., Moris, D., Hyer, J. M., Wu, L., Ratti, F., Marques, H. P., Soubrane, O., Paredes, A. Z., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have questioned the prognostic stratification of this classification schema, as well as the proposed treatment allocation of patients with a single large tumor.METHODS: Patients who underwent curative-intent hepatectomy for histologically proven hepatocellular carcinoma (HCC) between 1998 and 2017 were identified using an international multi-institutional database. Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed.RESULTS: Among 814 patients, 68 (8.4%) were BCLC-0, 310 (38.1%) were BCLC-A, 279 (34.3%) were BCLC-A1, and 157 (19.3%) were BCLC-B. Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 86.2%, 69.0%, 56.9%, and 49.9%, respectively (p<0.001). Among patients with very early- and early-stage HCC (BCLC 0, A, and A1), patients with BCLC stage A1 had the worstOS (p=0.0016). No difference in survival was noted among patients undergoing surgery for BCLC stage A1 and B HCC (5-year OS: 56.9% vs. 49.9%; p=0.259) even after adjusting for competing factors (hazard ratio 0.83, 95% confidence interval 0.54-1.28; p=0.40).CONCLUSION: Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-B tumors. Surgery provided acceptable long-term outcomes among select patients with BCLC-B HCC. Designation into BCLC stage B should not be considered an a priori contraindication to surgery.

  View details for DOI 10.1245/s10434-019-07580-9

  View details for PubMedID 31267302

• The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management Lopez-Aguiar, A. G., Ethun, C. G., Zaidi, M. Y., Rocha, F. G., Poultsides, G. A., Dillhoff, M., Fields, R. C., Idrees, K., Cho, C. S., Abbott, D. E., Cardona, K., Maithel, S. K. MOSBY-ELSEVIER. 2019: 15–21

  View details for DOI 10.1016/j.surg.2019.03.008

  View details for Web of Science ID 000472985600003

• Esophageal and Esophagogastric Junction Cancers, Version 2.2019 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ajani, J. A., D'Amico, T. A., Bentrem, D. J., Chao, J., Corvera, C., Das, P., Denlinger, C. S., Enzinger, P. C., Fanta, P., Farjah, F., Gerdes, H., Gibson, M., Glasgow, R. E., Hayman, J. A., Hochwald, S., Hofstetter, W. L., Ilson, D. H., Jaroszewski, D., Johung, K. L., Keswani, R. N., Kleinberg, L. R., Leong, S., Ly, Q. P., Matkowskyj, K. A., McNamara, M., Mulcahy, M. F., Paluri, R. K., Park, H., Perry, K. A., Pimiento, J., Poultsides, G. A., Roses, R., Strong, V. E., Wiesner, G., Willett, C. G., Wright, C. D., McMillian, N. R., Pluchino, L. A. 2019; 17 (7): 855–83

  Abstract

  Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

  View details for DOI 10.6004/jnccn.2019.0033

  View details for Web of Science ID 000477921900012

  View details for PubMedID 31319389

• Should Utilization of Lymphadenectomy Vary According to Morphologic Subtype of Intrahepatic Cholangiocarcinoma? ANNALS OF SURGICAL ONCOLOGY Zhang, X., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Itaru, E., Pawlik, T. M. 2019; 26 (7): 2242–50

  View details for DOI 10.1245/s10434-019-07336-5

  View details for Web of Science ID 000469880000042

• Comprehensive characterization of gastric cancer at single-cell resolution Chen, J., Sathe, A., Grimes, S., Greer, S., Lau, B., Renschler, A., Poultsides, G., Suarez, C., Ji, H. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1538-7445.SABCS18-151

  View details for Web of Science ID 000488129901333

• Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer HPB Tummers, W. S., Miller, S. E., Teraphongphom, N. T., van den Berg, N. S., Hasan, A., Longacre, T. A., Fisher, G. A., Bonsing, B. A., Vahrmeijer, A. L., Gambhir, S. S., Swijnenburg, R., Rosenthal, E. L., Poultsides, G. A. 2019; 21 (7): 883–90

  View details for DOI 10.1016/j.hpb.2018.11.008

  View details for Web of Science ID 000475487400014

• Features of synchronous versus metachronous metastasectomy in adrenal cortical carcinoma: Analysis from the US adrenocortical carcinoma database. Surgery Prendergast, K. M., Smith, P. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Pawlik, T. M., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Shirley, L. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Solorzano, C. C., Kiernan, C. M. 2019

  Abstract

  BACKGROUND: Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy.METHODS: Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively. Patients were categorized as synchronous if they underwent metastasectomy at the index adrenalectomy or metachronous if they underwent resection after recurrence of the disease. Factors associated with overall survival were assessed by univariate analysis.RESULTS: In the study, 84 patients with adrenocortical carcinoma underwent metastasectomy; 26 (31%) were synchronous and 58 (69%) were metachronous. Demographics were similar between groups. The synchronous group had more T4 tumors at the index resection (42 vs 3%, P < .001). The metachronous group had prolonged median survival after the index resection (86.3 vs 17.3 months, P < .001) and metastasectomy (36.9 vs 17.3 months, P= .007). Synchronous patients with R0 resections had improved survival compared to patients with R1/2 resections (P= .008). Margin status at metachronous metastasectomy was not associated with survival (P= .452).CONCLUSION: Select patients with metastatic adrenocortical carcinoma may benefit from metastasectomy. Patients with metachronous metastasectomy have a more durable survival benefit than those undergoing synchronous metastasectomy. This study highlights need for future studies examining differences in tumor biology that could explain outcome disparities in these distinct patient populations.

  View details for DOI 10.1016/j.surg.2019.05.024

  View details for PubMedID 31272813

• Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming GUT Koutsioumpa, M., Hatziapostolou, M., Polytarchou, C., Tolosa, E. J., Almada, L. L., Mahurkar-Joshi, S., Williams, J., Belen Tirado-Rodriguez, A., Huerta-Yepez, S., Karavias, D., Kourea, H., Poultsides, G. A., Struhl, K., Dawson, D. W., Donahue, T. R., Fernandez-Zapico, M. E., Iliopoulos, D. 2019; 68 (7): 1271–86

  View details for DOI 10.1136/gutjnl-2017-315690

  View details for Web of Science ID 000471840200018

• Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative. Journal of surgical oncology Chouliaras, K., Senehi, R., Ethun, C. G., Poultsides, G., Tran, T., Grignol, V., Gamblin, T. C., Roggin, K. K., Tseng, J., Fields, R. C., Weber, S. M., Russell, G. B., Levine, E. A., Cardona, K., Votanopoulos, K. 2019

  Abstract

  BACKGROUND AND OBJECTIVES: Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival.METHODS: Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated.RESULTS: Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P=.0002), tumor grade (P=.02), local recurrence (P=.0003) and distant recurrence (P<.0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P<.0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P<.0001). Median survival from the time of recurrence was 2.5 years.CONCLUSIONS: Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.

  View details for DOI 10.1002/jso.25606

  View details for PubMedID 31246290

• Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: An International Multi-Institutional Analysis. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Tsilimigras, D. I., Sahara, K., Moris, D., Hyer, J. M., Paredes, A. Z., Bagante, F., Merath, K., Farooq, A. S., Ratti, F., Marques, H. P., Soubrane, O., Azoulay, D., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019

  Abstract

  INTRODUCTION: Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (>1cm) versus narrow (<1cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy.METHODS: Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins.RESULTS: Among 404 patients, median patient age was 66years (IQR: 58-73). Most patients (n=326, 80.7%) had surgical margin <1cm, while 78 (19.3%) patients had a >1cm margin. The majority of patients had early recurrences (<24months) in both margin width groups (<1cm: 70.3% vs >1cm: 85.7%, p=0.141); recurrence site was mostly intrahepatic (<1cm: 77% vs >1cm: 61.9%, p=0.169). The 1-, 3-, and 5-year RFS among patients with margin <1cm were 77%, 48.9%, and 35.3% versus 81.7%, 65.8%, and 60.7% for patients with margin >1cm, respectively (p=0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: <1cm: 49.2% vs >1cm: 58.9%, p=0.169), whereas in the non-anatomic resection group, margin width >1cm was associated with a better 3-year RFS compared to margin <1cm (86.7% vs 47.3%, p=0.017). On multivariable analysis, margin >1cm remained protective against recurrence (HR=0.50, 95%CI 0.28-0.89), whereas Child-Pugh B (HR=2.13, 95%CI 1.09-4.15), AFP >20 ng/mL (HR=1.71, 95%CI 1.18-2.48), and presence of microscopic lymphovascular invasion (HR=1.48, 95%CI 1.01-2.18) were associated with a higher hazard of recurrence.CONCLUSION: Resection margins >1cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (<5cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.

  View details for DOI 10.1007/s11605-019-04275-0

  View details for PubMedID 31243714

• Resection of pancreatic neuroendocrine tumors: defining patterns and time course of recurrence. HPB : the official journal of the International Hepato Pancreato Biliary Association Dong, D., Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Dillhoff, M., Maithel, S. K., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: To define recurrence patterns and time course, as well as risk factors associated with recurrence following curative resection of pNETs.METHOD: Patients who underwent curative-intent resection for pNET between 1997 and 2016 were identified from the US Neuroendocrine Tumor Study Group. Data on baseline and tumor-specific characteristics, overall survival (OS), timing and first-site of recurrence, predictors and recurrence management were analyzed.RESULTS: Among 1020 patients, 154 (15.1%) patients developed recurrence. Among patients who experienced recurrence, 76 (49.4%) had liver-only recurrence, while 35 (22.7%) had pancreas-only recurrence. The proportion of liver-only recurrence increased from 54.3% within one-year after surgery to 61.5% from four-to-six years after surgery; whereas the proportion of pancreas-only recurrence decreased from 26.1% to 7.7% over these time periods. While liver-only recurrence was associated with tumor characteristics, pancreas-only recurrence was only associated with surgical margin status. Patients undergoing curative resection of recurrence had comparable OS with patients who had no recurrence (median OS, pancreas-only recurrence, 133.9 months; liver-only recurrence, not attained; no recurrence, 143.0 months, p=0.499) CONCLUSIONS: Different recurrence patterns and timing course, as well as risk factors suggest biological heterogeneity of pNET recurrence. A personalized approach to postoperative surveillance and treatment of recurrence disease should be considered.

  View details for DOI 10.1016/j.hpb.2019.05.020

  View details for PubMedID 31235429

• A Multi-institutional International Analysis of Textbook Outcomes Among Patients Undergoing Curative-Intent Resection of Intrahepatic Cholangiocarcinoma JAMA SURGERY Merath, K., Chen, Q., Bagante, F., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Weiss, M. J., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Cloyd, J. M., Pawlik, T. M. 2019; 154 (6)

  View details for DOI 10.1001/jamasurg.2019.0571

  View details for Web of Science ID 000472168400003

• Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases A Multi-institutional, International Analysis of 1099 Patients ANNALS OF SURGERY Margonis, G., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Barbon, C., Beer, A., Kamphues, C., Loes, I., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P., Cameron, J. L., Mischinger, H., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019; 269 (6): 1129–37

  View details for DOI 10.1097/SLA.0000000000002664

  View details for Web of Science ID 000480730100028

• What Is the Best Operation for Proximal Gastric Cancer and Distal Esophageal Cancer? SURGICAL CLINICS OF NORTH AMERICA Mazer, L. M., Poultsides, G. A. 2019; 99 (3): 457-+

  View details for DOI 10.1016/j.suc.2019.02.003

  View details for Web of Science ID 000470343500006

• Association of Perioperative Transfusion with Recurrence and Survival After Resection of Distal Cholangiocarcinoma: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium Lopez-Aguiar, A. G., Ethun, C. G., Pawlik, T. M., Tran, T., Poultsides, G. A., Isom, C. A., Idrees, K., Krasnick, B. A., Fields, R. C., Salem, A., Weber, S. M., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Beal, E. W., Schmidt, C., Shenoy, R., Hatzaras, I., Maithel, S. K. SPRINGER. 2019: 1814–23

  View details for DOI 10.1245/s10434-019-07306-x

  View details for Web of Science ID 000467643800035

• Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients. Annals of surgery Margonis, G. A., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Barbon, C., Beer, A., Kamphues, C., Loes, I. M., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P. E., Cameron, J. L., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019; 269 (6): 1129–37

  Abstract

  OBJECTIVE: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis.BACKGROUND: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery.METHODS: CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences.RESULTS: According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5).CONCLUSIONS: The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.

  View details for PubMedID 31082912

• Impact of body mass index on tumor recurrence among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma- a multi-institutional international analysis EJSO Merath, K., Mehta, R., Hyer, J., Bagante, F., Sahara, K., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Weiss, M. J., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Ejaz, A., Pawlik, T. M. 2019; 45 (6): 1084–91

  View details for DOI 10.1016/j.ejso.2019.03.004

  View details for Web of Science ID 000470941000024

• Gastric carcinoids: Does type of surgery or tumor affect survival? AMERICAN JOURNAL OF SURGERY Crown, A., Kennecke, H., Kozarek, R., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Idrees, K., Smith, P., Nathan, H., Beems, M., Abbott, D., Fisher, A., Fields, R. C., Davidson, J., Maithel, S. K., Rocha, F. G. 2019; 217 (5): 937–42

  View details for DOI 10.1016/j.amjsurg.2018.12.057

  View details for Web of Science ID 000464512000024

• Predicting Pancreatic Cancer Resectability and Outcomes Based on an Objective Quantitative Scoring System Toesca, D. S., Jeffrey, R., von Eyben, R., Pollom, E. L., Poullos, P. D., Poultsides, G. A., Fisher, G. A., Visser, B. C., Koong, A. C., Chang, D. T. LIPPINCOTT WILLIAMS & WILKINS. 2019: 622–28

  View details for DOI 10.1097/MPA.0000000000001314

  View details for Web of Science ID 000480685300015

• Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Hu, L., Zhang, X., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common.OBJECTIVE: The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC.METHODS: Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed.RESULTS: A total of 920 patients were included. With a median follow-up of 38months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0m) and extrahepatic-only recurrence (median 8.0m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0m; p<0.05). On multivariate analysis, surgical margin<10mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p=0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p<0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p=0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7months) versus other treatments (9.7months) [p<0.001].CONCLUSIONS: Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.

  View details for PubMedID 31020501

• Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group. Annals of surgical oncology Lopez-Aguiar, A. G., Zaidi, M. Y., Beal, E. W., Dillhoff, M., Cannon, J. G., Poultsides, G. A., Kanji, Z. S., Rocha, F. G., Marincola Smith, P., Idrees, K., Beems, M., Cho, C. S., Fisher, A. V., Weber, S. M., Krasnick, B. A., Fields, R. C., Cardona, K., Maithel, S. K. 2019

  Abstract

  BACKGROUND: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined.METHODS: Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined.RESULTS: Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n=158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p<0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size≥2cm (odds ratio [OR] 6.6; p<0.001), proximal location (OR 2.5; p<0.001), moderate versus well-differentiation (OR 2.1; p=0.006), and Ki-67≥3% (OR 3.1; p<0.001). LN metastases were also present in tumors without these risk factors:<2cm (9%), distal location (19%), well-differentiated (23%), and Ki-67<3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p=0.198; seven or more LNs: 67% vs. 86%; p=0.002).CONCLUSIONS: Tumor size≥2cm, proximal location, moderate differentiation, and Ki-67≥3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.

  View details for PubMedID 31004295

• Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the U.S. neuroendocrine tumor study group. Journal of surgical oncology Zhang, X., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Schmidt, C. R., Maithel, S. K., Pawlik, T. M., United States Neuroendocrine Tumor Study Group 2019

  Abstract

  BACKGROUND: To determine short- and long-term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic neuroendocrine tumor (pNET).METHODS: The data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multi-institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP.RESULTS: A total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000-2004: 9.3% vs 2013-2016: 54.8%; P<0.01). In the matched cohort (n=141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200mL, P<0.001), lower incidence of Clavien-Dindo≥III complications (12.1% vs 24.8%, P=0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, P=0.026). Patients who underwent MIDP had a lower incidence of recurrence (5-year cumulative recurrence, 10.1% vs 31.1%, P<0.001), yet equivalent overall survival (OS) rate (5-year OS, 92.1% vs 90.9%, P=0.550) compared with patients who underwent OPD.CONCLUSION: Patients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar long-term OS.

  View details for PubMedID 31001868

• Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience. HPB : the official journal of the International Hepato Pancreato Biliary Association Melstrom, L. G., Eng, O. S., Raoof, M., Singh, G., Fong, Y., Latorre, K., Choi, G. H., Salem, R., Bentrem, D. J., Lewandowski, R., Makris, E., Poultsides, G., Dhar, V. K., Chadalavada, S., Shah, S. A., Johnson, A. C., Sekhar, A., Kies, D., Maithel, S. K., Rocha, F., Alseidi, A., Hagendoorn, J., Borel Rinkes, I. H., Fisher, A. V., Ronnekleiv-Kelly, S., Weber, S. M., Winslow, E. R., Abbott, D. E. 2019

  Abstract

  BACKGROUND: Single institution reports demonstrate variable safety profiles when liver-directed therapy with Yttrium-90 (Y-90) is followed by hepatectomy. We hypothesized that in well-selected patients, hepatectomy after Y90 is feasible and safe.METHODS: Nine institutions contributed data for patients undergoing Y90 followed by hepatectomy (2008-2017). Clinicopathologic and perioperative data were analyzed, with 90-day morbidity and mortality as primary endpoints.RESULTS: Forty-seven patients were included. Median age was 59 (20-75) and 62% were male. Malignancies treated included hepatocellular cancer (n=14; 30%), colorectal cancer (n=11; 23%), cholangiocarcinoma (n=8; 17%), neuroendocrine (n=8; 17%) and other tumors (n=6). The distribution of Y-90 treatment was: right (n=30; 64%), bilobar (n=14; 30%), and left (n=3; 6%). Median future liver remnant (FLR) following Y90 was 44% (30-78). Resections were primarily right (n=16; 34%) and extended right (n=14; 30%) hepatectomies. The median time to resection from Y90 was 196 days (13-947). The 90-day complication rate was 43% and mortality was 2%. Risk factors for Clavien-Dindo Grade>3 complications included: number of Y-90-treated lobes (OR 4.5; 95% CI1.14-17.7; p=0.03), extent of surgery (p=0.04) and operative time (p=0.009).CONCLUSIONS: These data demonstrate that hepatectomy following Y-90 is safe in well-selected populations. This multi-disciplinary treatment paradigm should be more widely studied, and potentially adopted, for patients with inadequate FLR.

  View details for PubMedID 31005493

• KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases. HPB : the official journal of the International Hepato Pancreato Biliary Association Margonis, G. A., Amini, N., Andreatos, N., Sasaki, K., McVey, J., Mirza, M. B., Warner, S., Buettner, S., Barbon, C., Wang, J., Pulvirenti, A., Angelou, A., Kamphues, C., Antoniou, E., Pikoulis, E., Pawlik, T. M., Kaczirek, K., Poultsides, G., Wagner, D., Endo, I., Imai, K., Aucejo, F., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2019

  Abstract

  BACKGROUND: A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined.METHODS: Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response.RESULTS: 319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P=0.01) and wtKRAS status remained independently associated with a major response (P=0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P=0.023).CONCLUSIONS: Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.

  View details for PubMedID 30979646

• Evaluating the ACS NSQIP Risk Calculator in Primary Pancreatic Neuroendocrine Tumor: Results from the US Neuroendocrine Tumor Study Group. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Dave, A., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Kanji, Z., Ronnekleiv-Kelly, S., Rendell, V. R., Fields, R. C., Krasnick, B. A., Idrees, K., Smith, P. M., Nathan, H., Beems, M., Maithel, S. K., Pawlik, T. M., Schmidt, C. R., Dillhoff, M. E. 2019

  Abstract

  BACKGROUND: In a changing health care environment where patient outcomes will be more closely scrutinized, the ability to predict surgical complications is becoming increasingly important. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) online risk calculator is a popular tool to predict surgical risk. This paper aims to assess the applicability of the ACS NSQIP calculator to patients undergoing surgery for pancreatic neuroendocrine tumors (PNETs).METHODS: Using the US Neuroendocrine Tumor Study Group (USNET-SG), 890 patients who underwent pancreatic procedures between 1/1/2000-12/31/2016 were evaluated. Predicted and actual outcomes were compared using C-statistics and Brier scores.RESULTS: The most commonly performed procedure was distal pancreatectomy, followed by standard and pylorus-preserving pancreaticoduodenectomy. For the entire group of patients studied, C-statistics were highest for discharge destination (0.79) and cardiac complications (0.71), and less than 0.7 for all other complications. The Brier scores for surgical site infection (0.1441) and discharge to nursing/rehabilitation facility (0.0279) were below the Brier score cut-off, while the rest were equal to or above and therefore not useful for interpretation.CONCLUSION: This work indicates that the ACS NSQIP risk calculator is a valuable tool that should be used with caution and in coordination with clinical assessment for PNET clinical decision-making.

  View details for PubMedID 30941685

• Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular Carcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Sahara, K., Paredes, A. Z., Merath, K., Tsilimigras, D. I., Bagante, F., Ratti, F., Marques, H. P., Soubrane, O., Beal, E. W., Lam, V., Poultsides, G. A., Popescu, I., Alexandrescu, S., Martel, G., Aklile, W., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator (SRC) aims to help predict patient-specific risk for morbidity and mortality. The performance of the SRC among an elderly population undergoing curative-intent hepatectomy for hepatocellular carcinoma (HCC) remains unknown.METHODS: Patients >70years of age who underwent hepatectomy for HCC between 1998 and 2017 were identified using a multi-institutional international database. To estimate the performance of SRC, 12 observed postoperative outcomes were compared with median SRC-predicted risk, and C-statistics and Brier scores were calculated.RESULTS: Among 500 patients, median age was 75years (IQR 72-78). Most patients (n=324, 64.8%) underwent a minor hepatectomy, while 35.2% underwent a major hepatectomy. The observed incidence of venous thromboembolism (VTE) (3.2%) and renal failure (RF) (4.4%) exceeded the median predicted risk (VTE, 1.8%; IQR 1.5-3.1 and RF, 1.0%; IQR 0.5-2.0). In contrast, the observed incidence of 30-day readmission (7.0%) and non-home discharge (2.5%) was lower than median-predicted risk (30-day readmission, 9.4%; IQR 7.4-12.8 and non-home discharge, 5.7%; IQR 3.3-11.7). Only 57.8% and 71.2% of patients who experienced readmission (C-statistic, 0.578; 95%CI 0.468-0.688) or mortality (C-statistic, 0.712; 95%CI 0.508-0.917) were correctly identified by the model.CONCLUSION: Among elderly patients undergoing hepatectomy for HCC, the SRC underestimated the risk of complications such as VTE and RF, while being no better than chance in estimating the risk of readmission. The ACS SRC has limited clinical applicability in estimating perioperative risk among elderly patients being considered for hepatic resection of HCC.

  View details for PubMedID 30937717

• Should Utilization of Lymphadenectomy Vary According to Morphologic Subtype of Intrahepatic Cholangiocarcinoma? Annals of surgical oncology Zhang, X., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Pawlik, T. M. 2019

  Abstract

  OBJECTIVE: We sought to evaluate the utilization of lymphadenectomy (LND) and the incidence of lymph node metastasis (LNM) among different morphologic types of intrahepatic cholangiocarcinoma (ICC).METHODS: Clinical data of patients undergoing curative-intent resection for ICC between 1990 and 2017 were collected and analyzed. The preoperative nodal status was evaluated by imaging studies, and the morphologic and lymph node (LN) status was collected on final pathology report.RESULTS: Overall, 1032 patients had a mass-forming (MF) or intraductal growth (IG) ICC subtype, whereas 150 patients had a periductal infiltrating (PI) or MF+PI subtype. Among the 924 patients with MF/IG ICC subtype who had nodal assessment on preoperative imaging, 747 (80.8%) were node-negative, whereas 177 (19.2%) patients were suspicious for metastatic nodal disease. On final pathological analysis, 71 of 282 (25.2%) patients who had preoperative node-negative disease ultimately had LNM. In contrast, 79 of 135 (58.5%) patients with preoperative suspicious/metastatic LNs had pathologically confirmed LNM (odds ratio [OR] 4.2, p<0.001). Among the 129 patients with PI/MF+PI ICC subtype and preoperative nodal information, 72 (55.8%) were node-negative on preoperative imaging. In contrast, 57 (44.2%) patients had suspicious/metastatic LNs. On final pathologic examination, 45.3% (n=24) of patients believed to be node-negative on preoperative imaging had LNM; 68.0% (n=34) of patients who had suspicious/positive nodal disease on imaging ultimately had LNM (OR 2.6, p=0.009).CONCLUSION: Given the low accuracy of preoperative imaging evaluation of nodal status, routine LND should be performed at the time of resection for both MF/IG and PI/MF+PI ICC subtypes.

  View details for PubMedID 30927194

• Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Buettner, S., Ten Cate, D. W., Bagante, F., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Margonis, G. A., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., IJzermans, J. N., Pawlik, T. M., Koerkamp, B. G. 2019

  Abstract

  BACKGROUND: Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci.METHODS: Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ.RESULTS: One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2months, while the median survival of patients with 2 tumors was 21.2months; the median survival of patients with 3 or more tumors was 15.3months (p<0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8months versus 14.9months among patients with OM (p<0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90-1.57; p=0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48-2.64; p<0.001).CONCLUSION: Resection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.

  View details for PubMedID 30887301

• Association of Perioperative Transfusion with Recurrence and Survival After Resection of Distal Cholangiocarcinoma: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium. Annals of surgical oncology Lopez-Aguiar, A. G., Ethun, C. G., Pawlik, T. M., Tran, T., Poultsides, G. A., Isom, C. A., Idrees, K., Krasnick, B. A., Fields, R. C., Salem, A., Weber, S. M., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Beal, E. W., Schmidt, C., Shenoy, R., Hatzaras, I., Maithel, S. K. 2019

  Abstract

  BACKGROUND: Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in multiple malignancies. The effect of blood transfusion on recurrence and survival in distal cholangiocarcinoma (DCC) is not known.METHODS: All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000 to 2015 were included. Primary outcomes were recurrence-free (RFS) and overall survival (OS).RESULTS: Among 314 patients with DCC, 191 (61%) underwent curative-intent pancreaticoduodenectomy. Fifty-three patients (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared with no-transfusion, patients who received a transfusion were more likely to have (+) margins (28 vs 14%; p=0.034) and major complications (46 vs 16%; p<0.001). Transfusion was associated with worse median RFS (19 vs 32months; p=0.006) and OS (15 vs 29months; p=0.003), which persisted on multivariable (MV) analysis for both RFS [hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.1-3.0; p=0.031] and OS (HR 1.9; 95% CI 1.1-3.3; p=0.018), after controlling for portal vein resection, estimated blood loss (EBL), grade, lymphovascular invasion (LVI), and major complications. Similarly, transfusion of≥2 pRBCs was associated with lower RFS (17 vs 32months; p<0.001) and OS (14 vs 29months; p<0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95% CI 1.4-4.5; p=0.001) and OS (HR 4.0; 95% CI 2.2-7.5; p<0.001). The RFS and OS of patients transfused 1 unit was comparable to patients who were not transfused.CONCLUSION: Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit was not associated with the same adverse effects as≥2 units.

  View details for PubMedID 30877497

• Impact of body mass index on tumor recurrence among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma- a multi-institutional international analysis. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology Merath, K., Mehta, R., Hyer, J. M., Bagante, F., Sahara, K., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Weiss, M. J., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Ejaz, A., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: The association between body mass index (BMI) and long-term outcomes of patients with ICC has not been well defined. We sought to define the presentation and oncologic outcomes of patients with ICC undergoing curative-intent resection, according to their BMI category.METHODS: Patients who underwent resection of ICC were identified in a multi-institutional database. Patients were categorized as normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI≥30 kg/m2) according to the World Health Organization (WHO) definition. Impact of clinico-pathological factors on recurrence-free survival (RFS) was assessed using Cox proportional hazards model among patients in the three BMI categories.RESULTS: Among a total of 790 patients undergoing curative-intent resection of ICC in the analytic cohort, 399 (50.5%) had normal weight, 274 (34.7%) were overweight and 117 (14.8%) were obese. Caucasian patients were more likely to be obese (66.7%, n = 78) and overweight (47.1%, n = 129) compared with Asian (obese: 18.8%, n = 22; overweight: 46%, n = 126) and other races (obese: 14.5%, n = 17; overweight: 6.9%, n = 19)(p < 0.001). There were no differences in the presence of cirrhosis (10.9%, vs. 12.8%, vs. 12.9%), preoperative jaundice (8.6% vs. 9.5% vs. 12.0%), or levels of CA 19-9 (75, IQR 24.6-280 vs. 50.9, IQR 17.9-232 vs. 43, IQR 16.9-192.7) among the BMI groups (all p > 0.05). On multivariable analysis, increased BMI was an independent risk factor for tumor recurrence (OR 1.16, 95% CI 1.02-1.32, for every 5 unit increase).CONCLUSION: Increasing BMI was associated with incremental increases in the risk of recurrence following curative-intent resection of ICC. Future studies should aim to achieve a better understanding of BMI-related factors relative to prognosis of patients with ICC.

  View details for PubMedID 30871884

• The Impact of Extent of Liver Resection Among Patients with Neuroendocrine Liver Metastasis: an International Multi-institutional Study JOURNAL OF GASTROINTESTINAL SURGERY Sham, J. G., Ejaz, A., Gage, M. M., Bagante, F., Reames, B. N., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M. J., Marques, H., Aldrighetti, L., Pawlik, T. M., He, J. 2019; 23 (3): 484–91

  Abstract

  Liver resection in patients with neuroendocrine liver metastasis (NELM) provides a survival benefit, yet the optimal extent of resection remains unknown. We sought to examine outcomes of patients undergoing non-anatomic (NAR) versus anatomic liver resection (AR) for NELM using a large international cohort of patients.Two hundred and fifty-eight patients who underwent curative intent liver resection from January 1990 to December 2016 were identified from eight institutions. Patients were excluded if they underwent concurrent ablation, had extrahepatic disease, underwent a debulking operation, or had mixed anatomic and non-anatomic resections. Overall (OS) and recurrence-free (RFS) survival were compared among patients based on the extent of liver resection (AR vs. NAR).Most primary tumors were located in the pancreas (n = 117, 45.4%) or the small intestine (n = 65, 25.2%). Liver resection consisted of NAR (n = 126, 48.8%) or AR (n = 132, 51.2%) resection. The overwhelming majority of patients who underwent NAR had an estimated liver involvement of < 50% (NAR 109, 97.3% vs. AR n = 82, 65.6%; P < 0.001). Patients who underwent NAR also had higher rates of primary tumor lymph node metastasis (NAR n = 79, 71.2% vs. AR n = 37, 33.6%; P < 0.001) and microscopically positive margins (R1) (NAR n = 29, 25.7% vs. AR n = 16, 12.5%; P = 0.009). After a median follow-up of 47.7 months, 48 (18.6%) patients died and 37.0% (n = 95) had evidence of disease recurrence. Patients who underwent AR had both longer median OS (not reached) and RFS (not reached) versus patients who underwent NAR (median OS 138.3 months; median RFS 31.3 months) (both P < 0.01). After controlling for patient and disease-related factors, extent of liver resection was independently associated with an increased risk of recurrence (HR 2.39, 95% CI 1.04-5.48; P = 0.04) but not death (HR 1.92, 95% CI 0.40-9.28; P = 0.42).NAR was independently associated with a higher incidence of recurrence versus patients who undergo a formal anatomic hepatectomy among patients with NELM.

  View details for PubMedID 29980977

• Response to preoperative chemotherapy: impact of change in total burden score and mutational tumor status on prognosis of patients undergoing resection for colorectal liver metastases. HPB : the official journal of the International Hepato Pancreato Biliary Association Ruzzenente, A., Bagante, F., Ratti, F., Beal, E. W., Alexandrescu, S., Merath, K., Makris, E. A., Poultsides, G. A., Margonis, G. A., Weiss, M. J., Popescu, I., Aldrighetti, L., Guglielmi, A., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size.METHODS: Patients who underwent hepatectomy between 2010 and 2017 were identified using a multi-centric database. This study aimed to define the impact of preoperative chemotherapy response relative to initial tumor burden score (TBS) and determine impact of clinico-pathological variables on overall survival (OS).RESULTS: Among 784 patients who received preoperative chemotherapy, the regimen was oxaliplatin- (66%) or irinotecan-based (34%). Among patients with a TBS<6at diagnosis, genetic status was the most important prognostic variable. Patients with a TBS<6, 5-year OS was 55%, 35%, and 0% for patients with KRAS/NRAS/BRAF wild-type, KRAS/NRAS, and BRAF mutations, respectively. Among patients who presented with CRLM with a TBS≥6, only Delta-TBS was prognostically important and patients with a Delta-TBS≥-10% had a 5-year OS of 27% compared with 49% for patients with a Delta-TBS<-10%.CONCLUSIONS: Prognostic stratification of patients with CRLM receiving preoperative chemotherapy should be multi-faceted and include consideration of initial tumor burden, change in tumor burden due to chemotherapy, and tumor genetic status.

  View details for PubMedID 30792047

• Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer. HPB : the official journal of the International Hepato Pancreato Biliary Association Tummers, W. S., Miller, S. E., Teraphongphom, N. T., van den Berg, N. S., Hasan, A., Longacre, T. A., Fisher, G. A., Bonsing, B. A., Vahrmeijer, A. L., Gambhir, S. S., Swijnenburg, R., Rosenthal, E. L., Poultsides, G. A. 2019

  Abstract

  BACKGROUND: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC).METHODS: A dose-escalation prospective study was performed to assess feasibility of tumor detection within peripancreatic LNs using cetuximab-IRDye800 in PDAC patients. Fluorescent imaging of dissected LNs was analyzed exvivo macroscopically and microscopically and fluorescence was correlated with histopathology.RESULTS: A total of 144 LNs (72 in the low-dose and 72 in the high-dose cohort) were evaluated. Detection of metastatic LNs by fluorescence was better in the low-dose (50mg) cohort, where sensitivity and specificity was 100% and 78% macroscopically, and 91% and 66% microscopically. More importantly, this method was able to detect occult foci of tumor (measuring<5mm) with a sensitivity of 88% (15/17 LNs).CONCLUSION: This study provides proof of concept that intraoperative fluorescent imaging with cetuximab-IRDye800 can facilitate the detection of peripancreatic lymph nodes often containing subclinical foci of disease.

  View details for PubMedID 30723062

• Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity? Lee, R. M., DePalo, D. K., Lopez-Aguiar, A. G., Zaidi, M., Rocha, F. G., Kanji, Z. S., Poultsides, G. A., Makris, E., Dillhoff, M., Beal, E. W., Fields, R., Panni, R. Z., Idrees, K., Smith, P., Nathan, H., Beems, M., Abbott, D., Rendell, V., Maithel, S. K., Russell, M. C. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.4_suppl.376

  View details for Web of Science ID 000489107600405

• Complications after liver surgery: a benchmark analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Bagante, F., Ruzzenente, A., Beal, E. W., Campagnaro, T., Merath, K., Conci, S., Akgul, O., Alexandrescu, S., Marques, H. P., Lam, V., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Iacono, C., Guglielmi, A., Pawlik, T. M. 2019

  Abstract

  BACKGROUND: The best achievable short-term outcomes after liver surgery have not been identified. Several factors may influence the post-operative course of patients undergoing hepatectomy increasing the risk of post-operative complications. We sought to identify risk-adjusted benchmark values [BMV] for liver surgery.METHODS: The National Surgery Quality Improvement Program (NSQIP) database was used to develop Bayesian models to estimate risk-adjusted BMVs for overall and liver related (post-hepatectomy liver failure [PHLF], biliary leakage [BL]) complications. A separate international multi-institutional database was used to validate the risk-adjusted BMVs.RESULTS: Among the 11,243 patients included in the NSQIP database, the incidence of complications, PHLF, and BL was 36%, 5%, and 8%, respectively. The risk-adjusted BMVs for complication (range, 16-72%), PHLF (range, 1%-20%), and BL (range, 4%-22%) demonstrated a high variability based on patients characteristics. When tested using an international database including nine institutes, the risk-adjusted BMVs for complications ranged from 26% (Institute-4) to 43% (Institute-1), BMVs for PHLF between 3% (Institute-3) and 12% (Institute-5), while BMVs for BL ranged between 5% (Institute-4) and 9% (Institute-7).CONCLUSIONS: Multiple factors influence the risk of complications following hepatectomy. Risk-adjusted BMVs are likely much more applicable and appropriate in assessing "acceptable" benchmark outcomes following liver surgery.

  View details for PubMedID 30718185

• Resection margin distance in extrahepatic cholangiocarcinoma: How much is enough? Rahnemai-Azar, A. A., Ronnekleiv-Kelly, S., Abbott, D., Ethun, C., Poultsides, G. A., Thuy Tran, Fields, R., Krasnick, B., Martin, R. G., Scoggins, C., Idrees, K., Isom, C. A., Hatzaras, I., Shenoy, R., Shen, P., Perkins, J. D., Pawlik, T. M., Maithel, S. K., Weber, S. M. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.4_suppl.455

  View details for Web of Science ID 000489107600483

• Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Fisher, A. V., Lopez-Aguiar, A. G., Rendell, V. R., Pokrzywa, C., Rocha, F. G., Kanji, Z. S., Poultsides, G. A., Makris, E. A., Dillhoff, M. E., Beal, E. W., Fields, R. C., Panni, R. Z., Idrees, K., Smith, P. M., Cho, C. S., Beems, M. V., Maithel, S. K., Winslow, E. R., Abbott, D. E., Weber, S. M. 2019

  Abstract

  INTRO: Chromogranin A (CgA) may be prognostic for patients with neuroendocrine tumors; however, the clinical utility of this test is unclear.METHODS: Patients undergoing resection for pancreatic neuroendocrine tumors (pNET) were selected from the eight institutions of the US Neuroendocrine Tumor Study Group database. Cox regression was used to identify pre-operative variables that predicted recurrence-free survival (RFS), and those with p<0.1 were included in a risk score. The risk score was tested in a unique subset of the overall cohort.RESULTS: In the entire cohort of 287 patients, median follow-up time was 37months, and 5-year RFS was 73%. Cox regression analysis identified four variables for inclusion in the risk score: CgA >5x ULN (HR 4.3, p=0.01), tumor grade 2/3 (HR 3.7, p=0.01), resection for recurrent disease (HR 6.2, p<0.01), and tumor size >4cm (HR 4.5, p=0.1). Each variable was assigned 1 point. Risk-score testing in the unique validation cohort of 63 patients revealed a 95% negative predictive value for recurrence in patients with zero points.DISCUSSION: This simple pre-operative risk scoring system resulted in a high degree of specificity for identifying patients at low-risk for tumor recurrence. This test can be utilized pre-operatively to aid informed decision-making.

  View details for PubMedID 30659439

• What Is the Best Operation for Proximal Gastric Cancer and Distal Esophageal Cancer? The Surgical clinics of North America Mazer, L. M., Poultsides, G. A. 2019; 99 (3): 457–69

  Abstract

  Cancer of the gastroesophageal junction (GEJ) is increasing in incidence, likely as a result of rising obesity and gastroesophageal reflux disease rates. The tumors that arise here share features of esophageal and gastric cancer, and are classified based on their location in relationship to the GEJ. The definition of the GEJ itself, as well as optimal resection strategy, extent of lymph node dissection, resection margin length, and reconstruction methods are still very much a subject of debate. This article summarizes the available evidence on this topic, and highlights specific areas for further research.

  View details for PubMedID 31047035

• Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi-institutional analysis. Journal of surgical oncology Wu, L., Sahara, K., Tsilimigras, D. I., Maithel, S. K., Poultsides, G. A., Rocha, F. G., Weber, S. M., Fields, R. C., Idrees, K., Cho, C. S., Shen, F., Pawlik, T. M. 2019

  Abstract

  The benefit derived from lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) based on clinicopathological characteristics remains unclear.Patients undergoing surgery for pNET between 1997 and 2016 were identified using a multi-institutional dataset. The therapeutic index of LND relative to patient characteristics was calculated.Among 647 patients, the median number of lymph nodes (LNs) evaluated was 10 (interquartile range: 4-16) and approximately one quarter of patients had lymph node metastasis (LNM) (N = 159, 24.6%). Among patients with LNM, 5-year recurrence-free survival was 56.0%, reflecting a therapeutic index value of 13.8. The therapeutic index was highest among patients with a moderately/poorly-differentiated pNET (21.5), Ki-67 ≥ 3% (20.1), tumor size ≥2.0 cm (20.0), and tumor location at the head of the pancreas (20.0). Patients with ≥8 LNs evaluated had a higher therapeutic index than patients who had 1 to 7 LNs evaluated (≥8: 17.9 vs 1-7: 7.5; difference of index: 11.4).LND was mostly beneficial among patients with pNETs >2 cm, Ki-67 ≥ 3%, and lesions located at the pancreatic head as identification of LNM was most common among individuals with these tumor characteristics. Evaluation of ≥8 LNs was associated with a higher likelihood of identifying LNM as well as a higher therapeutic index, and therefore this number of LNs should be considered the goal.

  View details for DOI 10.1002/jso.25689

  View details for PubMedID 31468550

• Correction to: Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on Patients Undergoing Curative Intent Liver Surgery. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Spolverato, G., Bagante, F., Aldrighetti, L., Poultsides, G., Bauer, T. W., Fields, R. C., Marques, H. P., Weiss, M., Maithel, S. K., Pawlik, T. M. 2019

  Abstract

  There is an error in an author's name in this paper, Ryan C. Field should be Ryan C. Fields. The correct author list is above.

  View details for DOI 10.1007/s11605-019-04371-1

  View details for PubMedID 31529199

• Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group. HPB : the official journal of the International Hepato Pancreato Biliary Association Marincola Smith, P., Baechle, J., Solórzano, C. C., Tan, M., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E., Poultsides, G., Cannon, J. G., Rocha, F. G., Crown, A., Cho, C., Beems, M., Winslow, E. R., Rendell, V. R., Krasnick, B. A., Fields, R. C., Maithel, S. K., Bailey, C. E., Idrees, K. 2019

  Abstract

  Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection.A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression.Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia.PRBC transfusion is associated with worse survival for patients undergoing PNET resection.

  View details for DOI 10.1016/j.hpb.2019.10.2441

  View details for PubMedID 31806388

• Conditional disease-free survival after curative-intent liver resection for neuroendocrine liver metastasis. Journal of surgical oncology Sahara, K., Merath, K., Tsilimigras, D. I., Hyer, J. M., Guglielmi, A., Aldrighetti, L., Weiss, M., Fields, R. C., Poultsides, G. A., Maithel, S. K., Endo, I., Pawlik, T. M. 2019

  Abstract

  Neuroendocrine liver metastases (NELM) are typically associated with high recurrence rates following surgical resection. Conditional disease-free survival (CDFS) estimates may be more clinically relevant compared to actuarial survival estimates.CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with disease-free survival (DFS). Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as CDFS3  = DFS(x + 3)/DFS(x).A total of 521 patients met the inclusion criteria. While actuarial 3-year DFS gradually decreased from 49% at 1 year to 39% at 5 years, CDFS3 increased over time. CDFS3 at 5 years was estimated as 89% vs actuarial 8-year DFS of 39% (P < .001). The probability of remaining disease-free at 5 years after resection increased as patients remained disease-free. For example, the probability of being disease-free for an additional 3 years was 66.3% and 88.8% for patients who lived 2 and 5 years, respectively. Overall, CDFS3 in each subgroup increased postoperatively as years elapsed, however, the impact of each prognostic factor on CDFS3 changed over time.CDFS of patients who underwent resection of NELM exponentially improved as patients survived additional years without recurrence. CDFS provides more accurate prognostic measures compared with traditional DFS measures.

  View details for DOI 10.1002/jso.25713

  View details for PubMedID 31550406

• Trends in the Number of Lymph Nodes Evaluated Among Patients with Pancreatic Neuroendocrine Tumors in the United States: A Multi-Institutional and National Database Analysis. Annals of surgical oncology Sahara, K., Tsilimigras, D. I., Mehta, R., Moro, A., Paredes, A. Z., Lopez-Aguiar, A. G., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Poultsides, G. A., Makris, E., Cho, C., Beems, M., Dillhoff, M., Maithel, S. K., Endo, I., Pawlik, T. M. 2019

  Abstract

  The role of routine lymphadenectomy in the surgical treatment of pancreatic neuroendocrine tumors (pNET) remains poorly defined. The objective of the current study was to investigate trends in the number of lymph nodes (LN) evaluated for pNET treatment at a nationwide level.Patients undergoing surgery for pNET between 2000 and 2016 were identified in the U.S. Neuroendocrine Tumor Study Group (US-NETSG) database as well as the Surveillance, Epidemiology, and End Results (SEER) database. The number of LNs examined was evaluated over time.The median number of evaluated LNs increased roughly fourfold over the study period (US-NETSG, 2000: 3 LNs vs. 2016: 13 LNs; SEER, 2000: 3 LNs vs. 2016: 11 LNs, both p < 0.001). While no difference in 5-year OS and RFS was noted among patients who had 1-3 lymph node metastases (LNM) vs. ≥ 4 LNM between 2000-2007 (OS 73.5% vs. 69.9%, p = 0.12; RFS: 64.9% vs. 40.1%, p = 0.39), patients who underwent resection and LN evaluation during the period 2008-2016 had an incrementally worse survival if the patient had node negative disease, 1-3 LNM and ≥ 4 LNM (OS 86.8% vs. 82.7% vs. 74.9%, p < 0.001; RFS: 86.3% vs. 64.7% vs. 50.4%, p < 0.001). On multivariable analysis, a more recent year of diagnosis, pancreatic head tumor location, and tumor size > 2 cm were associated with 12 or more LNs evaluated in both US-NETSG and SEER databases.The number of LNs examined nearly quadrupled over the last decade. The increased number of LNs examined suggested a growing adoption of the AJCC staging manual recommendations regarding LN evaluation in the treatment of pNET.

  View details for DOI 10.1245/s10434-019-08120-1

  View details for PubMedID 31838609

• A Machine-Based Approach to Preoperatively Identify Patients with the Most and Least Benefit Associated with Resection for Intrahepatic Cholangiocarcinoma: An International Multi-institutional Analysis of 1146 Patients. Annals of surgical oncology Tsilimigras, D. I., Mehta, R., Moris, D., Sahara, K., Bagante, F., Paredes, A. Z., Moro, A., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Endo, I., Pawlik, T. M. 2019

  Abstract

  Accurate risk stratification and patient selection is necessary to identify patients who will benefit the most from surgery or be better treated with other non-surgical treatment strategies. We sought to identify which patients in the preoperative setting would likely derive the most or least benefit from resection of intrahepatic cholangiocarcinoma (ICC).Patients who underwent curative-intent resection for ICC between 1990 and 2017 were identified from an international multi-institutional database. A machine-based classification and regression tree (CART) was used to generate homogeneous groups of patients relative to overall survival (OS) based on preoperative factors.Among 1146 patients, CART analysis revealed tumor number and size, albumin-bilirubin (ALBI) grade and preoperative lymph node (LN) status as the strongest prognostic factors associated with OS among patients undergoing resection for ICC. In turn, four groups of patients with distinct outcomes were generated through machine learning: Group 1 (n = 228): single ICC, size ≤ 5 cm, ALBI grade I, negative preoperative LN status; Group 2 (n = 708): (1) single tumor > 5 cm, (2) single tumor ≤ 5 cm, ALBI grade 2/3, and (3) single tumor ≤ 5 cm, ALBI grade 1, metastatic/suspicious LNs; Group 3 (n = 150): 2-3 tumors; Group 4 (n = 60): ≥ 4 tumors. 5-year OS among Group 1, 2, 3, and 4 patients was 60.5%, 35.8%, 27.5%, and 3.8%, respectively (p < 0.001). Similarly, 5-year disease-free survival (DFS) among Group 1, 2, 3, and 4 patients was 47%, 27.2%, 6.8%, and 0%, respectively (p < 0.001).The machine-based CART model identified distinct prognostic groups of patients with distinct outcomes based on preoperative factors. Survival decision trees may be useful as guides in preoperative patient selection and risk stratification.

  View details for DOI 10.1245/s10434-019-08067-3

  View details for PubMedID 31728792

• Therapeutic Index Associated with Lymphadenectomy Among Patients with Intrahepatic Cholangiocarcinoma: Which Patients Benefit the Most from Nodal Evaluation? Annals of surgical oncology Sahara, K., Tsilimigras, D. I., Merath, K., Bagante, F., Guglielmi, A., Aldrighetti, L., Weiss, M., Bauer, T. W., Alexandrescu, S., Poultsides, G. A., Maithel, S. K., Marques, H. P., Martel, G., Pulitano, C., Shen, F., Soubrane, O., Koerkamp, B. G., Matsuyama, R., Endo, I., Pawlik, T. M. 2019

  Abstract

  Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear.Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup.Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)].The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM.

  View details for DOI 10.1245/s10434-019-07483-9

  View details for PubMedID 31152272

• The conundrum of < 2-cm pancreatic neuroendocrine tumors: A preoperative risk score to predict lymph node metastases and guide surgical management. Surgery Lopez-Aguiar, A. G., Ethun, C. G., Zaidi, M. Y., Rocha, F. G., Poultsides, G. A., Dillhoff, M., Fields, R. C., Idrees, K., Cho, C. S., Abbott, D. E., Cardona, K., Maithel, S. K. 2019

  Abstract

  Management of <2-cm pancreatic neuroendocrine tumors is controversial. Although often indolent, the oncologic heterogeneity of these tumors particularly related to lymph node metastases poses challenges when deciding between resection versus surveillance.We analyzed all patients who underwent resection of primary nonfunctional <2-cm with curative-intent at 8 institutions of the US Neuroendocrine Tumor Study Group from 2000 to 2016. Pancreatic neuroendocrine tumors with poor differentiation and Ki-67 > 20% were excluded. Our primary aim was to create a lymph node risk score that predicted lymph node metastases accurately for <2-cm pancreatic neuroendocrine tumors, utilizing readily available preoperative data.Of 695 patients with resected pancreatic neuroendocrine tumors, 309 were <2 cm. Of these small pancreatic neuroendocrine tumors, 25% were proximal (head/uncinate), 23% had a Ki-67 > 3%, and only 8% were moderately differentiated. Also, only 9% of all <2-cm pancreatic neuroendocrine tumors were lymph node (+). Indeed lymph node positivity was associated with worse 5-year recurrence-free survival compared with lymph node (-) disease (80% vs 96%; P = .007). Factors known preoperatively to be associated with lymph node metastases were proximal location (odds ratio 4.0; P = .002) and Ki-67 >3% (odds ratio 2.7; P = .05). Moderate differentiation was not associated with lymph node (+) disease. Location and Ki-67 were assigned a value weighted by their odds ratio: (distal= 1, proximal= 4, and Ki-67 < 3% = 1 and Ki-67 > 3% = 3), which formed a lymph node risk score ranging 1-7. Scores were categorized into low (1-2), intermediate (3-4), and high (5-7) risk groups. Incidence of lymph node metastases increased progressively based on risk group, with low = 3.2%, intermediate = 13.8%, and high = 20.5%. Only 3.4% of pancreatic neuroendocrine tumors with a Ki-67 < 3% in the distal pancreas were lymph node (+) compared with 21.4% of pancreatic neuroendocrine tumors with a Ki-67 > 3% in the head/uncinate.This simple and novel lymph node risk score utilizes readily available preoperative factors (tumor location and Ki-67) to stratify risk of lymph node metastases accurately s for < 2-cm pancreatic neuroendocrine tumors and may help guide management strategy.

  View details for PubMedID 31072670

• A Multi-Institutional International Analysis of Textbook Outcomes Among Patients Undergoing Curative-Intent Resection of Intrahepatic Cholangiocarcinoma. JAMA surgery Merath, K., Chen, Q., Bagante, F., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Weiss, M. J., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Cloyd, J. M., Pawlik, T. M. 2019: e190571

  Abstract

  Composite measures may be superior to individual measures for the analysis of hospital performance and quality of surgical care.To determine the incidence of a so-called textbook outcome, a composite measure of the quality of surgical care, among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.This cohort study involved an analysis of a multinational, multi-institutional cohort of patient from 15 major hepatobiliary centers in North America, Europe, Australia, and Asia who underwent curative-intent resection of intrahepatic cholangiocarcinoma between 1993 and 2015. Data analysis was conducted from April 2018 to May 2018.Hospital variation in the composite end point of textbook outcome, defined as negative margins, no perioperative transfusion, no postoperative surgical complications, no prolonged length of stay, no 30-day readmissions, and no 30-day mortality. Secondary end points were factors associated with achieving textbook outcomes.Among 687 patients (of whom 370 [53.9%] were men; median patient age, 61 [range, 18-86] years) undergoing curative-intent resection of intrahepatic cholangiocarcinoma, a textbook outcome was achieved in 175 patients (25.5%). Being 60 years or younger (odds ratio [OR], 1.61 [95% CI, 1.04-2.49]; P = .03), absence of preoperative jaundice (OR, 4.40 [95% CI, 1.28-15.15]; P = .02), no neoadjuvant chemotherapy (OR, 2.57 [95% CI, 1.05-6.29]; P = .04), T1a/T1b-stage disease (OR, 1.58 [95% CI, 1.01-2.49]; P = .049), N0 status (OR, 3.89 [95% CI, 1.77-8.54]; P = .001), and no bile duct resection (OR, 2.46 [95% CI, 1.25-4.84]; P = .009) were independently associated with achieving a textbook outcome after resection. A prolonged length of stay had the greatest negative association with a textbook outcome. A nomogram to assess the probability of textbook outcome was developed and had good accuracy in both the training data set (area under the curve, 0.755) and validation data set (area under the curve, 0.763).In this study, while hepatic resection for intrahepatic cholangiocarcinoma was performed with less than 5% mortality in specialized centers, a textbook outcome was achieved in only approximately 26% of patients. A textbook outcome may be useful for the reporting of patient-level hospital performance and hospital variation, leading to quality improvement efforts after resection of intrahepatic cholangiocarcinoma.

  View details for PubMedID 31017645

• Outcomes of Elderly Patients Undergoing Curative Resection for Retroperitoneal Sarcomas: Analysis From the US Sarcoma Collaborative. The Journal of surgical research Wilkinson, K. H., Ethun, C. G., Hembrook, M., Bedi, M., Charlson, J., Mogal, H., Tsai, S., Christians, K., Tran, T. B., Poultsides, G., Grignol, V., Howard, J. H., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Weber, S., Gamblin, T. C., Cardona, K., Clarke, C. N. 2019; 233: 154–62

  Abstract

  BACKGROUND: The postoperative outcomes of elderly patients undergoing resection of retroperitoneal sarcomas (RPS) have not been widely studied.METHODS: Patients undergoing surgical resection for primary or recurrent RPS between 2000 and 2015 at participating US Sarcoma Collaborative institutions were identified. Patient demographics, perioperative morbidity, mortality, length of stay, discharge to home, disease-specific survival, and disease-free survival were compared between elderly (≥70y, n=171) and nonelderly (<70y, n=494) patients.RESULTS: There was no difference in perioperative morbidity (total and major complications elderly versus nonelderly: 39% versus 35%; P=0.401 and 18% versus 17%; P=0.646, respectively) or mortality between elderly and nonelderly patients with each group experiencing a 1% 30-d mortality rate. Length of stay and 30-d readmission rates were similar (elderly versus nonelderly; 7d interquartile range [IQR: 5-9] versus 6d [IQR: 4-9], P=0.528 and 11% versus 12%, P=0.667). Elderly patients were more likely to be discharged to a skilled nursing or rehabilitation facility (elderly versus nonelderly; 19% versus 7%, P<0.001). There was no difference in 3-y disease-free survival between the elderly and nonelderly patients (41% versus 43%, P=0.65); however, elderly patients had a lower 3-y disease-specific survival (60% versus 76%, P<0.001). In elderly patients, the presence of multiple comorbidities and high-grade tumors were most predictive of outcomes.CONCLUSIONS: Advanced age was not associated with an increased risk of perioperative morbidity and mortality following resection of RPS in this multi-institutional review. Although short-term oncologic outcomes were similar in both groups, the risk of death after sarcoma recurrence was higher in elderly patients and may be related to comorbidity burden and tumor histology.

  View details for PubMedID 30502242

• The role of radiation therapy and margin width in localized soft-tissue sarcoma: Analysis from the US Sarcoma Collaborative. Journal of surgical oncology Gannon, N. P., King, D. M., Ethun, C. G., Charlson, J., Tran, T. B., Poultsides, G., Grignol, V., Howard, J. H., Tseng, J., Roggin, K. K., Votanopoulos, K., Krasnick, B., Fields, R. C., Cardona, K., Bedi, M. 2019

  Abstract

  Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR).From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups.LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively).RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.

  View details for DOI 10.1002/jso.25522

  View details for PubMedID 31172531

• The impact of unplanned excisions of truncal/extremity soft tissue sarcomas: A multi-institutional propensity score analysis from the US Sarcoma Collaborative. Journal of surgical oncology Zaidi, M. Y., Ethun, C. G., Liu, Y., Poultsides, G., Howard, J. H., Mogal, H., Tseng, J., Votanopoulos, K., Fields, R. C., Cardona, K. 2019

  Abstract

  Our aim was to compare outcomes in patients who underwent unplanned excisions (UE) of soft-tissue sarcomas (STS) against patients with planned excisions (PE).The retrospective 7-institution US Sarcoma Collaborative database was used. Patients with curative-intent resection of truncal/extremity STS between 2000 and 2016 were included. Propensity score weighting analysis (PSWA) was performed. Endpoints were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS).One thousand five hundred and ninety-six patients were included. Eighty-two percent (n = 1315) underwent PE and 18% (n = 281) underwent UE. Compared with PE, patients with UE were younger with smaller tumors with similar tumor grade. Unmatched analysis revealed PE was associated with worse DMFS (hazard ratio [HR] 1.95, P = .009) and DSS (HR 1.78, P = .039), but not LRFS compared with UE. On PSWA, UE had earlier LRFS (3-year LRFS: 80.5% vs 89.8%, P = .039), but not DMFS or DSS. By grade, patients with high-grade tumors and UE had worse LRFS (1-year LRFS: 90% vs 94%, P = .015), but similar DMFS and DSS compared with PE. In low-grade patients, UE and PE had similar LRFS, DMFS, or DSS.UE of STS is not associated with worse prognosis compared to PE, though UE is associated with earlier locoregional recurrence in patients with high-grade tumors. Multimodality therapy is needed to achieve improved outcomes in these patients.

  View details for DOI 10.1002/jso.25521

  View details for PubMedID 31172536

• Association of preoperative monocyte-to-lymphocyte and neutrophil-to-lymphocyte ratio with recurrence-free and overall survival after resection of pancreatic neuroendocrine tumors (US-NETSG). Journal of surgical oncology Panni, R. Z., Lopez-Aguiar, A. G., Liu, J., Poultsides, G. A., Rocha, F. G., Hawkins, W. G., Strasberg, S. M., Trikalinos, N. A., Maithel, S., Fields, R. C. 2019

  Abstract

  Preoperative systemic inflammatory response plays a crucial role in tumorigenesis, progression, and prognosis; and neutrophil, monocyte, and lymphocyte counts serve as important biomarkers. An altered monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and breast cancer. The aim of this study was to investigate the prognostic significance of MLR, NLR in patients with resectable PNETs.Patients undergoing surgery for PNETs between 2000 and 2016 were identified using a large, multi-center database. NLR and MLR were calculated and Contal and O'Quigley analysis was used to determine the optimal cutoff value.A total of 620 patients were included in the analytic cohort. The prognostic implications of blood count parameters were evaluated in both univariate and multivariate analysis. The univariate analysis revealed that low MLR and NLR is associated with significantly improved overall survival (OS; P < .01) and recurrence-free survival (RFS; P < .01). On multivariate analysis, in addition to tumor size and grade, NLR was an independent predictor of improved OS and RFS.In addition to established tumor-specific factors, preoperative NLR levels can serve as a valuable biomarker that can be used as a predictor of OS and RFS after resection of PNETs.

  View details for DOI 10.1002/jso.25629

  View details for PubMedID 31339198

• Management of Ileal Neuroendocrine Tumors with Liver Metastases. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Fisher, A. T., Titan, A. L., Foster, D. S., Worth, P. J., Poultsides, G. A., Visser, B. C., Dua, M. M., Norton, J. A. 2019

  Abstract

  Assessment of treating metastatic ileal neuroendocrine tumors (NETs) with complete resection of primary tumor, nodal and liver metastases, plus administration of long-acting somatostatin analogues (SSAs).A prospective database was queried for patients with ileal or pancreatic NETs with pathology-confirmed liver metastases and tumor somatostatin receptors. Patients did not have MEN-1 and had no previous treatment. The impacts of SSA treatment on the primary outcome of survival and secondary outcome of progression-free survival were assessed with Kaplan-Meier analysis. Log rank test was used to compare overall and progression-free survival among groups.Seventeen ileal NET patients and 36 pancreatic NET patients who underwent surgical resection between 2001 and 2018, who had pathology-confirmed liver metastases and confirmed tumor somatostatin receptors, did not have MEN-1, and had no previous treatment were identified. Median follow-up for patients with ileal NETs was 80 months (range 0-197 months) and 32 months (range 1-182 months) for pancreatic NETs. Five-year survival was 93% and 72% for ileal and pancreatic NET, respectively. Progression-free 5-year survival was 70% and 36% for ileal and pancreatic NET, respectively. Overall 5-year survival for pNETs was greater in those patients treated with SSA (79%) compared to those who underwent surgery alone (34%, p < 0.01). The average ECOG score was low for surviving patients with ileal (0.15) and pancreatic NET (0.73) indicating a good quality of life.Resection of primary lymph node and liver metastatic ileal or pancreatic NETs followed with continued SSAs is associated with an excellent progression-free and overall survival and minimal side effects.

  View details for DOI 10.1007/s11605-019-04309-7

  View details for PubMedID 31346887

• Lung Surveillance Strategy for High-Grade Soft Tissue Sarcomas: Chest X-Ray or CT Scan? Journal of the American College of Surgeons Gamboa, A. C., Ethun, C. G., Switchenko, J. M., Lipscomb, J., Poultsides, G. A., Grignol, V., Howard, J. H., Gamblin, T. C., Roggin, K. K., Votanopoulos, K., Fields, R. C., Maithel, S. K., Delman, K. A., Cardona, K. 2019

  Abstract

  Given the propensity for lung metastases (LM), NCCN guidelines recommend lung surveillance (LS) with either CXR or CT in high-grade soft tissue sarcoma (HG-STS). Considering survival, diagnostic sensitivity and cost, the optimal modality is unknown.The US Sarcoma Collaborative database (2000-2016) was reviewed for patients who underwent resection of a primary HG-STS. Primary outcome was overall survival (OS). Cost analysis was performed.Among 909pts, 83% had truncal/extremity, 17% had retroperitoneal (RP) tumors. Recurrence occurred in 48% of which 54% were LM. LS was performed with CT in 80% and CXR in 20%. Both groups were clinically similar although CT patients had more RP tumors and recurrences. Regardless of modality, 85-90% of LM were detected within the first 2yrs with a similar re-intervention rate. When considering age, tumor size, location, margin status, and receipt of radiation, LM was independently associated with worse OS(HR:4.26; p<0.01) while imaging modality was not(HR:1.01; p=0.97). CXR patients did not have an inferior 5-year OS compared to CT(71vs60%, p<0.01). When analyzing patients in whom no LM was detected, both cohorts had a similar 5-year OS(73vs74%, p=0.42), suggesting CXR was not missing clinically relevant lung nodules. When adhering to a guideline-specified protocol for 2018 projected 4,406 cases, surveillance with CXR for 5yrs results in savings of $5-8M/year to the US healthcare system.In this large multicenter study, LS with CXR did not result in worse overall survival when compared to CT. With considerable savings, a CXR-based protocol may optimize resource utilization for LS in HG-STS; prospective trials are needed.

  View details for DOI 10.1016/j.jamcollsurg.2019.07.010

  View details for PubMedID 31377411

• Trends in the Use of Adjuvant Chemotherapy for High-Grade Truncal and Extremity Soft Tissue Sarcomas. The Journal of surgical research Squires, M. H., Ethun, C. G., Suarez-Kelly, L. P., Yu, P. Y., Hughes, T. M., Shelby, R. D., Tran, T. B., Poultsides, G., Charlson, J., Gamblin, T. C., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Pollock, R. E., Grignol, V., Cardona, K., Howard, J. H. 2019; 245: 577–86

  Abstract

  In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers.The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS.949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P < 0.001), younger age (53.3 versus 63.7 years, P < 0.001), and receipt of adjuvant radiation (P < 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P < 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P < 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23).Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data.

  View details for DOI 10.1016/j.jss.2019.08.002

  View details for PubMedID 31494391

• Predictors of Disease-Free and Overall Survival in Retroperitoneal Sarcomas: A Modern 16-Year Multi-Institutional Study from the United States Sarcoma Collaboration (USSC). Sarcoma Schwartz, P. B., Vande Walle, K., Winslow, E. R., Ethun, C. G., Tran, T. B., Poultsides, G., Tseng, J., Roggin, K., Grignol, V., Howard, J. H., Krasnick, B. A., Fields, R. C., Mogal, H., Clarke, C. N., Senehi, R., Votanopoulos, K., Cardona, K., Abbott, D. E. 2019; 2019: 5395131

  Abstract

  Background: Retroperitoneal sarcomas (RPS) comprise approximately 15% of all soft-tissue sarcomas and frequently associated with significant morbidity and as little as 30% 5-year survival. Here, we provide a large, contemporary, and multi-institutional experience to determine which tumor, patient, and treatment characteristics are associated with long-term outcomes in RPS.Methods: 571 patients with primary RPS were identified from the United States Sarcoma Collaboration (USSC). RPS patients who underwent resection from January 2000 to April 2016 were included with patient, tumor, and treatment-specific variables investigated as independent predictors of survival. Survival analyses for disease-free and overall survival were conducted using Kaplan-Meier and Cox proportional hazards model methods.Results: The study cohort was 55% female, with a median age of 58.9years (IQR: 48.6-70.0). The most common tumor histiotypes were liposarcoma (34%) and leiomyosarcoma (28%). Median follow-up was 30.6months (IQR: 11.2-60.4). Median disease-free survival was 35.3months (95% CI: 27.6-43.0), with multivariate predictors of poorer disease-free survival including higher grade tumors, nodal-positive disease, and multivisceral resection. Median overall survival was 81.6months (95% CI: 66.3-96.8). Multivariate predictors of shorter overall survival included higher grade tumors, nodal-positive and multifocal disease, systemic chemotherapy, and grossly positive margins (R2) following resection.Conclusions: The strongest predictors of disease-free and overall survival are tumor-specific characteristics, while surgical factors are less impactful. Nonsurgical therapies are not associated with improved outcomes despite persistent interest and utilization. Complete macroscopic resection (R0/R1) remains a persistent potentially modifiable risk factor associated with improved overall survival in patients with retroperitoneal sarcomas.

  View details for DOI 10.1155/2019/5395131

  View details for PubMedID 31281208

• Hospital variation in Textbook Outcomes following curative-intent resection of hepatocellular carcinoma: an international multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Tsilimigras, D. I., Mehta, R., Merath, K., Bagante, F., Paredes, A. Z., Farooq, A., Ratti, F., Marques, H. P., Silva, S., Soubrane, O., Lam, V., Poultsides, G. A., Popescu, I., Grigorie, R., Alexandrescu, S., Martel, G., Workneh, A., Guglielmi, A., Hugh, T., Aldrighetti, L., Endo, I., Pawlik, T. M. 2019

  Abstract

  Composite measures such as "Textbook Outcome" (TO) may be superior to individual quality metrics to assess surgical care and hospital performance. However, the incidence and factors associated with TO after resection of HCC remain poorly defined.Hospital variation in the rates of TO, factors associated with achieving a TO and the impact of TO on long-term survival following resection for HCC were examined using an international multi-institutional database.Among 605 patients who underwent curative-intent resection of HCC, the unadjusted incidence of TO ranged from 50.9% to 77.7%. While achievement of each individual quality metric was relatively high (range, 74.5-98.0%), an overall TO was achieved among only 62.3% (n = 377) of patients. At the hospital level, TO ranged from 54.3% to 72.9%. Patients with BCLC-0 HCC (referent BCLC-B/C; OR: 4.17, 95%CI: 1.62-10.7) and ALBI grade 1 (referent ALBI grade 2/3; OR: 1.49, 95%CI: 1.06-2.11) had higher odds of achieving a TO. On multivariable analysis, TO was associated with improved overall survival (HR: 0.60, 95% CI: 0.42-0.85).Roughly 6 in 10 patients achieved a TO following resection for HCC. When achieved, TO was associated with better long-term outcomes. TO is a simple composite measure of both short- and long-term outcomes among patients undergoing resection for HCC.

  View details for DOI 10.1016/j.hpb.2019.12.005

  View details for PubMedID 31889626

• Gastric carcinoids: Does type of surgery or tumor affect survival? American journal of surgery Crown, A., Kennecke, H., Kozarek, R., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E. W., Poultsides, G. A., Makris, E., Idrees, K., Smith, P. M., Nathan, H., Beems, M., Abbott, D., Fisher, A. V., Fields, R. C., Davidson, J., Maithel, S. K., Rocha, F. G. 2018

  Abstract

  BACKGROUND: Gastric carcinoids are rare neuroendocrine tumors of the gastrointestinal tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients.METHODS: All patients who underwent resection of gastric carcinoids at 8 institutions from 2000 to 2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection, LR or formal gastrectomy, FG). Clinicopathological parameters, recurrence-free (RFS) and overall survival (OS) were compared between groups.RESULTS: Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p < 0.04 and p < 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p < 0.017). This trend persisted when type II and type IV groups were excluded (p < 0.045).CONCLUSION: Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.

  View details for PubMedID 30686481

• Staging laparoscopy among three subtypes of extra-hepatic biliary malignancy: a 15-year experience from 10 institutions. Journal of surgical oncology Davidson, J. T., Jin, L. X., Krasnick, B., Ethun, C. G., Pawlik, T. M., Poultsides, G. A., Idrees, K., Weber, S. M., Martin, R. C., Shen, P., Hatzaras, I., Maithel, S. K., Fields, R. C., and the U.S. Extrahepatic Biliary Malignancy Consortium,, 2018

  Abstract

  BACKGROUND: Staging laparoscopy (SL) is used to avoid resection failure and thus increase the curative resection rate. SL utilization in extra-hepatic biliary tumors (EHBT) is variable.METHODS: Data from 1090 patients with potentially resectable EHBT including gallbladder (GBC), distal (DC), and hilar (HC) subtypes were retrospectively collected from 10 academic centers (2000-2015).RESULTS: The SL utilization rate increased over time and was significantly higher in GBC than DC and HC. SL yield was 16.8% and did not differ between groups or over time. In patients undergoing attempted resection with prior SL, the curative resection rate did not differ between subtypes. In patients undergoing attempted resection without prior SL, the curative resection rate was less in GBC compared with DC or HC. After matching cohorts by inverse probability weighting, prior SL was associated with curative resection in GBC only (odds ratio [OR], 2.41, 95% CI, 1.36-4.27). On multivariable regression analysis, elevated carbohydrate antigen 19-9 (CA 19-9), low serum albumin, and GBC were strong predictors of distant disease on SL. After categorizing patients undergoing SL into low, intermediate, and high-risk groups based on these parameters, SL yield improved progressively from 10.0% to 19.6% to 52.6%.CONCLUSIONS: We recommend routine SL for patients with GBC, particularly with elevated CA19-9 level and/or decreased serum albumin.

  View details for PubMedID 30586170

• Actual 5-Year Survivors After Surgical Resection of Hilar Cholangiocarcinoma. Annals of surgical oncology Tran, T. B., Ethun, C. G., Pawlik, T. M., Schmidt, C., Beal, E. W., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Idrees, K., Isom, C. A., Hatzaras, I., Shenoy, R., Maithel, S. K., Poultsides, G. A. 2018

  Abstract

  BACKGROUND: The prevalence and characteristics of actual 5-year survivors after surgical treatment of hilar cholangiocarcinoma (HC) have not been described previously.METHODS: Patients who underwent resection for HC from 2000 to 2015 were analyzed through a multi-institutional registry from 10 U.S. academic medical centers. The clinicopathologic characteristics and both the perioperative and long-term outcomes for actual 5-year survivors were compared with those for non-survivors (patients who died within 5years after surgery). Patients alive at last encounter who had a follow-up period shorter than 5years were excluded from the study.RESULTS: The study identified 257 patients with HC who underwent curative-intent resection with an actuarial 5-year survival of 19%. Of 194 patients with a follow-up period longer than 5years, 23 (12%) were 5-year survivors. Compared with non-survivors, the 5-year survivors had a lower median pretreatment CA 19-9 level (116 vs. 34 U/L; P=0.008) and a lower rate of lymph node involvement (42% vs. 15%; P=0.027) and R1 margins (39% vs. 17%; P=0.042). However, the sole presence of these factors did not preclude a 5-year survival after surgery. The frequencies of bile duct resection alone, major hepatectomy, caudate lobe resection, portal vein or hepatic artery resection, preoperative biliary sepsis, intraoperative blood transfusion, serious postoperative complications, and receipt of adjuvant chemotherapy were comparable between the two groups.CONCLUSIONS: One in eight patients with HC reaches the 5-year survival milestone after resection. A 5-year survival can be achieved even in the presence of traditionally unfavorable clinicopathologic factors (elevated CA 19-9, nodal metastasis, and R1 margins).

  View details for PubMedID 30539494

• Long-term outcomes of patients with intraductal growth sub-type of intrahepatic cholangiocarcinoma HPB Bagante, F., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 20 (12): 1189–97

  Abstract

  Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC.The clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification.Compared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG, 35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (<18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69).While IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors.

  View details for PubMedID 29958811

• Hepatic Resection for Non-functional Neuroendocrine Liver Metastasis: Does the Presence of Unresected Primary Tumor or Extrahepatic Metastatic Disease Matter? ANNALS OF SURGICAL ONCOLOGY Xiang, J., Zhang, X., Beal, E. W., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S., Marques, H. P., Pawlik, T. M. 2018; 25 (13): 3928–35

  Abstract

  The objective of this study was to assess the impact of unresected primary tumor, as well as extrahepatic metastasis, on the long-term prognosis of patients undergoing hepatic resection for non-functional neuroendocrine liver metastasis (NF-NELM).Patients who underwent hepatic resection for NF-NELM were identified from a multi-institutional database. Data on clinical and pathological details, as well as the long-term overall survival (OS) were obtained and compared. Propensity score matching was performed to generate matched pairs of patients.Among the 332 patients with NF-NELM, 281 (84.6%) underwent primary tumor resection, while 51 (15.4%) did not. Patients who underwent primary resection were more likely to have a pancreatic primary and metachronous NELM. The long-term OS of patients who did and did not have the primary neuroendocrine tumor (NET) resected was comparable on both unmatched (10-year survival rate 66.8% vs. 54.0%, p = 0.192) and matched (10-year survival rate 75.7% vs. 60.4%, p = 0.271) analyses. In contrast, patients with NF-NELM and extrahepatic metastasis had a worse OS following resection compared with patients who had intrahepatic-only metastasis on unmatched (10-year survival rate 37.5% vs. 69.3%, p = 0.002) and matched (10-year survival rate 37.5% vs. 86.3%, p = 0.011) analyses. On multivariable analysis, while resection of the primary NET was not associated with OS (hazard ratio [HR] 0.7, 95% confidence interval [CI] 0.4-1.2, p = 0.195), the presence of extrahepatic metastasis was independently associated with long-term risk of death (HR 3.9, 95% CI 1.7-9.2, p = 0.002).While surgery should be considered for patients with NF-NELM who have an unresectable primary tumor, operative resection of NF-NELM may not be as beneficial in patients with extrahepatic disease.

  View details for PubMedID 30218247

• The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8-institution study from the US Neuroendocrine Tumor Study Group. Journal of surgical oncology Zaidi, M. Y., Lopez-Aguiar, A. G., Poultsides, G. A., Dillhoff, M., Rocha, F. G., Idrees, K., Nathan, H., Winslow, E. R., Fields, R. C., Cardona, K., Maithel, S. K., and other members of the US Neuroendocrine Tumor Study Group 2018

  Abstract

  BACKGROUND: The goals of resection of functional neuroendocrine tumors (NETs) are two-fold: Oncological benefit and symptom control. The interaction between the two is not well understood.METHODS: All patients with functional NETs of the pancreas, duodenum, and ampulla who underwent curative-intent resection between 2000 and 2016 were identified. Using Cox regression analysis, factors associated with reduced recurrence-free survival (RFS) were identified.RESULTS: Two-hundred and thirty patients underwent curative-intent resection. Fifty-three percent were insulinomas, 35% gastrinomas, and 12% were other types. Twenty-one percent had a known genetic syndrome, 23% had lymph node (LN) positivity, 80% underwent an R0 resection, and 14% had no postoperative symptom improvement (SI). Factors associated with reduced RFS included noninsulinoma histology, the presence of a known genetic syndrome, LN positivity, R1 margin, and lack of SI. On multivariable analysis, only the failure to achieve SI following resection was associated with reduced RFS. Considering only those patients with an R0 resection, failure to achieve SI was associated with worse 3-year RFS compared with patients having SI (36% vs 80%; P=0.006).CONCLUSIONS: Failure to achieve symptomatic improvement after resection of functional NETs is associated with worse RFS. These patients may benefit from short-interval surveillance imaging postoperatively to assess for earlier radiographical disease recurrence.

  View details for PubMedID 30481383

• Impact of microvascular invasion on clinical outcomes after curative-intent resection for intrahepatic cholangiocarcinoma. Journal of surgical oncology Hu, L., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Itaru, E., Pawlik, T. M. 2018

  Abstract

  BACKGROUND: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC.METHODS: A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI).RESULTS: A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P<0.01). On multivariable analysis, MiVI was an independent risk factor of DFS (hazard ratios [HR] 1.5; 95%confidence intervals [CI], 1.3-1.9; P<0.001), but not OS (HR 1.1; 95%CI, 0.9-1.3; P=0.379). While MiVI and MaVI patients had similar DFS (median, MiVI 14.0 vs MaVI 12.0 months, HR 0.9; 95%CI, 0.7-1.2; P=0.377), OS was better among MiVI patients (median, MiVI 39.0 vs MaVI 21.0 months, HR 0.7; 95%CI, 0.5-0.8; P=0.002). Whereas nodal metastasis, R1 margin, and postoperative morbidity were associated with early death (≤18 months) among patients with MiVI, only nodal metastasis was associated with late (>18 months) prognosis.CONCLUSIONS: Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence.

  View details for PubMedID 30466151

• Correction to: ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery. Annals of surgical oncology Tummers, W. S., Rosenthal, E. L., Vahrmeijer, A. L., Poultsides, G. A. 2018

  Abstract

  In the original version of this article, George A. Poultsides's middle initial was incorrect.

  View details for PubMedID 30426262

• Isolated pancreatic tail remnants after transgastric necrosectomy can be observed. The Journal of surgical research Dua, M. M., Jensen, C. W., Friedland, S., Worth, P. J., Poultsides, G. A., Norton, J. A., Park, W. G., Visser, B. C. 2018; 231: 109–15

  Abstract

  BACKGROUND: Severe necrotizing pancreatitis may result in midbody necrosis and ductal disruption leaving an isolated pancreatic tail. The purpose of this study was to characterize outcomes among patients with an isolated tail remnant who underwent transgastric drainage or necrosectomy (endoscopic or surgical) and determine the need for subsequent operative management.MATERIALS AND METHODS: Patients with necrotizing pancreatitis and retrogastric walled-off collections treated by surgical transgastric necrosectomy or endoscopic cystgastrostomy± necrosectomy between 2009 and 2017 were identified by a retrospective chart review. All available preprocedure and postprocedure imaging was reviewed for evidence of isolated distal pancreatic tail remnants.RESULTS: Seventy-four patients were included (40 surgical and 34 endoscopic). All the patients in the surgical group underwent laparoscopic transgastric necrosectomy; the endoscopic group consisted of 26 patients for pseudocyst drainage and eight patients for necrosectomy. A disconnected pancreatic tail was identified in 22 (29%) patients (13 laparoscopic and nine endoscopic). After the creation of the "cystgastrostomy," there were no external fistulas despite the viable tail. Of the 22 patients, four patients developed symptoms at a median of 23months (two, recurrent episodic pancreatitis; two, intractable pain). Two patients (both initially in endoscopic group) ultimately required distal pancreatectomy and splenectomy at 24 and 6months after index procedure.CONCLUSIONS: Patients with a walled-off retrogastric collection and an isolated viable tail are effectively managed by a transgastric approach. Despite this seemingly "unstable anatomy," the creation of an internal fistula via surgical or endoscopic "cystgastrostomy" avoids external fistulas/drains and the short-term necessity of surgical distal pancreatectomy. A very small subset requires intervention for late symptoms.

  View details for PubMedID 30278917

• Perioperative chemotherapy is not associated with improved survival in high-grade truncal sarcoma JOURNAL OF SURGICAL RESEARCH Yu, P. Y., Beal, E. W., Hughes, T. M., Suarez-Kelly, L. P., Shelby, R. D., Ethun, C. G., Tran, T. B., Poultsides, G., Charlson, J., Gamblin, T., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Krasnick, B. A., Fields, R. C., Pollock, R. E., Grignol, V., Cardona, K., Howard, J. 2018; 231: 248–56

  Abstract

  The treatment benefit of perioperative chemotherapy (CTX) for truncal soft tissue sarcoma (STS) is not well established. This study evaluates the association of CTX with survival for patients with resected primary high-grade truncal STS.Adult patients with high-grade truncal STS who had curative-intent resection from 2000 to 2016 at seven U.S. institutions were evaluated retrospectively. Patients were stratified by receipt of CTX. Kaplan-Meier curves with log-rank tests were used to compare overall survival (OS) and recurrence-free survival. Logistic regression models were used to evaluate characteristics associated with OS.Of patients with primary high-grade truncal STS, 235 underwent curative-intent resections. The most common histology was undifferentiated pleomorphic sarcoma and mean tumor size was 7.8 cm. Thirty percent of the patients received CTX (n = 70). Among patients receiving CTX, 34% (n = 24) had neoadjuvant CTX, 44% (n = 31) adjuvant CTX, and 21% (n = 15) had neoadjuvant and adjuvant CTX. Patients receiving CTX were more likely to receive radiation (51% versus 34%, P = 0.01), have deep tumors (86% versus 73%, P = 0.037) and solid organ invasion (14% versus 3%, P = 0.001). On univariate analysis, patients who received CTX had worse OS (P < 0.01) and a trend toward worse recurrence-free survival (P = 0.08). Margin status was the only variable associated with improved OS on multivariate analysis (odds ratio 4.36, 95% confidence interval 1.56, 12.13, P < 0.01).In this multi-institutional retrospective analysis of resected high-grade truncal STS, receipt of perioperative CTX was not associated with improved OS, which may be related to selection bias. Microscopically negative margin status was the only independent factor associated with OS.

  View details for PubMedID 30278937

• Prognostic Role of Lymph Node Positivity and Number of Lymph Nodes Needed for Accurately Staging Small Bowel Neuroendocrine Tumors. JAMA surgery Zaidi, M. Y., Lopez-Aguiar, A. G., Dillhoff, M., Beal, E., Poultsides, G., Makris, E., Rocha, F., Crown, A., Idrees, K., Marincola Smith, P., Nathan, H., Beems, M., Abbott, D., Barrett, J. R., Fields, R. C., Davidson, J., Cardona, K., Maithel, S. K. 2018

  Abstract

  Importance: Little information is available regarding the minimum number of lymph nodes needed to accurately stage patients when performing a mesenteric lymphadenectomy for small-bowel neuroendocrine tumors.Objectives: To determine the prognostic role of lymph node positivity and the ideal number of lymph nodes for accurately staging patients with small-bowel neuroendocrine tumors.Design, Setting, and Participants: This case series from the US Neuroendocrine Tumor Study Group, a collaboration among 8 US-based, academic tertiary care referral centers, obtained demographic, perioperative, and pathologic data from the group's database, Social Security Death Index, and publicly available obituaries. All patients in these institutions with small-bowel neuroendocrine tumors who underwent curative-intent surgical resection of a primary tumor between January 1, 2000, and December 31, 2015, were included (n=199). Patients with duodenal or ampullary tumors, other nonneuroendocrine concurrent malignant neoplasms, mortality of fewer than 30 days after the surgical procedure, and distant metastatic disease were excluded. Data analysis was conducted from September 1, 2017, to December 1, 2017.Main Outcomes and Measures: Primary study outcome was recurrence-free survival. Hypothesis was generated after data collection and data entry into the US Neuroendocrine Tumor Study Group database.Results: Of the 199 patients included, 112 (56.3%) were male and 87 (43.7%) female with a mean (SD) age of 60.3 (12.5) years and a mean (SD) body mass index of 29.5 (6.0). One hundred fifty-four patients (77.4%) had lymph node-positive disease. No difference in 3-year recurrence-free survival was found between patients with lymph node-positive and lymph node-negative disease. Patients with 4 positive lymph nodes had a worse 3-year recurrence-free survival compared with those with 1 to 3 or 0 positive lymph nodes (81.6% vs 91.4% vs 92.1%; P=.01). When examining patients with fewer than 8 resected lymph nodes, no difference in 3-year recurrence-free survival was observed among patients with 4 or more, 1 to 3, or 0 positive lymph nodes (100% vs 93.8% vs 91.7%; P=.87). Retrieval of 8 or more lymph nodes, however, accurately discriminated patients with 4 or more, 1 to 3, or 0 positive lymph nodes (3-year recurrence-free survival: 79.9% vs 89.6% vs 92.9%; P=.05).Conclusions and Relevance: The findings from this study suggest that, for patients undergoing curative-intent resection of small-bowel neuroendocrine tumors, accurate lymph node staging requires a minimum of 8 lymph nodes for examination, and 4 or more positive lymph nodes are associated with decreased 3-year recurrence-free survival compared with 1 to 3 or 0 positive lymph nodes; a thorough regional lymphadenectomy may be critical for accurate staging and management of this disease.

  View details for PubMedID 30383112

• Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection. Surgery Kimbrough, C. W., Beal, E. W., Dillhoff, M. E., Schmidt, C. R., Pawlik, T. M., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Crown, A., Abbott, D. E., Fisher, A. V., Fields, R. C., Krasnick, B. A., Idrees, K., Marincola-Smith, P., Cho, C. S., Beems, M., Maithel, S. K., Cloyd, J. M. 2018

  Abstract

  BACKGROUND: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized.METHODS: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome.RESULTS: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64-1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis.CONCLUSION: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.

  View details for PubMedID 30377003

• Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming. Gut Koutsioumpa, M., Hatziapostolou, M., Polytarchou, C., Tolosa, E. J., Almada, L. L., Mahurkar-Joshi, S., Williams, J., Tirado-Rodriguez, A. B., Huerta-Yepez, S., Karavias, D., Kourea, H., Poultsides, G. A., Struhl, K., Dawson, D. W., Donahue, T. R., Fernandez-Zapico, M. E., Iliopoulos, D. 2018

  Abstract

  OBJECTIVE: Despite advances in the identification of epigenetic alterations in pancreatic cancer, their biological roles in the pathobiology of this dismal neoplasm remain elusive. Here, we aimed to characterise the functional significance of histone lysine methyltransferases (KMTs) and demethylases (KDMs) in pancreatic tumourigenesis.DESIGN: DNA methylation sequencing and gene expression microarrays were employed to investigate CpG methylation and expression patterns of KMTs and KDMs in pancreatic cancer tissues versus normal tissues. Gene expression was assessed in five cohorts of patients by reverse transcription quantitative-PCR. Molecular analysis and functional assays were conducted in genetically modified cell lines. Cellular metabolic rates were measured using an XF24-3 Analyzer, while quantitative evaluation of lipids was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Subcutaneous xenograft mouse models were used to evaluate pancreatic tumour growth in vivo.RESULTS: We define a new antitumorous function of the histone lysine (K)-specific methyltransferase 2D (KMT2D) in pancreatic cancer. KMT2D is transcriptionally repressed in human pancreatic tumours through DNA methylation. Clinically, lower levels of this methyltransferase associate with poor prognosis and significant weight alterations. RNAi-based genetic inactivation of KMT2D promotes tumour growth and results in loss of H3K4me3 mark. In addition, KMT2D inhibition increases aerobic glycolysis and alters the lipidomic profiles of pancreatic cancer cells. Further analysis of this phenomenon identified the glucose transporter SLC2A3 as a mediator of KMT2D-induced changes in cellular, metabolic and proliferative rates.CONCLUSION: Together our findings define a new tumour suppressor function of KMT2D through the regulation of glucose/fatty acid metabolism in pancreatic cancer.

  View details for PubMedID 30337373

• Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Chakedis, J., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F. G., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Marincola-Smith, P., Cho, C., Beems, M., Pawlik, T. M., Maithel, S. K., Schmidt, C. R., Dillhoff, M. 2018

  Abstract

  INTRODUCTION: Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known.METHODS: We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group.RESULTS: Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n=223, 67.4%), GI bleeding (n=54, 16.3%), GI obstruction (n=49, 14.8%), and biliary obstruction (n=22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4weeks of diagnosis. The median overall survival was 110.4months, and operative intent predicted survival (p<0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5months) compared to debulking (89.2months), or palliative resection (50.0months; p<0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p=0.006), foregut NET (5.62, p=0.042), major complication (4.91, p=0.001), and high tumor grade (11.2, p<0.001). The conditional survival for patients who lived past 1year was 119months.CONCLUSIONS: Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.

  View details for PubMedID 30334178

• The prognostic significance of adrenocortical carcinomas identified incidentally. Journal of surgical oncology Rossfeld, K. K., Maithel, S. K., Prescott, J., Wang, T. S., Fields, R. C., Weber, S. M., Sicklick, J. K., Yopp, A. C., Duh, Q., Solorzano, C. C., Votanopoulos, K. I., Hatzaras, I., Poultsides, G. A., Shirley, L. A., and the U.S. Adrenocortical Carcinoma Study Group,, 2018

  Abstract

  BACKGROUND AND OBJECTIVES: Little is known regarding the difference in prognosis among patients who have an incidentally discovered adrenocortical carcinoma (ACC)vs those who present with signs or symptoms. We aimed to explore differences in the outcomes of these two populations.METHODS: Data were collected on patients who underwent resection of ACC at 1 of 13 institutions between January 1993 and December 2014. Presentations were categorized as incidental vs symptomatic and outcomes were compared.RESULTS: Among 227 patients, 100 were diagnosed incidentally while 127 patients presented with symptoms/signs. Clinical and pathological features were comparable among incidental vs nonincidental patients with ACC following the exceptions. Patients with incidentalomas were more likely to have a T1/T2 tumor (55.8% vs 34.8%; P<0.01) and less likely to have a functional tumor (33.7% vs 47.9%; P=0.04). Patients with an incidental ACC had improved median recurrence-free survival (RFS; 29.4 months) compared with patients with a nonincidental ACC (13.0 months; P=0.03); however, on multivariable analysis, incidental ACC was not an independent predictor of survival.CONCLUSIONS: Patients with resected ACC identified incidentally had an improved RFS compared with the patients who presented with symptoms or signs. This difference may be related to the patients with incidental tumors having earlier T-stage disease.

  View details for PubMedID 30332514

• ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery. Annals of surgical oncology Tummers, W. S., Rosenthal, E. L., Vahrmeijer, A. L., Poultsides, G. P. 2018

  View details for PubMedID 30315384

• Perioperative Management in Hepatic Resections: Comparative Effectiveness of Neuraxial Anesthesia and Disparity of Care Patterns ANESTHESIA AND ANALGESIA Zerillo, J., Agarwal, P., Poeran, J., Zubizarreta, N., Poultsides, G., Schwartz, M., Memtsoudis, S., Mazumdar, M., DeMaria, S. 2018; 127 (4): 855–63

  Abstract

  Complication rates after hepatic resection can be affected by management decisions of the hospital care team and/or disparities in care. This is true in many other surgical populations, but little study has been done regarding patients undergoing hepatectomy.Data from the claims-based national Premier Perspective database were used for 2006 to 2014. The analytical sample consisted of adults undergoing partial hepatectomy and total hepatic lobectomy with anesthesia care consisting of general anesthesia (GA) only or neuraxial and GA (n = 9442). The key independent variable was type of anesthesia that was categorized as GA versus GA + neuraxial. The outcomes examined were clinical complications and health care resource utilization. Unadjusted bivariate and adjusted multivariate analyses were conducted to examine the effects of the different types of anesthesia on clinical complications and health care resource utilization after controlling for patient- and hospital-level characteristics.Approximately 9% of patients were provided with GA + neuraxial anesthesia during hepatic resection. In multivariate analyses, no association was observed between types of anesthesia and clinical complications and/or health care utilization (eg, admission to intensive care unit). However, patients who received blood transfusions were significantly more likely to have complications and intensive care unit stays. In addition, certain disparities of care, including having surgery in a rural hospital, were associated with poorer outcomes.Neuraxial anesthesia utilization was not associated with improvement in clinical outcome or cost among patients undergoing hepatic resections when compared to patients receiving GA alone. Future research may focus on prospective data sources with more clinical information on such patients and examine the effects of GA + neuraxial anesthesia on various complications and health care resource utilization.

  View details for PubMedID 29933267

• Serum tumor markers enhance the predictive power of the AJCC and LCSGJ staging systems in resectable intrahepatic cholangiocarcinoma HPB Sasaki, K., Margonis, G. A., Andreatos, N., Chen, Q., Barbon, C., Bagante, F., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Endo, I., Aucejo, F. N., Pawlik, T. M. 2018; 20 (10): 956–65

  Abstract

  While several prognostic models have been developed to predict long-term outcomes in resectable intrahepatic cholangiocarcinoma (ICC), their prognostic discrimination remains limited. The addition of tumor markers might improve the prognostic power of the classification schemas proposed by the AJCC 8th edition and the Liver Cancer Study Group of Japan (LCSGJ).The prognostic discrimination of the AJCC and the LCSGJ were compared before and after the addition of CA 19-9 and CEA, using Harrell's C-index, net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) in an international, multi-institutional cohort.Eight hundred and five surgically treated patients with ICC that met the inclusion criteria were identified. On multivariable analysis, CEA5 ng/mL, 100IU/mL CA 19-9< 500IU/mL and CA 19-9500 IU/mL were associated with worse overall survival. The C-index of the AJCC and the LCSGJ improved from 0.540 to 0.626 and 0.553 to 0.626, respectively following incorporation of CA 19-9 and CEA. The NRI and IDI metrics confirmed the superiority of the modified AJCC and LCSGJ, compared to the original versions.The inclusion of preoperative CA 19-9 and CEA in the AJCC and LCSGJ staging schemas may improve prognostic discrimination among surgically treated patients with ICC.

  View details for PubMedID 29887261

• Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group. Surgery Zhang, X., Wu, Z., Cloyd, J., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Schmidt, C. R., Dillhoff, M., Maithel, S. K., Pawlik, T. M. 2018

  Abstract

  BACKGROUND: The impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long-term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin.METHODS: Patients who underwent curative-intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence-free survival were analyzed relative to surgical margin status using univariable and multivariable analyses.RESULTS: Among 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence-free survival (10-year recurrence-free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2-2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0-3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0-1.7, P = .060). In contrast, margin status was not associated with overall survival (10-year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6-6.2, P = .001) and recurrence-free survival (hazard ratio 2.6, 95% confidence interval 1.4-5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor-specific factors, such as cellular differentiation, perineural invasion, Ki-67 index, and major vascular invasion, rather than surgical margin, were associated with long-term outcomes.CONCLUSION: Margin status was not associated with long-term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.

  View details for PubMedID 30278986

• A novel, simplified, externally validated staging system for truncal/extremity soft tissue sarcomas: An analysis of the US Sarcoma Collaborative database. Journal of surgical oncology Johnson, A. C., Ethun, C. G., Liu, Y., Poultsides, G., Howard, J. H., Bedi, M., Charlson, J., Tseng, J., Roggin, K. K., Votanopoulos, K., Cullinan, D., Fields, R. C., Maithel, S. K., Cardona, K., and other members of the US Sarcoma Collaborative 2018

  Abstract

  BACKGROUND: The 8th edition AJCC staging system for truncal/extremity soft tissue sarcoma (STS) offers significant changes from the 7th. However the complexity of both limits their clinical utility.METHODS: Patients with truncal/extremity STS undergoing resection from 2000 to 2016 at seven institutions of the US Sarcoma Collaborative were analyzed. The proposed staging system was externally validated using the National Cancer Database (NCDB).RESULTS: Of 1318 patients, mean age was 59 years, and 54% were male. Median tumor size was 9cm; 72% were high grade. Applying 8th edition staging, there was no differentiation between stages IA/IB ( P=0.92), and clinically similar outcomes between stages II/IIIA. Receiver operating characteristic (ROC) analysis identified 7.5cm as the ideal tumor size discriminating 5-year OS for high-grade tumors. Therefore, a simplified staging system defining all low-grade tumors as stage I, high-grade<7.5cm as stage II, high-grade>7.5cm as stage III, and metastatic disease as stage IV improved stratification (all P<0.05). The C-statistic was noninferior to the 8th edition. External validation in the NCDB confirmed optimal stratification (all P<0.01).CONCLUSIONS: Our proposed staging system maintains prognostic significance between stages within a simplified system. For high-grade tumors, a cutoff of 7.5cm, instead of 5cm, maintains discrimination for survival and could be a more clinically applicable cutoff for future clinical trials.

  View details for PubMedID 30261111

• Early recurrence of well-differentiated (G1) neuroendocrine liver metastasis after curative-intent surgery: Risk factors and outcome. Journal of surgical oncology Xiang, J., Zhang, X., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Pawlik, T. M. 2018

  Abstract

  BACKGROUND: The objective of the current study was to identify the risk of early vs late recurrence of well-differentiated (G1) neuroendocrine liver metastasis (NELM) after curative-intent resection.METHODS: Patients who underwent curative-intent resection for well-differentiated NELM were identified from a multi-institutional database. Clinicopathological details, as well as the long-term overall (OS) and recurrence free survival (RFS) were obtained and compared. The optimal cutoff value to differentiate early and late recurrence was determined to be 1 year based on trend curve analysis.RESULTS: Among the 548 patients undergoing curative resection for NELM, 162 patients had a well-differentiated NELM. After a median follow-up of 69 months, 59 (36.4%) patients had tumor recurrence; 23 (39.0%) patients recurred within 1 year (early recurrence) after surgery, while 36 (61.0%) recurred after 1 year (late recurrence). Early recurrence was associated with worse outcome vs late recurrence (5-year OS, 72.4% vs 92.0%; P=0.020) and no recurrence (5-year OS, 72.4% vs 100.0%; P<0.001). In addition, postrecurrence survival was worse within 36 months after recurrence among patients who recurred early compared with patients who recurred late (survival after recurrence at 36 months: early recurrence, 71.6% vs late recurrence, 91.4%; P=0.047), although survival was comparable at 60 months (early recurrence, 71.6% vs late recurrence, 70.0%; P=0.304). On multivariable analysis, nonfunctional neuroendocrine tumors (hazard ratio [HR], 4.4; 95% confidence interval [CI], 1.2-16.7; P=0.029) and lymph node metastasis (HR, 3.6; 95% CI, 1.1-11.1; P=0.028) were independent risk factors for early recurrence, whereas lymph node metastasis (HR, 3.0; 95% CI, 1.2-7.8; P=0.020) and R1 resection (HR, 3.9; 95% CI, 1.4-10.5; P=0.008) were independently associated with late recurrence.CONCLUSIONS: Roughly, one-third of patients with well-differentiated NELM experienced a recurrence following curative-intent surgery. Among patients who recurred, two out of five patients recurred within 1 year after surgery. Early recurrence of well-differentiated NELM was associated with the hormone functional status and lymph node metastasis.

  View details for DOI 10.1002/jso.25246

  View details for PubMedID 30261105

• The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis. Journal of surgical oncology Margonis, G. A., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Galjart, B., Kamphues, C., Pawlik, T. M., Poultsides, G., Kaczirek, K., Lonning, P. E., Verhoef, C., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018

  Abstract

  BACKGROUND AND OBJECTIVES: In contrast with sporadic colorectal cancer liver metastases (CRLM), inflammatory bowel disease (IBD)-related CRLM have not been studied to date.METHODS: Patients who underwent resection for IBD-related and sporadic CRLM from 2000 to 2015 were identified from an international registry and matched for pertinent prognostic variables. Overall survival (OS) and recurrence-free survival (RFS) were subsequently assessed.RESULTS: Twenty-eight patients had IBD-related CRLM. Synchronous extrahepatic disease was more common in IBD-related CRLM patients than patients with sporadic CRLM (28.6% vs 8.3%; P<0.001), most commonly located in the lungs. In multivariable analysis, IBD did not have a significant influence on OS ( P=0.835), and had a hazard ratio (HR) close to 1 (HR, 0.95; 95% confidence interval [CI], 0.57-1.57). IBD was also not associated with inferior RFS (HR, 1.07; 95%CI, 0.68-1.68; P=0.780). Among patients with IBD-related CRLM, 9(50%) had isolated intrahepatic recurrence and 8(44.4%) isolated extrahepatic recurrence, while only 1(5.6%) developed combined recurrence. Of those who experienced recurrence after resection of IBD-related CRLM, 10 had their recurrence treated with curative intent.CONCLUSIONS: Patients with IBD-related CRLM had similar survival compared with patients with sporadic CRLM, even though they more often present with extrahepatic disease. In addition, patients with IBD-related CRLM may experience patterns of recurrence different from patients with sporadic CRLM.

  View details for PubMedID 30261094

• Defining Early Recurrence of Hilar Cholangiocarcinoma After Curative-intent Surgery: A Multi-institutional Study from the US Extrahepatic Biliary Malignancy Consortium WORLD JOURNAL OF SURGERY Zhang, X., Beal, E. W., Chakedis, J., Chen, Q., Lv, Y., Ethun, C. G., Salem, A., Weber, S. M., Tran, T., Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Buettner, S., Scoggins, C., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R., Pawlik, T. M. 2018; 42 (9): 2919–29

  Abstract

  Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection.A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late.With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence.Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.

  View details for PubMedID 29404753

• Preoperative prognostic nutritional index predicts survival of patients with intrahepatic cholangiocarcinoma after curative resection JOURNAL OF SURGICAL ONCOLOGY Akguel, O., Bagante, F., Olsen, G., Cloyd, J. M., Weiss, M., Merath, K., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 118 (3): 422–30

  Abstract

  Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy. We sought to examine the association between preoperative prognostic nutritional index (PNI) and long-term overall survival among patients with ICC who underwent curative-intent resection.Patients who underwent hepatectomy for ICC between 1990 and 2015 were identified using an international multi-institutional database. Clinic-pathological characteristics and long-term outcomes of patients with PNI ≥ 40 and <40 were compared using univariable and multivariable analyses.Among 637 patients, 53 patients had PNI < 40 (8.3%) and 584 patients had PNI ≥ 40 (91.7%). While there was no difference between PNI groups with regard to tumor size (P = .87), patients with PNI < 40 were more likely to have multifocal disease (PNI < 40, n = 16, 30.2% vs PNI ≥ 40, n = 65, 11.1%; P < 0.001), poorly differentiated or undifferentiated ICC (PNI < 40, n = 13, 25.5% vs PNI ≥ 40, n = 75, 13.1%; P = 0.020) and T2/T3/T4 disease vs patients with PNI ≥ 40 (PNI < 40, n = 38, 71.7% vs PNI ≥ 40, n = 265, 45.4%; P < 0.001). Patients with PNI ≥ 40 had better OS vs patients with PNI < 40 (5-year OS: PNI ≥ 40: 47.5%, 95% CI, 42.2 to 52.6% vs PNI < 40: 24.6%, 95% CI, 12.1 to 39.6%; P < 0.001). On multivariable analysis, PNI < 40 remained associated with increase risk of death (HR, 1.71; 95% CI, 1.15 to 2.53; P = 0.008).A low preoperative PNI was associated with a more aggressive ICC phenotype. After controlling for these factors, PNI remained independently associated with a markedly worse prognosis.

  View details for PubMedID 30084163

• Circulating tumor DNA (ctDNA) in B-cell lymphoma Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. M., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Green, M. R., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Davis, R., Levy, R., Ohgami, R. S., Kunder, C. A., Rossi, D., Westin, J., Diehn, M., Alizadeh, A. A. WILEY. 2018: 16–17

  View details for Web of Science ID 000444944200019

• The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma Buettner, S., Spolverato, G., Kimbrough, C. W., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T., Maithel, S. K., Pulitano, C., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J., IJzermans, J. M., Koerkamp, B., Pawlik, T. M. MOSBY-ELSEVIER. 2018: 411–18

  Abstract

  Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma.Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index).A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival (hazard ratio: 1.04, 95% CI: 1.01-1.07; P = .002). Patients could be stratified into low- versus high-risk groups based on standard tumor-specific factors such as lymph node status, tumor size, number, and vascular invasion (C index 0.62). When neutrophil-to-lymphocyte ratio was added to the prognostic model, the discriminatory ability of the model improved (C index 0.71).Elevated neutrophil-to-lymphocyte ratio was independently associated with worse overall survival and improved the prognostic estimation of long-term survival among patients with intrahepatic cholangiocarcinoma undergoing resection.

  View details for PubMedID 29903509

• Studying a Rare Disease Using Multi-Institutional Research Collaborations vs Big Data: Where Lies the Truth? JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Johnson, A. C., Ethun, C. G., Liu, Y., Lopez-Aguiar, A. G., Tran, T. B., Poultsides, G., Grignol, V., Howard, J., Bedi, M., Gamblin, T., Tseng, J., Roggin, K. K., Chouliaras, K., Votanopoulos, K., Cullinan, D., Fields, R. C., Delman, K. A., Wood, W. C., Cardona, K., Maithel, S. K. 2018; 227 (3): 357-+

  Abstract

  Multi-institutional collaborations provide granularity lacking in epidemiologic data sets to enable in-depth study of rare diseases. For patients with superficial, high-grade soft tissue sarcomas of the trunk and extremity, the value of radiation therapy (RT) is not clear. We aimed to use the 7-institution US Sarcoma Collaborative (USSC) and the National Cancer Database (NCDB) to investigate this issue.All adult patients with superficial truncal and extremity high-grade soft tissue sarcomas who underwent primary curative-intent resection from 2000 to 2016 at USSC institutions or were included in the NCDB from 2004 to 2013 were analyzed. Propensity score matching was performed. End points were locoregional recurrence-free survival (LRFS), overall survival (OS), and disease-specific survival (DSS).Of 4,153 patients in the USSC, 169 patients with superficial high-grade tumors underwent primary curative-intent resection, 38% of which received RT. On multivariable Cox-regression analysis, RT was not associated with improved LRFS (p = 0.56), OS (p = 0.31), or DSS (p = 0.20). On analysis of 51 propensity score-matched pairs, RT was still not associated with increased LRFS, OS, or DSS. Analysis of 631 propensity score-matched pairs in the NCDB demonstrated improved 5-year OS rate associated with RT (80% vs 70%; p = 0.02). The LRFS and DSS rates were not evaluable.Granular data afforded by collaborative research enables in-depth analysis of patient outcomes. The NCDB, although powered with large numbers, cannot assess many relevant outcomes (eg recurrence, DSS, or complications). In this study, the approaches yielded conflicting results. The USSC data suggested no value of radiation and the NCDB demonstrated improved OS, contradicting all randomized controlled trials in sarcoma. The pros and cons of either approach must be considered when applying results to clinical practice, and underscore the importance of randomized controlled trials.

  View details for PubMedID 29906615

• Role of Additional Organ Resection in Adrenocortical Carcinoma: Analysis of 167 Patients from the US Adrenocortical Carcinoma Database ANNALS OF SURGICAL ONCOLOGY Smith, P., Kiernan, C. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J., Pawlik, T., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J., Shirley, L. A., Fields, R. C., Jin, L., Weber, S., Salem, A., Sicklick, J., Gad, S., Yopp, A., Mansour, J., Duh, Q., Seiser, N., Votanopoulos, K., Levine, E. A., Poultsides, G., Solorzano, C. C. 2018; 25 (8): 2308–15

  Abstract

  Adrenocortical carcinoma (ACC) is a rare and aggressive cancer. This report describes factors and outcomes associated with resection of extra-adrenal organs en bloc during index adrenalectomy.Patients who underwent ACC resection for non-metastatic disease from 1993 to 2014 at 13 participating institutions of the US-ACC Group were included in the study. Factors associated with en bloc resection were assessed by uni- and multivariate analysis. The primary end point was overall survival.In this study, 167 patients were included and categorized as adrenalectomy with en bloc resection (AdEBR) if they had extra-adrenal organs removed or adrenalectomy (Ad) if they did not. The demographics were similar between the AdEBR (n = 68, 40.7%) and Ad groups, including age, gender, race, American Society of Anesthesiology (ASA) class, and body mass index (BMI). The AdEBR group had larger tumors (13 vs. 10 cm), more open operations (97.1 vs. 63.6%), and more lymph node dissections (LNDs) (36.8 vs. 12.1%). The most common organs removed were kidney (55.9%), liver (27.9%), and spleen (23.5%). Multiple organs were removed in 38.2% (n = 26) of the patients. Margin-negative resections were similar between the two groups. In the multivariate Cox regression adjusted for T and N stages, LND, margin, size, and hormone hypersecretion, en bloc resection was not associated with improved survival (hazard ratio [HR], 1.42; p = 0.323).The study findings validated current practice by showing that en bloc resection should occur at index adrenalectomy for ACC when a T4 lesion is suspected pre- or intraoperatively, or when it is necessary to avoid tumor rupture. However, in this study, when a negative margin resection was otherwise achieved, removal of extra-adrenal organs en bloc was not associated with additional survival benefit.

  View details for PubMedID 29868977

• Surgical Management of Intrahepatic Cholangiocarcinoma in Patients with Cirrhosis: Impact of Lymphadenectomy on Peri-Operative Outcomes WORLD JOURNAL OF SURGERY Bagante, F., Spolverato, G., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Ruzzenente, A., Pawlik, T. M. 2018; 42 (8): 2551–60

  Abstract

  The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC.A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non-cirrhosis groups.Cirrhosis was diagnosed in 118 (11.7%) patients. Among non-cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis (p < 0.001). LND was also less common among cirrhotic versus non-cirrhotic patients (19 vs. 50%, p < 0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively (p = 0.022). The propensity-matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) (p < 0.001). In the propensity-matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non-cirrhosis, 2.5 vs. cirrhosis, 2) (p = 0.95). While lymphadenectomy was associated with a higher risk of infections (non-cirrhosis, 0% vs. cirrhosis, 21%, p < 0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non-cirrhotic patients (p = 0.19).Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non-cirrhotic patients.

  View details for PubMedID 29299649

• Monitoring Gastric Myoelectric Activity After Pancreaticoduodenectomy for Diet "Readiness". American journal of physiology. Gastrointestinal and liver physiology Dua, M. M., Navalgund, A., Axelrod, S., Axelrod, L., Worth, P. J., Norton, J. A., Poultsides, G. A., Triadafilopoulos, G., Visser, B. C. 2018

  Abstract

  INTRODUCTION: Post-operative delayed gastric emptying (DGE) is a frustrating complication of pancreaticoduodenectomy (PD). We studied whether monitoring of post-operative gastric motor activity using a novel wireless patch system can identify patients at risk for DGE.METHODS: Eighty-one patients were prospectively studied since 2016; 75 patients were analyzed for this study. After PD, battery-operated wireless patches (G-Tech Medical) that acquire gastrointestinal myoelectrical signals are placed on the abdomen and transmit data by Bluetooth. Patients were divided into EARLY and LATE groups, by diet tolerance of 7 days (ERAS goal). Subgroup analysis was done of patients included after ERAS initiation.RESULTS: The EARLY and LATE groups had 50 and 25 patients, respectively, with length of stay (LOS) 7 and 11 days (p<0.05). Nasogastric insertion was required in 44% of the LATE group. Tolerance of food was noted by 6 vs 9 days in the EARLY vs LATE group (p<0.05) with higher cumulative gastric myoelectrical activity. Diminished gastric myoelectrical activity accurately identified delayed tolerance to regular diet in a logistical regression analysis (area under the curve (AUC), 0.81; 95% CI, 0.74-0.92). The gastric myoelectrical activity also identified delayed LOS status with an AUC of 0.75 (95% CI, 0.67-0.88). Stomach signal continued to be predictive in 90% of the ERAS cohort despite earlier oral intake.CONCLUSIONS: Measurement of gastric activity after PD can distinguish patients with shorter or longer times to diet. This non-invasive technology provides data to identify patients at risk for DGE and may guide timing of oral intake by gastric "readiness."

  View details for PubMedID 30048596

• Association of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer JAMA SURGERY Margonis, G., Buettner, S., Andreatos, N., Kim, Y., Wagner, D., Sasaki, K., Beer, A., Schwarz, C., Loes, I., Smolle, M., Kamphues, C., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lonning, P., Cameron, J. L., Burkhart, R. A., Gerger, A., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018; 153 (7): e180996

  Abstract

  BRAF mutations are reportedly associated with aggressive tumor biology. However, in contrast with primary colorectal cancer, the association of V600E and non-V600E BRAF mutations with survival and recurrence after resection of colorectal liver metastases (CRLM) has not been well studied.To investigate the prognostic association of BRAF mutations with survival and recurrence independently and compared with other prognostic determinants, such as KRAS mutations.In this cohort study, all patients who underwent resection for CRLM with curative intent from January 1, 2000, through December 31, 2016, at the institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and had data on BRAF and KRAS mutational status were retrospectively identified. Multivariate Cox proportional hazards regression models were used to assess long-term outcomes.Hepatectomy in patients with CRLM.The association of V600E and non-V600E BRAF mutations with disease-free survival (DFS) and overall survival (OS).Of 853 patients who met inclusion criteria (510 men [59.8%] and 343 women [40.2%]; mean [SD] age, 60.2 [12.4] years), 849 were included in the study analyses. Forty-three (5.1%) had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype; 480 (56.5%), a wtBRAF/wtKRAS genotype; and 326 (38.4%), a wtBRAF/mutKRAS genotype. Compared with the wtBRAF/wtKRAS genotype group, patients with a mutBRAF/wtKRAS genotype more frequently were female (27 [62.8%] vs 169 [35.2%]) and 65 years or older (22 [51.2%] vs 176 [36.9%]), had right-sided primary tumors (27 [62.8%] vs 83 [17.4%]), and presented with a metachronous liver metastasis (28 [64.3%] vs 229 [46.8%]). On multivariable analysis, V600E but not non-V600E BRAF mutation was associated with worse OS (hazard ratio [HR], 2.76; 95% CI, 1.74-4.37; P < .001) and DFS (HR, 2.04; 95% CI, 1.30-3.20; P = .002). The V600E BRAF mutation had a stronger association with OS and DFS than the KRAS mutations (β for OS, 10.15 vs 2.94; β for DFS, 7.14 vs 2.27).The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.

  View details for PubMedID 29799910

• Characterization of colorectal liver metastasis at single-cell resolution reveals dynamic interplay in the tumor microenvironment Sathe, A., Chen, J., Wood-Bouwens, C., Almeda, A., Lau, B., Grimes, S. M., Poultsides, G. A., Ji, H. AMER ASSOC CANCER RESEARCH. 2018

  View details for DOI 10.1158/1538-7445.AM2018-2126

  View details for Web of Science ID 000468818904508

• Integrated single-cell DNA and RNA analysis of intratumoral heterogeneity and immune lineages in colorectal and gastric tumor biopsies Lau, B., Andor, N., Sathe, A., Wood-Bouwens, C., Poultsides, G., Ji, H. AMER ASSOC CANCER RESEARCH. 2018

  View details for DOI 10.1158/1538-7445.AM2018-4347

  View details for Web of Science ID 000468819503011

• Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Annals of surgical oncology Tummers, W. S., Miller, S. E., Teraphongphom, N. T., Gomez, A., Steinberg, I., Huland, D. M., Hong, S., Kothapalli, S., Hasan, A., Ertsey, R., Bonsing, B. A., Vahrmeijer, A. L., Swijnenburg, R., Longacre, T. A., Fisher, G. A., Gambhir, S. S., Poultsides, G. A., Rosenthal, E. L. 2018; 25 (7): 1880–88

  Abstract

  BACKGROUND: Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor.METHODS: A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50mg or 100mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo.RESULTS: Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09±0.06) versus surrounding normal pancreatic tissue (0.02±0.01), and pancreatitis (0.04±0.01; p<0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue.CONCLUSIONS: The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.

  View details for PubMedID 29667116

• Association of perioperative transfusion with survival and recurrence after resection of gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium JOURNAL OF SURGICAL ONCOLOGY Lopez-Aguiar, A. G., Ethun, C. G., McInnis, M. R., Pawlik, T. M., Poultsides, G., Thuy Tran, Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E. W., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K. 2018; 117 (8): 1638–47

  Abstract

  Perioperative blood transfusion is associated with poor outcomes in several malignancies. Its effect in gallbladder cancer (GBC) is unknown.All patients with GBC who underwent curative-intent resection at 10-institutions from 2000 to 2015 were included. The effect of blood transfusion on overall survival (OS) and recurrence-free (RFS) was evaluated.Of 262 patients with curative-intent resection for GBC, 61 patients (23%) received blood transfusions. Radical cholecystectomy was the most common procedure (80%), but major hepatectomy was more frequent in the transfusion versus no-transfusion group (13% vs 4%; P = 0.02). The transfusion group was less likely to have incidentally discovered disease (57% vs 74%) and receive adjuvant therapy (29% vs 48%), but more likely to have preoperative jaundice (23% vs 11%), T3/T4 tumors (60% vs 39%), LVI (71% vs 40%), PNI (71% vs 48%), and major complications (39% vs 12%) (all P < 0.05). Transfusion was associated with lower median OS compared to no-transfusion (20 vs 32 mos; P < 0.001), which persisted on multivariable (MV) analysis (HR:1.9; 95%CI 1.1-3.5; P = 0.035), controlling for comorbidities, serum albumin, INR, preoperative jaundice, major hepatectomy, incidental discovery, margin status, T-Stage, LN status, and major complications. Median RFS of transfused patients was 13mo compared to 49mo for non-transfused patients (P = 0.1). Transfusion, however, was an independent predictor of decreased RFS on MV analysis (HR:2.3; 95%CI 1.1-5.1; P = 0.035).Perioperative blood transfusion is associated with decreased OS and RFS after resection for GCC, accounting for other adverse factors. Transfusions should thus be administered with well-defined protocols.

  View details for PubMedID 29761515

• Clinical Trigonometry: Right Hepatic Trisegmentectomy After Radiation Trisegmentectomy for Hepatocellular Carcinoma DIGESTIVE DISEASES AND SCIENCES Titan, A. L., Devereaux, K., Louie, J. D., Poultsides, G. A. 2018; 63 (6): 1419–23

  View details for PubMedID 29119415

• Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma SURGERY Zhang, X., Bagante, F., Chen, Q., Beal, E. W., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 163 (5): 1114–20

  Abstract

  Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.A total of 912 patients with mass-forming peripheral intrahepatic cholangiocarcinoma, 101 patients with hilar type intrahepatic cholangiocarcinoma, and 159 patients with hilar cholangiocarcinoma undergoing curative resection from 2000 to 2015 were included from two multi-institutional databases. Clinicopathologic characteristics and short- and long-term outcomes were compared among the 3 groups.Patients with hilar type intrahepatic cholangiocarcinoma had more aggressive tumor characteristics (eg, higher frequency of vascular invasion and lymph nodes metastasis) and experienced more extensive resections in comparison with either peripheral intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma patients. The odds of lymphadenectomy and R0 resection rate among patients with hilar type intrahepatic cholangiocarcinoma were comparable with hilar cholangiocarcinoma patients, but higher than peripheral intrahepatic cholangiocarcinoma patients (lymphadenectomy incidence, 85.1% vs 42.5%, P < .001; R0 rate, 75.2% vs 88.8%, P < .001). After curative surgery, patients with hilar type intrahepatic cholangiocarcinoma experienced a higher rate of technical-related complications compared with peripheral intrahepatic cholangiocarcinoma patients. Of note, hilar type intrahepatic cholangiocarcinoma was associated with worse disease-specific survival and recurrence-free survival after curative resection versus peripheral intrahepatic cholangiocarcinoma (median disease-specific survival, 26.0 vs 54.0 months, P < .001; median recurrence-free survival, 13.0 vs 18.0 months, P = .021) and hilar cholangiocarcinoma (median disease-specific survival, 26.0 vs 49.0 months, P = .003; median recurrence-free survival, 13.0 vs 33.4 months, P < .001).Mass-forming intrahepatic cholangiocarcinoma with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma, which showed distinct clinicopathologic characteristics, worse long-term outcomes after curative resection, in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.

  View details for PubMedID 29398035

• Double KRAS and BRAF Mutations in Surgically Treated Colorectal Cancer Liver Metastases: An International, Multi-institutional Case Series ANTICANCER RESEARCH Deshwar, A., Margonis, G., Andreatos, N., Barbon, C., Wang, J., Buettner, S., Wagner, D., Sasaki, K., Beer, A., Loes, I., Pikoulis, E., Damaskos, C., Garmpis, N., Kamphues, K., He, J., Kaczirek, K., Poultsides, G., Lonning, P., Mischinger, H., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weis, M. J. 2018; 38 (5): 2891–95

  Abstract

  While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is the first to report on the implications of concurrent KRAS/BRAF mutations among surgically treated patients, and the largest set of patients with surgically treated colorectal liver metastasis (CRLM) and data on KRAS/BRAF mutational status thus far described.We present cases from an international, multi-institutional cohort of patients that underwent hepatic resection for CRLM between 2000-2015 at seven tertiary centers. The incidence of KRAS/BRAF mutation in patients with CRLM was 0.5% (4/820). Of these cases, patient 1 (T2N1 primary, G13D/V600E), patient 2 (T3N1 primary, G12V/V600E) and patient 3 (T4N2 primary, G13D/D594N) succumbed to their disease within 485, 236 and 79 days respectively, post-hepatic resection. Patient 4 (T4 primary, G12S/G469S) was alive 416 days after hepatic resection.The present case series suggests that the incidence of concomitant KRAS/BRAF mutations in surgical cohorts may be higher than previously hypothesized, and associated with more variable survival outcomes than expected.

  View details for PubMedID 29715113

• Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival JOURNAL OF SURGICAL ONCOLOGY Zhang, X., Beal, E. W., Merath, K., Ethun, C. G., Salem, A., Weber, S. M., Thuy Tran, Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Weiss, M., Scoggins, C., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R., Pawlik, T. M. 2018; 117 (6): 1267–77

  Abstract

  The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD).Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients.The median decrease in total bilirubin levels after biliary drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs 4.9, P = 0.589) before surgery. There was no difference in baseline demographic characteristics, type of surgical procedure performed, final AJCC tumor stage or postoperative morbidity among patients who underwent EBD only versus PTBD (all P > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P = 0.571). The overall pattern of recurrence relative to regional or distant disease was also the same among patients undergoing PTBD and EBD (P = 0.669) CONCLUSIONS: Oncologic outcomes including DSS and RFS were similar among patients who underwent PTBD versus EBD with no difference in tumor recurrence location.

  View details for PubMedID 29205351

• Transplantation Versus Resection for Hilar Cholangiocarcinoma An Argument for Shifting Treatment Paradigms for Resectable Disease Ethun, C. G., Lopez-Aguiar, A. G., Anderson, D. J., Adams, A. B., Fields, R. C., Doyle, M. B., Chapman, W. C., Krasnick, B. A., Weber, S. M., Mezrich, J. D., Salem, A., Pawlik, T. M., Poultsides, G., Tran, T. B., Idrees, K., Isom, C. A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K. LIPPINCOTT WILLIAMS & WILKINS. 2018: 797–805

  Abstract

  To investigate the influence of type of surgery (transplant vs resection) on overall survival (OS) in patients with hilar cholangiocarcinoma (H-CCA).Outcomes after resection for H-CCA are poor, yet transplantation is currently only reserved for well-selected patients with unresectable disease.All patients with H-CCA who underwent resection from 2000 to 2015 at 10 institutions were included. Three institutions additionally had active H-CCA transplant protocols with similar selection criteria over similar time periods.Of 304 patients with suspected H-CCA, 234 underwent attempted resection and 70 were enrolled in a transplant protocol. Excluding incomplete/R2 resections (n = 43), patients who were enrolled, but did not undergo transplant (n = 24), and transplants without confirmed H-CCA diagnoses (n = 5), 191 patients underwent curative-intent resection and 41 curative-intent transplant. Compared with resection, transplant patients were younger (52 vs 65 years; P < 0.001), and more frequently had primary sclerosing cholangitis (PSC; 61% vs 2%; P < 0.001) and received chemotherapy and/or radiation (98% vs 57%; P < 0.001). Groups were otherwise similar in demographics and comorbidities. Patients who underwent transplant for confirmed H-CCA diagnosis had improved OS compared with resection (3-year: 72% vs 33%; 5-year: 64% vs 18%; P < 0.001). Among patients who underwent resection for tumors <3 cm with lymph-node negative disease, and excluding PSC patients, transplant was still associated with improved OS (3-year: 54% vs 44%; 5-year: 54% vs 29%; P = 0.03). Transplant remained associated with improved survival on intention-to-treat analysis, even after accounting for tumor size, lymph node status, and PSC (P = 0.049).Resection for hilar cholangiocarcinoma that meets criteria for transplantation (<3 cm, lymph-node negative disease) is associated with substantially decreased survival compared to transplant for the same criteria with unresectable disease. Prospective trials are needed and justified.

  View details for PubMedID 29064885

• The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma ANNALS OF SURGICAL ONCOLOGY Zhang, X., Squires, M. H., Bagante, F., Ethun, C. G., Salem, A., Weber, S. M., Thuy Tran, Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Weiss, M., Scoggins, C., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R., Pawlik, T. M. 2018; 25 (5): 1140–49

  Abstract

  The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA.Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status.Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829).Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

  View details for PubMedID 29470820

• Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the US Neuroendocrine Tumor Study Group Merath, K., Bagante, F., Beal, E. W., Lopez-Aguiar, A. G., Poultsides, G., Makris, E., Rocha, F., Kanji, Z., Weber, S., Fisher, A., Fields, R., Krasnick, B. A., Idrees, K., Smith, P. M., Cho, C., Beems, M., Schmidt, C. R., Dillhoff, M., Maithel, S. K., Pawlik, T. M. WILEY. 2018: 868–78

  Abstract

  The risk of recurrence after resection of non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative-intent resection.A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c-indices.Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05-1.10; P < 0.001). GEP-NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c-index: training set, 0.739; test set, 0.718).The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting.

  View details for PubMedID 29448303

  View details for PubMedCentralID PMC5992105

• The impact of caudate lobe resection on margin status and outcomes in patients with hilar cholangiocarcinoma: a multi-institutional analysis from the US Extrahepatic Biliary Malignancy Consortium SURGERY Bhutiani, N., Scoggins, C. R., McMasters, K. M., Ethun, C. G., Poultsides, G. A., Pawlik, T. M., Weber, S. M., Schmidt, C. R., Fields, R. C., Idrees, K., Hatzaras, L., Shen, P., Maithel, S. K., Martin, R. G. 2018; 163 (4): 726–31

  Abstract

  The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma.A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes.A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival.Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation.

  View details for PubMedID 29306541

• Preoperative Risk Score and Prediction of Long-Term Outcomes after Hepatectomy for Intrahepatic Cholangiocarcinoma Sasaki, K., Margonis, G. A., Andreatos, N., Bagante, F., Weiss, M., Barbon, C., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Aucejo, F. N., Pawlik, T. M. ELSEVIER SCIENCE INC. 2018: 393–405

  Abstract

  Accurate prediction of prognosis for patients with intrahepatic cholangiocarcinoma (ICC) remains a challenge. We sought to define a preoperative risk tool to predict long-term survival after resection of ICC.Patients who underwent hepatectomy for ICC at 1 of 16 major hepatobiliary centers between 1990 and 2015 were identified. Clinicopathologic data were analyzed and a prognostic model was developed based on the regression β-coefficients on data in training set. The model was subsequently assessed using a validation set.Among 538 patients, most patients had a solitary tumor (median tumor number 1; interquartile range 1 to 2) and median tumor size was 5.7 cm (interquartile range 4.0 to 8.0 cm). Median and 5-year overall survival was 39.0 months and 39.0%, respectively. On multivariable analyses, preoperative factors associated with long-term survival included tumor size (hazard ratio [HR] 1.12; 95% CI 1.06 to 1.18), natural logarithm carbohydrate antigen 19-9 level (HR 1.33; 95% CI 1.22 to 1.45), albumin level (HR 0.76; 95% CI 0.55 to 0.99), and neutrophil to lymphocyte ratio (HR 1.05; 95% CI 1.02 to 1.09). A weighted composite prognostic score was constructed based on these factors: [9 + (1.12 × tumor size) + (2.81 × natural logarithm carbohydrate antigen 19-9) + (0.50 × neutrophil to lymphocyte ratio) + (-2.79 × albumin)]. The model demonstrated good performance in the testing (area under the curve 0.696) and validation (0.691) datasets. The model performed better than both the T categories (area under the curve 0.532) and the cumulative stage classifications in the American Joint Committee on Cancer staging manual, 8th edition (area under the curve 0.559). When assessing risk of death within 1 year of operation, a risk score ≥25 had a positive predictive value of 59.8% compared with a positive predictive value of 35.3% for American Joint Committee on Cancer staging manual, 8th edition T4 disease and 31.8% for stage IIIB disease.Postsurgical long-term outcomes could be predicted using a composite weighted scoring system based on preoperative clinical parameters. The preoperative risk model can be used to inform patient to provider conversations and expectations before operation.

  View details for PubMedID 29274841

• Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium Schimizzi, G. V., Jin, L. X., Davidson, J. T., Krasnick, B. A., Ethun, C. G., Pawlik, T. M., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Weber, S. M., Salem, A., Hawkins, W. G., Strasberg, S. M., Doyle, M. B., Chapman, W. C., Martin, R. G., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Fields, R. C. ELSEVIER SCI LTD. 2018: 332–39

  Abstract

  Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined.Utilizing data from the U.S. Extrahepatic Biliary Malignancy Consortium, patients were grouped into those who underwent resection for HC based on VR status: no VR, portal vein resection (PVR), or hepatic artery resection (HAR). Perioperative and long-term survival outcomes were analyzed.Between 1998 and 2015, 201 patients underwent resection for HC, of which 31 (15%) underwent VR: 19 patients (9%) underwent PVR alone and 12 patients (6%) underwent HAR either with (n = 2) or without PVR (n = 10). Patients selected for VR tended to be younger with higher stage disease. Rates of postoperative complications and 30-day mortality were similar when stratified by vascular resection status. On multivariate analysis, receipt of PVR or HAR did not significantly affect OS or RFS.In a modern, multi-institutional cohort of patients undergoing curative-intent resection for HC, VR appears to be a safe procedure in a highly selected subset, although long-term survival outcomes appear equivalent. VR should be considered only in select patients based on tumor and patient characteristics.

  View details for PubMedID 29169904

  View details for PubMedCentralID PMC5970648

• Clinicopathologic score predicting lymph node metastasis in T1 gastric cancer. Surgery Tran, T. B., Worhunsky, D. J., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Weber, S. M., Schmidt, C., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2018; 163 (4): 889–93

  Abstract

  BACKGROUND: Although gastrectomy with adequate regional nodal examination is considered the standard of care for invasive gastric adenocarcinoma, endoscopic resection has been adopted increasingly in select patients with T1 gastric cancer. The objective of this study was to identify preoperative predictors of lymph node metastasis in patients in the United States with T1 gastric cancer.METHODS: Patients who underwent operative resection for T1 gastric cancer between 2000 and 2012 were identified from a multi-institutional database. Clinicopathologic predictors of lymph node metastasis were determined using univariate and multivariate logistic regression. A preoperative score was created, assigning points based on each variable's regression coefficient.RESULTS: Among 835 patients with gastric cancer undergoing curative-intent surgical resection, 176 patients (20.5%) had T1 disease confirmed on final pathology. Of those, 38 patients (22%) had lymph node metastasis. Independent predictors of lymph node involvement on multivariate analysis were poor differentiation, T1b stage, lymphovascular invasion, and tumor size >2cm. A clinicopathologic risk score composed of these 4 variables was created. Receiver operating curve analysis showed excellent discrimination (area under the curve=0.79) and 100% sensitivity in detecting lymph node metastasis when only one of the aforementioned factors was present.CONCLUSIONS: In this cohort of U.S. patients with T1 gastric adenocarcinoma, the lack of lymph node involvement could be predicted by the absence of several unfavorable factors, including T stage, poor differentiation, lymphovascular invasion, and size >2cm.

  View details for PubMedID 29398039

• Prospective Evaluation of Results of Reoperation in Zollinger-Ellison Syndrome. Annals of surgery Norton, J. A., Krampitz, G. W., Poultsides, G. A., Visser, B. C., Fraker, D. L., Alexander, H. R., Jensen, R. T. 2018; 267 (4): 782–88

  Abstract

  OBJECTIVE: To determine the role of reoperation in patients with persistent or recurrent Zollinger-Ellison Syndrome (ZES).BACKGROUND: Approximately, 0% to 60% of ZES patients are disease-free (DF) after an initial operation, but the tumor may recur.METHODS: A prospective database was queried.RESULTS: A total of 223 patients had an initial operation for possible cure of ZES and then were subsequently evaluated serially with cross sectional imaging-computed tomography, magnetic resonance imaging, ultrasound, more recently octreoscan-and functional studies for ZES activity. The mean age at first surgery was 49 years and with an 11-year mean follow-up 52 patients (23%) underwent reoperation when ZES recurred with imageable disease. Results in this group are analyzed in the current report. Reoperation occurred on a mean of 6 years after the initial surgery with a mean number of reoperations of 1 (range 1-5). After reoperation 18/52 patients were initially DF (35%); and after a mean follow-up of 8 years, 13/52 remained DF (25%). During follow-up, 9/52 reoperated patients (17%) died, of whom 7 patients died a disease-related death (13%). The overall survival from first surgery was 84% at 20 years and 68% at 30 years. Multiple endocrine neoplasia type 1 status did not affect survival, but DF interval and liver metastases did.CONCLUSIONS: These results demonstrate that a significant proportion of patients with ZES will develop resectable persistent or recurrent disease after an initial operation. These patients generally have prolonged survival after reoperation and 25% can be cured with repeat surgery, suggesting all ZES patients postresection should have systematic imaging, and if tumor recurs, advise repeat operation.

  View details for PubMedID 29517561

• Implications of Intrahepatic Cholangiocarcinoma Etiology on Recurrence and Prognosis after Curative-Intent Resection: a Multi-Institutional Study WORLD JOURNAL OF SURGERY Zhang, X., Chakedis, J., Bagante, F., Beal, E. W., Lv, Y., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 42 (3): 849–57

  Abstract

  We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype.986 patients with HBV-ICC (n = 201), stone-ICC (n = 103), and conventional ICC (n = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias.HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively).While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.

  View details for PubMedID 28879598

• Incidence and Prognosis of Primary Gastrinomas in the Hepatobiliary Tract JAMA SURGERY Norton, J. A., Foster, D. S., Blumgart, L. H., Poultsides, G. A., Visser, B. C., Fraker, D. L., Alexander, H., Jensen, R. T. 2018; 153 (3): e175083

  View details for PubMedID 29365025

• Accuracy of the ACS NSQIP Online Risk Calculator Depends on How You Look at It: Results from the United States Gastric Cancer Collaborative AMERICAN SURGEON Beal, E. W., Saunders, N. D., Kearney, J. F., Lyon, E., Wei, L., Squires, M. H., Jin, L. X., Worhunsky, D. J., Votanopoulos, K. I., Ejaz, A., Poultsides, G., Fields, R. C., Swords, D., Acher, A. W., Weber, S. M., Maithel, S. K., Pawlik, T., Schmidt, C. R. 2018; 84 (3): 358–64

  Abstract

  The objective of this study is to assess the accuracy of the American College of Surgeons National Surgical Quality Improvement Program online risk calculator for estimating risk after operation for gastric cancer using the United States Gastric Cancer Collaborative. Nine hundred and sixty-five patients who underwent resection of gastric adenocarcinoma between January 2000 and December 2012 at seven academic medical centers were included. Actual complication rates and outcomes for patients were compared. Most of the patients underwent total gastrectomy with Roux-en-Y reconstruction (404, 41.9%) and partial gastrectomy with gastrojejunostomy (239, 24.8%) or Roux-en-Y reconstruction (284, 29.4%). The C-statistic was highest for venous thromboembolism (0.690) and lowest for renal failure at (0.540). All C-statistics were less than 0.7. Brier scores ranged from 0.010 for venous thromboembolism to 0.238 for any complication. General estimates of risk for the cohort were variable in terms of accuracy. Improving the ability of surgeons to estimate preoperative risk for patients is critically important so that efforts at risk reduction can be personalized to each patient. The American College of Surgeons National Surgical Quality Improvement Program risk calculator is a rapid and easy-to-use tool and validation of the calculator is important as its use becomes more common.

  View details for Web of Science ID 000428720300018

  View details for PubMedID 29559049

• Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the US extrahepatic biliary malignancy consortium JOURNAL OF SURGICAL ONCOLOGY Krasnick, B. A., Jin, L. X., Davidson, J. T., Sanford, D. E., Ethun, C. G., Pawlik, T. M., Poultsides, G. A., Thuy Tran, Idrees, K., Hawkins, W. G., Chapman, W. C., Doyle, M. M., Weber, S. M., Strasberg, S. M., Salem, A., Martin, R. G., Isom, C. A., Scoggins, C., Schmidt, C. R., Shen, P., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Fields, R. C. 2018; 117 (3): 363–71

  Abstract

  Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection.We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis.A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded.AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.

  View details for PubMedID 29284072

  View details for PubMedCentralID PMC5924689

• Cytoreductive debulking surgery among patients with neuroendocrine liver metastasis: a multi-institutional analysis HPB Ejaz, A., Reames, B. N., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M. J., Marques, H. P., Aldrighetti, L., Pawlik, T. M. 2018; 20 (3): 277–84

  Abstract

  Management of neuroendocrine liver metastasis (NELM) in the setting of unresectable disease is poorly defined and the role of debulking remains controversial. The objective of the current study was to define outcomes following non-curative intent liver-directed therapy (debulking) among patients with NELM.612 patients were identified who underwent liver-directed therapy of NELM from a multi-institutional database. Outcomes were stratified according to curative (R0/R1) versus non-curative ≥ 80% debulking (R2).179 (29.2%) patients had an R2/debulking procedure. Patients undergoing debulking more commonly had more aggressive high-grade tumors (R0/R1: 12.8% vs. R2: 35.0%; P < 0.001) or liver disease burden that was bilateral (R0/R1: 52.8% vs. R2: 75.6%; P < 0.001). After a median follow-up of 51 months, median (R0/R1: not reached vs. R2: 87 months; P < 0.001) and 5-year survival (R0/R1: 85.2% vs. R2: 60.7%; P < 0.001) was higher among patients who underwent an R0/R1 resection compared with patients who underwent a debulking operation. Among patients with ≥50% NELM liver involvement, median and 5-year survival following debulking was 55.4 months and 40.6%, respectively.Debulking operations for NELM provided reasonable long-term survival. Hepatic debulking for patients with NELM is a reasonable therapeutic option for patients with grossly unresectable disease that may provide a survival benefit.

  View details for PubMedID 28964630

• The Limitations of Standard Clinicopathologic Features to Accurately Risk-Stratify Prognosis after Resection of Intrahepatic Cholangiocarcinoma JOURNAL OF GASTROINTESTINAL SURGERY Bagante, F., Merath, K., Squires, M. H., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2018; 22 (3): 477–85

  Abstract

  The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence.Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence.Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable."A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.

  View details for PubMedID 29352440

• A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group Poorman, C. E., Ethun, C. G., Postlewait, L. M., Tran, T. B., Prescott, J. D., Pawlik, T. M., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Staley, C. A., Poultsides, G. A., Maithel, S. K. SPRINGER. 2018: 520–27

  Abstract

  The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC.Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS).Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001).Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.

  View details for PubMedID 29164414

• Timing of disease occurrence and hepatic resection on long-term outcome of patients with neuroendocrine liver metastasis JOURNAL OF SURGICAL ONCOLOGY Zhang, X., Beal, E. W., Weiss, M., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Pawlik, T. M. 2018; 117 (2): 171–81

  Abstract

  The objective of the study was to evaluate the impact of timing of disease occurrence and hepatic resection on long-term outcome of neuroendocrine liver metastasis (NELM).A total of 420 patients undergoing curative-intent resection for NELM were identified from a multi-institutional database. Date of primary resection, NELM detection and resection, intraoperative details, disease-specific (DSS), and recurrence-free survival (RFS) were obtained.A total of 243 (57.9%) patients had synchronous NELM, while 177 (42.1%) developed metachronous NELM. On propensity score matching (PSM), patients with synchronous versus metachronous NELM had comparable DSS (10-year DSS, 76.2% vs 85.9%, P = 0.105), yet a worse RFS (10-year RFS, 34.1% vs 59.8%, P = 0.008). DSS and RFS were comparable regardless of operative approach (simultaneous vs staged, both P > 0.1). Among patients who developed metachronous NELM, no difference in long-term outcomes were identified between early (≤2 years, n = 102, 57.6%) and late (>2 years, n = 68, 42.4%) disease on PSM (both P > 0.1).Patients with synchronous NELM had a higher risk of tumor recurrence after hepatic resection versus patients with metachronous disease. The time to development of metachronous NELM did not affect long-term outcome. Curative-intent hepatic resection should be considered for patients who develop NELM regardless of the timing of disease presentation.

  View details for PubMedID 28940257

• Management of Borderline Resectable Pancreatic Cancer. International journal of radiation oncology, biology, physics Toesca, D. A., Koong, A. J., Poultsides, G. A., Visser, B. C., Haraldsdottir, S., Koong, A. C., Chang, D. T. 2018; 100 (5): 1155–74

  Abstract

  With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.

  View details for PubMedID 29722658

• Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients. Annals of surgery Margonis, G. A., Buettner, S., Andreatos, N., Wagner, D., Sasaki, K., Barbon, C., Beer, A., Kamphues, C., Løes, I. M., He, J., Pawlik, T. M., Kaczirek, K., Poultsides, G., Lønning, P. E., Cameron, J. L., Mischinger, H. J., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weiss, M. J. 2018

  Abstract

  To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis.CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery.CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences.According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5).The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.

  View details for PubMedID 29351098

• Performance of prognostic scores and staging systems in predicting long-term survival outcomes after surgery for intrahepatic cholangiocarcinoma JOURNAL OF SURGICAL ONCOLOGY Buettner, S., Galjart, B., van Vugt, J. A., Bagante, F., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T., Maithel, S. K., Pulitano, C., Margonis, G. A., Weiss, M., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J., IJzermans, J. M., Koerkamp, B., Pawlik, T. M. 2017; 116 (8): 1085–95

  Abstract

  We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort.The overall (OS) and disease free survival (DFS) prognostic discriminatory ability of various commonly used models were assessed in a large retrospective cohort. Harrell's concordance index (c-index) was used to determine accuracy of model prediction.Among 1054 ICC patients, median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and 39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and 44.4%, respectively. The prognostic models associated with the best OS prediction were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index 0.639). No model was proficient in predicting DFS. Only the Wang nomogram exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC staging system was 0.637 for OS and 0.582 for DFS.While the Wang nomogram had the best discriminatory ability relative to OS and DFS, no ICC staging system or nomogram demonstrated excellent prognostic discrimination. The AJCC staging for ICC performed reasonably, although its overall discrimination was only modest-to-good.

  View details for PubMedID 28703880

• The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis JOURNAL OF SURGICAL ONCOLOGY Ejaz, A., Reames, B. N., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M., Marques, H., Aldrighetti, L., Pawlik, T. M. 2017; 116 (7): 841–47

  View details for DOI 10.1002/jso.24727

  View details for Web of Science ID 000416926600007

• Predictors and Prognostic Implications of Perioperative Chemotherapy Completion in Gastric Cancer Karagkounis, G., Squires, M., Melis, M., Poultsides, G. A., Worhunsky, D., Jin, L. X., Fields, R. C., Spolverato, G., Pawlik, T. M., Votanopoulos, K. I., Levine, E. A., Schmidt, C., Bloomston, M., Cho, C. S., Weber, S., Masi, A., Berman, R., Pachter, H., Staley, C. A., Newman, E., Maithel, S. K., Hatzaras, I. SPRINGER. 2017: 1984–92

  Abstract

  Perioperative chemotherapy in gastric cancer is increasingly used since the "MAGIC" trial, while clinical practice data outside of trials remain limited. We sought to evaluate the predictors and prognostic implications of perioperative chemotherapy completion in patients undergoing curative-intent gastrectomy across multiple US institutions.Patients who underwent curative-intent resection of gastric adenocarcinoma between 2000 and 2012 in eight institutions of the US Gastric Cancer Collaborative were identified. Patients who received preoperative chemotherapy were included, while those who died within 90 days or with unknown adjuvant chemotherapy status were excluded. Predictors of chemotherapy completion and survival were identified using multivariable logistic regression and Cox proportional hazards.One hundred sixty three patients were included (median age 63.3, 36.8% female). The postoperative component of perioperative chemotherapy was administered in 112 (68.7%) patients. Factors independently associated with receipt of adjuvant chemotherapy were younger age (odds ratio (OR) 2.73, P = 0.03), T3 tumors (OR 14.3, P = 0.04), lymph node metastasis (OR 5.82, P = 0.03), and D2 lymphadenectomy (OR 4.12, P = 0.007), and, inversely, postoperative complications (OR 0.25, P = 0.008). Median overall survival (OS) was 25.1 months and 5-year OS was 36.5%. Predictors of OS were preexisting cardiac disease (hazard ratio (HR) 2.7, 95% CI 1.13-6.46), concurrent splenectomy (HR 4.11, 95% CI 1.68-10.0), tumor stage (reference stage I; stage II HR 2.62; 95% CI 0.99-6.94; stage III HR 4.86, 95% CI 1.81-13.02), and D2 lymphadenectomy (HR 0.43, 95% CI 0.19-0.95). After accounting for these factors, adjuvant chemotherapy administration was associated with improved OS (HR 0.33, 95% CI 0.14-0.82).Completion of perioperative chemotherapy was successful in two thirds of patients with gastric cancer and was independently associated with improved survival.

  View details for PubMedID 28963709

• The Effects of Travel Burden on Outcomes After Resection of Extrahepatic Biliary Malignancies: Results from the US Extrahepatic Biliary Consortium O'Connor, S. C., Mogal, H., Russell, G., Ethun, C., Fields, R. C., Jin, L., Hatzaras, I., Vitiello, G., Idrees, K., Isom, C. A., Martin, R., Scoggins, C., Pawlik, T. M., Schmidt, C., Poultsides, G., Tran, T. B., Weber, S., Salem, A., Maithel, S., Shen, P. SPRINGER. 2017: 2016–24

  Abstract

  Surgical resection of extrahepatic biliary malignancies has been increasingly centralized at high-volume tertiary care centers. While this has improved outcomes overall, increased travel burden has been associated with worse survival for many other malignancies. We hypothesized that longer travel distances are associated with worse outcomes for these patients as well.Data was analyzed from the US Extrahepatic Biliary Consortium database, which retrospectively reviewed patients who received resection of extrahepatic biliary malignancies at 10 high-volume centers. Driving distance to the patient's treatment center was measured for 1025 patients. These were divided into four quartiles for analysis: < 24.5, 24.5-57.2, 57.2-117, and < 117 mi. Cox proportional hazard models were then used to measure differences in overall survival.No difference was found between the groups in severity of disease or post-operative complications. The median overall survival in each quartile was as follows: 1st = 1.91, 2nd = 1.60, 3rd = 1.30, and 4th = 1.39 years. Patients in the 3rd and 4th quartile had a significantly lower median household income (p = 0.0001) and a greater proportion Caucasian race (p = 0.0001). However, neither of these was independently associated with overall survival. The two furthest quartiles were found to have decreased overall survival (HR = 1.39, CI = 1.12-1.73 and HR = 1.3, CI = 1.04-1.62), with quartile 3 remaining significant after multivariate analysis (HR = 1.45, CI = 1.04-2.0, p = 0.028).Longer travel distances were associated with decreased overall survival, especially in the 3rd quartile of our study. Patients traveling longer distances also had a lower household income, suggesting that these patients have significant barriers to care.

  View details for PubMedID 28986752

  View details for PubMedCentralID PMC5909109

• Neuroendocrine Liver Metastasis: Prognostic Implications of Primary Tumor Site on Patients Undergoing Curative Intent Liver Surgery Spolverato, G., Bagante, F., Aldrighetti, L., Poultsides, G., Bauer, T. W., Field, R. C., Marques, H. P., Weiss, M., Maithel, S. K., Pawlik, T. M. SPRINGER. 2017: 2039–47

  Abstract

  Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the current study was to define the association of primary tumor location on prognosis of patients undergoing curative intent liver resection for NELM.Between 1990 and 2014, 421 patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified and analyzed by location of the primary tumor (PNET vs. non-PNET). A propensity score-matched analysis was utilized to assess the impact of primary tumor location on long-term survival.Among the 421 patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). There were no differences in tumor burden and tumor site, while presence of extrahepatic disease was more common among patients with non-PNET NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29 72.5%; p = 0.010). Patients with PNET NELM were more likely to have non-functional disease compared with patients who had non-PNET NELM (non-functional, PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the final pathological specimen of the resected NELM, patients with PNET NELM were more likely to have a moderately differentiated tumor (59.3%), while patients with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%) (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%; p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5% vs. non-PNET 84.3%; p = 0.19).PNET patients more often present with non-functional NELM and moderately differentiated tumors. On propensity-matched analysis, factors such as extrahepatic disease and tumor grade, but not primary tumor location, were associated with prognosis of patients undergoing curative intent liver surgery for NELM.

  View details for PubMedID 28744737

• Evaluating the American College of Surgeons National Surgical Quality Improvement project risk calculator: results from the US Extrahepatic Biliary Malignancy Consortium Beal, E. W., Lyon, E., Kearney, J., Wei, L., Ethun, C. G., Black, S. M., Dillhoff, M., Salem, A., Weber, S. M., Tran, T. B., Poultsides, G., Shenoy, R., Hatzaras, I., Krasnick, B., Fields, R. C., Buttner, S., Scoggins, C. R., Martin, R. G., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Pawlik, T. M., Schmidt, C. R. ELSEVIER SCI LTD. 2017: 1104–11

  Abstract

  The objective of this study is to evaluate use of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online risk calculator for estimating common outcomes after operations for gallbladder cancer and extrahepatic cholangiocarcinoma.Subjects from the United States Extrahepatic Biliary Malignancy Consortium (USE-BMC) who underwent operation between January 1, 2000 and December 31, 2014 at 10 academic medical centers were included in this study. Calculator estimates of risk were compared to actual outcomes.The majority of patients underwent partial or major hepatectomy, Whipple procedures or extrahepatic bile duct resection. For the entire cohort, c-statistics for surgical site infection (0.635), reoperation (0.680) and readmission (0.565) were less than 0.7. The c-statistic for death was 0.740. For all outcomes the actual proportion of patients experiencing an event was much higher than the median predicted risk of that event. Similarly, the group of patients who experienced an outcome did have higher median predicted risk than those who did not.The ACS NSQIP risk calculator is easy to use but requires further modifications to more accurately estimate outcomes for some patient populations and operations for which validation studies show suboptimal performance.

  View details for PubMedID 28890310

  View details for PubMedCentralID PMC5915623

• Transgastric pancreatic necrosectomy-expedited return to prepancreatitis health JOURNAL OF SURGICAL RESEARCH Dua, M. M., Worhunsky, D. J., Malhotra, L., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2017; 219: 11–17

  Abstract

  The best operative strategy for necrotizing pancreatitis remains controversial. Traditional surgical necrosectomy is associated with significant morbidity; endoscopic and percutaneous strategies require repeated interventions with prolonged hospitalizations. We have developed a transgastric approach to pancreatic necrosectomy to overcome the shortcomings of the other techniques described.Patients with necrotizing pancreatitis treated from 2009 to 2016 at an academic center were retrospectively reviewed. Open or laparoscopic transgastric necrosectomy was performed if the area of necrosis was walled-off and in a retrogastric position on cross-sectional imaging. Study endpoints included postoperative complications and mortality.Forty-six patients underwent transgastric necrosectomy (nine open and 37 laparoscopic). Median (interquartile range) preoperative Acute Physiologic and Chronic Health Evaluation II score was 6 (3-12). Seventy percent of patients had >30% necrosis on preoperative imaging; infected necrosis was present in 35%. Median total length of stay (LOS) was 6 (3-12) d. No patient required a second operative debridement; four patients (9%) had short-term postoperative percutaneous drainage for residual fluid collections. Median follow-up was 1 y; there were no fistula or wound complications. Six patients (13%) had postoperative bleeding; five patients received treatment by image-guided embolization. There was one death in the cohort.Transgastric pancreatic necrosectomy allows for effective debridement with a single definitive operation. When anatomically suitable, this operative strategy offers expedited recovery and avoids long-term morbidity associated with fistulas and prolonged drainage.

  View details for PubMedID 29078869

• Surgical Site Infection Is Associated with Tumor Recurrence in Patients with Extrahepatic Biliary Malignancies JOURNAL OF GASTROINTESTINAL SURGERY Buettner, S., Ethun, C. G., Poultsides, G., Thuy Tran, Idrees, K., Isom, C. A., Weiss, M., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. G., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Koerkamp, B., Maithel, S. K., Pawlik, T. M. 2017; 21 (11): 1813–20

  Abstract

  Surgical site infections (SSI) are one of the most common complications after hepato-pancreato-biliary surgery. Infectious complications may lead to an associated immune-modulatory effect that inhibits the body's response to cancer surveillance. We sought to define the impact of SSI on long-term prognosis of patients undergoing surgical resection of extrahepatic biliary malignancies (EHBM).Patients undergoing surgery for EHBM between 2000 and 2014 were identified using a large, multi-center, national cohort dataset. Recurrence free survival (RFS) was calculated and a multivariable Cox proportional hazards model was utilized to identify potential risk factors for RFS including SSI.Seven hundred twenty-eight patients included in the analytic cohort; 236 (32.4%) patients had perihilar cholangiocarcinoma, 241 (33.1%) gallbladder cancer, and 251 (34.5%) distal cholangiocarcinoma. A major resection, liver resection, was performed in 205 (28.3%) patients, while 110 (15.2%) patients had a pancreaticoduodenectomy. The overall incidence of morbidity was 55.8%; among the 397 patients who experienced a complication, 161 patients specifically had an SSI. The SSI occurred as an infection of the surgical site (n = 70, 9.6%) or formation of an abscess in the operative bed (n = 91, 12.5%). SSI was associated with long-term survival as patients who experienced an SSI had a median RFS of 19.5 months compared with 30.5 months for those patients who did not have an SSI (HR 1.40, 95% CI 1.08-1.80; p = 0.01). Among 279 patients who had EHBM that had no associated lymph node metastases, well-to-moderate tumor differentiation, as well as an R0 resection margin, SSI remained associated with worse RFS (HR 1.84, 95% CI 1.03-3.29; p = 0.038), as well as overall survival (HR 1.87, 95% CI 1.18-2.97; p = 0.008).SSI was a relatively common occurrence following surgery for EHBM as 1 in 10 patients experienced an SSI. In addition to standard tumor-specific factors, the occurrence of postoperative SSI was adversely associated with long-term survival.

  View details for PubMedID 28913712

  View details for PubMedCentralID PMC5905431

• Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma (vol 40, pg 1383, 2017) CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY Chan, L. S., Sze, D. Y., Poultsides, G. A., Louie, J. D., Abdelrazek Mohammed, M. A., Wang, D. S. 2017; 40 (10): 1657

  View details for PubMedID 28534185

• Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy. Surgery Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R. C., Weber, S. M., Votanopoulos, K. I., Kooby, D. A., Worhunsky, D. J., Jin, L. X., Hawkins, W. G., Acher, A. W., Cho, C. S., Saunders, N., Levine, E. A., Schmidt, C. R., Maithel, S. K., Pawlik, T. M. 2017

  Abstract

  The impact of adjuvant chemotherapy and chemo-radiation therapy in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio on the relative benefit of adjuvant chemotherapy or chemo-radiation therapy among patients having undergone curative-intent resection for gastric cancer.Using the multi-institutional US Gastric Cancer Collaborative database, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of lymph node ratio on overall survival among patients who received chemotherapy or chemo-radiation therapy was evaluated.Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based chemo-radiation therapy, whereas the remaining 141 (19.6%) received chemotherapy. Median overall survival was 40.9 months, and 5-year overall survival was 40.3%. According to lymph node ratio categories, 5-year overall survival for patients with a lymph node ratio of 0, 0.01-0.10, >0.10-0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse overall survival included involvement of the gastroesophageal junction (hazard ratio 1.8), T-stage (3-4: hazard ratio 2.1), lymphovascular invasion (hazard ratio 1.4), and lymph node ratio (>0.25: hazard ratio 2.3; all P < .05). In contrast, receipt of adjuvant chemo-radiation therapy was associated with an improved overall survival in the multivariable model (versus resection alone: hazard ratio 0.40; versus chemotherapy: hazard ratio 0.45, both P < .001). The benefit of chemo-radiation therapy for resected gastric cancer was noted only among patients with lymph node ratio >0.25 (versus resection alone: hazard ratio R 0.34; versus chemotherapy: hazard ratio 0.45, both P < .001). In contrast, there was no noted overall survival benefit of chemotherapy or chemo-radiation therapy among patients with lymph node ratio ≤0.25 (all P > .05).Adjuvant chemotherapy or chemo-radiation therapy was utilized in more than one-half of patients undergoing curative-intent resection for gastric cancer. Lymph node ratio may be a useful tool to select patients for adjuvant chemo-radiation therapy, because the benefit of chemo-radiation therapy was isolated to patients with greater degrees of lymphatic spread (ie, lymph node ratio >0.25).

  View details for DOI 10.1016/j.surg.2017.03.023

  View details for PubMedID 28578142

• Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases. HPB Buettner, S., van Vugt, J. L., Gaspersz, M. P., Coelen, R. J., Roos, E., Labeur, T. A., Margonis, G. A., Ethun, C. G., Maithel, S. K., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., IJzermans, J. N., van Gulik, T. M., Pawlik, T. M., Groot Koerkamp, B. 2017

  Abstract

  The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy.Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers.In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97-2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09-2.69) were independent poor prognostic factors in the resected cohort.Patients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.

  View details for DOI 10.1016/j.hpb.2017.04.014

  View details for PubMedID 28549744

• Management and outcomes of patients with recurrent neuroendocrine liver metastasis after curative surgery: An international multi-institutional analysis. Journal of surgical oncology Spolverato, G., Bagante, F., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Weiss, M., Pawlik, T. M. 2017

  Abstract

  We sought to characterize the treatment, as well as define the long-term outcomes, of patients with recurrent neuroendocrine liver metastasis (NELM).Between 1990 and 2014, 322 patients undergoing curative intent liver surgery for NELM were identified from a multi-institutional database. Recurrences were classified as intrahepatic, extrahepatic, and both intra- and extra-hepatic.Overall, median, 1-, 5-, 10-year DFS were 3.1 years, 75.5%, 40.4%, and 32.1%, respectively. After curative intent liver surgery, 209 patients (64.9%) recurred within a median follow-up of 4.5 years, while 113 (35.1%) patients were alive without disease with a follow-up time ≥3 years. The site of recurrence was intrahepatic only (n = 111, 65.7%), extrahepatic only (n = 19, 11.2%), or intra- and extra-hepatic (n = 39, 23.1%). Compared with intrahepatic only recurrence, extrahepatic only, and combined intra- and extra-hepatic recurrence were associated with a worse long-term outcome (10-year OS: intrahepatic only, 42.5%, 95%CI, 24.9-59.0 vs extrahepatic only, 0% and combined intra- and extra-hepatic, 21.5%, 95%CI, 5.3-44.0) (P < 0.001). Most patients were treated with repeat surgery (n = 49, 36.6%), while 34 (23.5%) patients received a somatostatin analogue, 27 (18.6%) systemic cytotoxic chemotherapy, and 27 (21.4%) patients had intra-arterial therapy. Ten-year OS among patients who underwent repeat surgery or intra-arterial treatments was 60.3% (95%CI, 34.1-78.8) and 52.0% (95%CI, 30.6-69.9), respectively. Patients who received somatostatin analogues (45.9% 95%CI, 22.3-66.9) or systemic chemotherapy (0%) had a shorter long-term survival (P = 0.001).Recurrence after surgery for NELM occurred among half of patients. Repeat liver resection for recurrence may offer a reasonable 5-year survival benefit.

  View details for DOI 10.1002/jso.24670

  View details for PubMedID 28513896

• Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially Curable? Journal of gastrointestinal surgery Tran, T. B., Norton, J. A., Ethun, C. G., Pawlik, T. M., Buettner, S., Schmidt, C., Beal, E. W., Hawkins, W. G., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Idrees, K., Isom, C. A., Hatzaras, I., Shenoy, R., Maithel, S. K., Poultsides, G. A. 2017

  Abstract

  Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent.Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients.Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was not significantly higher. Overall survival after resection was worse in jaundiced patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within the jaundiced patients revealed a more favorable survival after resection in the presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the absence of lymphovascular invasion (40 vs. 14 months; P = 0.014).Jaundice is a powerful preoperative clinical sign of inoperability and poor outcome among gallbladder cancer patients. However, some of these patients may still achieve long-term survival after resection, especially when preoperative CA19-9 levels are low and no lymphovascular invasion is noted pathologically.

  View details for DOI 10.1007/s11605-017-3440-z

  View details for PubMedID 28497252

• Impact of Morphological Status on Long-Term Outcome Among Patients Undergoing Liver Surgery for Intrahepatic Cholangiocarcinoma. Annals of surgical oncology Bagante, F., Spolverato, G., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Groot Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017

  Abstract

  The influence of morphological status on the long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) is poorly defined. We sought to study the impact of morphological status on overall survival (OS) of patients undergoing curative-intent resection for ICC.A total of 1083 patients who underwent liver resection for ICC between 1990 and 2015 were identified. Data on clinicopathological characteristics, operative details, and morphological status were recorded and analyzed. A propensity score-matched analysis was performed to reduce confounding biases.Among 1083 patients, 941(86.9%) had a mass-forming (MF) or intraductal-growth (IG) type, while 142 (13.1%) had a periductal-infiltrating (PI) or MF with PI components (MF + PI) ICC. Patients with an MF/IG ICC had a 5-year OS of 41.8% (95% confidence interval [CI] 37.7-45.9) compared with 25.5% (95% CI 17.3-34.4) for patients with a PI/MF + PI (p < 0.001). Morphological type was found to be an independent predictor of OS as patients with a PI/MF + PI ICC had a higher hazard of death (hazard ratio [HR] 1.42, 95% CI 1.11-1.82; p = 0.006) compared with patients who had an MF/IG ICC. Compared with T1a-T1b-T2 MF/IG tumors, T1a-T1b-T2 PI/MF + PI and T3-T4 PI/MF + PI tumors were associated with an increased risk of death (HR 1.47 vs. 3.59). Conversely, patients with T3-T4 MF/IG tumors had a similar risk of death compared with T1a-T1b-T2 MF/IG patients (p = 0.95).Among patients undergoing curative-intent resection of ICC, morphological status was a predictor of long-term outcome. Patients with PI or MF + PI ICC had an approximately 45% increased risk of death long-term compared with patients who had an MF or IG ICC.

  View details for DOI 10.1245/s10434-017-5870-y

  View details for PubMedID 28466403

• A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium ANNALS OF SURGICAL ONCOLOGY Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Merchant, N., Cardona, K., Maithel, S. K. 2017; 24 (5): 1343-1350

  View details for DOI 10.1245/s10434-016-5637-x

  View details for Web of Science ID 000399013200030

• Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma. Cardiovascular and interventional radiology Chan, L. S., Sze, D. Y., Poultsides, G. A., Louie, J. D., Abdelrazek Mohammed, M. A., Wang, D. S. 2017

  Abstract

  Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare mixed cell type primary liver cancer with limited data to guide management. Transarterial radioembolization with yttrium-90 microspheres (RE) is an emerging treatment option for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. This study explored the safety and efficacy of RE for unresectable cHCC-CC.Patients with histopathologically confirmed cHCC-CC treated with RE were retrospectively evaluated. Clinical and biochemical toxicities were assessed using the Common Toxicity Criteria for Adverse Events v4.03. Radiological response was analyzed using the Response Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST criteria. Survival times were calculated and prognostic variables identified.Ten patients (median age 59 years; six men, four women) with unresectable cHCC-CC underwent 14 RE treatments with resin (n = 6 patients) or glass (n = 4 patients) microspheres. Clinical toxicities were limited to grade 1-2 fatigue, anorexia, nausea, or abdominal pain. No significant biochemical toxicities were observed. Median overall survivals from the first RE treatment and from initial diagnosis were 10.2 and 17.7 months, respectively. Six of seven patients with elevated tumor biomarker levels before RE showed decreased levels after treatment (median decrease of 72%, range 13-80%). Best hepatic radiological response was 60% partial response and 40% stable disease by modified RECIST, and 100% stable disease by RECIST v1.1. Poor performance status and the presence of macrovascular invasion were identified as predictors of reduced survival after RE.RE appears to be a safe and promising treatment option for patients with unresectable cHCC-CC.Level 4.

  View details for DOI 10.1007/s00270-017-1648-7

  View details for PubMedID 28432387

• Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging System. Journal of gastrointestinal surgery Bagante, F., Spolverato, G., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Groot Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017

  Abstract

  The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus <6 HLNs.Patients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified.Among 1154 patients undergoing hepatectomy for ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN). Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged according the AJCC eighth edition staging system, N1 patients had a 3-fold increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001).Only one fourth of patients undergoing hepatectomy for ICC had adequate nodal staging according to the AJCC eighth edition. While the six HLN cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN was associated with long-term survival of N1 patients.

  View details for DOI 10.1007/s11605-017-3426-x

  View details for PubMedID 28424987

• Surgical Management of Pancreatic Cysts: A Shifting Paradigm Toward Selective Resection. Digestive diseases and sciences Gerry, J. M., Poultsides, G. A. 2017

  Abstract

  Due to the widespread use of high-quality cross-sectional imaging, pancreatic cystic neoplasms are being diagnosed with increasing frequency. Clinicians are therefore asked to counsel a growing number of patients with pancreatic cysts diagnosed incidentally at an early, asymptomatic stage. Over the last two decades, accumulating knowledge on the biologic behavior of these neoplasms along with improved diagnostics through imaging and endoscopic cyst fluid analysis have allowed for a selective therapeutic approach toward these neoplasms. On one end of the management spectrum, observation is recommended for typically benign lesions (serous cystadenoma), and on the other end, upfront resection is recommended for likely malignant lesions (main duct IPMN, mucinous cystadenoma, solid pseudopapillary tumor, and cystic pancreatic neuroendocrine tumors). In between, management of premalignant lesions (branch duct IPMN) is dictated by the presence of high-risk features. In general, resection should be considered whenever the risk of malignancy is higher than the risk of the operation. This review aims to describe the evolution and current status of evidence guiding the selection of patients with pancreatic cystic neoplasms for surgical resection, along with a specific discussion on the type of resection required and expected outcomes.

  View details for DOI 10.1007/s10620-017-4570-6

  View details for PubMedID 28421458

• Impact of major vascular resection on outcomes and survival in patients with intrahepatic cholangiocarcinoma: A multi-institutional analysis. Journal of surgical oncology Reames, B. N., Ejaz, A., Koerkamp, B. G., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Martel, G., Marsh, J. W., Pawlik, T. M. 2017

  Abstract

  Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database.A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative and survival outcomes.Of 1087 patients who underwent resection, 128 (11.8%) also underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV resections, 9 [7.0%] combined resections). Despite more advanced disease, major vascular resection was not associated with the risk of any complication (OR = 0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post-operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32-3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737, 95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40) survival were similar among patients who did and did not undergo major vascular resection (both P > 0.05).Among patients with ICC, major vascular resection was not associated with worse perioperative or oncologic outcomes. Concurrent major vascular resection should be considered in appropriately selected patients with ICC undergoing hepatectomy.

  View details for DOI 10.1002/jso.24633

  View details for PubMedID 28411373

• Surrogate End Points for Overall Survival in Metastatic, Locally Advanced, or Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis of 24 Randomized Controlled Trials. Annals of surgical oncology Makris, E. A., MacBarb, R., Harvey, D. J., Poultsides, G. A. 2017

  Abstract

  Overall survival (OS) has traditionally been the primary end point in studies evaluating the clinical benefit of first-line chemotherapy in metastatic, locally advanced, or unresectable pancreatic cancer (MLAUPC). Given the prolonged follow-up assessment required to obtain OS and its potential to be confounded by second-line treatments, this study sought to determine whether progression-free survival (PFS), response rate (RR), or disease control rate (DCR) can serve as a reliable surrogate for OS.A systematic review and meta-analysis was performed including all phase 3 clinical trials for MLAUPC, with gemcitabine as the control arm of the trial. The hazard ratios (HRs) for OS and PFS and odds ratios (ORs) for RR and DCR were recorded. A weighted Pearson correlation coefficient was estimated for the association between OS and the other outcomes. The primary analysis used a random effects weighting model, whereas the secondary analyses used a fixed effects- or sample size-weighted approach.For the study, 24 randomized controlled trials were identified. The Pearson correlation coefficient between OS and PFS was 0.86 (95% confidence interval [CI] 0.67-0.94; p < 0.001). Sensitivity analysis of the studies with little to no crossover further showed a correlation coefficient of 0.91 (95% CI 0.76-0.97; p < 0.001). The correlation coefficient between OS and RR was 0.45 (95% CI 0.07-0.72; p = 0.02) and between OS and DCR was 0.74 (95% CI 0.38-0.90; p < 0.001).First-line chemotherapy trials for MLAUPC show a robust correlation between OS and PFS, affirming its role as a surrogate of OS.

  View details for DOI 10.1245/s10434-017-5826-2

  View details for PubMedID 28397190

• Surgical Considerations in the Management of Gastric Adenocarcinoma SURGICAL CLINICS OF NORTH AMERICA Makris, E. A., Poultsides, G. A. 2017; 97 (2): 295-?

  Abstract

  Since Theodor Billroth and César Roux perfected the methods of postgastrectomy reconstruction in as early as the late nineteenth century, surgical management of gastric cancer has made incremental progress. The longstanding and contentious debate on the optimal extent of lymph node dissection for gastric cancer seems to have settled in favor of D2 dissection. Pylorus-preserving distal (central) gastrectomy has emerged as a less invasive, function-preserving option for T1N0 middle-third gastric cancers. Frozen section analysis of margins seems partially helpful in this direction. Last, the role of palliative gastrectomy in patients with metastatic seems less important than initially thought.

  View details for DOI 10.1016/j.suc.2016.11.006

  View details for Web of Science ID 000399266300006

  View details for PubMedID 28325188

• Fukuoka and AGA Criteria Have Superior Diagnostic Accuracy for Advanced Cystic Neoplasms than Sendai Criteria. Digestive diseases and sciences Sighinolfi, M., Quan, S. Y., Lee, Y., Ibaseta, A., Pham, K., Dua, M. M., Poultsides, G. A., Visser, B. C., Norton, J. A., Park, W. G. 2017; 62 (3): 626-632

  Abstract

  The aim of this study was to compare the American Gastroenterological Association guidelines (AGA criteria), the 2012 (Fukuoka criteria), and 2006 (Sendai criteria) International Consensus Guidelines for the diagnosis of advanced pancreatic cystic neoplasms.All patients who underwent surgical resection of a pancreatic cyst from August 2007 through January 2016 were retrospectively analyzed at a single tertiary academic center. Relevant clinical and imaging variables along with pathology results were collected to determine appropriate classification for each guideline. Advanced pancreatic cystic neoplasms were defined by the presence of either high-grade dysplasia or cystic adenocarcinoma. Diagnostic accuracy was measured by ROC analysis.A total of 209 patients were included. Both the AGA and Fukuoka criteria had a higher diagnostic accuracy for advanced neoplastic cysts than the Sendai criteria: AGA ROC 0.76 (95% CI 0.69-0.81), Fukuoka ROC 0.78 (95% CI 0.74-0.82), and Sendai ROC 0.65 (95% CI 0.61-0.69) (p < 0.0001). There was no difference between the Fukuoka and the AGA criteria. While the sensitivity was higher in the Fukuoka criteria compared to the AGA criteria (97.7 vs. 88.6%), the specificity was higher in the AGA criteria compared to the Fukuoka criteria (62.4 vs. 58.2%).In a surgical series of patients with pancreatic cysts, the AGA and Fukuoka criteria had superior diagnostic accuracy for advanced neoplastic cysts compared to the original Sendai criteria.

  View details for DOI 10.1007/s10620-017-4460-y

  View details for PubMedID 28116593

• Routine port-site excision in incidentally discovered gallbladder cancer is not associated with improved survival: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium. Journal of surgical oncology Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B. A., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K. 2017

  Abstract

  Current data on the utility of port-site excision (PSE) during re-resection for incidentally discovered gallbladder cancer (IGBC) in the US are conflicting and limited to single-institution series.All patients with IGBC who underwent curative re-resection at 10 institutions from 2000 to 2015 were included. Patients with and without PSE were compared. Primary outcome was overall survival (OS).Of 449 pts with GBC, 266 were incidentally discovered, of which 193(73%) underwent curative re-resection and had port-site data; 47 pts(24%) underwent PSE, 146(76%) did not. The PSE rate remained similar over time (2000-2004: 33%; 2005-2009: 22%; 2010-2015:22%; P = 0.36). Both groups had similar demographics, operative procedures, and post-operative complications. There was no difference in T-stage (T1: 9 vs. 11%; T2: 52 vs. 52%; T3: 39 vs. 38%; P = 0.96) or LN involvement (36 vs. 41%; P = 0.7) between groups. A 3-year OS was similar between PSE and no PSE groups (65 vs. 43%; P = 0.07). On univariable analysis, residual disease at re-resection (HR = 2.1, 95% CI 1.4-3.3; P = 0.001), high tumor grade, and advanced T-stage were associated with decreased OS. Only grade and T-stage, but not PSE, persisted on multivariable analysis. Distant disease recurrence-rate was identical between PSE and no PSE groups (80 vs. 81%; P = 1.0).Port-site excision during re-resection for IGBC is not associated with improved overall survival and has the same distant disease recurrence compared to no port-site excision. Routine port-site excision is not recommended.

  View details for DOI 10.1002/jso.24591

  View details for PubMedID 28230242

• Comparative performances of the 7th and the 8th editions of the American Joint Committee on Cancer staging systems for intrahepatic cholangiocarcinoma. Journal of surgical oncology Spolverato, G., Bagante, F., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017

  Abstract

  We sought to evaluate and validate the 8th edition of the AJCC classification using a multi-institutional cohort of patients with intrahepatic cholangiocarcinoma (ICC).Patients undergoing curative-intent hepatic resection for ICC between 1990 and 2015 at 14 major hepatobiliary centers were included and were staged according to 7th and 8th editions AJCC criteria.A total of 1154 patients underwent liver resection for ICC. When patients were staged using the AJCC 7th edition, T2a, T2b, and T4 patients had a higher hazard ratio (HR) of death compared with T1 (T2a, HR 1.43, P = 0.004; T2b, HR 1.99, P < 0.001; T4, HR 2.20, P < 0.001). T3 patients had a higher HR of death compared with T1 patients (HR 1.30, P = 0.029) but lower than T2a and T2b. According to AJCC 8th edition, T1b, T2, and T4 patients were at higher risk of death compared with T1a patients (T1b, HR 1.91, P < 0.001; T2, HR 2.29, P < 0.001; T4, HR 4.16, P < 0.001). As in the AJCC 7th edition, AJCC 8th edition T3 patients had a higher HR of death compared with T1 patients (HR 1.65, P  = 0.001) but lower than T1b and T2. AJCC 8th edition. T-category performed slightly better than AJCC 7th edition with a C-index of 0.609 versus 0.590.A staging system that perfectly discriminates between stages has not yet been developed, but the AJCC 8th edition was able to better stratify the risk of death of Stage III and T3 patients.

  View details for DOI 10.1002/jso.24569

  View details for PubMedID 28194791

• Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium JAMA SURGERY Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T., Buettner, S., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Kooby, D. A., Maithel, S. K. 2017; 152 (2): 143-148

  View details for DOI 10.1001/jamasurg.2016.3642

  View details for Web of Science ID 000395623800010

• Minimally Invasive Resection of Adrenocortical Carcinoma: a Multi-Institutional Study of 201 Patients JOURNAL OF GASTROINTESTINAL SURGERY Lee, C. W., Salem, A. I., Schneider, D. F., Leverson, G. E., Tran, T. B., Poultsides, G. A., Postlewait, L. M., Maithel, S. K., Wang, T. S., Hatzaras, I., Shenoy, R., Phay, J. E., Shirley, L., Fields, R. C., Jin, L. X., Pawlik, T. M., Prescott, J. D., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Weber, S. M. 2017; 21 (2): 352-362

  Abstract

  Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery.Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA.A total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3 %, MIS, vs. 30.9 %, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p < 0.001). There was no difference in rates of intraoperative tumor rupture (p = 0.612) or R0 resection (p = 0.953). Only EBL (p = 0.038) and T stage (p = 0.045) were independent prognostic indicators of overall survival after adjusting for significant factors. The surgical approach was not associated with overall or disease-free survival.MIS adrenalectomy may be utilized for preoperatively determined ACC ≤ 10.0 cm; however, OA should be utilized for adrenal masses with either preoperative or intraoperative evidence of local invasion or enlarged lymph nodes, regardless of size.

  View details for DOI 10.1007/s11605-016-3262-4

  View details for Web of Science ID 000393825300019

• Neuroendocrine liver metastasis: The chance to be cured after liver surgery. Journal of surgical oncology Bagante, F., Spolverato, G., Merath, K., Postlewait, L. M., Poultsides, G. A., Mullen, M. G., Bauer, T. W., Fields, R. C., Lamelas, J., Marques, H. P., Aldrighetti, L., Tran, T., Maithel, S. K., Pawlik, T. M. 2017

  Abstract

  Neuroendocrine liver metastasis tumors (NELM) are a heterogeneous group of neoplasms with varied histologic features and a wide range of clinical behaviors. We aimed to identify the fraction of patients cured after liver surgery for NELM.Cure fraction models were used to analyze 376 patients who underwent hepatectomy with curative intent for NELM.The median and 5-year disease-free survival (DFS) were 4.5 years and 46%, respectively. The probability of being cured from NELM by liver surgery was 44%; the time to cure was 5.1 years. In a multivariable cure model, type of neuroendocrine tumor (NET), grade of tumor differentiation, and rate of liver involvement resulted as independent predictors of cure. The cure fraction for patients with well differentiated NELM from gastrointestinal NET or a functional pancreatic NET, and with <50% of liver-involvement was 95%. Patients who had moderately/poorly differentiated NELM from a non-functional pancreatic NET, and with <50% of liver-involvement was 43%. In the presence of all the three unfavorable prognostic factors (nonfunctional PNET, liver involvement >50%, moderately/poorly differentiation), the cure fraction was 8%.Statistical cure after surgery for NELM is possible, and allow for a more accurate prediction of long-term outcome among patients with NELM undergoing liver resection.

  View details for DOI 10.1002/jso.24563

  View details for PubMedID 28146608

• The effect of preoperative chemotherapy treatment in surgically treated intrahepatic cholangiocarcinoma patients-A multi-institutional analysis. Journal of surgical oncology Buettner, S., Koerkamp, B. G., Ejaz, A., Buisman, F. E., Kim, Y., Margonis, G. A., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., IJzermans, J. N., Pawlik, T. M. 2017

  Abstract

  While preoperative chemotherapy (pCT) is utilized in many intra-abdominal cancers, the use of pCT among patients with intrahepatic cholangiocarcinoma (ICC) remains ill defined. As such, the objective of the current study was to examine the impact of pCT among patients undergoing curative-intent resection for ICC.Patients who underwent hepatectomy for ICC were identified from a multi-institutional international cohort. The association between pCT with peri-operative and long-term clinical outcomes was assessed.Of the 1 057 patients who were identified and met the inclusion criteria, 62 patients (5.9%) received pCT. These patients were noticed to have more advanced disease. Median OS (pCT:46.9 months vs no pCT:37.4 months; P = 0.900) and DFS (pCT: 34.1 months vs no pCT: 29.1 months; P = 0.909) were similar between the two groups. In a subgroup analysis of propensity-score matched patients, there was longer OS (pCT:46.9 months vs no pCT:29.4 months) and DFS (pCT:34.1 months vs no pCT:14.0 months); however this did not reach statistical significance (both P > 0.05).In conclusion, pCT utilization among patients with ICC was higher among patients with more advanced disease. Short-term post-operative outcomes were not affected by pCT use and receipt of pCT resulted in equivalent OS and DFS following curative-intent resection.

  View details for DOI 10.1002/jso.24524

  View details for PubMedID 28105651

• Gastric Staging System for Gastroesophageal Junction Cancer in a Western Population. American surgeon Adeshuko, F. A., Squires, M. H., Poultsides, G., Pawlik, T. M., Weber, S. M., Schmidt, C., Votanopoulos, K., Fields, R. C., Maithel, S. K., Cardona, K. 2017; 83 (1): 82-89

  Abstract

  Controversy exists over the staging of gastroesophageal junction (GEJ) adenocarcinomas. The aim of our study was to assess the adequacy of the American Joint Committee on Cancer 7th edition esophageal (E7) and gastric (G7) staging systems for GEJ tumors in a western population. All patients with GEJ adenocarcinoma who underwent curative resection from 2000 to 2012 were identified from the United States Gastric Cancer Collaborative database and assessed according to the E7 and G7 systems. Fifty-one patients were identified. Neither the E7 nor G7 system adequately stratified patients by T or N stage with a loss of distinctiveness between T1 to 4 and N0 to 3 tumors. On final stage analysis, the outcomes were similar between both systems; however, neither system, with the exception of the G7 stage I versus II, adequately stratified patients by stage (E7: I vs II, P = 0.07; II vs III, P = 0.23; G7: I vs II, P = 0.02; II vs III, P = 0.13). Histologic grade was not associated with survival (P = 0.27) and did not improve the ability to stratify patients in the E7 system. Our study identifies limitations in the proper stratification of patients with GEJ adenocarcinoma using either the American Joint Committee on Cancer 7th esophageal or gastric systems. The classification of GEJ adenocarcinoma within either system needs to be further studied in a larger patient population.

  View details for PubMedID 28234131

• The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis. Journal of surgical oncology Ejaz, A., Reames, B. N., Maithel, S., Poultsides, G. A., Bauer, T. W., Fields, R. C., Weiss, M., Marques, H. P., Aldrighetti, L., Pawlik, T. M. 2017; 116 (7): 841–47

  Abstract

  Management of neuroendocrine liver metastasis (NELM) in the presence of extrahepatic disease (EHD) is controversial. We sought to examine outcomes of patients undergoing liver-directed therapy (resection, ablation, or both) for NELM in the presence of EHD using a large international cohort of patients.612 patients who underwent liver-directed therapy were identified from eight institutions. Postoperative outcomes, as well as and overall (OS) were compared among patients with and without EHD.Most primary tumors were located in the pancreas (N = 254;41.8%) or the small bowel (N = 188;30.9%). Patients underwent surgery alone (N = 471;77.0%), ablation alone (N = 15;2.5%), or a combined approach (N = 126;20.6%). Patients with EHD had more high-grade tumors (EHD: 44.4% vs no EHD: 16.1%; P < 0.001). EHD was often the peritoneum (N = 29;41.4%) or lung (N = 19;27.1%). Among 70 patients with EHD, 20.0% (N = 14) underwent concurrent resection for EHD. After median follow-up of 51 months, 174 (28.4%) patients died with a median OS of 140.4 months. Patients with EHD had a shorter median OS versus patients who did not have EHD (EHD: 87 months vs no EHD: not reached; P = 0.002). EHD was independently associated with an increased risk of death (HR: 2.56, 95%CI 1.16-5.62; P = 0.02).Patients with NELM and EHD had more aggressive tumors, conferring a twofold increased risk of death. Surgical treatment of NELM among patients with EHD should be individualized.

  View details for PubMedID 28650564

• Impact of adjuvant chemotherapy on survival in patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis. HPB : the official journal of the International Hepato Pancreato Biliary Association Reames, B. N., Bagante, F., Ejaz, A., Spolverato, G., Ruzzenente, A., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Koerkamp, B. G., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017; 19 (10): 901–9

  Abstract

  The benefit of adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma (ICC) is unclear. The aim of the current study was to investigate the impact of adjuvant chemotherapy on survival among patients undergoing resection of ICC using a multi-institutional database.1154 ICC patients undergoing curative-intent hepatectomy between 1990 and 2015 were identified from 14 institutions. Cox proportional hazard modeling was used to determine the impact of adjuvant chemotherapy on overall survival (OS).Following resection, 347 (30%) patients received adjuvant chemotherapy, most commonly a gemcitabine-based regimen (n = 184, 52%). Patients with T2/T3/T4 disease were more likely to receive adjuvant therapy compared with patients with T1a/T1b disease (OR 2.5, 95%CI 1.89-3.23; P < 0.001). Among patients who did and did not receive adjuvant therapy, patients with T2/T3/T4 tumors had a 5-year OS of 37% (95%CI 28.9-44.4) versus 30% (95%CI 23.8-35.6), respectively (p = 0.006). Similarly patients with N1 disease who received adjuvant chemotherapy tended to have improved 5-year OS (18.3%, 95%CI 9.0-30.1 vs. no adjuvant therapy 12%, 95%CI 3.9-24.4; P = 0.050).While adjuvant chemotherapy did not influence the prognosis of all ICC patients following surgical resection, it was associated with a potential survival benefit in subgroups of patients at increased risk for recurrence, such as those with advanced tumors.

  View details for PubMedID 28728891

• Early Recurrence of Neuroendocrine Liver Metastasis After Curative Hepatectomy: Risk Factors, Prognosis, and Treatment. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Zhang, X. F., Beal, E. W., Chakedis, J., Lv, Y., Bagante, F., Aldrighetti, L., Poultsides, G. A., Bauer, T. W., Fields, R. C., Maithel, S. K., Marques, H. P., Weiss, M., Pawlik, T. M. 2017; 21 (11): 1821–30

  Abstract

  Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection.A total of 481 patients who underwent curative-intent resection for NELM were identified from a multi-institutional database. Data on clinicopathological characteristics, intraoperative details, and outcomes were documented. The optimal cutoff value to differentiate early and late recurrence was determined to be 3 years based on linear regression.With a median follow-up of 60 months, 223 (46.4%) patients developed a recurrence, including 158 (70.9%) early and 65 (29.1%) late recurrences. On multivariable analysis, pancreatic NET, primary tumor lymph node metastasis, and a microscopic positive surgical margin were independent risk factors for early intrahepatic recurrence. While recurrence patterns and treatments were comparable among patients with early and late recurrences, early recurrence was associated with worse disease-specific survival than late recurrences (10-year NELM-specific survival, 44.5 vs 75.8%, p < 0.001). Among the 34 (21.5%) patients who underwent curative treatment for early recurrence, post-recurrence disease-specific survival was better than non-curatively treated patients (10-year NELM-specific survival, 54.2 vs 26.3%, p = 0.028), yet similar to patients with late recurrences treated with curative intent (10-year NELM-specific survival, 54.2 vs 37.4%, p = 0.519).Early recurrence after surgery for NELM was associated with the pancreatic type, primary lymph node metastasis, and extrahepatic disease. Re-treatment with curative intent prolonged survival after recurrence, and therefore, operative intervention even for early recurrences of NELM should be considered.

  View details for PubMedID 28730354

• Perioperative and Long-Term Outcome for Intrahepatic Cholangiocarcinoma: Impact of Major Versus Minor Hepatectomy. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Zhang, X. F., Bagante, F., Chakedis, J., Moris, D., Beal, E. W., Weiss, M., Popescu, I., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Groot Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017; 21 (11): 1841–50

  Abstract

  The objective of the current study was to investigate both short- and long-term outcomes of patients undergoing curative-intent resection for intrahepatic cholangiocarcinoma (ICC) stratified by extent of hepatic resection relative to overall final pathological margin status.One thousand twenty-three patients with ICC who underwent curative-intent resection were identified from a multi-institutional database. Demographic, clinicopathological, and operative data, as well as overall (OS) and recurrence-free survival (RFS) were compared among patients undergoing major and minor resection before and after propensity score matching.Overall, 608 (59.4%) patients underwent major hepatectomy, while 415 (40.6%) had a minor resection. Major hepatectomy was more frequently performed among patients who had large, multiple, and bilobar tumors. Roughly half of patients (n = 294, 48.4%) developed a postoperative complication following major hepatectomy versus only one fourth of patients (n = 113, 27.2%) after minor resection (p < 0.001). In the propensity model, patients who underwent major hepatectomy had an equivalent OS and RFS versus patients who had a minor hepatectomy (median OS, 38 vs. 37 months, p = 0.556; and median RFS, 20 vs. 18 months, p = 0.635). Patients undergoing major resection had comparable OS and RFS with wide surgical margin (≥10 and 5-9 mm), but improved RFS when surgical margin was narrow (1-4 mm) versus minor resection in the propensity model. In the Cox regression model, tumor characteristics and surgical margin were independently associated with long-term outcome.Major hepatectomy for ICC was not associated with an overall survival benefit, yet was associated with increased perioperative morbidity. Margin width, rather than the extent of resection, affected long-term outcomes. Radical parenchymal-sparing resection should be advocated if a margin clearance of ≥5 mm can be achieved.

  View details for PubMedID 28744741

• Defining Long-Term Survivors Following Resection of Intrahepatic Cholangiocarcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Bagante, F., Spolverato, G., Weiss, M., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Soubrane, O., Martel, G., Groot Koerkamp, B., Guglielmi, A., Itaru, E., Pawlik, T. M. 2017; 21 (11): 1888–97

  Abstract

  Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival.Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5).Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived < 5 years, as well as patients were alive yet had < 5 years of follow-up, 153 patients (22.5%) who survived ≥ 5 years were included in the LT group, while 526 patients (77.5%) who died < 5 years from the date of surgery were included in the non-LT group. Factors associated with not surviving to 5 years included perineural invasion (OR 4.78, 95% CI, 1.92-11.8; p = 0.001), intrahepatic metastasis (OR 3.75, 95% CI, 0.85-16.6, p = 0.082), satellite lesions (OR 2.12, 95% CI, 1.15-3.90, p = 0.016), N1 status (OR 4.64, 95% CI, 1.77-12.2; p = 0.002), ICC > 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT.While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.

  View details for PubMedID 28840497

• Diagnostic staging laparoscopy in gastric cancer treatment: A cost-effectiveness analysis. Journal of surgical oncology Li, K., Cannon, J. G., Jiang, S. Y., Sambare, T. D., Owens, D. K., Bendavid, E., Poultsides, G. A. 2017

  Abstract

  Accurate preoperative staging helps avert morbidity, mortality, and cost associated with non-therapeutic laparotomy in gastric cancer (GC) patients. Diagnostic staging laparoscopy (DSL) can detect metastases with high sensitivity, but its cost-effectiveness has not been previously studied. We developed a decision analysis model to assess the cost-effectiveness of preoperative DSL in GC workup.Analysis was based on a hypothetical cohort of GC patients in the U.S. for whom initial imaging shows no metastases. The cost-effectiveness of DSL was measured as cost per quality-adjusted life-year (QALY) gained. Drivers of cost-effectiveness were assessed in sensitivity analysis.Preoperative DSL required an investment of $107 012 per QALY. In sensitivity analysis, DSL became cost-effective at a threshold of $100 000/QALY when the probability of occult metastases exceeded 31.5% or when test sensitivity for metastases exceeded 86.3%. The likelihood of cost-effectiveness increased from 46% to 93% when both parameters were set at maximum reported values.The cost-effectiveness of DSL for GC patients is highly dependent on patient and test characteristics, and is more likely when DSL is used selectively where procedure yield is high, such as for locally advanced disease or in detecting peritoneal and superficial versus deep liver lesions.

  View details for PubMedID 29205366

• Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer. World journal of surgery Spolverato, G., Bagante, F., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Winslow, E., Cho, C., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2017; 41 (1): 224-231

  Abstract

  While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC).Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age.The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 ≥ 50 who also had lymph node metastasis.Examining an "all comer" cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship.

  View details for DOI 10.1007/s00268-016-3691-y

  View details for PubMedID 27549595

• A Multi-Institutional Study Comparing the Use of the American Joint Committee on Cancer 7th Edition Esophageal versus Gastric Staging System for Gastroesophageal Junction Cancer in a Western Population AMERICAN SURGEON Adeshuko, F. A., Squires, M. H., Poultsides, G., Pawlik, T. M., Weber, S. M., Schmidt, C., Votanopoulos, K., Fields, R. C., Maithel, S. K., Cardona, K. 2017; 83 (1): 82-89

  View details for Web of Science ID 000394144000030

• Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability ANNALS OF SURGERY Kim, Y., Margonis, G. A., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Glenn, J. A., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2017; 265 (1): 197-204

  Abstract

  To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC).ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery.CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x).One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%).DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

  View details for DOI 10.1097/SLA.0000000000001527

  View details for PubMedID 28009746

• An Untapped Resource: Left Renal Vein Interposition Graft for Portal Vein Reconstruction During Pancreaticoduodenectomy DIGESTIVE DISEASES AND SCIENCES Tran, T. B., Mell, M. W., Poultsides, G. A. 2017; 62 (1): 68-71

  View details for DOI 10.1007/s10620-016-4050-4

  View details for Web of Science ID 000392312200012

  View details for PubMedID 26825845

• Oncologic Procedures Amenable to Fluorescence-guided Surgery. Annals of surgery Tipirneni, K. E., Warram, J. M., Moore, L. S., Prince, A. C., de Boer, E., Jani, A. H., Wapnir, I. L., Liao, J. C., Bouvet, M., Behnke, N. K., Hawn, M. T., Poultsides, G. A., Vahrmeijer, A. L., Carroll, W. R., Zinn, K. R., Rosenthal, E. 2016

  Abstract

  Although fluorescence imaging is being applied to a wide range of cancers, it remains unclear which disease populations will benefit greatest. Therefore, we review the potential of this technology to improve outcomes in surgical oncology with attention to the various surgical procedures while exploring trial endpoints that may be optimal for each tumor type.For many tumors, primary treatment is surgical resection with negative margins, which corresponds to improved survival and a reduction in subsequent adjuvant therapies. Despite unfavorable effect on patient outcomes, margin positivity rate has not changed significantly over the years. Thus, patients often experience high rates of re-excision, radical resections, and overtreatment. However, fluorescence-guided surgery (FGS) has brought forth new light by allowing detection of subclinical disease not readily visible with the naked eye.We performed a systematic review of clinicatrials.gov using search terms "fluorescence," "image-guided surgery," and "near-infrared imaging" to identify trials utilizing FGS for those received on or before May 2016.fluorescence surgery for tumor debulking, wide local excision, whole-organ resection, and peritoneal metastases.fluorescence in situ hybridization, fluorescence imaging for lymph node mapping, nonmalignant lesions, nonsurgical purposes, or image guidance without fluorescence.Initial search produced 844 entries, which was narrowed down to 68 trials. Review of literature and clinical trials identified 3 primary resection methods for utilizing FGS: (1) debulking, (2) wide local excision, and (3) whole organ excision.The use of FGS as a surgical guide enhancement has the potential to improve survival and quality of life outcomes for patients. And, as the number of clinical trials rise each year, it is apparent that FGS has great potential for a broad range of clinical applications.

  View details for DOI 10.1097/SLA.0000000000002127

  View details for PubMedID 28045715

• Distal Cholangiocarcinoma and Pancreas Adenocarcinoma: Are They Really the Same Disease? A 13-Institution Study from the US Extrahepatic Biliary Malignancy Consortium and the Central Pancreas Consortium. Journal of the American College of Surgeons Ethun, C. G., Lopez-Aguiar, A. G., Pawlik, T. M., Poultsides, G., Idrees, K., Fields, R. C., Weber, S. M., Cho, C., Martin, R. C., Scoggins, C. R., Shen, P., Schmidt, C., Hatzaras, I., Bentrem, D., Ahmad, S., Abbott, D., Kim, H. J., Merchant, N., Staley, C. A., Kooby, D. A., Maithel, S. K. 2016

  Abstract

  Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases.This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums. Primary endpoint was disease-specific survival (DSS).Of 1,463 patients, 224 (15%) had DC and 1,239 (85%) had PDAC. Compared with PDAC, DC patients were less likely to be margin-positive (19% vs 25%; p = 0.005), lymph node (LN)-positive (55% vs 69%; p < 0.001), and receive adjuvant therapy (57% vs 71%; p < 0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. Distal cholangiocarcinoma was associated with improved median DSS (40 months) compared with PDAC (22 months; p < 0.001), which persisted on multivariable analysis (hazard ratio 0.65; 95% CI 0.50 to 0.84; p = 0.001). Lymph node involvement was the only factor independently associated with decreased DSS for both DC and PDAC. The DC/LN-positive patients had similar DSS as PDAC/LN-negative patients (p = 0.74). Adjuvant therapy (chemotherapy ± radiation) was associated with improved median DSS for PDAC/LN-positive patients (21 vs 13 months; p = 0.001), but not for DC patients (38 vs 40 months; p = 0.62), regardless of LN status.Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. Distal cholangiocarcinoma has a favorable prognosis compared with PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Therefore, treatment paradigms used for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored.

  View details for DOI 10.1016/j.jamcollsurg.2016.12.006

  View details for PubMedID 28017812

• Enumeration and targeted analysis of KRAS, BRAF and PIK3CA mutations in CTCs captured by a label-free platform: Comparison to ctDNA and tissue in metastatic colorectal cancer ONCOTARGET Kidess-Sigal, E., Liu, H. E., Triboulet, M. M., Che, J., Ramani, V. C., Visser, B. C., Poultsides, G. A., Longacre, T. A., Marziali, A., Vysotskaia, V., Wiggin, M., Heirich, K., Hanft, V., Keilholz, U., Tinhofer, I., Norton, J. A., Lee, M., Sollier-Christen, E., Jeffrey, S. S. 2016; 7 (51): 85349-85364

  Abstract

  Treatment of advanced colorectal cancer (CRC) requires multimodal therapeutic approaches and need for monitoring tumor plasticity. Liquid biopsy biomarkers, including CTCs and ctDNA, hold promise for evaluating treatment response in real-time and guiding therapeutic modifications. From 15 patients with advanced CRC undergoing liver metastasectomy with curative intent, we collected 41 blood samples at different time points before and after surgery for CTC isolation and quantification using label-free Vortex technology. For mutational profiling, KRAS, BRAF, and PIK3CA hotspot mutations were analyzed in CTCs and ctDNA from 23 samples, nine matched liver metastases and three primary tumor samples. Mutational patterns were compared. 80% of patient blood samples were positive for CTCs, using a healthy baseline value as threshold (0.4 CTCs/mL), and 81.4% of captured cells were EpCAM+ CTCs. At least one mutation was detected in 78% of our blood samples. Among 23 matched CTC and ctDNA samples, we found a concordance of 78.2% for KRAS, 73.9% for BRAF and 91.3% for PIK3CA mutations. In several cases, CTCs exhibited a mutation that was not detected in ctDNA, and vice versa. Complementary assessment of both CTCs and ctDNA appears advantageous to assess dynamic tumor profiles.

  View details for DOI 10.18632/oncotarget.13350

  View details for PubMedID 27863403

• Actual 10-Year Survivors Following Resection of Adrenocortical Carcinoma JOURNAL OF SURGICAL ONCOLOGY Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Wang, T. S., Glenn, J., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Hatzaras, I., Shenoy, R., Pawlik, T. M., Norton, J. A., Poultsides, G. A. 2016; 114 (8): 971-976

  Abstract

  Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long-term survivors following surgical resection for ACC have not been previously reported.Patients who underwent resection for ACC at one of 13 academic institutions participating in the US Adrenocortical Carcinoma Group from 1993 to 2014 were analyzed. Patients were stratified into four groups: early mortality (died within 2 years), late mortality (died within 2-5 years), actual 5-year survivor (survived at least 5 years), and actual 10-year survivor (survived at least 10 years). Patients with less than 5 years of follow-up were excluded.Among the 180 patients available for analysis, there were 49 actual 5-year survivors (27%) and 12 actual 10-year survivors (7%). Patients who experienced early mortality had higher rates of cortisol-secreting tumors, nodal metastasis, synchronous distant metastasis, and R1 or R2 resections (all P < 0.05). The need for multi-visceral resection, perioperative blood transfusion, and adjuvant therapy correlated with early mortality. However, nodal involvement, distant metastasis, and R1 resection did not preclude patients from becoming actual 10-year survivors. Ten of twelve actual 10-year survivors were women, and of the seven 10-year survivors who experienced disease recurrence, five had undergone repeat surgery to resect the recurrence.Surgery for ACC can offer a 1 in 4 chance of actual 5-year survival and a 1 in 15 chance of actual 10-year survival. Long-term survival was often achieved with repeat resection for local or distant recurrence, further underscoring the important role of surgery in managing patients with ACC. J. Surg. Oncol. 2016;114:971-976. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24439

  View details for PubMedID 27633419

• Development and Validation of Biopsy-Free Genotyping for Molecular Subtyping of Diffuse Large B-Cell Lymphoma 58th Annual Meeting and Exposition of the American-Society-of-Hematology Scherer, F., Kurtz, D. M., Newman, A. M., Esfahani, M. S., Craig, A., Stehr, H., Lovejoy, A. F., Chabon, J. J., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Davis, E. R., Gaidano, G., Kunder, C. A., Rossi, D., Westin, J. R., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2016

  View details for Web of Science ID 000394446803093

• Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit? ANNALS OF SURGICAL ONCOLOGY Gerry, J. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Wang, T. S., Glenn, J. A., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Hatzaras, I., Shenoy, R., Pawlik, T. M., Norton, J. A., Poultsides, G. A. 2016; 23: S708-S713

  Abstract

  Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear.Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon's effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups.Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p < .001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p = .72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection.In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon's effort to dissect peritumoral lymph nodes was independently associated with improved overall survival.

  View details for DOI 10.1245/s10434-016-5536-1

  View details for Web of Science ID 000391508800027

  View details for PubMedCentralID PMC5257294

• Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit? Annals of surgical oncology Gerry, J. M., Tran, T. B., Postlewait, L. M., Maithel, S. K., Prescott, J. D., Wang, T. S., Glenn, J. A., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Hatzaras, I., Shenoy, R., Pawlik, T. M., Norton, J. A., Poultsides, G. A. 2016; 23: 708-713

  Abstract

  Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear.Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon's effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups.Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p < .001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p = .72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection.In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon's effort to dissect peritumoral lymph nodes was independently associated with improved overall survival.

  View details for PubMedID 27590329

• Changing Odds of Survival Over Time among Patients Undergoing Surgical Resection of Gallbladder Carcinoma. Annals of surgical oncology Buettner, S., Margonis, G. A., Kim, Y., Gani, F., Ethun, C. G., Poultsides, G. A., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 23 (13): 4401-4409

  Abstract

  While survival after malignancies is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant by accounting for "accrued" survival time as time progresses. We sought to compare actuarial and CS among patients with gallbladder carcinoma (GBC) .A total of 312 patients who underwent curative intent surgery for GBC between 2000 and 2014 were identified using a multi-institutional database. Overall survival (OS) was estimated using the Kaplan-Meier method. CS was calculated as the probability of surviving an additional 3 years at year "x" after surgery using the formula CS3 = S(x+3)/Sx.Among all patients, the median actuarial OS was 24.8 months (IQR 13.3-88.9). While actuarial survival decreased over time, 3-year CS (CS3) increased, with CS3 at 2 years after surgery noted to be 61.8 % compared with the 5-year actuarial OS of 31.6 %. Factors associated with reduced actuarial OS were positive margin status (HR 3.61, 95 % CI 2.47-5.26), increasing tumor size (HR = 1.02, 95 % CI 1.01-1.02), higher tumor grade (HR 2.98, 95 % CI 1.47-6.04), residual disease at repeat resection (HR = 2.78, 95 % CI 1.49-3.49, p < 0.001), and lymph node metastasis (HR = 1.95, 95 % CI 1.39-2.75, all p < 0.001). The calculated CS3 exceeded the actuarial survival within each high-risk patient subgroup. For example, patients with residual disease at repeat resection had an actuarial survival 23.1 % at 5 years versus a CS3 of 56.3 % in patients alive at 2 years (Δ = 33.2 %).CS provides a more accurate, dynamic estimate for survival, especially among high-risk patients. CS estimates can be used to accurately predict survival and guide clinical decision making.

  View details for PubMedID 27495279

• Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA SCIENCE TRANSLATIONAL MEDICINE Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. F., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Kunder, C. A., Diehn, M., Alizadeh, A. A. 2016; 8 (364)

  Abstract

  Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy.

  View details for DOI 10.1126/scitranslmed.aai8545

  View details for PubMedID 27831904

• A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium. Annals of surgical oncology Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Merchant, N., Cardona, K., Maithel, S. K. 2016: -?

  Abstract

  This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes.All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS).Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3-4, intermediate: 5-7, high: 8-10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS.By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.

  View details for PubMedID 27812827

• Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium. JAMA surgery Ethun, C. G., Postlewait, L. M., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Kooby, D. A., Maithel, S. K. 2016

  Abstract

  The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known.To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival.This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included.Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks.Primary outcome was overall survival.Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis.The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy.

  View details for DOI 10.1001/jamasurg.2016.3642

  View details for PubMedID 27784058

• Minimally Invasive Resection of Adrenocortical Carcinoma: a Multi-Institutional Study of 201 Patients. Journal of gastrointestinal surgery Lee, C. W., Md, A. I., Schneider, D. F., Leverson, G. E., Tran, T. B., Poultsides, G. A., Postlewait, L. M., Maithel, S. K., Wang, T. S., Hatzaras, I., Shenoy, R., Phay, J. E., Shirley, L., Fields, R. C., Jin, L. X., Pawlik, T. M., Prescott, J. D., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Weber, S. M. 2016: -?

  Abstract

  Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery.Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA.A total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3 %, MIS, vs. 30.9 %, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p < 0.001). There was no difference in rates of intraoperative tumor rupture (p = 0.612) or R0 resection (p = 0.953). Only EBL (p = 0.038) and T stage (p = 0.045) were independent prognostic indicators of overall survival after adjusting for significant factors. The surgical approach was not associated with overall or disease-free survival.MIS adrenalectomy may be utilized for preoperatively determined ACC ≤ 10.0 cm; however, OA should be utilized for adrenal masses with either preoperative or intraoperative evidence of local invasion or enlarged lymph nodes, regardless of size.

  View details for PubMedID 27770290

• A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma. Journal of gastrointestinal surgery Buettner, S., van Vugt, J. L., Gani, F., Groot Koerkamp, B., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Guglielmi, A., IJzermans, J. N., Pawlik, T. M. 2016; 20 (10): 1716-1724

  Abstract

  Although widely used, the 7th edition American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (PHC) may be limited. Disease-specific nomograms have been proposed as a better means to predict long-term survival for individual patients. We sought to externally validate a recently proposed nomogram by Memorial Sloan Kettering Cancer Center (MSKCC) for PHC, as well as identify factors to improve the prediction of prognosis for patients with PHC.Four hundred seven patients who underwent surgery for PHC between 1988 and 2014 were identified using an international, multi-center database. Standard clinicopathologic and outcome data were collected. The predictive power of the AJCC staging system and nomogram were assessed.Median survival was 24.4 months; 3- and 5-year survival was 37.2 and 20.8 %, respectively. The AJCC 7th edition staging system (C-index 0.570) and the recently proposed PHC nomogram (C-index 0.587) both performed poorly. A revised nomogram based on age, lymphovascular invasion, perineural invasion, and lymph node metastases performed better (C-index 0.682). The calibration plot of the revised PHC nomogram demonstrated good calibration.The 7th edition AJCC staging system and the MSKCC nomogram had a poor ability to predict long-term survival for individual patients with PHC. A revised nomogram provided more accurate prediction of survival, but will need to be externally validated.

  View details for DOI 10.1007/s11605-016-3203-2

  View details for PubMedID 27412318

• Gastric Cancer, Version 3.2016 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ajani, J. A., D'Amico, T. A., Almhanna, K., Bentrem, D. J., Chao, J., Das, P., Denlinger, C. S., Fanta, P., Farjah, F., Fuchs, C. S., Gerdes, H., Gibson, M., Glasgow, R. E., Hayman, J. A., Hochwald, S., Hofstetter, W. L., Ilson, D. H., Jaroszewski, D., Johung, K. L., Keswani, R. N., Kleinberg, L. R., Korn, W. M., Leong, S., Linn, C., Lockhart, A. C., Ly, Q. P., Mulcahy, M. F., Orringer, M. B., Perry, K. A., Poultsides, G. A., Scott, W. J., Strong, V. E., Washington, M. K., Weksler, B., Willett, C. G., Wright, C. D., Zelman, D., McMillian, N., Sundar, H. 2016; 14 (10): 1286-1312

  View details for Web of Science ID 000385057100009

• Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network Ajani, J. A., D'Amico, T. A., Almhanna, K., Bentrem, D. J., Chao, J., Das, P., Denlinger, C. S., Fanta, P., Farjah, F., Fuchs, C. S., Gerdes, H., Gibson, M., Glasgow, R. E., Hayman, J. A., Hochwald, S., Hofstetter, W. L., Ilson, D. H., Jaroszewski, D., Johung, K. L., Keswani, R. N., Kleinberg, L. R., Korn, W. M., Leong, S., Linn, C., Lockhart, A. C., Ly, Q. P., Mulcahy, M. F., Orringer, M. B., Perry, K. A., Poultsides, G. A., Scott, W. J., Strong, V. E., Washington, M. K., Weksler, B., Willett, C. G., Wright, C. D., Zelman, D., McMillian, N., Sundar, H. 2016; 14 (10): 1286-1312

  Abstract

  Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.

  View details for PubMedID 27697982

• Proposal for a new T-stage classification system for distal cholangiocarcinoma: a 10-institution study from the U.S. Extrahepatic Biliary Malignancy Consortium. HPB Postlewait, L. M., Ethun, C. G., Le, N., Pawlik, T. M., Buettner, S., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Vitiello, G., Cardona, K., Maithel, S. K. 2016; 18 (10): 793-799

  Abstract

  Seventh AJCC distal cholangiocarcinoma T-stage classification inadequately separates patients by survival. This retrospective study aimed to define a novel T-stage system to better stratify patients after resection.Curative-intent pancreaticoduodenectomies for distal cholangiocarcinoma (1/2000-5/2015) at 10 US institutions were included. Relationships between tumor characteristics and overall survival (OS) were assessed and incorporated into a novel T-stage classification.176 patients (median follow-up: 24mo) were included. Current AJCC T-stage was not associated with OS (T1: 23mo, T2: 20mo, T3: 25mo, T4: 12mo; p = 0.355). Tumor size ≥3 cm and presence of lymphovascular invasion (LVI) were associated with decreased OS on univariate and multivariable analyses. Patients were stratified into 3 groups [T1: size <3 cm and (-)LVI (n = 69; 39.2%); T2: size ≥3 cm and (-)LVI or size <3 cm and (+)LVI (n = 82; 46.6%); and T3: size ≥3 cm and (+)LVI (n = 25; 14.2%)]. Each progressive proposed T-stage was associated with decreased median OS (T1: 35mo; T2: 20mo; T3: 8mo; p = 0.002).Current AJCC distal cholangiocarcinoma T-stage does not adequately stratify patients by survival. This proposed T-stage classification, based on tumor size and LVI, better differentiates patient outcomes after resection and could be considered for incorporation into the next AJCC distal cholangiocarcinoma staging system.

  View details for DOI 10.1016/j.hpb.2016.07.009

  View details for PubMedID 27506989

  View details for PubMedCentralID PMC5061021

• A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma JOURNAL OF GASTROINTESTINAL SURGERY Buettner, S., van Vugt, J. L., Gani, F., Koerkamp, B. G., Margonis, G. A., Ethun, C. G., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Guglielmi, A., IJzermans, J. N., Pawlik, T. M. 2016; 20 (10): 1716-1724

  View details for DOI 10.1007/s11605-016-3203-2

  View details for Web of Science ID 000384552600007

• Laparoscopic hepatectomy in cirrhotics: safe if you adjust technique. Surgical endoscopy Worhunsky, D. J., Dua, M. M., Tran, T. B., Siu, B., Poultsides, G. A., Norton, J. A., Visser, B. C. 2016; 30 (10): 4307-4314

  Abstract

  Minimally invasive liver surgery is a growing field, and a small number of recent reports have suggested that laparoscopic liver resection (LLR) is feasible even in patients with cirrhosis. However, parenchymal transection of the cirrhotic liver is challenging due to fibrosis and portal hypertension. There is a paucity of data regarding the technical modifications necessary to safely transect the diseased parenchyma.Patients undergoing LLR by a single surgeon between 2008 and 2015 were reviewed. Patients with cirrhosis were compared to those without cirrhosis to examine differences in surgical technique, intraoperative characteristics, and outcomes (including liver-related morbidity and general postoperative complication rates).A total of 167 patients underwent LLR during the study period. Forty-eight (29 %) had cirrhosis, of which 43 (90 %) had hepatitis C. Most had Child-Pugh class A disease (85 %). Compared to noncirrhotics, patients with cirrhosis were older, had more comorbidities, and were more likely to have hepatocellular carcinoma. Precoagulation before parenchymal transection was used more frequently in cirrhotics (65 vs. 15 %, P < 0.001), and mean portal triad clamping time was longer (32 vs. 22 min, P = 0.002). There were few conversions to open surgery, though hand-assisted laparoscopy was used as an alternative to converting to open in three patients with cirrhosis. Blood loss was relatively low for both groups. Although there were more postoperative complications among cirrhotics (38 vs. 13 %, P = 0.001), this was almost entirely due to a higher rate of minor (Clavien-Dindo I or II) complications. Liver-related morbidity, major complications, and mortality rates were similar.LLR is safe for selected patients with cirrhosis. The added complexity associated with the division of diseased liver parenchyma may be overcome with some form of technique modification, including more liberal use of precoagulation, portal triad clamping, or a hand-assist port.

  View details for DOI 10.1007/s00464-016-4748-6

  View details for PubMedID 26895906

• Elevated NLR in gallbladder cancer and cholangiocarcinoma - making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium. HPB Beal, E. W., Wei, L., Ethun, C. G., Black, S. M., Dillhoff, M., Salem, A., Weber, S. M., Tran, T., Poultsides, G., Son, A. Y., Hatzaras, I., Jin, L., Fields, R. C., Buettner, S., Pawlik, T. M., Scoggins, C., Martin, R. C., Isom, C. A., Idrees, K., Mogal, H. D., Shen, P., Maithel, S. K., Schmidt, C. R. 2016

  Abstract

  Gallbladder and extrahepatic biliary malignancies are aggressive tumors with high risk of recurrence and death. We hypothesize that elevated preoperative Neutrophil-Lymphocyte Ratios (NLR) are associated with poor prognosis among patients undergoing resection of gallbladder or extrahepatic biliary cancers.Patients who underwent complete surgical resection between 2000-2014 were identified from 10 academic centers (n=525). Overall (OS) and recurrence-free survival (RFS) were analyzed by stratifying patients with normal (<5) versus elevated (>5) NLR.Overall, 375 patients had NLR <5 while 150 patients had NLR >5. Median OS was 24.5 months among patients with NLR<5 versus 17.0 months among patients with NLR>5 (p<0.001). NLR was also associated with OS in subgroup analysis of patients with gallbladder cancer. In fact, on multivariable analysis, NLR>5, dyspnea and preoperative peak bilirubin were independently associated with OS in patients with gallbladder cancer. Median RFS was 26.8 months in patients with NLR<5 versus 22.7 months among patients with NLR>5 (p=0.030). NLR>5 was independently associated with worse RFS for patients with gallbladder cancer.Elevated NLR was associated with worse outcomes in patients with gallbladder and extrahepatic biliary cancers after curative-intent resection. NLR is easily measured and may provide important prognostic information.

  View details for DOI 10.1016/j.hpb.2016.08.006

  View details for PubMedID 27683047

  View details for PubMedCentralID PMC5094484

• Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma. Journal of the American College of Surgeons Tran, T. B., Maithel, S. K., Pawlik, T. M., Wang, T. S., Hatzaras, I., Phay, J. E., Fields, R. C., Weber, S. M., Sicklick, J. K., Yopp, A. C., Duh, Q., Solorzano, C. C., Votanopoulos, K. I., Poultsides, G. A. 2016

  Abstract

  Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC.Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival.Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p = 0.0006, area under the curve = 0.78).Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence.

  View details for DOI 10.1016/j.jamcollsurg.2016.08.568

  View details for PubMedID 27618748

• The significance of underlying cardiac comorbidity on major adverse cardiac events after major liver resection. HPB Tran, T. B., Worhunsky, D. J., Spain, D. A., Dua, M. M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2016; 18 (9): 742-747

  Abstract

  The risk of postoperative adverse events in patients with underlying cardiac disease undergoing major hepatectomy remains poorly characterized.The NSQIP database was used to identify patients undergoing hemihepatectomy and trisectionectomy. Patient characteristics and postoperative outcomes were evaluated.From 2005 to 2012, 5227 patients underwent major hepatectomy. Of those, 289 (5.5%) had prior major cardiac disease: 5.6% angina, 3.1% congestive heart failure, 1% myocardial infarction, 54% percutaneous coronary intervention, and 46% cardiac surgery. Thirty-day mortality was higher in patients with cardiac comorbidity (6.9% vs. 3.7%, P = 0.008), including the incidence of postoperative cardiac arrest requiring cardiopulmonary resuscitation (3.8% vs. 1.2%, P = 0.001) and myocardial infarction (1.7% vs. 0.4%, P = 0.011). Multivariate analysis revealed that functional impairment, older age, and malnutrition, but not cardiac comorbidity, were significant predictors of 30-day mortality. However, prior percutaneous coronary intervention was independently associated with postoperative cardiac arrest (OR 2.999, P = 0.008).While cardiac comorbidity is not a predictor of mortality after major hepatectomy, prior percutaneous coronary intervention is independently associated with postoperative cardiac arrest. Careful patient selection and preoperative optimization is fundamental in patients with prior percutaneous coronary intervention being considered for major hepatectomy as restrictive fluid management and low central venous pressure anesthesia may not be tolerated well by all patients.

  View details for DOI 10.1016/j.hpb.2016.06.012

  View details for PubMedID 27593591

• Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis. Surgery Cloyd, J. M., Kopecky, K. E., Norton, J. A., Kunz, P. L., Fisher, G. A., Visser, B. C., Dua, M. M., Park, W. G., Poultsides, G. A. 2016; 160 (3): 708-713

  Abstract

  Although most pancreatic neuroendocrine tumors are solid, approximately 10% are cystic. Some studies have suggested that cystic pancreatic neuroendocrine tumors are associated with a more favorable prognosis.A retrospective review of all patients with pancreatic neuroendocrine tumors who underwent operative resection between 1999 and 2014 at a single academic medical center was performed. Based on cross-sectional imaging performed before operation, pancreatic neuroendocrine tumors were classified according to the size of the cystic component relative to the total tumor size: purely cystic (100%), mostly cystic (≥50%), mostly solid (<50%), and purely solid (0%). Clinicopathologic characteristics and recurrence-free survival were assessed between groups.In the study, 214 patients met inclusion criteria: 8 with purely cystic tumors, 7 with mostly cystic tumors, 15 with mostly solid tumors, and 184 with purely solid tumors. The groups differed in terms of tumor size (1.5 ± 0.5, 3.0 ± 1.7, 3.7 ± 2.6, and 4.0 ± 3.5 cm), lymph node positivity (0%, 0%, 26.7%, and 34.2%), intermediate or high grade (0%, 16.7%, 20.0%, and 31.0%), synchronous liver metastases (0%, 14.3%, 20.0%, and 26.6%) and need for pancreaticoduodenectomy (0%, 0%, 6.7%, and 25.0%), respectively. No cases of purely cystic pancreatic neuroendocrine tumors were associated with synchronous liver or lymph node metastasis, intermediate/high grade, recurrence, or death due to disease. Among patients presenting without metastatic disease, 10-year recurrence-free survival was 100% in patients with purely and mostly cystic tumors versus 53.0% in patients with purely and mostly solid tumors; however, this difference did not reach statistical significance.Pancreatic neuroendocrine tumors demonstrate a spectrum of biologic behavior with an increasing cystic component being associated with more favorable clinicopathologic features and prognosis. Purely cystic pancreatic neuroendocrine tumors may represent 1 subset that can be safely observed without immediate resection.

  View details for DOI 10.1016/j.surg.2016.04.005

  View details for PubMedID 27216830

• Impact of Chemotherapy and External-Beam Radiation Therapy on Outcomes among Patients with Resected Gallbladder Cancer: A Multi-institutional Analysis. Annals of surgical oncology Kim, Y., Amini, N., Wilson, A., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Cardona, K., Maithel, S. K., Pawlik, T. M. 2016; 23 (9): 2998-3008

  Abstract

  Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) for the treatment of gallbladder cancer (GBC) remains varied. We sought to define the utilization and effect of adjuvant therapy for patients with GBC.Using a multi-institutional national database, 291 patients with GBC who underwent curative-intent resection between 2000 and 2015 were included. Patients with metastasis or an R2 margin were excluded.Median patient age was 66.6 years. Most patients had a T2 (46.2 %) or T3 (38.6 %) lesion, and 37.8 % of patients had lymph node (LN) metastasis. A total of 186 (63.9 %) patients underwent surgery alone, 61 (21.0 %) received CTx, and 44 (15.1 %) patients received cXRT. On multivariable analysis, factors associated with worse overall survival (OS) included T3/T4 stage [hazard ratio (HR) 1.82], LN-metastasis (HR 1.84), lymphovascular invasion (HR 2.02), perineural invasion (HR 1.42), and R1 surgical margin status (HR 2.06); all P < 0.05). In contrast, receipt of CTx/cXRT was associated with improved OS (CTx, HR 0.38; cXRT, HR 0.26; P < 0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS) (CTx, HR 0.61; cXRT, HR 0.43; P < 0.05). Of note, only patients with high-risk features, such as AJCC T3/T4 stage (HR 0.41), LN metastasis (HR 0.45), and R1 disease (HR 0.21) (all P < 0.05) derived an OS benefit from CTx/cXRT.Adjuvant CTx/cXRT was utilized in 36 % of patients undergoing curative-intent resection for GBC. After adjusted analyses, CTx/cXRT were independently associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics.

  View details for DOI 10.1245/s10434-016-5262-8

  View details for PubMedID 27169772

• Prognostic Implications of Lymph Node Status for Patients With Gallbladder Cancer: A Multi-Institutional Study. Annals of surgical oncology Amini, N., Kim, Y., Wilson, A., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 23 (9): 3016-3023

  Abstract

  Although the American Joint Committee on Cancer (AJCC) classification is the most accepted lymph node (LN) staging system for gallbladder adenocarcinoma (GBA), other LN prognostic schemes have been proposed. This study sought to define the performance of the AJCC LN staging system relative to the number of metastatic LNs (NMLN), the log odds of metastatic LN (LODDS), and the LN ratio (LNR).Patients who underwent curative-intent resection for GBA between 2000 and 2015 were identified from a multi-institutional database. The prognostic performance of various LN staging systems was compared by Harrell's C and the Akaike information criterion (AIC).Altogether, 214 patients with a median age of 66.7 years (interquartile range [IQR] 56.5-73.1) were identified. A total of 1334 LNs were retrieved, with a median of 4 (IQR 2-8) LNs per patient. Patients with LN metastasis had an increased risk of death (hazard ratio [HR] 1.87; 95 % confidence interval [CI] 1.24-2.82; P = 0.003) and recurrence (HR 2.28; 95 % CI 1.37-3.80; P = 0.002). In the entire cohort, LNR, analyzed as either a continuous scale (C-index, 0.603; AIC, 803.5) or a discrete scale (C-index, 0.609; AIC, 802.2), provided better prognostic discrimination. Among the patients with four or more LNs examined, LODDS (C-index, 0.621; AIC, 363.8) had the best performance versus LNR (C-index, 0.615; AIC, 368.7), AJCC LN staging system (C-index, 0.601; AIC, 373.4), and NMLN (C-index, 0.613; AIC, 369.5).Both LODDS and LNR performed better than the AJCC LN staging system. Among the patients who had four or more LNs examined, LODDS performed better than LNR. Both LODDS and LNR should be incorporated into the AJCC LN staging system for GBA.

  View details for DOI 10.1245/s10434-016-5243-y

  View details for PubMedID 27150440

• Rates and patterns of recurrence after curative intent resection for gallbladder cancer: a multi-institution analysis from the US Extra-hepatic Biliary Malignancy Consortium. HPB Margonis, G. A., Gani, F., Buettner, S., Amini, N., Sasaki, K., Andreatos, N., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016

  Abstract

  Gallbladder cancer is a relatively rare malignancy. The current study aimed to define the incidence and patterns of recurrence following gallbladder cancer resection.Using a multi-institutional cohort we identified 217 patient undergoing curative intent surgery for gallbladder cancer. Patterns of recurrence were classified as locoregional and distant recurrence.At last follow-up, 76 patients (35.0%) had experienced a recurrence (locoregional only, n = 12, 15.8%; distant only, n = 50, 65.8%; locoregional and distant, n = 14, 18.4%). Median time to recurrence was 9.5 months (IQR 4.7-17.6) and was not associated with recurrence site (all p > 0.05). On multivariable analysis, T3 disease (HR = 8.44, p = 0.014), lymphovascular invasion (HR = 4.24, p < 0.001) and residual disease (HR = 2.04, p = 0.042) were associated with an increased risk of recurrence. Patients who recurred demonstrated a worse 1-, 3- and 5-year OS (1-year OS: 91.3% vs. 68.6%, p = 0.001, 3-year OS: 79.3% vs. 28.7%, p < 0.001, and 5-year OS: 75.9% vs. 16.0%, p < 0.001). After adjusting for other risk factors, recurrence was independently associated with a decreased OS (HR = 3.71, p = 0.006). Of note, receipt of adjuvant therapy was associated with improved OS (HR = 0.56, p = 0.027) among those patients who developed a tumor recurrence.Over one-third of patients experienced a recurrence after gallbladder cancer surgery. While chemotherapy did not decrease the rate of recurrence, patients who experienced recurrence after administration of adjuvant treatment faired better than patients who did not receive adjuvant therapy.

  View details for DOI 10.1016/j.hpb.2016.05.016

  View details for PubMedID 27527802

  View details for PubMedCentralID PMC5094487

• Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging. PLoS medicine Eberlin, L. S., Margulis, K., Planell-Mendez, I., Zare, R. N., Tibshirani, R., Longacre, T. A., Jalali, M., Norton, J. A., Poultsides, G. A. 2016; 13 (8)

  Abstract

  Surgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery.Our methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study. Careful evaluation of the long-term benefits to patients of the use of DESI-MSI for surgical margin evaluation is also needed to determine its value in clinical practice.Our findings provide evidence that the molecular information obtained by DESI-MSI/Lasso from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens. With further development, we believe the described methodology could be routinely used for intraoperative surgical margin assessment of pancreatic cancer.

  View details for DOI 10.1371/journal.pmed.1002108

  View details for PubMedID 27575375

• The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis. HPB Margonis, G. A., Buettner, S., Sasaki, K., Kim, Y., Ratti, F., Russolillo, N., Ferrero, A., Berger, N., Gamblin, T. C., Poultsides, G., Tran, T., Postlewait, L. M., Maithel, S., Michaels, A. D., Bauer, T. W., Marques, H., Barroso, E., Aldrighetti, L., Pawlik, T. M. 2016; 18 (8): 700-705

  Abstract

  Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM).Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed.Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS.In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection.

  View details for DOI 10.1016/j.hpb.2016.05.014

  View details for PubMedID 27485066

  View details for PubMedCentralID PMC4972375

• Interaction of Postoperative Morbidity and Receipt of Adjuvant Therapy on Long-Term Survival After Resection for Gastric Adenocarcinoma: Results From the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Jin, L. X., Sanford, D. E., Squires, M. H., Moses, L. E., Yan, Y., Poultsides, G. A., Votanopoulos, K. I., Weber, S. M., Bloomston, M., Pawlik, T. M., Hawkins, W. G., Linehan, D. C., Schmidt, C., Worhunsky, D. J., Acher, A. W., Cardona, K., Cho, C. S., Kooby, D. A., Levine, E. A., Winslow, E., Saunders, N., Spolverato, G., Colditz, G. A., Maithel, S. K., Fields, R. C. 2016; 23 (8): 2398-2408

  Abstract

  Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival.We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression.Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001).Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.

  View details for DOI 10.1245/s10434-016-5121-7

  View details for Web of Science ID 000379189900008

  View details for PubMedID 27006126

• Assessing Trends in Palliative Surgery for Extrahepatic Biliary Malignancies: A 15-Year Multicenter Study JOURNAL OF GASTROINTESTINAL SURGERY Buettner, S., Wilson, A., Margonis, G. A., Gani, F., Ethun, C. G., Poultsides, G. A., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 20 (8): 1444-1452

  Abstract

  Extrahepatic biliary malignancies are often diagnosed at an advanced stage. We compared patients with unresectable perihilar cholangiocarcinoma (PHCC) and gallbladder cancer (GBC) who underwent a palliative procedure versus an aborted laparotomy.Seven hundred seventy-seven patients who underwent surgery for PHCC or GBC between 2000 and 2014 were identified. Uni- and multivariable analyses were performed to identify factors associated with outcome.Utilization of preoperative imaging increased over time (CT use, 80.1 % pre-2009 vs. 90 % post-2009) (p < 0.001). The proportion of the patients undergoing curative-intent resection also increased (2000-2004, 67.0 % vs. 2005-2009, 74.5 % vs. 2010-2014, 78.8 %; p = 0.001). The planned surgery was aborted in 106 (13.7 %) patients and 94 (12.1 %) had a palliative procedure. A higher incidence of postoperative complications (19.2 vs. 3.8 %, p = 0.001) including deep surgical site infections (8.3 vs. 1.1 %), bleeding (4.8 vs. 0 %), bile leak (6.0 vs. 0 %) and longer length of stay (7 vs. 4.5 days) were observed among the patients who underwent a palliative surgical procedure versus an aborted non-therapeutic, non-palliative laparotomy (all p < 0.05). OS was comparable among the patients who underwent a palliative procedure (8.7 months) versus an aborted laparotomy (7.8 months) (p = 0.23).Increased use of advanced imaging modalities was accompanied by increased curative-intent surgery. Compared with patients in whom surgery was aborted, patients who underwent surgical palliation demonstrated an increased incidence of postoperative morbidity with comparable survival.

  View details for DOI 10.1007/s11605-016-3155-6

  View details for Web of Science ID 000379528800005

  View details for PubMedID 27121233

• Assessing the impact of common bile duct resection in the surgical management of gallbladder cancer. Journal of surgical oncology Gani, F., Buettner, S., Margonis, G. A., Ethun, C. G., Poultsides, G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 114 (2): 176-180

  Abstract

  Although radical re-resection for gallbladder cancer (GBC) has been advocated, the optimal extent of re-resection remains unknown. The current study aimed to assess the impact of common bile duct (CBD) resection on survival among patients undergoing surgery for GBC.Patients undergoing curative-intent surgery for GBC were identified using a multi-institutional cohort of patients. Multivariable Cox-proportional hazards regression was performed to identify risk factors for a poor overall survival (OS).Among the 449 patients identified, 26.9% underwent a concomitant CBD resection. The median number of lymph nodes harvested did not differ based on CBD resection (CBD, 4 [IQR: 2-9] vs. no CBD, 3 [IQR: 1-7], P = 0.108). While patients who underwent a CBD resection had a worse OS, after adjusting for potential confounders, CBD resection did not impact OS (HR = 1.40, 95%CI 0.87-2.27, P = 0.170). Rather, the presence of advanced disease (T3: HR = 3.11, 95%CI 1.22-7.96, P = 0.018; T4: HR = 7.24, 95%CI 1.70-30.85, P = 0.007) and the presence of disease at the surgical margin (HR = 2.58, 95%CI 1.26-5.31, P = 0.010) were predictive of a worse OS.CBD resection did not yield a higher lymph node count and was not associated with an improved survival. Routine CBD excision in the re-resection of GBC is unwarranted and should only be performed selectively. J. Surg. Oncol. 2016;114:176-180. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24283

  View details for PubMedID 27198742

• To Roux or not to Roux: a comparison between Roux-en-Y and Billroth II reconstruction following partial gastrectomy for gastric cancer GASTRIC CANCER Tran, T. B., Worhunsky, D. J., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Cho, C. S., Weber, S. M., Schmidt, C., Levine, E. A., Bloomston, M., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2016; 19 (3): 994-1001

  Abstract

  Although the extent of resection frequently dictates the method of reconstruction following distal subtotal gastrectomy, it is unclear whether Roux-en-Y gastrojejunostomy compared with Billroth II gastrojejunostomy is associated with superior perioperative outcomes.Patients who underwent resection for gastric cancer with Roux-en-Y or Billroth II reconstruction between 2000 and 2012 in seven academic institutions (US Gastric Cancer Collaborative) were identified. Patients who underwent total gastrectomy, gastric wedge, or palliative resections (metastatic disease or R2 resections) were excluded.Of a total of 965 patients, 447 met the inclusion criteria. A comparison between the Roux-en-Y (n = 257) and Billroth II (n = 190) groups demonstrated no differences in patient and tumor characteristics, except for Billroth II patients having a higher proportion of antral tumors (71 % vs. 50 %, p < 0.001). Roux-en-Y operations were slightly longer (244 min vs. 212 min, p < 0.001) and associated with somewhat higher blood loss (243 ml vs. 205 ml, p = 0.033). However, there were no significant differences in the length of hospital stay (8 days vs. 7 days), readmission rate (17 % vs. 18 %), 90-day mortality (5.1 % vs. 4.7 %), incidence (39 % vs. 41 %) and severity of complications, dependency on jejunostomy tube feeding at discharge (13 % vs. 12 %), same-patient decrease in serum albumin level from the preoperative to the postoperative value at 30, 60, and 90 days, receipt of adjuvant therapy (50 % vs. 53 %), or 5-year survival (44 % vs. 41 %).Although long-term quality-of-life parameters were not compared, this study did not show an advantage of Roux-en-Y gastrojejunostomy over Billroth II gastrojejunostomy in short-term perioperative outcomes. Both techniques should be regarded as equally acceptable reconstructive options following partial gastrectomy for gastric cancer.

  View details for DOI 10.1007/s10120-015-0547-3

  View details for PubMedID 26400843

• Defining when to offer operative treatment for intrahepatic cholangiocarcinoma: A regret-based decision curves analysis SURGERY Bagante, F., Spolverato, G., Cucchetti, A., Gani, F., Popescu, I., Ruzzenente, A., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Sandroussi, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Gugliehni, A., Pawlik, T. M. 2016; 160 (1): 106-117

  Abstract

  Regret-based decision curve analysis (DCA) is a framework that assesses the medical decision process according to physician attitudes (expected regret) relative to disease-based factors. We sought to apply this methodology to decisions around the operative management of intrahepatic cholangiocarcinoma (ICC).Utilizing a multicentric database of 799 patients who underwent liver resection for ICC, we developed a prognostic nomogram. DCA tested 3 strategies: (1) perform an operation on all patients, (2) never perform an operation, and (3) use the nomogram to select patients for an operation.Four preoperative variables were included in the nomogram: major vascular invasion (HR = 1.36), tumor number (multifocal, HR = 1.18), tumor size (>5 cm, HR = 1.45), and suspicious lymph nodes on imaging (HR = 1.47; all P < .05). The regret-DCA was assessed using an online survey of 50 physicians, expert in the treatment of ICC. For a patient with a multifocal ICC, largest lesion measuring >5 cm, one suspicious malignant lymph node, and vascular invasion on imaging, the 1-year predicted survival was 52% according to the nomogram. Based on the therapeutic decision of the regret-DCA, 60% of physicians would advise against an operation for this scenario. Conversely, all physicians recommended an operation to a patient with an early ICC (single nodule measuring 3 cm, no suspicious lymph nodes, and no vascular invasion at imaging).By integrating a nomogram based on preoperative variables and a regret-based DCA, we were able to define the elements of how decisions rely on medical knowledge (postoperative survival predicted by a nomogram, severity disease assessment) and physician attitudes (regret of commission and omission).

  View details for DOI 10.1016/j.surg.2016.01.023

  View details for Web of Science ID 000378022500016

  View details for PubMedID 27046702

• Readmission Following Gastric Cancer Resection: Risk Factors and Survival JOURNAL OF GASTROINTESTINAL SURGERY Acher, A. W., Squires, M. H., Fields, R. C., Poultsides, G. A., Schmidt, C., Votanopoulos, K. I., Pawlik, T. M., Jin, L. X., Ejaz, A., Kooby, D. A., Bloomston, M., Worhunsky, D., Levine, E. A., Saunders, N., Winslow, E., Cho, C. S., Leverson, G., Maithel, S. K., Weber, S. M. 2016; 20 (7): 1284-1294

  Abstract

  This study utilized a multi-institutional database to evaluate risk factors for readmission in patients undergoing curative gastrectomy for gastric adenocarcinoma with the intent of describing both perioperative risk factors and the relationship of readmission to survival.Patients who underwent curative resection of gastric adenocarcinoma from 2000 to 2012 from seven academic institutions of the US Gastric Cancer Collaborative were analyzed. In-hospital deaths and palliative surgeries were excluded, and readmission was defined as within 30 days of discharge. Univariate and multivariable logistic regression analyses were employed and survival analysis conducted.Of the 855 patients, 121 patients (14.2 %) were readmitted. Univariate analysis identified advanced age (p < 0.0128), American Society of Anesthesiology status ≥3 (p = 0.0045), preexisting cardiac disease (p < 0.0001), hypertension (p = 0.0142), history of smoking (p = 0.0254), increased preoperative blood urea nitrogen (BUN; p = 0.0426), concomitant pancreatectomy (p = 0.0056), increased operation time (p = 0.0384), estimated blood loss (p = 0.0196), 25th percentile length of stay (<7 days, p = 0.0166), 75th percentile length of stay (>12 days, p = 0.0256), postoperative complication (p < 0.0001), and total gastrectomy (p = 0.0167) as risk factors for readmission. Multivariable analysis identified cardiac disease (odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.6-3.3, p < 0.0001), postoperative complication (OR 2.3, 95 % CI 1.6-5.4, p < 0.0001), and pancreatectomy (OR 2.2, 95 % CI 1.1-4.1, p = 0.0202) as independent risk factors for readmission. There was an association of decreased overall median survival in readmitted patients (39 months for readmitted vs. 103 months for non-readmitted). This was due to decreased survival in readmitted stage 1 (p = 0.0039), while there was no difference in survival for other stages. Stage I readmitted patients had a higher incidence of cardiac disease than stage I non-readmitted patients (58 vs. 24 %, respectively, p = 0.0002).Within this multi-institutional study investigating readmission in patients undergoing curative resection for gastric cancer, cardiac disease, postoperative complication, and concomitant pancreatectomy were identified as significant risk factors for readmission. Readmission was associated with decreased overall median survival, but on further analysis, this was driven by differences in survival for stage I disease only.

  View details for DOI 10.1007/s11605-015-3070-2

  View details for Web of Science ID 000378866200002

  View details for PubMedID 27102802

• A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma BMC CANCER Palumbo, T., Poultsides, G. A., Kouraklis, G., Liakakos, T., Drakaki, A., Peros, G., Hatziapostolou, M., Iliopoulos, D. 2016; 16

  Abstract

  Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo.A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors.The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas.Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma.

  View details for DOI 10.1186/s12885-016-2384-0

  View details for Web of Science ID 000376965700001

  View details for PubMedID 27259577

  View details for PubMedCentralID PMC4893280

• Optimal Extent of Lymphadenectomy for Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative JOURNAL OF SURGICAL ONCOLOGY Randle, R. W., Swords, D. S., Levine, E. A., Fino, N. F., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Pawlik, T. M., Jin, L. X., Spolverato, G., Schmidt, C., Worhunsky, D., Cho, C. S., Maithel, S. K., Votanopoulos, K. I. 2016; 113 (7): 750-755

  Abstract

  The optimal extent of lymphadenectomy in the treatment of gastric adenocarcinoma is debated. We compared gastrectomy outcomes following limited (D1) or extended (D2) lymphadenectomy.Using the multi-institutional US Gastric Cancer Collaborative database, we reviewed the morbidity, mortality, recurrence, and overall survival (OS) of patients receiving D1 or D2 lymphadenectomies.Between 2000 and 2012, 266 and 461 patients received a D1 and D2 lymphadenectomy, respectively. ASA class, mean number of comorbidities, grade, and stage were similar between groups. While major morbidity was similar (P = 0.85), mortality was worse for those receiving a D1 lymphadenectomy (4.9% vs. 1.3%, P = 0.004). D2 lymphadenectomy was associated with improved median OS in stage I (4.7 years for D1 vs. not reached for D2, P = 0.003), stage II (3.6 years for D1 vs. 6.3 for D2, P = 0.42), and stage III patients (1.3 years for D1 vs. 2.1 for D2, P = 0.01). After adjusting for predictors of OS, D2 lymphadenectomy remained a significant predictor of improved survival (HR 1.5, 95%CI 1.1-2.0, P = 0.008).D2 lymphadenectomy can be performed without increased risk of morbidity and mortality. Additionally, D2 lymphadenectomy is associated with improved survival especially in early stages, and should be considered for gastric adenocarcinoma patients. J. Surg. Oncol. 2016;113:750-755. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24227

  View details for Web of Science ID 000377392600006

  View details for PubMedID 26996496

  View details for PubMedCentralID PMC4874863

• An economic analysis of pancreaticoduodenectomy: should costs drive consumer decisions? AMERICAN JOURNAL OF SURGERY Tran, T. B., Dua, M. M., Worhunsky, D. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2016; 211 (6): 991-?

  Abstract

  Consumer groups campaign for cost transparency believing that patients will select hospitals accordingly. We sought to determine whether the cost of pancreaticoduodenectomy (PD) should be considered in choosing a hospital.Using the Nationwide Inpatient Sample database, we analyzed charges for patients who underwent PD from 2000 to 2010. Outcomes were stratified by hospital volume.A total of 15,599 PDs were performed in 1,186 hospitals. The median cost was $87,444 (interquartile range $16,015 to $144,869). High volume hospitals (HVH) had shorter hospital stay (11 vs 15 days, P < .001) and mortality (3% vs 7.6%, P < .001). PD performed at low volume hospitals had higher charges compared with HVH ($97,923 vs $81,581, P < .001). On multivariate analysis, HVH was associated with a lower risk of mortality, while extremes in hospital costs, cardiac comorbidity, and any complication were significant predictors of mortality.Although PDs performed at HVH are associated with better outcomes and lower hospital charges, costs should not be the primary determinant when selecting a hospital.

  View details for DOI 10.1016/j.amjsurg.2015.10.028

  View details for PubMedID 26902956

• Outcomes after resection of cortisol-secreting adrenocortical carcinoma AMERICAN JOURNAL OF SURGERY Margonis, G. A., Kim, Y., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Glenn, J. A., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 211 (6): 1106-1113

  Abstract

  We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC).The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed.The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01).Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important.

  View details for DOI 10.1016/j.amjsurg.2015.09.020

  View details for PubMedID 26810939

• Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Vorvis, C., Hatziapostolou, M., Mahurkar-Joshi, S., Koutsioumpa, M., Williams, J., Donahue, T. R., Poultsides, G. A., Eibl, G., Iliopoulos, D. 2016; 310 (11): G1124-G1137

  Abstract

  Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with low survival rates and limited therapeutic options. Thus elucidation of signaling pathways involved in PDAC pathogenesis is essential for identifying novel potential therapeutic gene targets. Here, we used a systems approach to elucidate those pathways by integrating gene and microRNA profiling analyses together with CRISPR/Cas9 technology to identify novel transcription factors involved in PDAC pathogenesis. FOXA2 transcription factor was found to be significantly downregulated in PDAC relative to control pancreatic tissues. Functional experiments revealed that FOXA2 has a tumor suppressor function through inhibition of pancreatic cancer cell growth, migration, invasion, and colony formation. In situ hybridization analysis revealed miR-199a to be significantly upregulated in pancreatic cancer. Bioinformatics and luciferase analyses showed that miR-199a negatively but directly regulates FOXA2 expression through binding in its 3'-untranslated region (UTR). Evaluation of the functional importance of miR-199a on pancreatic cancer revealed that miR-199a acts as an inhibitor of FOXA2 expression, inducing an increase in pancreatic cancer cell proliferation, migration, and invasion. Additionally, gene ontology and network analyses in PANC-1 cells treated with a small interfering RNA (siRNA) against FOXA2 revealed an enrichment for cell invasion mechanisms through PLAUR and ERK activation. FOXA2 deletion (FOXA2Δ) by using two CRISPR/Cas9 vectors in PANC-1 cells induced tumor growth in vivo resulting in upregulation of PLAUR and ERK pathways in FOXA2Δ xenograft tumors. We have identified FOXA2 as a novel tumor suppressor in pancreatic cancer and it is regulated directly by miR-199a, thereby enhancing our understanding of how microRNAs interplay with the transcription factors to affect pancreatic oncogenesis.

  View details for DOI 10.1152/ajpgi.00035.2016

  View details for Web of Science ID 000377433200025

  View details for PubMedID 27151939

  View details for PubMedCentralID PMC5005285

• Conditional probability of long-term survival after resection of hilar cholangiocarcinoma HPB Buettner, S., Margonis, G. A., Kim, Y., Gani, F., Ethun, C. G., Poultsides, G., Thuy Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C. R., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, L., Shenoy, R., Maithel, S. K., Pawlik, T. M. 2016; 18 (6): 510-517

  Abstract

  While traditional survival analyses focus on factors determined at the time of surgery, conditional survival (CS) estimates prognosis relative to time following treatment. We sought to compare actuarial and CS among patients undergoing curative intent surgery for hilar cholangiocarcinoma.242 patients undergoing surgery between 2000 and 2014 were identified using a multi-institutional database. CS was calculated as the probability of surviving an additional 3 years, given that the patient had already survived "x" years from surgery.Median patient age was 67 years (IQR: 57-73) and most patients were male (n = 140, 57.9%). Lymph node metastases were noted in 79 (32.6%) patients while an R0 margin was obtained in 66.1% (n = 160). Median OS was 22.3 months. Actuarial survival decreased over time from 46.3% at 2 years following surgery to 18.2% at 5 years; in contrast, the 3-year CS (CS3) increased with time (CS3 at 2 years was 39.3% versus 54.4% at 5 years). CS3 exceeded actuarial survival for high-risk patients with patients with perineural invasion demonstrating an actuarial survival of 15.4% at 5 years versus CS3 of 37.6% at 2 years following surgery (Δ = 22.2%).CS provides a more accurate, dynamic estimate for survival, especially among high-risk patients.

  View details for DOI 10.1016/j.hpb.2016.04.001

  View details for Web of Science ID 000379638400004

  View details for PubMedID 27317955

  View details for PubMedCentralID PMC4913135

• The First Decade of Laparoscopic Pancreaticoduodenectomy in the United States: Costs and Outcomes Using the Nationwide Inpatient Sample SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Tran, T. B., Dua, M. M., Worhunsky, D. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2016; 30 (5): 1778-1783

  Abstract

  Minimally invasive pancreaticoduodenectomy (PD) remains an uncommon procedure, and the safety and efficacy remain uncertain beyond single institution case series. The aim of this study is to compare outcomes and costs between laparoscopic (LPD) and open PD (OPD) using a large population-based database.The Nationwide Inpatient Sample database (a sample of approximately 20 % of all hospital discharges) was analyzed to identify patients who underwent PD from 2000 to 2010. Patient demographics, comorbidities, hospital characteristics, inflation-adjusted total charges, and complications were evaluated using univariate and multivariate logistic regression. Hospitals were categorized as high-volume hospitals (HVH) if more than 20 PD (open and laparoscopic) were performed annually, while those performing fewer than 20 PD were classified as low-volume hospitals.Of the 15,574 PD identified, 681 cases were LPD (4.4 %). Compared to OPD, patients who underwent LPD were slightly older (65 vs. 67 years; p = 0.001) and were more commonly treated at HVH (56.6 vs. 66.1 %; p < 0.001). Higher rates of complications were observed in OPD than LPD (46 vs. 39.4 %; p = 0.001), though mortality rates were comparable (5 vs. 3.8 %, p = 0.27). Inflation-adjusted median hospital charges were similar between OPD and LPD ($87,577 vs. $81,833, p = 0.199). However, hospital stay was slightly longer in the OPD group compared to LPD group (12 vs. 11 days, p < 0.001). Stratifying outcomes by hospital volume, LPD at HVH resulted in shorter hospital stays (9 vs. 13 days, p < 0.001), which translated into significantly lower median hospital charges ($76,572 vs. $106,367, p < 0.001).Contrary to fears regarding the potential for compromised outcomes early in the learning curve, LPD morbidity in its first decade is modestly reduced, while hospital costs are comparable to OPD. In high-volume pancreatic hospitals, LPD is associated with a reduction in length of stay and hospital costs.

  View details for DOI 10.1007/s00464-015-4444-y

  View details for PubMedID 26275542

• Perihilar Cholangiocarcinoma: Number of Nodes Examined and Optimal Lymph Node Prognostic Scheme JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Bagante, F., Thuy Tran, T., Spolverato, G., Ruzzenente, A., Buttner, S., Ethun, C. G., Koerkamp, B. G., Conci, S., Idrees, K., Isom, C. A., Fields, R. C., Krasnick, B., Weber, S. M., Salem, A., Martin, R. C., Scoggins, C., Shen, P., Mogal, H. D., Schmidt, C., Beal, E., Hatzaras, I., Vitiello, G., IJzermans, J. N., Maithel, S. K., Poultsides, G., Guglielmi, A., Pawlik, T. M. 2016; 222 (5): 750-?

  Abstract

  The role of routine lymphadenectomy for perihilar cholangiocarcinoma is still controversial and no study has defined the minimum number of lymph nodes examined (TNLE). We sought to assess the prognostic performance of American Joint Committee on Cancer/Union Internationale Contre le Cancer (7(th) edition) N stage, lymph node ratio, and log odds (LODDS; logarithm of the ratio between metastatic and nonmetastatic nodes) in patients with perihilar cholangiocarcinoma and identify the optimal TNLE to accurately stage patients.A multi-institutional database was queried to identify 437 patients who underwent hepatectomy for perihilar cholangiocarcinoma between 1995 and 2014. The prognostic abilities of the lymph node staging systems were assessed using the Harrell's c-index. A Bayesian model was developed to identify the minimum TNLE.One hundred and fifty-eight (36.2%) patients had lymph node metastasis. Median TNLE was 3 (interquartile range, 1 to 7). The LODDS had a slightly better prognostic performance than lymph node ratio and American Joint Committee on Cancer, in particular among patients with <4 TNLE (c-index = 0.568). For 2 TNLE, the Bayesian model showed a poor discriminatory ability to distinguish patients with favorable and poor prognosis. When TNLE was >2, the hazard ratio for N1 patients was statistically significant and the hazard ratio for N1 patients increased from 1.51 with 4 TNLE to 2.10 with 10 TNLE. Although the 5-year overall survival of N1 patients was only slightly affected by TNLE, the 5-year overall survival of N0 patients increased significantly with TNLE.Perihilar cholangiocarcinoma patients undergoing radical resection should ideally have at least 4 lymph nodes harvested to be accurately staged. In addition, although LODDS performed better at determining prognosis among patients with <4 TNLE, both lymph node ratio and LODDS outperformed compared with American Joint Committee on Cancer N stage among patients with ≥4 TNLE.

  View details for DOI 10.1016/j.jamcollsurg.2016.02.012

  View details for Web of Science ID 000375130300008

  View details for PubMedID 27113512

• Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Krampitz, G. W., George, B. M., Willingham, S. B., Volkmer, J., Weiskopf, K., Jahchan, N., Newman, A. M., Sahoo, D., Zemek, A. J., Yanovsky, R. L., Nguyen, J. K., Schnorr, P. J., Mazur, P. K., Sage, J., Longacre, T. A., Visser, B. C., Poultsides, G. A., Norton, J. A., Weissman, I. L. 2016; 113 (16): 4464-4469

  Abstract

  Pancreatic neuroendocrine tumors (PanNETs) are a type of pancreatic cancer with limited therapeutic options. Consequently, most patients with advanced disease die from tumor progression. Current evidence indicates that a subset of cancer cells is responsible for tumor development, metastasis, and recurrence, and targeting these tumor-initiating cells is necessary to eradicate tumors. However, tumor-initiating cells and the biological processes that promote pathogenesis remain largely uncharacterized in PanNETs. Here we profile primary and metastatic tumors from an index patient and demonstrate that MET proto-oncogene activation is important for tumor growth in PanNET xenograft models. We identify a highly tumorigenic cell population within several independent surgically acquired PanNETs characterized by increased cell-surface protein CD90 expression and aldehyde dehydrogenase A1 (ALDHA1) activity, and provide in vitro and in vivo evidence for their stem-like properties. We performed proteomic profiling of 332 antigens in two cell lines and four primary tumors, and showed that CD47, a cell-surface protein that acts as a "don't eat me" signal co-opted by cancers to evade innate immune surveillance, is ubiquitously expressed. Moreover, CD47 coexpresses with MET and is enriched in CD90(hi)cells. Furthermore, blocking CD47 signaling promotes engulfment of tumor cells by macrophages in vitro and inhibits xenograft tumor growth, prevents metastases, and prolongs survival in vivo.

  View details for DOI 10.1073/pnas.1600007113

  View details for PubMedID 27035983

• Is Linitis Plastica a Contraindication for Surgical Resection: A Multi-Institution Study of the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Blackham, A. U., Swords, D. S., Levine, E. A., Fino, N. F., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Pawlik, T. M., Jin, L. X., Spolverato, G., Schmidt, C., Worhunsky, D., Cho, C. S., Maithel, S. K., Votanopoulos, K. I. 2016; 23 (4): 1203-1211

  Abstract

  Current staging and treatment guidelines for gastric adenocarcinoma do not differentiate between linitis plastic (LP) and non-LP cancers. Significant controversy exists regarding the surgical management of LP patients.Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 gastric cancer patients who underwent resection between 2000 and 2012 were identified. Clinicopathologic and outcomes data of 58 LP patients were compared to 811 non-LP patients.Stage III/IV disease was more common at presentation in LP patients compared with non-LP patients (90 vs. 44 %, p < 0.01). Despite the fact that most LP patients underwent total gastrectomy (88 vs. 39 %, p < 0.01), final positive margins were more common in LP patients (33 vs. 7 %, p < 0.01). The use of frozen section allowed 15 intraoperative positive margins in 38 patients to be converted to negative final margins. Median overall survival (OS) was significantly worse in patients with LP (11.6 vs. 37.8 months, p < 0.01). There was no difference in median OS of LP patients based on stage (I/II, 17.3 mo; III, 10.6 mo; IV, 12.0 mo; p = 0.46). LP and non-LP patients who underwent optimal resection (negative margin and D2/3 lymphadenectomy) had better survival compared with those with nonoptimal resections. The median OS for optimally resected stage III LP (n = 22) and stage III non-LP (n = 185) patients was nearly identical (26.7 vs. 25.3 mo; p = 0.69).Future staging systems and treatment guidelines should differentiate between LP and non-LP gastric cancers. Long-term survival in select LP patients who undergo optimal resections is comparable to optimally resected non-LP patients.

  View details for DOI 10.1245/s10434-015-4947-8

  View details for Web of Science ID 000371333200022

  View details for PubMedID 26530447

• Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma JAMA SURGERY Kim, Y., Margonis, G. A., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A. I., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. 2016; 151 (4): 365-373

  Abstract

  Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined.To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction.Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015.The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves.In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63-5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47-15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95-3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27-4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02-3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00-3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05-16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51-5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS).Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.

  View details for DOI 10.1001/jamasurg.2015.4516

  View details for PubMedID 26676603

• Stage-Specific Prognostic Effect of Race in Patients with Resectable Gastric Adenocarcinoma: An 8-Institution Study of the US Gastric Cancer Collaborative. Journal of the American College of Surgeons Wang, A., Squires, M. H., Melis, M., Poultsides, G. A., Norton, J. A., Jin, L. X., Fields, R. C., Spolverato, G., Pawlik, T. M., Votanopoulos, K. I., Levine, E. A., Schmidt, C., Bloomston, M., Cho, C. S., Weber, S., Berman, R., Pachter, H. L., Newman, E., Staley, C. A., Maithel, S. K., Hatzaras, I. 2016; 222 (4): 633-643

  Abstract

  Gastric cancer constitutes a major public health problem. This study sought to evaluate the relevance of race in gastric cancer and its prognostic effect in the overall outcomes of patients with gastric adenocarcinoma.Patients who underwent curative intent resection of gastric adenocarcinoma in 8 institutions of the US Gastric Cancer Collaborative were included, from 2000 to 2012. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic data. Multivariate Cox proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival.There were 1,077 patients included in the study, the majority of whom were of Caucasian race (n = 698, 68%), followed by African-American (n = 164, 15%), Asian (n = 132, 12%), Hispanic (n = 34, 3.2%), and other (n = 49, 4.5%). Clinicopathologic data were similarly distributed among the 5 groups. Mean follow-up was 27.1 months. By multivariate, stage-specific analysis, Asian race was a significant predictor of recurrence (all stages hazard ratio [HR] 0.45 95% CI [0.23, 0.97], p = 0.041) and of overall survival (all stages HR 0.35 95% CI [0.18, 0.68], p = 0.002). Recurrence-free survival was significantly increased in the Asian population compared with the non-Asian population (25th percentile: 38.6 vs 17.7 months, p = 0.0096), as was overall median survival (141 vs 38.8 months, p < 0.001).Patients of Asian race undergoing curative gastrectomy for gastric adenocarcinoma appear to have a better prognosis stage for stage. Further studies are required to elucidate the underlying etiology of this phenomenon.

  View details for DOI 10.1016/j.jamcollsurg.2015.12.043

  View details for PubMedID 26905187

• Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group. Journal of the American College of Surgeons Postlewait, L. M., Ethun, C. G., Tran, T. B., Prescott, J. D., Pawlik, T. M., Wang, T. S., Glenn, J., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Staley, C. A., Poultsides, G. A., Maithel, S. K. 2016; 222 (4): 480-490

  Abstract

  Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines.Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS).Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS.When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.

  View details for DOI 10.1016/j.jamcollsurg.2015.12.013

  View details for PubMedID 26775162

• Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2016; 23 (4): 1225-1233

  Abstract

  Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC).Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS).Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034).Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited.

  View details for DOI 10.1245/s10434-015-4953-x

  View details for Web of Science ID 000371333200025

  View details for PubMedID 26553442

• A multi-institutional analysis of elderly patients undergoing a liver resection for intrahepatic cholangiocarcinoma JOURNAL OF SURGICAL ONCOLOGY Vitale, A., Spolverato, G., Bagante, F., Gani, F., Popescu, I., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Sandroussi, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2016; 113 (4): 420-426

  Abstract

  Little is known regarding postoperative outcomes of elderly patients undergoing liver surgery for intrahepatic cholangiocarcinoma (ICC).Five hundred and eighty-four patients undergoing liver resection for ICC between 1990 and 2015 were identified. Perioperative morbidity, mortality, overall survival (OS), and disease-free survival (DFS) were compared between elderly (>70 year, n = 129) and non-elderly (≤70 years, n = 455) patients.Older patients had a higher incidence of complications (elderly vs. non-elderly; 52.7% vs. 42.6%; P = 0.03), as well as major complications (elderly vs. non-elderly; 24.0% vs. 14.9%; P = 0.01); 30-day (0.1% vs. 3.3%; P > 0.05), and 90-day mortality (2.3% vs. 5.5%; P > 0.05) were comparable. Five-year OS and DFS were comparable between the elderly and non-elderly patients (OS, 13.3% vs. 24.4%; and DFS; 7.3% vs. 12.0%; P > 0.05). On propensity score matching, DFS and OS were also comparable among non-elderly versus elderly patients. Poor tumor grade was associated with worse DFS among elderly patients (HR = 1.6, 95%CI 1.0-2.6; P = 0.04), whereas periductal invasion (HR = 1.9, 95% CI 1.1-3.5; P = 0.03) and nodal disease (HR = 2.3, 95% CI 1.3-3.9; P = 0.003) were predictive of shorter DFS among non-elderly patients.Elderly patients undergoing liver surgery for ICC demonstrated an increased risk of perioperative complications, but comparable long-term DFS and OS compared with younger patients. Rather, tumor characteristics were more predictive of worse long-term outcomes. J. Surg. Oncol. 2016;113:420-426. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24148

  View details for Web of Science ID 000374711400012

  View details for PubMedID 27100027

• Incidence of Perioperative Complications Following Resection of Adrenocortical Carcinoma and Its Association with Long-Term Survival WORLD JOURNAL OF SURGERY Margonis, G. A., Amini, N., Kim, Y., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Moses, L. E., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 40 (3): 706-714

  Abstract

  The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival.Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed.A total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure (n = 169, 66.8 %). A postoperative complication occurred in 99 patients for a morbidity of 37.4 %; five patients (1.9 %) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95 % CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95 % CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95 % CI 2.24-13.80; P < 0.001).Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective.

  View details for DOI 10.1007/s00268-015-3307-y

  View details for PubMedID 26546184

• Albumin and Neutrophil-Lymphocyte Ratio (NLR) Predict Survival in Patients With Pancreatic Adenocarcinoma Treated With SBRT. American journal of clinical oncology Alagappan, M., Pollom, E. L., von Eyben, R., Kozak, M. M., Aggarwal, S., Poultsides, G. A., Koong, A. C., Chang, D. T. 2016: -?

  Abstract

  To determine if pretreatment nutritional status and inflammatory markers correlate with survival in patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT).We retrospectively reviewed 208 patients with newly diagnosed, locally advanced pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2014. Laboratory values were collected before SBRT, including hemoglobin, platelets, albumin, red blood cell, white blood cell, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and tumor markers CA 19-9 and CEA. Patients were followed every 3 months with computed tomography (CT) and/or positron emission tomography-CT imaging to monitor for local recurrence and overall survival (OS).Median follow-up after SBRT was 7.5 months (interquartile range, 4.6 to 12.0 mo) for all patients. Median OS for patients with NLR>5 compared with NLR≤5 was 6.9 and 8.5 months, respectively (P=0.0057). On univariate analysis, receipt of chemotherapy (P=0.05, hazard ratio [HR]=0.69), increased albumin (P=0.002, HR=0.64), increased red blood cell (P=0.05, HR=0.75), increased lymphocyte count (P=0.002, HR=0.66), decreased CEA (P=0.01, HR=0.96), and NLR≤5 (P=0.01, HR=0.65) correlated with improved OS. On multivariate analysis, higher albumin (P=0.03, HR=0.70), receipt of chemotherapy (P=0.007, HR=0.56), and NLR≤5 (P=0.02, HR=0.66) correlated with better survival.Preradiotherapy low albumin levels and NLR>5 correlate with decreased survival in patients with locally advanced pancreatic adenocarcinoma treated with SBRT, indicating the prognostic value of systemic inflammatory markers (such as NLR) and a role of nutritional supplementation to improve outcomes in these patients. Further investigation is warranted.

  View details for PubMedID 26757436

• Statin and Metformin Use Prolongs Survival in Patients With Resectable Pancreatic Cancer. Pancreas Kozak, M. M., Anderson, E. M., von Eyben, R., Pai, J. S., Poultsides, G. A., Visser, B. C., Norton, J. A., Koong, A. C., Chang, D. T. 2016; 45 (1): 64-70

  Abstract

  The aim of this study was to investigate the impact of statin and metformin therapy on disease outcome for patients with pancreatic ductal adenocarcinoma (PDAC).This retrospective study included 171 PDAC patients who underwent surgical resection at the Stanford Cancer Institute between 1998 and 2013. No patients received neoadjuvant therapy. Statin and metformin use was defined as use during initial consult and continuing upon discharge from the hospital after surgery. Dose of each medication was recorded, as was the type of statin taken.The median follow-up for all patients was 11.23 months (range, 0.2-105.0 months). Among the 171 patients included in our analysis, 18 patients (10.5%) took metformin and 34 patients (19.9%) took statins. Statin use was associated with better overall survival (OS) in patients with PDAC (P = 0.011). Metformin use was also associated with better OS (P = 0.035). The use of statins remained significant on multivariate analysis for OS (P = 0.014; hazards ratio, 0.33; 95% confidence interval, 0.139-0.799), but metformin use did not (P = 0.33; hazards ratio 0.60, 95% confidence interval, 0.211-1.675).Statin and metformin use is associated with improved OS in patients with resectable PDAC. These medications should be further investigated for possible long-term use in the general population.

  View details for DOI 10.1097/MPA.0000000000000470

  View details for PubMedID 26474429

• Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection. Annals of surgical oncology Spolverato, G., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Clark Gamblin, T., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Tran, T. B., Wallis Marsh, J., Pawlik, T. M. 2016; 23 (1): 235–43

  Abstract

  Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes.Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed.A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001).Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit.

  View details for PubMedID 26059651

• Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence. Annals of surgical oncology Amini, N., Margonis, G. A., Kim, Y., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q. Y., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 126–33

  Abstract

  Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC.Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence.A total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01).Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.

  View details for PubMedID 26282907

• Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes. Annals of surgical oncology Margonis, G. A., Kim, Y., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q. Y., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 134–41

  Abstract

  The influence of surgical margin status on long-term outcomes of patients undergoing adrenal resection for ACC remains not well defined. We studied the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ACC.A total of 165 patients who underwent adrenal resection for ACC and met inclusion criteria were identified form a multi-institutional database. Clinicopathological data, pathologic margin status, and long-term outcomes were assessed. Patients were stratified into two groups based on margin status: R0 (margin >1 mm) versus R1.R0 resection was achieved in 126 patients (76.4 %), whereas 39 patients (23.6 %) had an R1 resection. Median and 5-year OS for patients undergoing R0 resection were 96.3 months and 64.8 % versus 25.1 months and 33.8 % for patients undergoing an R1 resection (both p < 0.001). On multivariable analysis, surgical margin status was an independent predictor of worse OS (hazard ratio [HR] 2.22, 95 % confidence interval [CI] 1.03-4.77; p = 0.04). The incidence of recurrence also differed between the two groups; 5-year RFS was 30.3 % among patients with an R0 resection versus 13.8 % among patients who had an R1 resection (p = 0.03). Lymph node metastasis (N1) was an independent predictor of RFS (HR 2.70, 95 % CI 1.04-6.99; p = 0.04).A positive margin after ACC resection was associated with worse long-term survival. Patient selection and an emphasis on surgical technique to achieve R0 margins are pivotal to optimizing the best chance for long-term outcome among patients with ACC.

  View details for PubMedID 26286195

• Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes ANNALS OF SURGICAL ONCOLOGY Margonis, G. A., Kim, Y., Prescott, J. D., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 134-141

  View details for DOI 10.1245/s10434-015-4803-x

  View details for Web of Science ID 000367458100023

• Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence ANNALS OF SURGICAL ONCOLOGY Amini, N., Margonis, G. A., Kim, Y., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2016; 23 (1): 126-133

  View details for DOI 10.1245/s10434-015-4810-y

  View details for Web of Science ID 000367458100022

• Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection ANNALS OF SURGICAL ONCOLOGY Spolverato, G., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Tran, T. B., Marsh, J. W., Pawlik, T. M. 2016; 23 (1): 235-243

  View details for DOI 10.1245/s10434-015-4642-9

  View details for Web of Science ID 000367458100036

• Gastric Remnant Cancer: A Distinct Entity or Simply Another Proximal Gastric Cancer? JOURNAL OF SURGICAL ONCOLOGY Tran, T. B., Hatzaras, I., Worhunsky, D. J., Vitiello, G. A., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2015; 112 (8): 877-882

  Abstract

  The purpose of this study was to compare outcomes following resection of gastric remnant (GRC) and conventional gastric cancer.Patients who underwent resection for gastric cancer in 8 academic institutions from 2000-2012 were evaluated to compare morbidity, mortality, and survival based on history of prior gastrectomy.Of the 979 patients who underwent gastrectomy with curative-intent during the 12-year study period, 55 patients (5.8%) presented with GRC and 924 patients (94.4%) presented with conventional gastric cancer. Patients with GRC were slightly older (median 69 vs. 66 years). GRC was associated with higher rates of complication (56% vs. 41%, P = 0.028), longer operative times (301 vs. 237 min, P < 0.001), higher intraoperative blood loss (300 vs. 200 ml, P = 0.012), and greater need for blood transfusion (43% vs. 23%, P = 0.001). There were no significant differences in 30-day (3.6% vs. 4%) or 90-day mortality (9% vs. 8%) between the two groups. Overall survival rates were similar between GRC and conventional gastric cancer (5-year 20.3% vs. 38.6%, P = 0.446). Multivariate analysis revealed that history of gastrectomy was not predictive of survival while established predictors (older age, advanced T-stage, nodal involvement, blood transfusion, multivisceral resection, and any complication) were associated with poor survival.Despite higher morbidity, prognosis after resection of gastric remnant cancer is similar to conventional gastric cancer. J. Surg. Oncol. 2015;112:877-882. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24080

  View details for Web of Science ID 000367671700015

• Outcomes of Gastric Cancer Resection in Octogenarians: A Multi-institutional Study of the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Tran, T. B., Worhunsky, D. J., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2015; 22 (13): 4371-4379

  Abstract

  As the U.S. population ages, an increasing number of elderly patients with gastric adenocarcinoma are being evaluated for surgical resection. This study aimed to describe the short- and long-term outcomes after gastric cancer resection for patients 80 years of age or older.Patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012 at seven U.S. academic institutions were analyzed. The main outcome measures included postoperative morbidity, mortality, survival, and failure to rescue (defined as death after any complication).Of 953 patients who underwent distal or total gastrectomy during the 12-year study period, 127 (13 %) were 80 years of age or older. Although the type of postoperative complications did not differ between the two groups, octogenarians had a higher incidence of any (54 vs 41 %; p = 0.006) and of major (28 vs 17 %; p = 0.006) postoperative complications. This translated into higher 30-day (10.2 vs 3.6 %; p = 0.001) and 90-day mortality (19.7 vs 7.9 %; p = 0.001) rates, with correspondingly higher failure-to-rescue rates (17.4 vs 8 %; p = 0.015). However, disease-specific survival after resection was equivalent between the two groups (5-year survival: 46 vs 53 %; p = 0.676). In the multivariate analysis, age of 80 years or older, blood transfusion, and albumin and creatinine levels all were independent predictors of 90-day mortality. Stage, tumor grade, race, blood transfusion, and adjuvant therapy, but not age, were independently associated with disease-specific survival.Perioperative mortality and failure-to-rescue from complications is substantial for octogenarians undergoing gastric cancer resection. However, if the operation can be performed safely, the long-term cancer-specific outcome appears similar to that for younger patients.

  View details for DOI 10.1245/s10434-015-4530-3

  View details for PubMedID 25822782

• Gastric remnant cancer: A distinct entity or simply another proximal gastric cancer? Journal of surgical oncology Tran, T. B., Hatzaras, I., Worhunsky, D. J., Vitiello, G. A., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Norton, J. A., Poultsides, G. A. 2015; 112 (8): 877-882

  Abstract

  The purpose of this study was to compare outcomes following resection of gastric remnant (GRC) and conventional gastric cancer.Patients who underwent resection for gastric cancer in 8 academic institutions from 2000-2012 were evaluated to compare morbidity, mortality, and survival based on history of prior gastrectomy.Of the 979 patients who underwent gastrectomy with curative-intent during the 12-year study period, 55 patients (5.8%) presented with GRC and 924 patients (94.4%) presented with conventional gastric cancer. Patients with GRC were slightly older (median 69 vs. 66 years). GRC was associated with higher rates of complication (56% vs. 41%, P = 0.028), longer operative times (301 vs. 237 min, P < 0.001), higher intraoperative blood loss (300 vs. 200 ml, P = 0.012), and greater need for blood transfusion (43% vs. 23%, P = 0.001). There were no significant differences in 30-day (3.6% vs. 4%) or 90-day mortality (9% vs. 8%) between the two groups. Overall survival rates were similar between GRC and conventional gastric cancer (5-year 20.3% vs. 38.6%, P = 0.446). Multivariate analysis revealed that history of gastrectomy was not predictive of survival while established predictors (older age, advanced T-stage, nodal involvement, blood transfusion, multivisceral resection, and any complication) were associated with poor survival.Despite higher morbidity, prognosis after resection of gastric remnant cancer is similar to conventional gastric cancer. J. Surg. Oncol. 2015;112:877-882. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24080

  View details for PubMedID 26511335

• Intrahepatic Cholangiocarcinoma: Prognosis of Patients Who Did Not Undergo Lymphadenectomy JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Bagante, F., Gani, F., Spolverato, G., Xu, L., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 221 (6): 1031-?

  Abstract

  The role of routine lymphadenectomy (LD) among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) remains poorly defined. This study aimed to evaluate the role of routine LD as well as to quantify the impact of not assessing nodal station on disease-specific survival (DSS) among patients undergoing liver surgery for ICC.Using data from 12 major hepatobiliary centers, 561 patients undergoing liver surgery for ICC between 1990 and 2012 were identified. The association between nodal status and DSS was assessed using Cox proportional and Aalen's linear hazards models.Among the 272 (48.5%) patients who underwent LD, 123 (45.2%) had lymph node metastasis (N1). Although differences in DSS were noted between N0 and Nx patients within the first 18 months after surgery (DSS at 18 months: N0 vs Nx, 70.2% vs 60.6%, respectively, p = 0.019) among patients who had survived to 18 months, the DSS at 60 months of Nx patients was comparable to that of N0 patients (p = 0.48). Conversely, although the DSS of N1 and Nx patients was comparable in the short-term (DSS at 18 months: p = 0.13), among patients who had survived to 18 months, N1 patients had a lower DSS compared with Nx patients (DSS at 60 months among patients who had survived to 18 months: N1 vs Nx, 15.2% vs 45.8%, respectively, p < 0.001; all p values were based on the log-rank test comparing 2 survival curves).Although Nx patients and N1 patients had comparable DSS in the short-term, Nx patients who survived past 18 months had a survival comparable to that of N0 patients. Lack of nodal staging may lead to heterogeneous and potentially incorrect prognostic classification of patients with ICC.

  View details for DOI 10.1016/j.jamcollsurg.2015.09.012

  View details for Web of Science ID 000365346600007

  View details for PubMedID 26474514

• Value of Peritoneal Drain Placement After Total Gastrectomy for Gastric Adenocarcinoma: A Multi-institutional Analysis from the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Dann, G. C., Squires, M. H., Postlewait, L. M., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D. S., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K., Cardona, K. 2015; 22: S888-S897

  View details for DOI 10.1245/s10434-015-4636-7

  View details for Web of Science ID 000367288100082

• Prognostic Performance of Different Lymph Node Staging Systems After Curative Intent Resection for Gastric Adenocarcinoma ANNALS OF SURGERY Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D. A., Worhunsky, D., Saunders, N., Cho, C. S., Levine, E. A., Maithel, S. K., Pawlik, T. M. 2015; 262 (6): 991-998

  View details for DOI 10.1097/SLA.0000000000001040

  View details for Web of Science ID 000367910100015

• Factors Associated With Recurrence and Survival in Lymph Node-negative Gastric Adenocarcinoma A 7-Institution Study of the US Gastric Cancer Collaborative ANNALS OF SURGERY Jin, L. X., Moses, L. E., Squires, M. H., Poultsides, G. A., Votanopoulos, K., Weber, S. M., Bloomston, M., Pawlik, T. M., Hawkins, W. G., Linehan, D. C., Strasberg, S. M., Schmidt, C., Worhunsky, D. J., Acher, A. W., Cardona, K., Cho, C. S., Kooby, D. A., Levine, E., Winslow, E. R., Saunders, N. D., Spolverato, G., Maithel, S. K., Fields, R. C. 2015; 262 (6): 999-1005

  View details for DOI 10.1097/SLA.0000000000001084

  View details for Web of Science ID 000367910100016

• The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 22: S832-S839

  View details for DOI 10.1245/s10434-015-4724-8

  View details for Web of Science ID 000367288100075

• Value of Peritoneal Drain Placement After Total Gastrectomy for Gastric Adenocarcinoma: A Multi-institutional Analysis from the US Gastric Cancer Collaborative. Annals of surgical oncology Dann, G. C., Squires, M. H., Postlewait, L. M., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D. S., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K., Cardona, K. 2015; 22: 888-897

  Abstract

  The effect of routine drainage after abdominal surgery with enteric anastomoses is controversial. In particular, the role of peritoneal drain (PD) placement after total gastrectomy for adenocarcinoma is not well established.Patients who underwent total gastrectomy for gastric adenocarcinoma (GAC) at seven institutions from the US Gastric Cancer Collaborative, from 2000 to 2012, were identified. The association of PD placement with postoperative outcomes was analyzed.Overall, 344 patients were identified and 253 (74 %) patients received a PD. The anastomotic leak rate was 9 %. Those with PD placement had similar American Society of Anesthesiologists score, tumor size, TNM stage, and the need for additional organ resection when compared with their counterparts. No difference was observed in the rate of any complication (54 vs. 48 %; p = 0.45), major complication (25 vs. 24 %; p = 0.90), or 30-day mortality (7 vs. 4 %; p = 0.51) between the two groups. In addition, no difference in anastomotic leak (9 vs. 10 %; p = 0.90), the need for secondary drainage (10 vs. 9 %; p = 0.92), or reoperation (13 vs. 8 %; p = 0.28) was identified. On multivariate analysis, PD placement was not associated with decreased postoperative complications. Subset analysis, stratified by patients who did not undergo concomitant pancreatectomy (n = 319) or those who experienced anastomotic leak (n = 31), similarly demonstrated no association of PD placement with reduced complications or mortality.PD placement after total gastrectomy for GAC is associated with neither a decrease in the frequency and severity of adverse postoperative outcomes, including anastomotic leak and mortality, nor a decrease in the need for secondary drainage procedures or reoperation. Routine use of PDs is not warranted.

  View details for DOI 10.1245/s10434-015-4636-7

  View details for PubMedID 26023037

• The Prognostic Value of Signet-Ring Cell Histology in Resected Gastric Adenocarcinoma. Annals of surgical oncology Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 22: 832-839

  Abstract

  Conflicting data exist on the prognostic implication of signet-ring cell (SRC) histology in gastric adenocarcinoma (GAC).All patients who underwent curative-intent resection of GAC from the seven institutions of the U.S. Gastric Cancer Collaborative between 2000 and 2012 were included. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Stage-specific analyses were performed.A total of 768 patients met the inclusion criteria. SRC was present in 40.6 % of patients and was associated with female sex (52.9 vs. 38.6 %; p < 0.001), younger age (61 vs. 67 years; p < 0.001), poor differentiation (94.8 vs. 50.3 %; p < 0.001), perineural invasion (PNI) (41.4 vs. 23 %; p < 0.001), microscopically positive resection margins (R1, 24.7 vs. 8.6 %; p < 0.001), distal location (82.2 vs. 70.1 %; p < 0.001), receipt of adjuvant therapy (63 vs. 51.2 %; p = 0.002), and more advanced stage (stage 3: 55.2 vs. 36.5 %; p < 0.001). SRC was associated with earlier recurrence (56.7 months vs. median not reached; p = 0.009) and decreased OS (33.7 vs. 46.6 months; p = 0.011). When accounting for other adverse pathologic features, PNI (hazard ratio [HR] 1.57; p = 0.016) and higher stage (HR 2.64; p < 0.001) were associated with decreased RFS, but SRC was not. Although PNI (HR 1.52; p = 0.007), higher stage (HR 2.11; p < 0.001), greater size (HR 1.05; p = 0.016), and adjuvant therapy (HR 0.50; p < 0.001) were associated with OS, SRC was not. Similarly, when accounting for adverse pathologic factors on multivariate analysis, stage-specific analyses showed no association between SRC and RFS or OS.SRC histology is associated with adverse pathologic features including poor differentiation, higher stage, and microscopically positive resection margins but is not independently associated with reduced RFS or OS. Identification of signet-ring histology during preoperative evaluation should not, in isolation, dictate treatment strategy.

  View details for DOI 10.1245/s10434-015-4724-8

  View details for PubMedID 26156656

• Incidence and Risk Factors Associated with Readmission After Surgical Treatment for Adrenocortical Carcinoma JOURNAL OF GASTROINTESTINAL SURGERY Valero-Elizondo, J., Kim, Y., Prescott, J. D., Margonis, G. A., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Glenn, J. A., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2015; 19 (12): 2154-2161

  View details for DOI 10.1007/s11605-015-2917-x

  View details for PubMedID 26286367

• Multivisceral Resection for Gastric Cancer: Results from the US Gastric Cancer Collaborative. Annals of surgical oncology Tran, T. B., Worhunsky, D. J., Norton, J. A., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Poultsides, G. A. 2015; 22: 840-847

  Abstract

  Resection of an adjacent organ during gastrectomy for gastric cancer is occasionally necessary to achieve margin clearance. The short- and long-term outcomes of this approach remain unclear.Patients who underwent gastric cancer resection in seven U.S. academic institutions from 2000 to 2012 were evaluated to compare perioperative morbidity, mortality, and survival outcomes, stratified by the need for and type of multivisceral resection (MVR).Of 835 patients undergoing curative-intent gastrectomy, 159 (19 %) had MVR. The most common adjacent organs resected were the spleen (48 %), pancreas (27 %), liver segments 2/3 (14 %), and colon (13 %). As extent of resection increased (gastrectomy only, n = 676; MVR without pancreatectomy, n = 116; and MVR with pancreatectomy, n = 43), perioperative morbidity was higher: any complication (45, 60, 59 %, p = 0.012), major complication (17, 31, 33 %, p = 0.001), anastomotic leak (5, 11, 19 %, p < 0.001), and respiratory failure (9, 15, 22 %, p = 0.012). However, perioperative mortality did not significantly increase (30-day: 3, 4, 2 %, p = 0.74; 90-day: 6, 8, 9 %, p = 0.61). Overall survival after resection decreased as extent of resection increased (5-year: 42, 28, 6 %). After controlling for age, race, T stage, N stage, grade, margin status, perineural invasion, adjuvant therapy, and blood transfusion, MVR with pancreatectomy (HR 1.67, p = 0.044), but not MVR without pancreatectomy (HR 0.97, p = 0.759), remained an independent predictor of poor survival.In this modern, multi-institutional cohort of gastric cancer patients, multivisceral resection was associated with higher perioperative morbidity but not significantly higher perioperative mortality. If concomitant pancreatectomy is anticipated, patients should be selected with extreme caution because long-term survival remains poor.

  View details for DOI 10.1245/s10434-015-4694-x

  View details for PubMedID 26148757

• Multivisceral Resection for Gastric Cancer: Results from the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Tran, T. B., Worhunsky, D. J., Norton, J. A., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Poultsides, G. A. 2015; 22: S840-S847

  Abstract

  Resection of an adjacent organ during gastrectomy for gastric cancer is occasionally necessary to achieve margin clearance. The short- and long-term outcomes of this approach remain unclear.Patients who underwent gastric cancer resection in seven U.S. academic institutions from 2000 to 2012 were evaluated to compare perioperative morbidity, mortality, and survival outcomes, stratified by the need for and type of multivisceral resection (MVR).Of 835 patients undergoing curative-intent gastrectomy, 159 (19 %) had MVR. The most common adjacent organs resected were the spleen (48 %), pancreas (27 %), liver segments 2/3 (14 %), and colon (13 %). As extent of resection increased (gastrectomy only, n = 676; MVR without pancreatectomy, n = 116; and MVR with pancreatectomy, n = 43), perioperative morbidity was higher: any complication (45, 60, 59 %, p = 0.012), major complication (17, 31, 33 %, p = 0.001), anastomotic leak (5, 11, 19 %, p < 0.001), and respiratory failure (9, 15, 22 %, p = 0.012). However, perioperative mortality did not significantly increase (30-day: 3, 4, 2 %, p = 0.74; 90-day: 6, 8, 9 %, p = 0.61). Overall survival after resection decreased as extent of resection increased (5-year: 42, 28, 6 %). After controlling for age, race, T stage, N stage, grade, margin status, perineural invasion, adjuvant therapy, and blood transfusion, MVR with pancreatectomy (HR 1.67, p = 0.044), but not MVR without pancreatectomy (HR 0.97, p = 0.759), remained an independent predictor of poor survival.In this modern, multi-institutional cohort of gastric cancer patients, multivisceral resection was associated with higher perioperative morbidity but not significantly higher perioperative mortality. If concomitant pancreatectomy is anticipated, patients should be selected with extreme caution because long-term survival remains poor.

  View details for DOI 10.1245/s10434-015-4694-x

  View details for Web of Science ID 000367288100076

• Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma? CANCER Spolverato, G., Vitale, A., Cucchetti, A., Popescu, I., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Sandroussi, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 121 (22): 3998-4006

  View details for DOI 10.1002/cncr.29619

  View details for PubMedID 26264223

• Severe acute pancreatitis in the community: confusion reigns JOURNAL OF SURGICAL RESEARCH Dua, M. M., Worhunsky, D. J., Tran, T. B., Rumma, R. T., Poultsides, G. A., Norton, J. A., Park, W. G., Visser, B. C. 2015; 199 (1): 44-50

  Abstract

  The management of acute pancreatitis (AP) has evolved through enhanced understanding of the disease. Despite several evidence-based practice guidelines for AP, our hypothesis is that many hospitals still use historical treatments rather than adhere to the current guidelines, which have demonstrated shorter hospital stays, decreased infectious complications, decreased morbidity, and decreased mortality.Seventy-eight patients transferred to our institution with AP from 2010-2014 were retrospectively studied to compare pretransfer versus posttransfer adherence to current practice guidelines. Primary measures included use of antibiotics (abx), enteral nutrition, drainage of asymptomatic pseudocysts, and interventions for necrosis in the early phase (<4 wk).Pretransfer, abx were given to 51 patients; however, posttransfer, abx were discontinued in 33 patients and started in 6 patients within 24 h of admission (pretransfer versus posttransfer abx, 51 versus 24, P < 0.001). Empiric abx for AP were used in 36 patients pretransfer versus 9 patients posttransfer (P < 0.001). Patients were initially nil per os or on total parenteral nutrition in 89%; this was reduced to 17% within 72 h by starting a diet or enteric feeds (pretransfer versus posttransfer feeding, 9 versus 65 patients, P < 0.001). Fifteen transfer patients had pseudocysts that were believed to "require drainage"; five patients received intervention but >4 wk from initial episode of AP. Pretransfer, five patients had pancreatic debridement in the early phase, which resulted in prolonged postoperative length of stay compared with eight patients requiring debridement, which were delayed (early versus late, 56 versus 16 d, P < 0.05).There is still great confusion in the treatment of AP in community hospitals. Primary principles in the care of these patients are not routinely followed despite established guidelines. Increased dissemination is required to prevent lengthy hospitalizations and long-term morbidity.

  View details for DOI 10.1016/j.jss.2015.04.054

  View details for PubMedID 25972313

• The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma ANNALS OF SURGICAL ONCOLOGY Spolverato, G., Yakoob, M. Y., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 22 (12): 4020-4028

  View details for DOI 10.1245/s10434-015-4472-9

  View details for Web of Science ID 000362513100041

  View details for PubMedID 25762481

• Locally Advanced Intrahepatic Cholangiocarcinoma: Complete Pathologic Response to Neoadjuvant Chemotherapy Followed by Left Hepatic Trisectionectomy and Caudate Lobectomy DIGESTIVE DISEASES AND SCIENCES Tran, T. B., Bal, C. K., Schaberg, K., Longacre, T. A., Chatrath, B. S., Poultsides, G. A. 2015; 60 (11): 3226-3229

  View details for DOI 10.1007/s10620-015-3640-x

  View details for Web of Science ID 000363542700012

  View details for PubMedID 25824976

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study ANNALS OF SURGERY Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632-640

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion.Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

  View details for DOI 10.1097/SLA.0000000000001455

  View details for Web of Science ID 000367999800009

• Hepato-pancreatectomy: how morbid? Results from the national surgical quality improvement project HPB Tran, T. B., Dua, M. M., Spain, D. A., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 17 (9): 763-769

  Abstract

  Simultaneous resection of both the liver and the pancreas carries significant complexity. The objective of this study was to investigate peri-operative outcomes after a synchronous hepatectomy and pancreatectomy (SHP).The American College of Surgeons National Surgical Quality Improvement Project database was queried to identify patients who underwent SHP. Resections were categorized as '< hemihepatectomy', '≥ hemihepatectomy' (hemihepatectomy and trisectionectomy), 'PD' (pancreaticoduodenectomy and total pancreatectomy) and 'distal' (distal pancreatectomy and enucleation).From 2005 to 2013, 480 patients underwent SHP. Patients were stratified based on the extent of resection: '< hemihepatectomy + distal (n = 224)', '≥ hemihepatectomy + distal' (n = 49), '< hemihepatectomy + PD' (n = 83) and '≥ hemihepatectomy + PD' (n = 24). Although the first three groups had a reasonable and comparable safety profile (morbidity 33-51% and mortality 0-6.6%), the '≥ hemihepatectomy + PD' group was associated with an 87.5% morbidity (organ space infection 58.3%, re-intubation 12.5%, reoperation 25% and septic shock 25%), 8.3% 30-day mortality and 18.2% in-hospital mortality.A synchronous hemihepatectomy (or trisectionectomy) with PD remains a highly morbid combination and should be reserved for patients who have undergone extremely cautious selection.

  View details for DOI 10.1111/hpb.12426

  View details for Web of Science ID 000359853800004

• Hepato-pancreatectomy: how morbid? Results from the national surgical quality improvement project. HPB Tran, T. B., Dua, M. M., Spain, D. A., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 17 (9): 763-769

  Abstract

  Simultaneous resection of both the liver and the pancreas carries significant complexity. The objective of this study was to investigate peri-operative outcomes after a synchronous hepatectomy and pancreatectomy (SHP).The American College of Surgeons National Surgical Quality Improvement Project database was queried to identify patients who underwent SHP. Resections were categorized as '< hemihepatectomy', '≥ hemihepatectomy' (hemihepatectomy and trisectionectomy), 'PD' (pancreaticoduodenectomy and total pancreatectomy) and 'distal' (distal pancreatectomy and enucleation).From 2005 to 2013, 480 patients underwent SHP. Patients were stratified based on the extent of resection: '< hemihepatectomy + distal (n = 224)', '≥ hemihepatectomy + distal' (n = 49), '< hemihepatectomy + PD' (n = 83) and '≥ hemihepatectomy + PD' (n = 24). Although the first three groups had a reasonable and comparable safety profile (morbidity 33-51% and mortality 0-6.6%), the '≥ hemihepatectomy + PD' group was associated with an 87.5% morbidity (organ space infection 58.3%, re-intubation 12.5%, reoperation 25% and septic shock 25%), 8.3% 30-day mortality and 18.2% in-hospital mortality.A synchronous hemihepatectomy (or trisectionectomy) with PD remains a highly morbid combination and should be reserved for patients who have undergone extremely cautious selection.

  View details for DOI 10.1111/hpb.12426

  View details for PubMedID 26058463

• Effect of Perioperative Transfusion on Recurrence and Survival after Gastric Cancer Resection: A 7-Institution Analysis of 765 Patients from the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K. 2015; 221 (3): 767-777

  View details for DOI 10.1016/j.jamcollsurg.2015.06.012

  View details for Web of Science ID 000360093800016

• Effect of Perioperative Transfusion on Recurrence and Survival after Gastric Cancer Resection: A 7-Institution Analysis of 765 Patients from the US Gastric Cancer Collaborative. Journal of the American College of Surgeons Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Staley, C. A., Maithel, S. K. 2015; 221 (3): 767-777

  Abstract

  The prognostic effect of perioperative blood transfusion on recurrence and survival in patients undergoing resection of gastric adenocarcinoma (GAC) remains controversial.All patients who underwent resection for GAC from 2000 to 2012 at the 7 institutions of the US Gastric Cancer Collaborative were identified. The effect of transfusion on recurrence-free (RFS) and overall survival (OS) in the context of adverse clinicopathologic variables was examined by univariate and multivariate regression analyses.Of 965 patients, 765 underwent curative intent R0 resection. Median follow-up was 44 months; 30-day mortalities were excluded. Median estimated blood loss (EBL) was 200 mL, and 168 patients (22%) received perioperative allogeneic blood transfusions. Transfused patients were less likely to receive adjuvant therapy (44% vs 56%; p = 0.01). Transfusion was associated with significantly decreased median RFS (13.5 vs 37.2 months, p < 0.001). Median OS was similarly decreased in patients receiving transfusions (18.6 vs 49.8 months, p < 0.001). On multivariate analysis, transfusion remained an independent risk factor for decreased RFS (hazard ratio [HR] 1.63; 95% CI 1.13 to 2.37; p = 0.010) and decreased OS (HR 1.79; 95% CI 1.21 to 2.67; p = 0.004), regardless of EBL or need for splenectomy. Timing (intraoperative vs postoperative) and volume of transfusion did not alter the negative prognostic effect of transfusion on survival.Perioperative allogeneic blood transfusion is associated with decreased RFS and OS after resection of gastric cancer, independent of adverse clinicopathologic factors. This supports the judicious use of perioperative transfusion during resection of gastric cancer.

  View details for DOI 10.1016/j.jamcollsurg.2015.06.012

  View details for PubMedID 26228017

• Pancreatectomy with vein reconstruction: technique matters HPB Dua, M. M., Tran, T. B., Klausner, J., Hwa, K. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 17 (9): 824-831

  Abstract

  A variety of techniques have been described for portal vein (PV) and/or superior mesenteric vein (SMV) resection/reconstruction during a pancreatectomy. The ideal strategy remains unclear.Patients who underwent PV/SMV resection/reconstruction during a pancreatectomy from 2005 to 2014 were identified. Medical records and imaging were retrospectively reviewed for operative details and outcomes, with particular emphasis on patency.Ninety patients underwent vein resection/reconstruction with one of five techniques: (i) longitudinal venorrhaphy (LV, n = 17); (ii) transverse venorrhaphy (TV, n = 9); (iii) primary end-to-end (n = 28); (iv) patch venoplasty (PV, n = 17); and (v) interposition graft (IG, n = 19). With a median follow-up of 316 days, thrombosis was observed in 16/90 (18%). The rate of thrombosis varied according to technique. All patients with primary end-to-end or TV remained patent. LV, PV and IG were all associated with significant rates of thrombosis (P = 0.001 versus no thrombosis). Comparing thrombosed to patent, there were no differences with respect to pancreatectomy type, pre-operative knowledge of vein involvement and neoadjuvant therapy. Prophylactic aspirin was used in 69% of the total cohort (66% of patent, 81% of thrombosed) and showed no protective benefit.Primary end-to-end and TV have superior patency than the alternatives after PV/SMV resection and should be the preferred techniques for short (<3 cm) reconstructions.

  View details for DOI 10.1111/hpb.12463

  View details for Web of Science ID 000359853800013

  View details for PubMedCentralID PMC4557658

• Pancreatectomy with vein reconstruction: technique matters. HPB Dua, M. M., Tran, T. B., Klausner, J., Hwa, K. J., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 17 (9): 824-831

  Abstract

  A variety of techniques have been described for portal vein (PV) and/or superior mesenteric vein (SMV) resection/reconstruction during a pancreatectomy. The ideal strategy remains unclear.Patients who underwent PV/SMV resection/reconstruction during a pancreatectomy from 2005 to 2014 were identified. Medical records and imaging were retrospectively reviewed for operative details and outcomes, with particular emphasis on patency.Ninety patients underwent vein resection/reconstruction with one of five techniques: (i) longitudinal venorrhaphy (LV, n = 17); (ii) transverse venorrhaphy (TV, n = 9); (iii) primary end-to-end (n = 28); (iv) patch venoplasty (PV, n = 17); and (v) interposition graft (IG, n = 19). With a median follow-up of 316 days, thrombosis was observed in 16/90 (18%). The rate of thrombosis varied according to technique. All patients with primary end-to-end or TV remained patent. LV, PV and IG were all associated with significant rates of thrombosis (P = 0.001 versus no thrombosis). Comparing thrombosed to patent, there were no differences with respect to pancreatectomy type, pre-operative knowledge of vein involvement and neoadjuvant therapy. Prophylactic aspirin was used in 69% of the total cohort (66% of patent, 81% of thrombosed) and showed no protective benefit.Primary end-to-end and TV have superior patency than the alternatives after PV/SMV resection and should be the preferred techniques for short (<3 cm) reconstructions.

  View details for DOI 10.1111/hpb.12463

  View details for PubMedID 26223388

• Non-functional neuroendocrine tumors of the pancreas: Advances in diagnosis and management. World journal of gastroenterology Cloyd, J. M., Poultsides, G. A. 2015; 21 (32): 9512-9525

  Abstract

  Nonfunctional neuroendocrine tumors of the pancreas (NF-PNETs) are a heterogeneous group of neoplasms. Although rare, the incidence of NF-PNETs is increasing significantly. The classification of PNETs has evolved over the past decades and is now based on a proliferation grading system. While most NF-PNETs are slow growing, tumors with more aggressive biology may become incurable once they progress to unresectable metastatic disease. Tumors of higher grade can be suspected preoperatively based on the presence of calcifications, hypoenhancement on arterial phase computed tomography, positron emission technology avidity and lack of octreotide scan uptake. Surgery is the only curative treatment and is recommended for most patients for whom complete resection is possible. Liver-directed therapies (thermal ablation, transarterial embolization) can be useful in controlling unresectable hepatic metastatic disease. In the presence of unresectable progressive disease, somatostatin analogues, everolimus and sunitinib can prolong progression-free survival. This article provides a comprehensive review of NF-PNETs with special emphasis on recent advances in diagnosis and management.

  View details for DOI 10.3748/wjg.v21.i32.9512

  View details for PubMedID 26327759

  View details for PubMedCentralID PMC4548112

• Impact of Complications on Long-Term Survival After Resection of Intrahepatic Cholangiocarcinoma CANCER Spolverato, G., Yakoob, M. Y., Kim, Y., Alexandrescu, S., Marques, H. P., Lamelas, J., Aldrighetti, L., Gamblin, T. C., Maithel, S. K., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 121 (16): 2730-2739

  Abstract

  The impact of postoperative complications on the long-term outcomes of patients undergoing surgery for cancer is unclear. The objective of the current study was to define the incidence of complications among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) and identify the association between morbidity and long-term outcomes.A total of 583 patients undergoing surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. The association between the occurrence and severity of postoperative complications on long-term survival was analyzed.The median age of the patients was 59.9 years and the majority of patients were male (52.3%). A total of 91 patients (15.6%) and 153 patients (26.2%) developed a major and minor postoperative complication, respectively; 18 patients (3.5%) died within 90 days of surgery. Median, 1-year, 3-year, and 5-year recurrence-free survival were 10.0 months, 43.3%, 16.7%, and 11.1%, respectively. Postoperative complications (hazard ratio [HR], 1.37, 95% confidence interval [95% CI], 1.08-1.73 [P = .01]) and severity of complications (major vs none: HR, 1.55; 95% CI, 1.14-2.11 [P = .01]; minor vs none: HR, 1.30; 95% CI, 0.99-1.70 [P = .06]) independently predicted shorter recurrence-free survival. Median, 1-year, 3-year, and 5-year overall survival was 27.8 months, 76.8%, 39.0%, and 23.4%, respectively. Postoperative complications (HR, 1.64; 95% CI, 1.30-2.08 [P<.001]) and severity of complications (major vs none: HR, 1.79; 95% CI, 1.31-2.44 [P<.001]; minor vs none: HR, 1.50; 95% CI, 1.15-1.95 [P<.01]) independently predicted shorter overall survival.Postoperative complications were found to be independent predictors of worse long-term outcomes. The prevention and management of postoperative complications is crucial to increase both short-term and long-term survival. Cancer 2015;121:2730-2739. © 2015 American Cancer Society.

  View details for DOI 10.1002/cncr.29419

  View details for Web of Science ID 000359190400013

  View details for PubMedID 25903409

• An assessment of feeding jejunostomy tube placement at the time of resection for gastric adenocarcinoma: A seven-institution analysis of 837 patients from the US gastric cancer collaborative JOURNAL OF SURGICAL ONCOLOGY Dann, G. C., Squires, M. H., Postlewait, L. M., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 112 (2): 195-202

  View details for DOI 10.1002/jso.23983

  View details for Web of Science ID 000360094300013

• The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative JOURNAL OF SURGICAL ONCOLOGY Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 112 (2): 203-207

  View details for DOI 10.1002/jso.23971

  View details for Web of Science ID 000360094300014

• Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Gholami, S., Janson, L., Worhunsky, D. J., Tran, T. B., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S. M., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Efron, B., Norton, J. A., Poultsides, G. A. 2015; 221 (2): 291-299

  Abstract

  Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection.We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased.The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.

  View details for DOI 10.1016/j.jamcollsurg.2015.04.024

  View details for Web of Science ID 000358384400013

• Prognostic relevance of lymph node ratio and total lymph node count for small bowel adenocarcinoma SURGERY Tran, T. B., Qadan, M., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C. 2015; 158 (2): 486-493

  Abstract

  Nodal metastasis is a known prognostic factor for small bowel adenocarcinoma. The goals of this study were to evaluate the number of lymph nodes (LNs) that should be retrieved and the impact of lymph node ratio (LNR) on survival.Surveillance, Epidemiology, and End Results was queried to identify patients with small bowel adenocarcinoma who underwent resection from 1988 to 2010. Survival was calculated with the Kaplan-Meier method. Multivariate analysis identified predictors of survival.A total of 2,772 patients underwent resection with at least one node retrieved, and this sample included equal numbers of duodenal (n = 1,387) and jejunoileal (n = 1,386) adenocarcinomas. There were 1,371 patients with no nodal metastasis (N0, 49.4%), 928 N1 (33.5%), and 474 N2 (17.1%). The median numbers of LNs examined for duodenal and jejunoileal cancers were 9 and 8, respectively. Cut-point analysis demonstrated that harvesting at least 9 for jejunoileal and 5 LN for duodenal cancers resulted in the greatest survival difference. Increasing LNR at both sites was associated with decreased overall median survival (LNR = 0, 71 months; LNR 0-0.02, 35 months; LNR 0.21-0.4, 25 months; and LNR >0.4, 16 months; P < .001). Multivariate analysis confirmed number of LNs examined, T-stage, LN positivity, and LNR were independent predictors of survival.LNR has a profound impact on survival in patients with small bowel adenocarcinoma. To achieve adequate staging, we recommend retrieving a minimum of 5 LN for duodenal and 9 LN for jejunoileal adenocarcinomas.

  View details for DOI 10.1016/j.surg.2015.03.048

  View details for Web of Science ID 000358108500023

• Neutrophil-lymphocyte and platelet-lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma JOURNAL OF SURGICAL ONCOLOGY Bagante, F., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2015; 112 (2): 164-172

  View details for DOI 10.1002/jso.23982

  View details for Web of Science ID 000360094300008

• Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway BMC CANCER Drakaki, A., Hatziapostolou, M., Polytarchou, C., Vorvis, C., Poultsides, G. A., Souglakos, J., Georgoulias, V., Iliopoulos, D. 2015; 15

  View details for DOI 10.1186/s12885-015-1562-9

  View details for Web of Science ID 000358353900003

• Is Hepatic Resection for Large or Multifocal Intrahepatic Cholangiocarcinoma Justified? Results from a Multi-Institutional Collaboration ANNALS OF SURGICAL ONCOLOGY Spolverato, G., Kim, Y., Alexandrescu, S., Popescu, I., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Miura, J., Maithel, S. K., Squires, M. H., Pulitano, C., Sandroussi, C., Mentha, G., Bauer, T. W., Newhook, T., Shen, F., Poultsides, G. A., Marsh, J. W., Pawlik, T. M. 2015; 22 (7): 2218-2225

  Abstract

  The role of surgical resection for patients with large or multifocal intrahepatic cholangiocarcinoma (ICC) remains unclear. This study evaluated the long-term outcome of patients who underwent hepatic resection for large (≥7 cm) or multifocal (≥2) ICC.Between 1990 and 2013, 557 patients who underwent liver resection for ICC were identified from a multi-institutional database. Clinicopathologic characteristics, operative details, and long-term survival data were evaluated.Of the 557 patients, 215 (38.6 %) had a small, solitary ICC (group A) and 342 (61.4 %) had a large or multifocal ICC (group B). The patients in group B underwent an extended hepatectomy more frequently (16.9 vs. 30.4 %; P < 0.001). At the final pathology exam, the patients in group B were more likely to show evidence of vascular invasion (22.5 vs. 38.5 %), direct invasion of contiguous organs (6.5 vs. 12.9 %), and nodal metastasis (13.3 vs. 21.0 %) (all P < 0.05). Interestingly, the incidences of postoperative complications (39.3 vs. 46.8 %) and hospital mortality (1.1 vs. 3.7 %) were similar between the two groups (both P > 0.05). The group A patients had better rates for 5-year overall survival (OS) (30.5 vs. 18.7 %; P < 0.05) and disease-free survival (DFS) (22.6 vs. 8.2 %; P < 0.05) than the group B patients. For the patients in group B, the factors associated with a worse OS included more than three tumor nodules [hazard ratio (HR), 1.56], nodal metastasis (HR, 1.47), and poor differentiation (HR, 1.48).Liver resection can be performed safely for patients with large or multifocal ICC. The long-term outcome for these patients can be stratified on the basis of a prognostic score that includes tumor number, nodal metastasis, and poor differentiation.

  View details for DOI 10.1245/s10434-014-4223-3

  View details for Web of Science ID 000355748300017

  View details for PubMedID 25354576

• Readmission After Liver Resection for Intrahepatic Cholangiocarcinoma: a Multi-Institutional Analysis JOURNAL OF GASTROINTESTINAL SURGERY Spolverato, G., Maqsood, H., Vitale, A., Alexandrescu, S., Marques, H. P., Aldrighetti, L., Gamblin, T. C., Pulitano, C., Bauer, T. W., Shen, F., Poultsides, G., Maithel, S., Marsh, J. W., Pawlik, T. M. 2015; 19 (7): 1334-1341

  Abstract

  The objective of the current study was to define the incidence of 30-day readmission after hepatic resection for intrahepatic cholangiocarcinoma (ICC). In particular, we sought to identify risk factors associated with a higher risk of readmission among patients undergoing resection for ICC.Patients who underwent hepatic resection for ICC at 12 major hepatobiliary centers in the USA, Europe, Australia, and Asia between 1990 and 2013 were identified. Thirty-day readmission and clinicopathologic characteristics associated with higher risk of readmission were examined.Among 602 patients, 401 (68.3 %) patients underwent a major hepatectomy and 256 (43.3 %) experienced at least one post-operative complication. Overall 30-day readmission was 7.8 % (n = 47). Risk factors associated with readmission included pre-operative jaundice (odds ratio (OR) 2.45) and the presence of a major complication (OR 3.38). In fact, 95.7 % of readmitted patients had experienced a post-operative complication versus only 38.8 % of non-readmitted patients (P < 0.001). Among patients who were readmitted, repeat hospitalization was associated with a median LOS of 6.5 days (interquartile range (IQR) 4.0-11.5) and one patient died during readmission.Readmission after hepatic resection for ICC occurred in 1 in 13 patients. Patients with pre-operative jaundice and those who experienced a complication had over a threefold higher risk of being readmitted.

  View details for DOI 10.1007/s11605-015-2826-z

  View details for Web of Science ID 000356458900016

  View details for PubMedID 25903853

• Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts. American journal of gastroenterology Zikos, T., Pham, K., Bowen, R., Chen, A. M., Banerjee, S., Friedland, S., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C., Park, W. G. 2015; 110 (6): 909-914

  Abstract

  Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip.Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed.Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00).Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

  View details for DOI 10.1038/ajg.2015.148

  View details for PubMedID 25986360

• Conditional Probability of Long-term Survival After Liver Resection for Intrahepatic Cholangiocarcinoma A Multi-institutional Analysis of 535 Patients JAMA SURGERY Spolverato, G., Kim, Y., Ejaz, A., Alexandrescu, S., Marques, H., Aldrighetti, L., Gamblin, C., Pulitano, C., Bauer, T. W., Shen, F., Sandroussi, C., Poultsides, G., Maithel, S. K., Pawlik, T. M. 2015; 150 (6): 538-545

  Abstract

  Whereas conventional actuarial overall survival (OS) estimates rely exclusively on static factors determined around the time of surgery, conditional survival (CS) estimates take into account the years that a patient has already survived.To define the CS of patients following liver resection for intrahepatic cholangiocarcinoma (ICC).Between January 1, 1990, and December 31, 2013, a total of 535 patients who underwent resection of ICC were identified from an international multi-institutional database. In this retrospective international study conducted from January to June 2014, clinicopathological characteristics, operative details, and long-term survival data were analyzed. Conditional survival estimates were calculated as the probability of survival for an additional 3 years.Resection of ICC.Overall survival and CS.While actuarial OS decreased over time from 39% at 3 years to 16% at 8 years (P = .002), the 3-year CS (CS3) increased over time among those patients who survived. The CS3 at 5 years-the probability of surviving to postoperative year 8 after having already survived to postoperative year 5-was 65% compared with 8-year OS of 16% (P = .002). Factors that were associated with worse OS included larger tumor size (hazard ratio [HR], 1.02; 95% CI, 1.00-1.05; P = .05), multifocal disease (HR, 1.49; 95% CI, 1.19-1.86; P = .01), lymph node metastasis (HR, 2.21; 95% CI, 1.67-2.93; P < .01), and vascular invasion (HR, 1.39; 95% CI, 1.10-1.75; P = .006). The calculated CS3 exceeded the actuarial survival for all high-risk subgroups. For example, patients with lymph node metastasis had an actuarial OS of 11% at 6 years vs a CS3 of 49% at 3 years (Δ38%). Similarly, patients with vascular invasion had an actuarial OS of 15% at 6 years compared with a CS3 of 50% at 3 years (Δ35%).Conditional survival estimates may provide critical quantitative information about the changing probability of survival over time among patients undergoing liver resection for ICC. Therefore, such estimates can be of significant value to patients and health care professionals.

  View details for DOI 10.1001/jamasurg.2015.0219

  View details for Web of Science ID 000356615400011

  View details for PubMedID 25831462

• Presentation and Clinical Outcomes of Choledochal Cysts in Children and Adults A Multi-institutional Analysis JAMA SURGERY Soares, K. C., Kim, Y., Spolverato, G., Maithel, S., Bauer, T. W., Marques, H., Sobral, M., Knoblich, M., Tran, T., Aldrighetti, L., Jabbour, N., Poultsides, G. A., Gamblin, T. C., Pawlik, T. M. 2015; 150 (6): 577-584

  Abstract

  Choledochal cysts (CCs) are rare, with risk of infection and cancer.To characterize the natural history, management, and long-term implications of CC disease.A total of 394 patients who underwent resection of a CC between January 1, 1972, and April 11, 2014, were identified from an international multi-institutional database. Patients were followed up through September 27, 2014. Clinicopathologic characteristics, operative details, and outcome data were analyzed from May 1, 2014, to October 14, 2014.Resection of CC.Management, morbidity, and overall survival.Among 394 patients, there were 135 children (34.3%) and 318 women (80.7%). Adults were more likely to present with abdominal pain (71.8% vs 40.7%; P < .001) and children were more likely to have jaundice (31.9% vs 11.6%; P < .001). Preoperative interventions were more commonly performed in adults (64.5% vs 31.1%; P < .001), including endoscopic retrograde pancreatography (55.6% vs 27.4%; P < .001), percutaneous transhepatic cholangiography (17.4% vs 5.9%; P < .001), and endobiliary stenting (18.1% vs 4.4%; P < .001)). Type I CCs were more often seen in children vs adults (79.7% vs 64.9%; P = .003); type IV CCs predominated in the adult population (23.9% vs 12.0%; P = .006). Extrahepatic bile duct resection with hepaticoenterostomy was the most frequently performed procedure in both age groups (80.3%). Perioperative morbidity was higher in adults (35.1% vs 16.3%; P < .001). On pathologic examination, 10 patients (2.5%) had cholangiocarcinoma. After a median follow-up of 28 months, 5-year overall survival was 95.5%. On follow-up, 13 patients (3.3%), presented with biliary cancer.Presentation of CC varied between children and adults, and resection was associated with a degree of morbidity. Although concomitant cancer was uncommon, it occurred in 3.0% of the patients. Long-term surveillance is indicated given the possibility of future development of biliary cancer after CC resection.

  View details for DOI 10.1001/jamasurg.2015.0226

  View details for Web of Science ID 000356615400021

  View details for PubMedID 25923827

• Extracorporeal Pringle for laparoscopic liver resection SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Dua, M. M., Worhunsky, D. J., Hwa, K., Poultsides, G. A., Norton, J. A., Visser, B. C. 2015; 29 (6): 1348-1355

  Abstract

  A primary concern during laparoscopic liver resection (lapLR) is hemorrhage during parenchymal transection. Intermittent pedicle clamping is an effective method to minimize blood loss during open liver surgery; however, inflow occlusion techniques are challenging to reproduce during laparoscopy. The purpose of this study is to describe the safety and efficacy of a facile method for Pringle maneuver during lapLR.154 patients who underwent lapLR from 2007 to 2013 were retrospectively reviewed. For Pringle, the hepatoduodenal ligament is encircled with an umbilical tape which is externalized through a flexible Rumel tourniquet running alongside a port used for the operation. The internal end of the catheter is close to the pedicle and the external end is extracorporeal, allowing for easy external occlusion. Patients who underwent Pringle Maneuver (PM, n = 88) were compared to patients who had "No Occlusion" (NO, n = 66) with respect to patient characteristics, operative outcomes, changes in postoperative liver function, and complications.Annual placement of the tourniquet and vascular occlusion increased from 35.7 to 82.8 % (p = 0.004) and 21.4 to 62.1 % (p = 0.02), respectively. Median occlusion time was 24 min (IQR 15-34.3, min 5, max 70). Peak transaminase levels were comparable between groups (AST 298 ± 32 vs 405 ± 47 U/L, p = 0.15; ALT 272 ± 27 vs 372 ± 34 U/L, p = 0.14, NO and PM, respectively). Postoperative transaminase and bilirubin levels for both groups were not significantly different with similar recovery to baseline. Subgroup analysis of cirrhotic patients who underwent Pringle demonstrated similar transaminase profiles compared to non-cirrhotic patients. There were two conversions (1.3 %) and postoperative 30-day mortality was 0.65 %.Extracorporeal tourniquet placement in lapLR is a quick and safe method of gaining control for inflow occlusion. Routine adoption of laparoscopic Pringle maneuver facilitates low conversion rates without liver injury.

  View details for DOI 10.1007/s00464-014-3801-6

  View details for PubMedID 25159645

• A Nomogram to Predict Overall Survival and Disease-Free Survival After Curative Resection of Gastric Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Kim, Y., Spolverato, G., Ejaz, A., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D., Worhunsky, D., Saunders, N., Levine, E. A., Cho, C. S., Maithel, S. K., Pawlik, T. M. 2015; 22 (6): 1828-1835

  Abstract

  The American Cancer Society projects there will be over 22,000 new cases, resulting in nearly 11,000 deaths, related to gastric adenocarcinoma in the US in 2014. The aim of the current study was to find clinicopathologic variables associated with disease-free survival (DFS) and overall survival (OS) following curative resection of gastric adenocarcinoma, and create a nomogram for individual risk prediction.A nomogram to predict DFS and OS following surgical resection of gastric adenocarcinoma was constructed using a multi-institutional cohort of patients who underwent surgery for primary gastric adenocarcinoma at seven major institutions in the US between January 2000 and August 2013. Discrimination and calibration of the nomogram were tested by C-statistic, Kaplan-Meier curves, and calibration plots.A total of 719 patients who underwent surgery for primary gastric adenocarcinoma were included in the study. Using the backward selection of clinically relevant variables with Akaike information criteria, age, sex, tumor site, depth of invasion, and lymph node ratio (LNR) were selected as factors predictive of OS, while age, tumor site, depth of invasion, and LNR were incorporated in the prediction of DFS. A nomogram was constructed to predict OS and DFS using these variables. Discrimination and calibration of the nomogram revealed good predictive abilities (C-index, DFS 0.711; OS 0.702).Independent predictors of recurrence and death following surgery for primary gastric adenocarcinoma were used to create a nomogram to predict DFS and OS. The nomogram was able to stratify patients into prognostic groups, and performed well on internal validation.

  View details for DOI 10.1245/s10434-014-4230-4

  View details for Web of Science ID 000354226600014

  View details for PubMedID 25388061

• Predictive Factors for Surgery Among Patients with Pancreatic Cysts in the Absence of High-Risk Features for Malignancy JOURNAL OF GASTROINTESTINAL SURGERY Quan, S. Y., Visser, B. C., Poultsides, G. A., Norton, J. A., Chen, A. M., Banerjee, S., Friedland, S., Park, W. G. 2015; 19 (6): 1101-1105

  Abstract

  Without a reliable biopsy technique for pancreatic cysts, consensus-based guidelines are used to guide surgical utilization. The primary objective of this study was to characterize the proportion of operations performed outside of these guidelines.A 5-year retrospective review between July 1, 2007, and June 30, 2012, was performed of consecutive patients seen at a single tertiary medical center for a pancreatic cyst. Manual chart review for relevant clinical variables and cyst characteristics was performed.During this period, 148 patients underwent surgery, and of these, 23 (16 %) patients had no high-risk criteria by the 2006 Sendai criteria. None of these harbored high-grade dysplastic or cancerous lesions. A high cyst carcinoembryonic antigen (CEA) level (35 %), patient anxiety (26 %), and physician concern (22 %) were explicit reasons to proceed to surgery. An elevated cyst CEA level >192 ng/ml was the most significant predictor (OR 5.14 (95 % confidence interval (CI) 1.47-18.0) for surgery without high-risk criteria.A high cyst CEA level was significantly associated with the decision to operate outside of consensus-based guidelines. The misuse of cyst CEA in the management of pancreatic cysts negatively impacts patient anxiety, increases physician uncertainty, and leads to surgery with minimal benefit.

  View details for DOI 10.1007/s11605-015-2786-3

  View details for PubMedID 25749855

• Leiomyosarcoma: One Disease or Distinct Biologic Entities Based on Site of Origin? JOURNAL OF SURGICAL ONCOLOGY Worhunsky, D. J., Gupta, M., Gholami, S., Tran, T. B., Ganjoo, K. N., van de Rijn, M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 111 (7): 808-812

  Abstract

  Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin.Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years.Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS.

  View details for DOI 10.1002/jso.23904

  View details for PubMedID 25920434

• Impact of body mass index on perioperative outcomes and survival after resection for gastric cancer JOURNAL OF SURGICAL RESEARCH Ejaz, A., Spolverato, G., Kim, Y., Poultsides, G. A., Fields, R. C., Bloomston, M., Cho, C. S., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 195 (1): 74-82

  Abstract

  Among patients undergoing resection for gastric cancer, the impact of body mass index (BMI) on outcomes is not well understood. We sought to define the impact of non-normal BMI on short- and long-term outcomes after gastric cancer resection.We identified 775 patients who underwent gastrectomy for adenocarcinoma between 2000 and 2012 from the multi-institutional US Gastric Cancer Collaborative. Clinicopathologic characteristics, operative details, and oncologic outcomes were collected, and patients were stratified according to BMI.Most patients in the cohort were classified as having normal BMI (n = 338, 43.6%), followed by overweight (n = 229, 29.6%), obese (n = 153, 19.7%), and underweight (n = 55, 7.1%). After stratifying by BMI, there were no significant differences in the incidence of postoperative blood transfusions, perioperative morbidity, postoperative infectious complications, length of stay, perioperative 30-d in-hospital death, or readmission across groups (all P > 0.05). BMI did not impact overall or recurrence-free survival after stratifying by stage (all P > 0.05). However, underweight patients with low preoperative albumin levels had worse overall survival (OS) compared with that of patients of normal BMI.BMI did not impact perioperative morbidity, recurrence-free, or OS in patients undergoing gastric resection for adenocarcinoma. Underweight patients with BMI <18.5 kg/m(2) and low preoperative albumin levels, however, had a significantly decreased OS after gastrectomy for cancer. These high-risk patients should have their nutritional status optimized both before and after gastrectomy in an attempt to modify this risk factor and, in turn, achieve better outcomes.

  View details for DOI 10.1016/j.jss.2014.12.048

  View details for Web of Science ID 000352139900011

  View details for PubMedID 25619462

• Minimally Invasive Resection of Choledochal Cyst: a Feasible and Safe Surgical Option JOURNAL OF GASTROINTESTINAL SURGERY Margonis, G. A., Spolverato, G., Kim, Y., Marques, H., Poultsides, G., Maithel, S., Aldrighetti, L., Bauer, T. W., Jabbour, N., Gamblin, T. C., Soares, K., Pawlik, T. M. 2015; 19 (5): 858-865

  Abstract

  The use of minimally invasive surgery (MIS) for choledochal cyst (CC) has not been well documented. We sought to define the overall utilization and outcomes associated with the use of the open versus MIS approach for CC. We examined the factors associated with receipt of MIS for CC, as well as characterized perioperative and long-term outcomes following open versus MIS for CC.Between 1972 and 2014, a total of 368 patients who underwent resection for CC were identified from an international, multicenter database. A 2:1 propensity score matching was used to create comparable cohorts of patients to assess the effect of MIS on short-term outcomes.Three hundred thirty-two patients had an open procedure, whereas 36 patients underwent an MIS approach. Children were more likely to be treated with a MIS approach (children, 24.0 % vs. adults, 2.1 %; P<0.001). Conversely, patients who had any medical comorbidity were less likely to undergo MIS surgery (open, 26.2 % vs. MIS, 2.8 %; P=0.002). In the propensity-matched cohort, MIS resection was associated with decreased length of stay (open, 7 days vs. MIS, 5 days), lower estimated blood loss (open, 50 mL vs. MIS, 17.5 mL), and longer operative time (open, 237 min vs. MIS, 301 min) compared with open surgery (all P<0.05). The overall and degree of complication did not differ between the open (grades I-II, n=13; grades III-IV, n=15) versus MIS (grades I-II, n=5; grades III-IV, n=5) cohorts (P=0.85). Five-year overall survival was 98.6 % (open, 98.0 % vs. MIS, 100.0 %; P=0.45); no patient who underwent MIS developed a subsequent cholangiocarcinoma.MIS resection of CC was demonstrated to be a feasible and safe approach with acceptable short-term outcomes in the pediatric population. MIS for benign CC disease was associated with similar perioperative morbidity but a shorter length of stay and a lower blood loss when compared with open resection.

  View details for DOI 10.1007/s11605-014-2722-y

  View details for Web of Science ID 000353198400009

  View details for PubMedID 25519084

• Is It Time to Abandon the 5-cm Margin Rule During Resection of Distal Gastric Adenocarcinoma? A Multi-Institution Study of the U.S. Gastric Cancer Collaborative. Annals of surgical oncology Squires Iii, M. H., Kooby, D. A., Poultsides, G. A., Pawlik, T. M., Weber, S. M., Schmidt, C. R., Votanopoulos, K. I., Fields, R. C., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Bloomston, M., Winslow, E. R., Russell, M. C., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 22 (4): 1243-1251

  Abstract

  A proximal margin distance of 5 cm is advocated for resection of gastric adenocarcinoma (GAC). We assessed the prognostic value of proximal margin (PM) distance on survival outcomes after resection of distal GAC.All patients who underwent resection of distal GAC (antrum/body) from 2000 to 2012 at seven institutions of the U.S. Gastric Cancer Collaborative were included. Patients with positive distal margins or macroscopic residual disease were excluded. The prognostic value of PM distance (assessed in 0.5-cm increments) on overall (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier and multivariate regression analysis.A total of 465 patients underwent resection of distal GAC. Of these, 435 had R0 resections; 30 patients had a positive PM. 143 patients had stage I, and 322 had stage II-III tumors. Median follow-up was 44 months. Average PM distance was 4.8 cm. Median OS for patients with PM of 3.1-5.0 cm (n = 110) was superior to patients with PM ≤ 3.0 cm (n = 176) (48.1 vs. 29.3 months; p = 0.01), while a margin >5.0 cm (n = 179) offered equivalent survival to PM 3.1-5.0 cm (50.6 months, p = 0.72). The prognostic value of margin distance was stage specific. On multivariate analysis of stage I patients, PM 3.1-5.0 cm remained associated with improved OS [hazard ratio (HR), 0.16; 95 % confidence interval (95 % CI), 0.04-0.60; p = 0.01]. In stage II-III, neither PM 3.1-5.0 cm nor PM > 5.0 cm was significantly associated with OS; OS was dictated by T stage and nodal involvement.The prognostic value of proximal margin distance after resection of distal gastric cancer appears stage specific. In stage I, a 3.1- to 5.0-cm proximal margin is associated with the same improved OS as a > 5.0-cm margin. In stage II-III disease, other adverse pathologic factors more strongly impact survival than proximal margin distance.

  View details for DOI 10.1245/s10434-014-4138-z

  View details for PubMedID 25316491

• Clinicopathological features and prognosis of gastric cardia adenocarcinoma: A multi-institutional U.S. study. Journal of surgical oncology Amini, N., Spolverato, G., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 111 (3): 285-292

  Abstract

  Potential differences in presentation and outcome of patients with gastric cardia adenocarcinoma (GCA) and non-cardia adenocarcinoma may exist. The aim of the present study was to compare the clinicopathological characteristics and the prognosis of GCA versus non-cardia adenocarcinoma.Patients with gastric adenocarcinoma who underwent gastric resection between 2000-2012 were identified. Clinicopathological characteristics and outcomes were analyzed based on tumor site using a 1:2 matched-control, as well as a multivariable Cox model.Among 743 patients, 80 (10.7%) patients were diagnosed with GCA. Patients with GCA were more likely to have intestinal tumor type (GCA: 80.4% versus non-cardia: 64.2%, P = 0.04) or advanced AJCC T stage tumors (GCA 71.8% versus non-cardia 59.2%, P = 0.03). GCA patients more likely underwent a total gastrectomy (GCA: 85.7% vs. non-cardia: 39.8%) and had a longer length-of-stay (GCA: 10 days vs. non-cardia: 8 days) (both P < 0.05). Outcomes in early stage I patients were worse among GCA (disease-free survival, 44.2%; overall survival, 42.3%) versus non-GCA (disease-free survival, 60.8%; overall survival, 63.0%) patients(both P < 0.05).In general, disease-free survival and overall survival were similar between patients with GCA versus non-cardia adenocarcinoma. However, long-term outcome was worse among patients with GCA and early stage disease. J. Surg. Oncol. 2015 111:285-292. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.23799

  View details for PubMedID 25308915

• Compliance With Gastric Cancer Guidelines is Associated With Improved Outcomes. Journal of the National Comprehensive Cancer Network Worhunsky, D. J., Ma, Y., Zak, Y., Poultsides, G. A., Norton, J. A., Rhoads, K. F., Visser, B. C. 2015; 13 (3): 319-325

  Abstract

  Limited data are available on the implementation and effectiveness of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer.We sought to assess rates of compliance with NCCN Guidelines, specifically stage-specific therapy during the initial episode of care, and to determine its impact on outcomes.The California Cancer Registry was used to identify cases of gastric cancer from 2001 to 2006. Logistic regression and Cox proportional hazard models were used to predict guideline compliance and the adjusted hazard ratio for mortality. Patients with TNM staging or summary stage (SS) were also analyzed separately.Compliance with NCCN Guidelines occurred in just 45.5% of patients overall. Patients older than 55 years were less likely to receive guideline-compliant care, and compliance was associated with a median survival of 20 versus 7 months for noncompliant care (P<.001). Compliant care was also associated with a 55% decreased hazard of mortality (P<.001). Further analysis revealed that 50% of patients had complete TNM staging versus an SS, and TNM-staged patients were more likely to receive compliant care (odds ratio, 1.59; P<.001). TNM-staged patients receiving compliant care had a median survival of 25.3 months compared with 15.1 months for compliant SS patients.Compliance with NCCN Guidelines and stage-specific therapy at presentation for the treatment of patients with gastric cancer was poor, which was a significant finding given that compliant care was associated with a 55% reduction in the hazard of death. Additionally, patients with TNM-staged cancer were more likely to receive compliant care, perhaps a result of having received more intensive therapy. Combined with the improved survival among compliant TNM-staged patients, these differences have meaningful implications for health services research.

  View details for PubMedID 25736009

• Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform ONCOTARGET Kidess, E., Heirich, K., Wiggin, M., Vysotskaia, V., Visser, B. C., Marziali, A., Wiedenmann, B., Norton, J. A., Lee, M., Jeffrey, S. S., Poultsides, G. A. 2015; 6 (4): 2549-2561

  Abstract

  Circulating tumor DNA (ctDNA) holds promise as a non-invasive means for tumor monitoring in solid malignancies. Assays with high sensitivity and multiplexed analysis of mutations are needed to enable broad application.We developed a new assay based on sequence-specific synchronous coefficient of drag alteration (SCODA) technology, which enriches for mutant DNA to achieve high sensitivity and specificity. This assay was applied to plasma and tumor tissue from non-metastatic and metastatic colorectal cancer (CRC) patients, including patients undergoing surgical resection for CRC liver metastases.Across multiple characterization experiments, the assay demonstrated a limit of detection of 0.001% (1 molecule in 100,000) for the majority of the 46 mutations in the panel. In CRC patient samples (n=38), detected mutations were concordant in tissue and plasma for 93% of metastatic patients versus 54% of non-metastatic patients. For three patients, ctDNA identified additional mutations not detected in tumor tissue. In patients undergoing liver metastatectomy, ctDNA anticipated tumor recurrence earlier than carcinoembryonic antigen (CEA) value or imaging.The multiplexed SCODA mutation enrichment and detection method can be applied to mutation profiling and quantitation of ctDNA, and is likely to have particular utility in the metastatic setting, including patients undergoing metastatectomy.

  View details for PubMedID 25575824

• Does the extent of resection impact survival for duodenal adenocarcinoma? Analysis of 1,611 cases. Annals of surgical oncology Cloyd, J. M., Norton, J. A., Visser, B. C., Poultsides, G. A. 2015; 22 (2): 573-580

  Abstract

  Because duodenal adenocarcinoma (DA) is relatively rare, few studies have investigated the impact of resection type on long-term outcomes.The Surveillance, Epidemiology, and End Results database was used to identify all patients between 1988 and 2010 with DA. Patients were divided into two groups based on the type of surgery received: simple resection (SR), defined as a simple removal of the primary site, and radical resection (RR), defined as removal of the primary site with a resection in continuity with other organs. Differences in disease-specific survival (DSS) and overall survival (OS) were compared.Of the 1,611 patients included, 746 (46.3 %) underwent SR and 865 (53.7 %) underwent RR. As expected, patients undergoing RR were more likely to present with poorly differentiated and large tumors, as well as advanced stage disease. Despite greater lymph node (LN) retrieval (11.0 vs. 6.8; p < 0.0001), RR was not associated with improved survival (5-year DSS and OS rates of 52.8 and 41.3 % for SR vs. 48.8 and 37.6 % for RR; p > 0.05). On univariate Cox proportional hazards regression analysis, the type of surgery was not associated with OS (odds ratio [OR] 0.98; 95 % confidence interval [CI] 0.87-1.11). Increasing TNM stages, tumor grade, fewer LNs removed, LN ratio, and absence of radiation were associated with worse survival. After controlling for confounding factors, type of surgery still did not influence OS (OR 1.11; 95 % CI 0.97-1.27).Radical resection (e.g., in the form of pancreaticoduodenectomy) does not appear to impact survival compared with simple segmental resection for DA.

  View details for DOI 10.1245/s10434-014-4020-z

  View details for PubMedID 25160736

• Esophageal and Esophagogastric Junction Cancers, Version 1.2015 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ajani, J. A., D'Amico, T. A., Almhanna, K., Bentrem, D. J., Besh, S., Chao, J., Das, P., Denlinger, C., Fanta, P., Fuchs, C. S., Gerdes, H., Glasgow, R. E., Hayman, J. A., Hochwald, S., Hofstetter, W. L., Ilson, D. H., Jaroszewski, D., Jasperson, K., Keswani, R. N., Kleinberg, L. R., Korn, W. M., Leong, S., Lockhart, A. C., Mulcahy, M. F., Orringer, M. B., Posey, J. A., Poultsides, G. A., Sasson, A. R., Scott, W. J., Strong, V. E., Varghese, T. K., Washington, M. K., Willett, C. G., Wright, C. D., Zelman, D., McMillian, N., Sundar, H. 2015; 13 (2): 194-227

  Abstract

  Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.

  View details for Web of Science ID 000349834400011

  View details for PubMedID 25691612

• Can the Risk of Non-home Discharge After Resection of Gastric Adenocarcinoma Be Predicted: a Seven-Institution Study of the US Gastric Cancer Collaborative. Journal of gastrointestinal surgery Acher, A. W., Squires, M. H., Fields, R. C., Poultsides, G. A., Schmidt, C., Votanopoulos, K. I., Pawlik, T. M., Jin, L. X., Ejaz, A., Kooby, D. A., Bloomston, M., Worhunsky, D., Levine, E. A., Saunders, N., Winslow, E., Cho, C. S., Meredith, K., Leverson, G., Maithel, S. K., Weber, S. M. 2015; 19 (2): 207-216

  Abstract

  There are no validated methods to preoperatively identify patients with increased risk of discharge to skilled nursing facilities following resection of gastric cancer. We sought to identify preoperative predictors of non-home discharge to optimize transition of care to skilled nursing facility.Patients who underwent resection of gastric cancer from 2000 to 2012 from seven participating institutions of the US Gastric Cancer Collaborative were analyzed. Fisher's exact tests, Student t tests, and logistic regression analyses identified preoperative variables associated with non-home discharge. A prediction tool was created and validated through c-indices. Survival analysis was conducted according to the methods of Kaplan and Meier.Out of the 918 patients identified, 93 (10 %) were discharged to nonhome location. Univariate analysis identified advancing age, American Society of Anesthesiology (ASA) score, hypertension, decreasing preoperative albumin, and lack of neoadjuvant chemotherapy as risk factors for non-home discharge (NHD). Multivariable analysis identified advanced age (odds ratio (OR) = 1.07, 95 % confidence interval (CI) = 1.04-1.10, p < 0.0001), depressed preoperative albumin (OR = 2.17, 95 % CI = 1.47-3.19, p = 0.0001), and total gastrectomy (OR = 2.56, 95 % CI = 1.53-4.3, p = 0.0003) as risk factors for NHD. The c-index of the model and the validation population were 0.76 and 0.8, respectively. Additionally, there was an association of decreased overall survival in patients discharged to nonhome location (35.5 months, home discharge, vs 12 months, NHD, p < 0.0001).Older patients with compromised nutritional status have greater risk of NHD following resection of gastric cancer. The prediction tool can augment preoperative planning to optimize transition of care to skilled nursing facility.

  View details for DOI 10.1007/s11605-014-2690-2

  View details for PubMedID 25373704

• Conditional Survival after Surgical Resection of Gastric Cancer: A Multi-Institutional Analysis of the US Gastric Cancer Collaborative. Annals of surgical oncology Kim, Y., Ejaz, A., Spolverato, G., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D., Worhunsky, D., Saunders, N., Cho, C. S., Levine, E. A., Maithel, S. K., Pawlik, T. M. 2015; 22 (2): 557-564

  Abstract

  Survival estimates following surgical resection of gastric adenocarcinoma are traditionally reported as survival from the date of surgery. Conditional survival (CS) estimates, however, may be more clinically relevant by accounting for time already survived. We assessed CS following surgical resection for gastric adenocarcinoma.We analyzed 807 patients who underwent resection for gastric adenocarcinoma from 2000 to 2012 at seven participating institutions in the U.S. Gastric Cancer Collaborative. Cox proportional hazards models were used to evaluate factors associated with overall survival. Three-year CS estimates at "x" year after surgery were calculated as follows: CS3 = S(x+3)/S(x).Overall 1-, 3-, and 5-year overall survival rates after gastric resection were 42, 34, and 30 %, respectively. Using CS estimates, the probability of surviving an additional 3 years given that the patient had survived at 1, 3, and 5 years were 56, 71, and 82 %, respectively. Patients with higher risk at baseline (i.e., stage III or IV disease, lymphovascular invasion) demonstrated the greatest increase in CS over time.Survival estimates following surgical resection of gastric adenocarcinoma is dynamic; the probability of survival increases with time already survived. Patients with worse prognostic features at the time of surgery had the greatest increases in CS over time. Conditional survival estimates provide important information about the changing probability of survival over time and should be used among patients with resected gastric adenocarcinoma to guide subsequent follow-up strategies.

  View details for DOI 10.1245/s10434-014-4116-5

  View details for PubMedID 25287440

• Use of Endoscopic Ultrasound in the Preoperative Staging of Gastric Cancer: A Multi-Institutional Study of the US Gastric Cancer Collaborative JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R. C., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2015; 220 (1): 48-56

  Abstract

  Endoscopic ultrasound (EUS) can be used to guide the therapeutic plan for patients with gastric adenocarcinoma (GAC), but data on its use and accuracy remain poorly defined. We sought to define the use of EUS, as well as characterize the diagnostic accuracy of EUS among patients with GAC.We identified 960 patients who underwent resection of GAC between 2000 and 2012 from 7 major academic institutions participating in the US Gastric Cancer Collaborative. Clinicopathologic and EUS data were collected and analyzed using chi and kappa statistics.Of 960 patients, 223 (23.2%) underwent evaluation with preoperative EUS. Among patients who underwent EUS, 74 (33.2%) received neoadjuvant chemotherapy; 149 (66.8%) proceeded directly to resection. Among patients who did not receive neoadjuvant therapy and received curative intent gastric resection, the EUS T classifications were T1 (33.3%), T2 (35.6%), T3 (18.9%), T4 (12.1%) and the N classifications were N0 (68.1%) and N ≥ 1 (31.9%). In contrast, when tumor stage was based on the final surgical specimen, there was a higher proportion of cases with more advanced T stage (T1, 36.4%; T2, 14.4%; T3, 23.5%; T4, 25.7%) and N stage (N0, 51.3%; N ≥ 1, 48.7%). The agreement of preoperative EUS compared with surgical staging for T (kappa = 0.28, p < 0.001) and N (kappa = 0.33, p < 0.001) classification was only fair.Less than one-quarter of patients with GAC underwent preoperative EUS staging. In patients who did not receive preoperative chemotherapy, tumor stage on EUS often did not correlate with T stage and N stage on final pathologic analysis. Endoscopic ultrasound should be combined with other staging modalities to optimize staging of patients with GAC.

  View details for DOI 10.1016/j.jamcollsurg.2014.06.023

  View details for Web of Science ID 000346362800007

  View details for PubMedID 25283742

• Prognostic relevance of lymph node ratio and total lymph node count for small bowel adenocarcinoma. Surgery Tran, T. B., Qadan, M., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C. 2015; 158 (2): 486–93

  Abstract

  Nodal metastasis is a known prognostic factor for small bowel adenocarcinoma. The goals of this study were to evaluate the number of lymph nodes (LNs) that should be retrieved and the impact of lymph node ratio (LNR) on survival.Surveillance, Epidemiology, and End Results was queried to identify patients with small bowel adenocarcinoma who underwent resection from 1988 to 2010. Survival was calculated with the Kaplan-Meier method. Multivariate analysis identified predictors of survival.A total of 2,772 patients underwent resection with at least one node retrieved, and this sample included equal numbers of duodenal (n = 1,387) and jejunoileal (n = 1,386) adenocarcinomas. There were 1,371 patients with no nodal metastasis (N0, 49.4%), 928 N1 (33.5%), and 474 N2 (17.1%). The median numbers of LNs examined for duodenal and jejunoileal cancers were 9 and 8, respectively. Cut-point analysis demonstrated that harvesting at least 9 for jejunoileal and 5 LN for duodenal cancers resulted in the greatest survival difference. Increasing LNR at both sites was associated with decreased overall median survival (LNR = 0, 71 months; LNR 0-0.02, 35 months; LNR 0.21-0.4, 25 months; and LNR >0.4, 16 months; P < .001). Multivariate analysis confirmed number of LNs examined, T-stage, LN positivity, and LNR were independent predictors of survival.LNR has a profound impact on survival in patients with small bowel adenocarcinoma. To achieve adequate staging, we recommend retrieving a minimum of 5 LN for duodenal and 9 LN for jejunoileal adenocarcinomas.

  View details for PubMedID 26013988

• Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative. Journal of the American College of Surgeons Gholami, S., Janson, L., Worhunsky, D. J., Tran, T. B., Squires, M. H., Jin, L. X., Spolverato, G., Votanopoulos, K. I., Schmidt, C., Weber, S. M., Bloomston, M., Cho, C. S., Levine, E. A., Fields, R. C., Pawlik, T. M., Maithel, S. K., Efron, B., Norton, J. A., Poultsides, G. A. 2015; 221 (2): 291–99

  Abstract

  Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection.We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased.The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.

  View details for PubMedID 26206635

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study. Annals of surgery Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632–40

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion.Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection.

  View details for PubMedID 26366542

• Prognostic Performance of Different Lymph Node Staging Systems After Curative Intent Resection for Gastric Adenocarcinoma. Annals of surgery Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Votanopoulos, K., Acher, A. W., Jin, L. X., Hawkins, W. G., Schmidt, C., Kooby, D. A., Worhunsky, D., Saunders, N., Cho, C. S., Levine, E. A., Maithel, S. K., Pawlik, T. M. 2015; 262 (6): 991–98

  Abstract

  To compare the prognostic performance of American Joint Committee on Cancer/International Union Against Cancer seventh N stage relative to lymph node ratio (LNR), log odds of metastatic lymph nodes (LODDS), and N score in gastric adenocarcinoma.Metastatic disease to the regional LN basin is a strong predictor of worse long-term outcome following curative intent resection of gastric adenocarcinoma.A total of 804 patients who underwent surgical resection of gastric adenocarcinoma were identified from a multi-institutional database. The relative discriminative abilities of the different LN staging/scoring systems were assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index (c statistic).Of the 804 patients, 333 (41.4%) had no lymph node metastasis, whereas 471 (58.6%) had lymph node metastasis. Patients with ≥N1 disease had an increased risk of death (hazards ratio = 2.09, 95% confidence interval: 1.68-2.61; P < 0.001]. When assessed using categorical cutoff values, LNR had a somewhat better prognostic performance (C index: 0.630; AIC: 4321.9) than the American Joint Committee on Cancer seventh edition (C index: 0.615; AIC: 4341.9), LODDS (C index: 0.615; AIC: 4323.4), or N score (C index: 0.620; AIC: 4324.6). When LN status was modeled as a continuous variable, the LODDS staging system (C index: 0.636; AIC: 4304.0) outperformed other staging/scoring systems including the N score (C index: 0.632; AIC: 4308.4) and LNR (C index: 0.631; AIC: 4225.8). Among patients with LNR scores of 0 or 1, there was a residual heterogeneity of outcomes that was better stratified and characterized by the LODDS.When assessed as a categorical variable, LNR was the most powerful manner to stratify patients on the basis of LN status. LODDS was a better predicator of survival when LN status was modeled as a continuous variable, especially among those patients with either very low or high LNR.

  View details for PubMedID 25563867

• Factors Associated With Recurrence and Survival in Lymph Node-negative Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative. Annals of surgery Jin, L. X., Moses, L. E., Squires, M. H., Poultsides, G. A., Votanopoulos, K., Weber, S. M., Bloomston, M., Pawlik, T. M., Hawkins, W. G., Linehan, D. C., Strasberg, S. M., Schmidt, C., Worhunsky, D. J., Acher, A. W., Cardona, K., Cho, C. S., Kooby, D. A., Levine, E., Winslow, E. R., Saunders, N. D., Spolverato, G., Maithel, S. K., Fields, R. C. 2015; 262 (6): 999–1005

  Abstract

  To determine pathologic features associated with recurrence and survival in patients with lymph node-negative gastric adenocarcinoma.Multi-institutional retrospective analysis.Lymph node status is among the most important predictors of recurrence after gastrectomy for gastric adenocarcinoma. Pathologic features predictive of recurrence in patients with node-negative disease are less well established.Patients who underwent curative resection for gastric adenocarcinoma between 2000 and 2012 from 7 institutions of the US Gastric Cancer Collaborative were analyzed, excluding 30-day mortalities and stage IV disease. Competing risks regression and multivariate Cox regression were used to determine pathologic features associated with time to recurrence and overall survival. Differences in cumulative incidence of recurrence were assessed using the Gray method (for univariate nonparametric analyses) and the Fine and Gray method (for multivariate analyses) and shown as subhazard ratios (SHRs) and adjusted subhazard ratios (aSHRs), respectively.Of 805 patients who met inclusion criteria, 317 (39%) had node-negative disease, of which 54 (17%) recurred. By 2 and 5 years, 66% and 88% of patients, respectively, experienced recurrence. On multivariate competing risks regression, only T-stage 3 or higher was associated with shorter time to recurrence [aSHR = 2.7; 95% confidence interval (CI), 1.5-5.2]. Multivariate Cox regression showed T-stage 3 or higher [hazard ratio (HR) = 1.8; 95% CI, 1.2-2.8], lymphovascular invasion (HR = 2.2; 95% CI, 1.4-3.4), and signet ring histology (HR = 2.1; 95% CI, 1.2-3.6) to be associated with decreased overall survival.Despite absence of lymph node involvement, patients with T-stage 3 or higher have a significantly shorter time to recurrence. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens.

  View details for PubMedID 25607760

• Neutrophil-lymphocyte and platelet-lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma. Journal of surgical oncology Bagante, F., Tran, T. B., Postlewait, L. M., Maithel, S. K., Wang, T. S., Evans, D. B., Hatzaras, I., Shenoy, R., Phay, J. E., Keplinger, K., Fields, R. C., Jin, L. X., Weber, S. M., Salem, A., Sicklick, J. K., Gad, S., Yopp, A. C., Mansour, J. C., Duh, Q. Y., Seiser, N., Solorzano, C. C., Kiernan, C. M., Votanopoulos, K. I., Levine, E. A., Poultsides, G. A., Pawlik, T. M. 2015; 112 (2): 164–72

  Abstract

  The systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC).Patients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed.Among 84 patients with ACC, 29 (34.%) had NLR > 5 while 32 (40.5%) had PLR > 190. NLR and PLR were associated with larger tumors (NLR > 5: ≤ 5 cm, 0% vs. >5 cm, 39.7%; PLR > 190: ≤ 5cm, 0% vs. >5 cm, 45.7%), as well as need to resect of other organs (NLR > 5: other organ resected 48.8% vs. not resected 20.9%; PLR > 190: other organ resected 25.0% vs. not resected 56.4%)(all P < 0.05). Five-year RFS was associated with an elevated NLR (NLR ≤ 5, 14.2% vs. NLR> 5, 10.5%) and PLR (PLR ≤ 190: 19.4% vs. PLR > 190: 5.2%) (both P < 0.05). On multivariate survival analyses, PLR remained a predictor of RFS (HR 1.72), while NLR was associated with both DSS (HR 2.21) and RFS (HR 1.99) (both P < 0.05).Immune markers such as NLR and PLR may be useful to stratify patients with regards to prognosis following surgery for ACC.

  View details for PubMedID 26234285

• An assessment of feeding jejunostomy tube placement at the time of resection for gastric adenocarcinoma: A seven-institution analysis of 837 patients from the U.S. gastric cancer collaborative. Journal of surgical oncology Dann, G. C., Squires, M. H., Postlewait, L. M., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Levine, E. A., Jin, L. X., Cho, C. S., Winslow, E. R., Russell, M. C., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 112 (2): 195–202

  Abstract

  Jejunostomy feeding tubes (J-tubes) are often placed during resection for gastric adenocarcinoma (GAC). Their effect on postoperative complications and receipt of adjuvant therapy is unclear.Patients who underwent curative-intent resection of GAC at seven institutions of the U.S. Gastric Cancer Collaborative from 2000 to 2012 were identified. The associations of J-tubes with postoperative complications and receipt of adjuvant therapy were determined.Of 837 patients, 265 (32%) received a J-tube. Patients receiving J-tubes demonstrated greater incidence of preoperative weight loss, lower BMI, greater extent of resection, and more advanced TNM stage. J-tube placement was associated with increased infectious complications (36% vs. 19%; P < 0.001), including surgical-site (14% vs. 6%; P < 0.001) and deep intra-abdominal (11% vs. 4%; P < 0.001) infections. On multivariate analysis, J-tubes remained independently associated with increased risk of infectious complications (all: HR = 1.93; P = 0.001; surgical-site: HR = 2.85; P = 0.001; deep intra-abdominal: HR = 2.13; P = 0.04). J-tubes were not associated with increased receipt of adjuvant therapy (HR = 0.82; P = 0.34). Subset analyses of patients undergoing total and subtotal gastrectomy similarly demonstrated an association of J-tubes with increased risk of infectious outcomes and no association with increased receipt of adjuvant therapy.J-tube placement after resection of gastric adenocarcinoma is associated with increased postoperative infectious outcomes and is not associated with increased receipt of adjuvant therapy. Selective use of J-tubes is recommended.

  View details for PubMedID 26240027

• The importance of the proximal resection margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer Collaborative. Journal of surgical oncology Postlewait, L. M., Squires, M. H., Kooby, D. A., Poultsides, G. A., Weber, S. M., Bloomston, M., Fields, R. C., Pawlik, T. M., Votanopoulos, K. I., Schmidt, C. R., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Swords, D., Jin, L. X., Cho, C. S., Winslow, E. R., Cardona, K., Staley, C. A., Maithel, S. K. 2015; 112 (2): 203–7

  Abstract

  A 5 cm margin is advocated for distal gastric adenocarcinoma (GAC). The optimal proximal resection margin (PM) length for proximal GAC is not established.Patients who underwent curative-intent resection for proximal GAC from 2000 to 2012 at 7 centers in the US Gastric Cancer Collaborative were included. PM length was sequentially dichotomized and analyzed at 0.5 cm increments (0.5-6.5 cm). Outcomes after negative margin (R0) and positive microscopic margin (R1) resections were compared. Primary endpoints were local recurrence (LR) and overall survival (OS).All patients (n = 162) had R0 distal margins. 151 (93.2%) had an R0-PM with mean length of 2.6 cm (median:1.7 cm; range:0.1-15 cm). A greater PM distance was not associated with LR or OS. An R1-PM was associated with higher N-stage (N3:73% vs. 26%; P = 0.007) and increased LR (HR6.1; P = 0.009) but not associated with decreased OS. On multivariate analysis, an R1-PM was also not independently associated with LR.For resection of proximal gastric adenocarcinoma, proximal margin length is not associated with local recurrence or overall survival. An R1 margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing resection of proximal gastric adenocarcinoma, efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned.

  View details for PubMedID 26272801

• Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway. BMC cancer Drakaki, A., Hatziapostolou, M., Polytarchou, C., Vorvis, C., Poultsides, G. A., Souglakos, J., Georgoulias, V., Iliopoulos, D. 2015; 15: 542-?

  Abstract

  Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors.MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets.A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3'UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3'UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels.Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis.

  View details for DOI 10.1186/s12885-015-1562-9

  View details for PubMedID 26206264

  View details for PubMedCentralID PMC4512159

• Utility of the Proximal Margin Frozen Section for Resection of Gastric Adenocarcinoma: A 7-Institution Study of the US Gastric Cancer Collaborative ANNALS OF SURGICAL ONCOLOGY Squires, M. H., Kooby, D. A., Pawlik, T. M., Weber, S. M., Poultsides, G., Schmidt, C., Votanopoulos, K., Fields, R. C., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Jin, L. X., Levine, E., Cho, C. S., Bloomston, M., Winslow, E., Cardona, K., Staley, C. A., Maithel, S. K. 2014; 21 (13): 4202-4210

  View details for DOI 10.1245/s10434-014-3834-z

  View details for Web of Science ID 000344626400024

• Utility of the proximal margin frozen section for resection of gastric adenocarcinoma: a 7-Institution Study of the US Gastric Cancer Collaborative. Annals of surgical oncology Squires, M. H., Kooby, D. A., Pawlik, T. M., Weber, S. M., Poultsides, G., Schmidt, C., Votanopoulos, K., Fields, R. C., Ejaz, A., Acher, A. W., Worhunsky, D. J., Saunders, N., Jin, L. X., Levine, E., Cho, C. S., Bloomston, M., Winslow, E., Cardona, K., Staley, C. A., Maithel, S. K. 2014; 21 (13): 4202-4210

  Abstract

  The proximal gastric margin dictates the extent of resection for gastric adenocarcinoma (GAC). The value of achieving negative margins via additional gastric resection after a positive proximal margin frozen section (FS) is unknown.The US Gastric Cancer Collaborative includes all patients who underwent resection of GAC at seven institutions from 2000-2012. Intraoperative proximal margin FS data and final permanent section (PS) data were classified as R0 or R1, respectively; positive distal margins were excluded. The primary aim was to evaluate the impact on local recurrence of converting a positive proximal FS-R1 margin to a PS-R0 final margin by additional resection. Secondary endpoints were recurrence-free survival (RFS) and overall survival (OS).Of 860 patients, 520 had a proximal margin FS and 67 were positive. Of these, 48 were converted to R0 on PS by additional resection. R0 proximal margin was achieved in 447 patients (86 %), PS-R1 in 25 (5 %), and converted FS-R1-to-PS-R0 in 48 (9 %). The median follow-up was 44 months. Local recurrence was significantly decreased in the converted FS-R1-to-PS-R0 group compared to the PS-R1 group (10 vs. 32 %; p = 0.01). Median RFS was similar between the FS-R1-to-PS-R0 and PS-R1 cohorts (25 vs. 20 months; p = 0.49), compared to 37 months for the PS-R0 group. Median OS was similar between the FS-R1-to-PS-R0 conversion and PS-R1 groups (36 vs. 26 months; p = 0.14) compared to 50 months for the PS-R0 group. On multivariate analysis, increasing T-stage and N-stage were associated with worse OS; the FS-R1-to-PS-R0 proximal margin conversion was not significantly associated with improved RFS (p = 0.68) or OS (p = 0.44).Conversion of a positive intraoperative proximal margin frozen section during gastric cancer resection may decrease local recurrence, but it is not associated with improved RFS or OS. This may guide decisions regarding the extent of resection.

  View details for DOI 10.1245/s10434-014-3834-z

  View details for PubMedID 25047464

• Single-versus Multifraction Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma: Outcomes and Toxicity INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollom, E. L., Alagappan, M., von Eyben, R., Kunz, P. L., Fisher, G. A., Ford, J. A., Poultsides, G. A., Visser, B. C., Norton, J. A., Kamaya, A., Cox, V. L., Columbo, L. A., Koong, A. C., Chang, D. T. 2014; 90 (4): 918-925

  Abstract

  We report updated outcomes of single- versus multifraction stereotactic body radiation therapy (SBRT) for unresectable pancreatic adenocarcinoma.We included 167 patients with unresectable pancreatic adenocarcinoma treated at our institution from 2002 to 2013, with 1-fraction (45.5% of patient) or 5-fraction (54.5% of patients) SBRT. The majority of patients (87.5%) received chemotherapy.Median follow-up was 7.9 months (range: 0.1-63.6). The 6- and 12-month cumulative incidence rates (CIR) of local recurrence for patients treated with single-fraction SBRT were 5.3% (95% confidence interval [CI], 0.2%-10.4%) and 9.5% (95% CI, 2.7%-16.2%), respectively. The 6- and 12-month CIR with multifraction SBRT were 3.4% (95% CI, 0.0-7.2%) and 11.7% (95% CI, 4.8%-18.6%), respectively. Median survival from diagnosis for all patients was 13.6 months (95% CI, 12.2-15.0 months). The 6- and 12- month survival rates from SBRT for the single-fraction group were 67.0% (95% CI, 57.2%-78.5%) and 30.8% (95% CI, 21.9%-43.6%), respectively. The 6- and 12- month survival rates for the multifraction group were 75.7% (95% CI, 67.2%-85.3%) and 34.9% (95% CI, 26.1%-46.8%), respectively. There were no differences in CIR or survival rates between the single- and multifraction groups. The 6- and 12-month cumulative incidence rates of gastrointestinal toxicity grade ≥3 were 8.1% (95% CI, 1.8%-14.4%) and 12.3% (95% CI, 4.7%-20.0%), respectively, in the single-fraction group, and both were 5.6% (95% CI, 0.8%-10.5%) in the multifraction group. There were significantly fewer instances of toxicity grade ≥2 with multifraction SBRT (P=.005). Local recurrence and toxicity grade ≥2 were independent predictors of worse survival.Multifraction SBRT for pancreatic cancer significantly reduces gastrointestinal toxicity without compromising local control.

  View details for DOI 10.1016/j.ijrobp.2014.06.066

  View details for Web of Science ID 000344734300029

• Single- versus multifraction stereotactic body radiation therapy for pancreatic adenocarcinoma: outcomes and toxicity. International journal of radiation oncology, biology, physics Pollom, E. L., Alagappan, M., von Eyben, R., Kunz, P. L., Fisher, G. A., Ford, J. A., Poultsides, G. A., Visser, B. C., Norton, J. A., Kamaya, A., Cox, V. L., Columbo, L. A., Koong, A. C., Chang, D. T. 2014; 90 (4): 918-925

  Abstract

  We report updated outcomes of single- versus multifraction stereotactic body radiation therapy (SBRT) for unresectable pancreatic adenocarcinoma.We included 167 patients with unresectable pancreatic adenocarcinoma treated at our institution from 2002 to 2013, with 1-fraction (45.5% of patient) or 5-fraction (54.5% of patients) SBRT. The majority of patients (87.5%) received chemotherapy.Median follow-up was 7.9 months (range: 0.1-63.6). The 6- and 12-month cumulative incidence rates (CIR) of local recurrence for patients treated with single-fraction SBRT were 5.3% (95% confidence interval [CI], 0.2%-10.4%) and 9.5% (95% CI, 2.7%-16.2%), respectively. The 6- and 12-month CIR with multifraction SBRT were 3.4% (95% CI, 0.0-7.2%) and 11.7% (95% CI, 4.8%-18.6%), respectively. Median survival from diagnosis for all patients was 13.6 months (95% CI, 12.2-15.0 months). The 6- and 12- month survival rates from SBRT for the single-fraction group were 67.0% (95% CI, 57.2%-78.5%) and 30.8% (95% CI, 21.9%-43.6%), respectively. The 6- and 12- month survival rates for the multifraction group were 75.7% (95% CI, 67.2%-85.3%) and 34.9% (95% CI, 26.1%-46.8%), respectively. There were no differences in CIR or survival rates between the single- and multifraction groups. The 6- and 12-month cumulative incidence rates of gastrointestinal toxicity grade ≥3 were 8.1% (95% CI, 1.8%-14.4%) and 12.3% (95% CI, 4.7%-20.0%), respectively, in the single-fraction group, and both were 5.6% (95% CI, 0.8%-10.5%) in the multifraction group. There were significantly fewer instances of toxicity grade ≥2 with multifraction SBRT (P=.005). Local recurrence and toxicity grade ≥2 were independent predictors of worse survival.Multifraction SBRT for pancreatic cancer significantly reduces gastrointestinal toxicity without compromising local control.

  View details for DOI 10.1016/j.ijrobp.2014.06.066

  View details for PubMedID 25585785

• Rates and Patterns of Recurrence after Curative Intent Resection for Gastric Cancer: A United States Multi-Institutional Analysis JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R. C., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2014; 219 (4): 664-675

  View details for DOI 10.1016/j.jamcollsurg.2014.03.062

  View details for Web of Science ID 000342422500010

• Rates and patterns of recurrence after curative intent resection for gastric cancer: a United States multi-institutional analysis. Journal of the American College of Surgeons Spolverato, G., Ejaz, A., Kim, Y., Squires, M. H., Poultsides, G. A., Fields, R. C., Schmidt, C., Weber, S. M., Votanopoulos, K., Maithel, S. K., Pawlik, T. M. 2014; 219 (4): 664-675

  Abstract

  Reports on recurrence and outcomes of US patients with gastric cancer are scarce. The aim of this study was to determine incidence and pattern of recurrence after curative intent surgery for gastric cancer.Using the multi-institutional US Gastric Cancer Collaborative database, we identified 817 patients undergoing curative intent resection for gastric cancer between 2000 and 2012. Patterns and rates of recurrence along with associated risk factors were identified using adjusted regression analysis. Recurrences were classified as locoregional, peritoneal, or hematogenous.Median patient age was 65.8 years (interquartile range [IQR] 56.4, 74.7); the majority of patients were male (n = 462, 56.6%) and white (n = 511, 62.5%). At the time of surgery, the majority of patients underwent a partial gastrectomy (n = 481, 59.2%) with a complete R0 resection achieved in 91.6% (n = 748) of patients. At the time of last follow-up, 244 (29.9%) of 817 patients developed a recurrence; 163 (66.8%) patients had recurrence at only a single site; the remaining 81 (33.2%) had multiple sites of initial recurrence. Among patients who recurred at a single site, recurrence was most common at a distant location and included hematogenous (n = 57, 23.4%) or peritoneal (n = 47, 19.3%) only metastasis. Tumors at the gastroesophageal junction (odds ratio [OR] 3.18, 95% CI 1.08 to 9.40; p = 0.04) were associated with higher risk of locoregional recurrence, while the presence of multiple lesions (OR 10.82, 95% CI 3.56 to 32.85; p < 0.001) remained associated with an increased risk of distant hematogenous recurrence after adjusted analysis. Recurrence was associated with worse survival, with a median recurrence-free survival of 10.8 months (IQR 8.9, 12.8) among those who experienced a recurrence.Nearly one-third of patients experienced recurrence after gastric cancer surgery. The most common site of recurrence was distant.

  View details for DOI 10.1016/j.jamcollsurg.2014.03.062

  View details for PubMedID 25154671

• Impact of external-beam radiation therapy on outcomes among patients with resected gastric cancer: a multi-institutional analysis. Annals of surgical oncology Ejaz, A., Spolverato, G., Kim, Y., Squires, M. H., Poultsides, G., Fields, R., Bloomston, M., Weber, S. M., Votanopoulos, K., Worhunsky, D. J., Swords, D., Jin, L. X., Schmidt, C., Acher, A. W., Saunders, N., Cho, C. S., Herman, J. M., Maithel, S. K., Pawlik, T. M. 2014; 21 (11): 3412-3421

  Abstract

  Use of perioperative chemotherapy (CTx) alone versus chemoradiation therapy (cXRT) in the treatment of resectable gastric cancer remains varied. We sought to define the utilization and effect of CTx alone versus cXRT on patients having undergone curative-intent resection for gastric cancer.Using the multi-institutional US Gastric Cancer Collaborative database, we identified 505 gastric cancer patients between 2000 and 2012 who received perioperative therapy in addition to curative-intent resection. The impact of perioperative therapy on survival was analyzed by the use of propensity-score matching of clinicopathologic factors among patients who received CTx alone versus cXRT.Median patient age was 62 years, and most patients were male (58.2 %). Most patients had a T3 (38.7 %) or T4 (36.8 %) lesion and lymph node metastasis (73.4 %). A total of 211 (42.8 %) patients received perioperative CTx alone, whereas the remaining 294 (58.2 %) patients received cXRT. Factors associated with receipt of cXRT were younger age (odds ratio, 1.93) and lymph node metastasis (odds ratio, 4.02; both P < 0.05). At a median follow-up of 28 months, the median overall survival (OS) was 33.4 months, and the 5-year OS was 36.7 %. Factors associated with worse overall survival included large tumor size [hazard ratio (HR), 1.83], T3 (HR 2.96) or T4 (HR 4.02) tumors, and lymph node metastasis (HR 1.57; all P < 0.05). In contrast, receipt of cXRT was associated with improved long-term OS (CTx alone, 20.9 months; cXRT, 46.7 months; HR 0.51; P < 0.001).cXRT was utilized in 58 % of patients undergoing curative-intent resection for gastric cancer. With propensity score-matched analysis, cXRT was an independent factor associated with improved recurrence-free survival and OS.

  View details for DOI 10.1245/s10434-014-3776-5

  View details for PubMedID 24845728

• Laparoscopic transgastric necrosectomy for the management of pancreatic necrosis. Journal of the American College of Surgeons Worhunsky, D. J., Qadan, M., Dua, M. M., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2014; 219 (4): 735-743

  Abstract

  Traditional open necrosectomy for pancreatic necrosis is associated with significant morbidity and mortality. Although minimally invasive techniques have been described and offer some promise, each has considerable limitations. This study assesses the safety and effectiveness of laparoscopic transgastric necrosectomy (LTN), a novel technique for the management of necrotizing pancreatitis.Between 2009 and 2013, patients with retrogastric pancreatic necrosis requiring debridement were evaluated for LTN. Debridement was performed via a laparoscopic transgastric approach using 2 to 3 ports and the wide cystgastrostomy left open. Patient demographics, disease severity, operative characteristics, and outcomes were collected and analyzed.Twenty-one patients (13 men, median age 54 years; interquartile range [IQR] 46 to 62 years) underwent LTN during the study period. The duration between pancreatitis onset and debridement was 65 days (IQR 53 to 124 years). Indications for operation included infection (7 patients) and persistent unwellness (14 patients). Median duration of LTN was 170 minutes (IQR 136 to 199 minutes); there were no conversions. Control of the necrosis was achieved via the single procedure in 19 of 21 patients. Median postoperative hospital stay was 5 days (IQR 3 to 14 days) and the majority (71%) of patients experienced no (n = 9) or only minor postoperative complications (n = 6) by Clavien-Dindo grade. Complications of Clavien-Dindo grade 3 or higher developed in 6 patients, including 1 death (5%). With a median follow-up of 11 months (IQR 7 to 22 months), none of the patients required additional operative debridement or had pancreatic/enteric fistulae or wound complications develop.Laparoscopic transgastric necrosectomy is a novel, minimally invasive technique for the management of pancreatic necrosis that allows for debridement in a single operation. When feasible, LTN can reduce the morbidity associated with traditional open necrosectomy and avoid the limitations of other minimally invasive approaches.

  View details for DOI 10.1016/j.jamcollsurg.2014.04.012

  View details for PubMedID 25158913

• Laparoscopic Transgastric Necrosectomy for the Management of Pancreatic Necrosis JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Worhunsky, D. J., Qadan, M., Dua, M. M., Park, W. G., Poultsides, G. A., Norton, J. A., Visser, B. C. 2014; 219 (4): 735-743

  Abstract

  Traditional open necrosectomy for pancreatic necrosis is associated with significant morbidity and mortality. Although minimally invasive techniques have been described and offer some promise, each has considerable limitations. This study assesses the safety and effectiveness of laparoscopic transgastric necrosectomy (LTN), a novel technique for the management of necrotizing pancreatitis.Between 2009 and 2013, patients with retrogastric pancreatic necrosis requiring debridement were evaluated for LTN. Debridement was performed via a laparoscopic transgastric approach using 2 to 3 ports and the wide cystgastrostomy left open. Patient demographics, disease severity, operative characteristics, and outcomes were collected and analyzed.Twenty-one patients (13 men, median age 54 years; interquartile range [IQR] 46 to 62 years) underwent LTN during the study period. The duration between pancreatitis onset and debridement was 65 days (IQR 53 to 124 years). Indications for operation included infection (7 patients) and persistent unwellness (14 patients). Median duration of LTN was 170 minutes (IQR 136 to 199 minutes); there were no conversions. Control of the necrosis was achieved via the single procedure in 19 of 21 patients. Median postoperative hospital stay was 5 days (IQR 3 to 14 days) and the majority (71%) of patients experienced no (n = 9) or only minor postoperative complications (n = 6) by Clavien-Dindo grade. Complications of Clavien-Dindo grade 3 or higher developed in 6 patients, including 1 death (5%). With a median follow-up of 11 months (IQR 7 to 22 months), none of the patients required additional operative debridement or had pancreatic/enteric fistulae or wound complications develop.Laparoscopic transgastric necrosectomy is a novel, minimally invasive technique for the management of pancreatic necrosis that allows for debridement in a single operation. When feasible, LTN can reduce the morbidity associated with traditional open necrosectomy and avoid the limitations of other minimally invasive approaches.

  View details for DOI 10.1016/j.jamcollsurg.2014.04.012

  View details for Web of Science ID 000342422500018

• Impact of External-Beam Radiation Therapy on Outcomes Among Patients with Resected Gastric Cancer: A Multi-institutional Analysis ANNALS OF SURGICAL ONCOLOGY Ejaz, A., Spolverato, G., Kim, Y., Squires, M. H., Poultsides, G., Fields, R., Bloomston, M., Weber, S. M., Votanopoulos, K., Worhunsky, D. J., Swords, D., Jin, L. X., Schmidt, C., Acher, A. W., Saunders, N., Cho, C. S., Herman, J. M., Maithel, S. K., Pawlik, T. M. 2014; 21 (11): 3412-3421

  View details for DOI 10.1245/s10434-014-3776-5

  View details for Web of Science ID 000342144900013

• A Multi-institutional Analysis of Open Versus Minimally-Invasive Surgery for Gastric Adenocarcinoma: Results of the US Gastric Cancer Collaborative JOURNAL OF GASTROINTESTINAL SURGERY Spolverato, G., Kim, Y., Ejaz, A., Valero, V., Squires, M. H., Poultsides, G., Fields, R. C., Bloomston, M., Weber, S. M., Acher, A. W., Votanopoulos, K., Schmidt, C., Cho, C. S., Maithel, S. K., Pawlik, T. M. 2014; 18 (9): 1563-1574

  Abstract

  Surgical experience with minimally invasive surgery (MIS) has increased; however, published reports on MIS resection of gastric adenocarcinoma are limited.Between 2000 and 2012, 880 patients who underwent surgical resection of gastric adenocarcinoma were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified by operative approach (open vs. MIS) and analyzed.Overall, 70 (8 %) patients had a MIS approach. Patients who underwent a MIS resection were more likely to have a smaller tumor (open 4.5 cm vs. MIS 3.0 cm, p < 0.001). MIS resections were associated with lower estimated blood loss (open 250 cc vs. MIS 150 cc) and longer operative time (open 232 min vs. MIS 271 min) compared with open surgery (both p < 0.05). An R0 resection was achieved in most patients (open 90.9 % vs. MIS 98.6 %, p = 0.03) and median lymph node yield was good in both groups (open 17 vs. MIS 14, p = 0.10). MIS had a similar incidence of complications (open 33.1 % vs. MIS 20 %, p = 0.07) and a similar length of stay (open 9 days vs. MIS 7 days, p = 0.13) compared with open surgery. In the propensity-matched analysis, median recurrence-free and overall were not impacted by operative approach.An MIS approach to gastric cancer was associated with adequate lymph node retrieval, a high incidence of R0 resection, and comparable long-term oncological outcomes versus open gastrectomy.

  View details for DOI 10.1007/s11605-014-2562-9

  View details for Web of Science ID 000340936300003

  View details for PubMedID 24912915

• Laparoscopic spleen-preserving distal pancreatectomy: the technique must suit the lesion. Journal of gastrointestinal surgery Worhunsky, D. J., Zak, Y., Dua, M. M., Poultsides, G. A., Norton, J. A., Visser, B. C. 2014; 18 (8): 1445-1451

  Abstract

  Splenic preservation is currently recommended during minimally invasive surgery for benign tumors of the distal pancreas. The aim of this study was to evaluate the outcomes of patients undergoing laparoscopic spleen-preserving distal pancreatectomy, with particular attention paid to the technique used for spleen preservation (splenic vessel ligation vs preservation). A review of consecutive patients who underwent laparoscopic distal pancreatectomy with the intention of splenic preservation was conducted. Patient demographics, operative data, and outcomes were collected and analyzed. Fifty-five consecutive patients underwent laparoscopic distal pancreatectomy with the intention of splenic preservation; 5 required splenectomy (9 %). Of the remaining 50 patients, 31 (62 %) had splenic vessel ligation, and 19 (38 %) had vessel preservation. Patient demographics and tumor size were similar. The vessel ligation group had significantly more pancreas removed (95 vs 52 mm, P < 0.001) and longer operative times (256 vs 201 min, P = 0.008). Postoperative outcomes, complication rates, and splenic viability were similar between groups. Laparoscopic spleen-preserving distal pancreatectomy is a safe operation with a high rate of success (91 %). Vessel ligation was the chosen technical strategy for lesions that required resection of a greater length of pancreas. We found no advantage to either technique with respect to outcomes and splenic preservation. Operative approach should reflect technical considerations including location in the pancreas.

  View details for DOI 10.1007/s11605-014-2561-x

  View details for PubMedID 24939598

• Pancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness. HPB Worhunsky, D. J., Krampitz, G. W., Poullos, P. D., Visser, B. C., Kunz, P. L., Fisher, G. A., Norton, J. A., Poultsides, G. A. 2014; 16 (4): 304-311

  Abstract

  Contrary to pancreatic adenocarcinoma, pancreatic neuroendocrine tumours (PNET) are commonly hyperenhancing on arterial phase computed tomography (APCT). However, a subset of these tumours can be hypoenhancing. The prognostic significance of the CT appearance of these tumors remains unclear.From 2001 to 2012, 146 patients with well-differentiated PNET underwent surgical resection. The degree of tumour enhancement on APCT was recorded and correlated with clinicopathological variables and overall survival.APCT images were available for re-review in 118 patients (81%). The majority had hyperenhancing tumours (n = 80, 68%), 12 (10%) were isoenhancing (including cases where no mass was visualized) and 26 (22%) were hypoenhancing. Hypoenhancing PNET were larger, more commonly intermediate grade, and had higher rates of lymph node and synchronous liver metastases. Hypoenhancing PNET were also associated with significantly worse overall survival after a resection as opposed to isoenhancing and hyperenhancing tumours (5-year, 54% versus 89% versus 93%). On multivariate analysis of factors available pre-operatively, only hypoenhancement (HR 2.32, P = 0.02) was independently associated with survival.Hypoenhancement on APCT was noted in 22% of well-differentiated PNET and was an independent predictor of poor outcome. This information can inform pre-operative decisions in the multidisciplinary treatment of these neoplasms.

  View details for DOI 10.1111/hpb.12139

  View details for PubMedID 23991643

• Does chronic kidney disease affect outcomes after major abdominal surgery? Results from the national surgical quality improvement program. Journal of gastrointestinal surgery Cloyd, J. M., Ma, Y., Morton, J. M., Kurella Tamura, M., Poultsides, G. A., Visser, B. C. 2014; 18 (3): 605-612

  Abstract

  The impact of chronic kidney disease (CKD) and end-stage renal disease on outcomes following major abdominal surgery is not well defined.The 2008 NSQIP database was queried to identify adult patients undergoing complex abdominal surgery (major colorectal, hepatobiliary, pancreatic, gastric, and esophageal operations). Thirty-day morbidity and mortality in patients on hemodialysis (HD) versus patients not on HD were compared. The impact of preoperative renal insufficiency, measured by glomerular filtration rate (GFR), on morbidity and mortality was then assessed in non-dialysis patients.Of 24,572 patients who underwent major abdominal operations, excluding emergency cases, only 149 (0.6 %) were on HD preoperatively. Thirty-day mortality in the HD group was 12.8 % compared to 1.8 % for those not on HD (p < 0.0001). Overall complication rate was 23.5 versus 12.3 % (p < 0.0001). In particular, rates of pneumonia (6.7 vs 3.0 %, p < 0.05) and sepsis (12.8 vs 5.3 %, p < 0.001) were higher in patients on HD. In patients not on HD, GFR was significantly predictive of postoperative mortality after controlling for age, gender, race, emergency status, and comorbidities. Compared to patients with normal preoperative kidney function (GFR, 75-90 ml/min/1.73 m(2)), even modest CKD (GFR, 45-60 ml/min/1.73 m(2)) was associated with increased postoperative mortality (odds ratio (OR), 1.62). With greater impairment in kidney function, postoperative mortality was even more marked (GFR, 30-45 ml/min/1.73 m(2) and OR, 2.84; GFR, 15-30 ml/min/1.73 m(2) and OR, 5.56). In addition, CKD was independently associated with increased postoperative complications.Any degree of preoperative kidney impairment, even mild asymptomatic disease, is associated with clinically significant increases in 30-day postoperative morbidity and mortality following major abdominal surgery.

  View details for DOI 10.1007/s11605-013-2390-3

  View details for PubMedID 24241964

• Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging. Proceedings of the National Academy of Sciences of the United States of America Eberlin, L. S., Tibshirani, R. J., Zhang, J., Longacre, T. A., Berry, G. J., Bingham, D. B., Norton, J. A., Zare, R. N., Poultsides, G. A. 2014; 111 (7): 2436-2441

  Abstract

  Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, here, the Lasso method (which stands for least absolute shrinkage and selection operator and which is a multiclass logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The methodology developed with 28 frozen training samples of clear histopathologic diagnosis showed an overall accuracy value of 98% for the 12,480 pixels evaluated in cross-validation (CV), and 97% when a completely independent set of samples was tested. By applying an additional spatial smoothing technique, the accuracy for both CV and the independent set of samples was 99% compared with histological diagnoses. To test our method for clinical use, we applied it to a total of 21 tissue-margin samples prospectively obtained from nine gastric-cancer patients. The results obtained suggest that DESI-MSI/Lasso may be valuable for routine intraoperative assessment of the specimen margins during gastric-cancer surgery.

  View details for DOI 10.1073/pnas.1400274111

  View details for PubMedID 24550265

• Postoperative serum amylase predicts pancreatic fistula formation following pancreaticoduodenectomy. Journal of gastrointestinal surgery Cloyd, J. M., Kastenberg, Z. J., Visser, B. C., Poultsides, G. A., Norton, J. A. 2014; 18 (2): 348-353

  Abstract

  Early identification of patients at risk for developing pancreatic fistula (PF) after pancreaticoduodenectomy (PD) may facilitate prevention or treatment strategies aimed at reducing its associated morbidity.A retrospective review of 176 consecutive PD performed between 2006 and 2011 was conducted in order to analyze the association between the serum amylase on postoperative day 1 (POD1) and the development of PF.Serum amylase was recorded on POD1 in 146 of 176 PD cases (83.0 %). Twenty-seven patients (18.5 %) developed a postoperative PF: 6 type A, 19 type B, and 2 type C. Patients with a PF had a mean serum amylase on POD1 of 659 ± 581 compared to 246 ± 368 in those without a fistula (p < 0.001). On logistic regression, a serum amylase >140 U/L on POD1 was strongly associated with developing a PF (OR, 5.48; 95 % CI, 1.94-15.44). Sensitivity and specificity of a postoperative serum amylase >140 U/L was 81.5 and 55.5 %, respectively. Positive and negative predictive values were 29.3 and 93.0 %, respectively.An elevated serum amylase on POD1 may be used, in addition to other prognostic factors, to help stratify risk for developing PF following PD.

  View details for DOI 10.1007/s11605-013-2293-3

  View details for PubMedID 23903930

• Reassessment of the Current American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Tumors JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Qadan, M., Ma, Y., Visser, B. C., Kunz, P. L., Fisher, G. A., Norton, J. A., Poultsides, G. A. 2014; 218 (2): 188-195

  Abstract

  Adopting a unified staging system for pancreatic neuroendocrine tumors (PNETs) has been challenging. Currently, the American Joint Committee on Cancer (AJCC) recommends use of the pancreatic adenocarcinoma staging system for PNETs. We sought to explore the prognostic usefulness of the pancreatic adenocarcinoma staging system for PNETs.The Surveillance, Epidemiology, and End Results program data were used to identify patients with PNETs who underwent curative-intent surgical resection from 1983 to 2008. The discriminatory ability of the AJCC system was examined and a new TNM system was devised using extent of disease variables.In 1,202 patients identified, lymph node metastasis was associated with worse 10-year overall survival after resection (51% vs 63%; p < 0.0001), as was the presence of distant metastatic disease (35% vs 62%; p < 0.0001). The current AJCC system (recorded by the Surveillance, Epidemiology, and End Results program in 412 patients since 2004) distinguished 5-year overall survival only between stages I and II (p = 0.01), but not between stages II and III (p = 0.97), or stages III and IV (p = 0.36). By modifying the T stage to be based on size alone (0.1 to 1.0 cm, 1.1 to 2.0 cm, 2.1 to 4.0 cm, and >4.0 cm) and revising the TNM subgroups, we propose a novel TNM system with improved discriminatory ability between disease stages (stages I vs II; p = 0.16; II vs III; p < 0.0001; and III vs IV; p = 0.008).In this study evaluating the current AJCC staging system for PNETs, there were no significant differences detected between stages II and III or stages III and IV. We propose a novel TNM system that might better discriminate between outcomes after surgical resection of PNETs.

  View details for DOI 10.1016/j.jamcollsurg.2013.11.001

  View details for PubMedID 24321190

• False positive 18F-fluorodeoxyglucose positron emission tomography/computed tomography liver lesion mimicking metastasis in 2 patients with gastroesophageal cancer. Practical radiation oncology Paudel, N., Kunz, P. L., Poultsides, G. A., Koong, A. C., Chang, D. T. 2014; 4 (6): 368-371

  View details for DOI 10.1016/j.prro.2013.11.005

  View details for PubMedID 25407856

• Gastrointestinal stromal tumor: an unusual cause of gastrointestinal bleeding. Digestive diseases and sciences Wong, R. J., Longacre, T. A., Poultsides, G., Park, W., Rothenberg, M. E. 2013; 58 (11): 3112-3116

  View details for DOI 10.1007/s10620-013-2678-x

  View details for PubMedID 23633157

• Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine. Gastrointestinal endoscopy Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-302 e2

  Abstract

  BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

  View details for DOI 10.1016/j.gie.2013.02.037

  View details for PubMedID 23566642

• Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine GASTROINTESTINAL ENDOSCOPY Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-?

  Abstract

  BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

  View details for DOI 10.1016/j.gie.2013.02.037

  View details for Web of Science ID 000321825200015

  View details for PubMedID 23566642

• Colorectal cancer diagnostics: biomarkers, cell-free DNA, circulating tumor cells and defining heterogeneous populations by single-cell analysis. Expert review of molecular diagnostics Kin, C., Kidess, E., Poultsides, G. A., Visser, B. C., Jeffrey, S. S. 2013; 13 (6): 581-599

  Abstract

  Reliable biomarkers are needed to guide treatment of colorectal cancer, as well as for surveillance to detect recurrence and monitor therapeutic response. In this review, the authors discuss the use of various biomarkers in addition to serum carcinoembryonic antigen, the current surveillance method for metastatic recurrence after resection. The clinical relevance of mutations including microsatellite instability, KRAS, BRAF and SMAD4 is addressed. The role of circulating tumor cells and cell-free DNA with regards to their implementation into clinical use is discussed, as well as how single-cell analysis may fit into a monitoring program. The detection and characterization of circulating tumor cells and cell-free DNA in colorectal cancer patients will not only improve the understanding of the development of metastasis, but may also supplant the use of other biomarkers.

  View details for DOI 10.1586/14737159.2013.811896

  View details for PubMedID 23895128

• Seventh Edition (2010) of the AJCC/UICC Staging System for Gastric Adenocarcinoma: Is there Room for Improvement? ANNALS OF SURGICAL ONCOLOGY Patel, M. I., Rhoads, K. F., Ma, Y., Ford, J. M., Visser, B. C., Kunz, P. L., Fisher, G. A., Chang, D. T., Koong, A., Norton, J. A., Poultsides, G. A. 2013; 20 (5): 1631-1638

  Abstract

  The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database.California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method.Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory abilityIn this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

  View details for DOI 10.1245/s10434-012-2724-5

  View details for PubMedID 23149854

• Iliocaval and aortoiliac reconstruction following en bloc retroperitoneal leiomyosarcoma resection. Journal of vascular surgery Ohman, J. W., Chandra, V., Poultsides, G., Harris, E. J. 2013; 57 (3): 850-?

  View details for DOI 10.1016/j.jvs.2012.01.048

  View details for PubMedID 23446129

• Hospital readmission after a pancreaticoduodenectomy: an emerging quality metric? HPB Kastenberg, Z. J., Morton, J. M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2013; 15 (2): 142-148

  Abstract

  Hospital readmission has attracted attention from policymakers as a measure of quality and a target for cost reduction. The aim of the study was to evaluate the frequency and patterns of rehospitalization after a pancreaticoduodenectomy (PD).The records of all patients undergoing a PD at an academic medical centre for malignant or benign diagnoses between January 2006 and September 2011 were retrospectively reviewed. The incidence, aetiology and predictors of subsequent readmission(s) were analysed.Of 257 consecutive patients who underwent a PD, 50 (19.7%) were readmitted within 30 days from discharge. Both the presence of any post-operative complication (P = 0.049) and discharge to a nursing/rehabilitation facility or to home with health care services (P = 0.018) were associated with readmission. The most common reasons for readmission were diet intolerance (36.0%), pancreatic fistula/abscess (26.0%) and superficial wound infection (8.0%). Nine (18.0%) readmissions had lengths of stay of 2 days or less and in four of those (8.0%) diagnostic evaluation was eventually negative.Approximately one-fifth of patients require hospital readmission within 30 days of discharge after a PD. A small fraction of these readmissions are short (2 days or less) and may be preventable or manageable in the outpatient setting.

  View details for DOI 10.1111/j.1477-2574.2012.00563.x

  View details for PubMedID 23297725

• Diagnostic Utility of Metabolomic-Derived Biomarkers for Pancreatic Cysts Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., NORTON, J. A., Banerjee, S., Chen, A. M., Friedland, S., Pasricha, P. J., Lowe, A. W., Peltz, G. LIPPINCOTT WILLIAMS & WILKINS. 2012: 1394–94

  View details for Web of Science ID 000310360500241

• Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors ARCHIVES OF SURGERY Krampitz, G. W., Norton, J. A., Poultsides, G. A., Visser, B. C., Sun, L., Jensen, R. T. 2012; 147 (9): 820-827

  Abstract

  Lymph node metastases decrease survival in patients with pancreatic neuroendocrine tumors (pNETs).Prospective database searches.National Institutes of Health (NIH) and Stanford University Hospital (SUH).A total of 326 patients underwent surgical exploration for pNETs at the NIH (n = 216) and SUH (n = 110).Overall survival, disease-related survival, and time to development of liver metastases.Forty patients (12.3%) underwent enucleation and 305 (93.6%) underwent resection. Of the patients who underwent resection, 117 (35.9%) had partial pancreatectomy and 30 (9.2%) had a Whipple procedure. Forty-one patients also had liver resections, 21 had wedge resections, and 20 had lobectomies. Mean follow-up was 8.1 years (range, 0.3-28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (P < .001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared with those with none (P < .001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (P < .001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of the number of lymph nodes involved (P = .004).As expected, liver metastases decrease survival of patients with pNETs. Patients with lymph node metastases alone have a shorter time to the development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease disease-related survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNETs.

  View details for PubMedID 22987171

• Pathologic Response to Preoperative Chemotherapy in Colorectal Liver Metastases: Fibrosis, not Necrosis, Predicts Outcome ANNALS OF SURGICAL ONCOLOGY Poultsides, G. A., Bao, F., Servais, E. L., Hernandez-Boussard, T., DeMatteo, R. P., Allen, P. J., Fong, Y., Kemeny, N. E., Saltz, L. B., Klimstra, D. S., Jarnagin, W. R., Shia, J., D'Angelica, M. I. 2012; 19 (9): 2797-2804

  Abstract

  Pathologic response to preoperative chemotherapy for colorectal liver metastases (CLM) is associated with survival after hepatectomy. Histologically, dominant response patterns include fibrosis, necrosis and/or acellular mucin, but some of these changes can appear without previous chemotherapy and their individual correlation with outcome is unknown.Pathology slides from patients who underwent CLM resection (irrespective of preoperative chemotherapy status) were rereviewed by a blinded pathologist. Pathologic response was recorded as the summation of percentage necrosis, fibrosis and acellular mucin. Associations between pathologic response, its components, preoperative chemotherapy, and survival were analyzed.Pathology slides were rereviewed in 366 patients undergoing CLM resection from 2003 to 2007. Preoperative chemotherapy was administered in 249 (68 %) patients, who, when compared to no preoperative chemotherapy patients, had higher rates of overall pathologic response (57 vs. 46 %, P < .01), fibrosis (21 vs. 12 %, P < .01) and acellular mucin (6 vs. 3 %, P = .05) but similar rates of necrosis (30 vs. 31 %, P = .30). In patients receiving preoperative chemotherapy, overall pathologic response ≥ 75 % (5 year, 83 vs. 47 %, P < .01) and fibrosis ≥ 40 % (5 year, 87 vs. 51 %, P < .01) independently correlated with disease-specific survival after hepatectomy. Preoperative hepatic artery infusion chemotherapy (P = .04) and bevacizumab (P = .05) were marginally associated with overall pathologic response and fibrosis, respectively.Fibrosis is the predominant chemotherapy-related pathologic alteration driving the association of treatment response with survival after CLM resection. Necrosis in CLM is not related to chemotherapy or outcome.

  View details for DOI 10.1245/s10434-012-2335-1

  View details for Web of Science ID 000308357100005

  View details for PubMedID 22476753

• Failure to comply with NCCN guidelines for the management of pancreatic cancer compromises outcomes HPB Visser, B. C., Ma, Y., Zak, Y., Poultsides, G. A., Norton, J. A., Rhoads, K. F. 2012; 14 (8): 539-547

  Abstract

  There are little data available regarding compliance with the National Comprehensive Cancer Network (NCCN) guidelines. We investigated variation in the management of pancreatic cancer (PC) among large hospitals in California, USA, specifically to evaluate whether compliance with NCCN guidelines correlates with patient outcomes.The California Cancer Registry was used to identify patients treated for PC from 2001 to 2006. Only hospitals with ≥ 400 beds were included to limit evaluation to centres possessing resources to provide multimodality care (n= 50). Risk-adjusted multivariable models evaluated predictors of adherence to stage-specific NCCN guidelines for PC and mortality.In all, 3706 patients were treated for PC in large hospitals during the study period. Compliance with NCCN guidelines was only 34.5%. Patients were less likely to get recommended therapy with advanced age and low socioeconomic status (SES). Using multilevel analysis, controlling for patient factors (including demographics and comorbidities), hospital factors (e.g. size, academic affiliation and case volume), compliance with NCCN guidelines was associated with a reduced risk of mortality [odds ratio (OR) for death 0.64 (0.53-0.77, P < 0.0001)].There is relatively poor overall compliance with the NCCN PC guidelines in California's large hospitals. Higher compliance rates are correlated with improved survival. Compliance is an important potential measure of the quality of care.

  View details for DOI 10.1111/j.1477-2574.2012.00496.x

  View details for PubMedID 22762402

• Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis ANNALS OF SURGICAL ONCOLOGY Poultsides, G. A., Huang, L. C., Chen, Y., Visser, B. C., Pai, R. K., Jeffrey, R. B., Park, W. G., Chen, A. M., Kunz, P. L., Fisher, G. A., Norton, J. A. 2012; 19 (7): 2295-2303

  Abstract

  Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear.From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival.Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications.Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.

  View details for DOI 10.1245/s10434-012-2305-7

  View details for PubMedID 22396008

• Hybrid Treatment of Celiac Artery Compression (Median Arcuate Ligament) Syndrome DIGESTIVE DISEASES AND SCIENCES Palmer, O. P., Tedesco, M., Casey, K., Lee, J. T., Poultsides, G. A. 2012; 57 (7): 1782-1785

  View details for DOI 10.1007/s10620-011-2019-x

  View details for PubMedID 22212729

• Duodenal Adenocarcinoma: Clinicopathologic Analysis and Implications for Treatment 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology Poultsides, G. A., Huang, L. C., Cameron, J. L., Tuli, R., Lan, L., Hruban, R. H., Pawlik, T. M., Herman, J. M., Edil, B. H., Ahuja, N., Choti, M. A., Wolfgang, C. L., Schulick, R. D. SPRINGER. 2012: 1928–35

  Abstract

  Duodenal adenocarcinoma is a rare cancer usually studied as a group with periampullary or small bowel adenocarcinoma; therefore, its natural history is poorly understood.Patients with duodenal adenocarcinoma were identified from a single-institution pancreaticoduodenectomy database. Patients with adenocarcinoma arising from the ampulla of Vater were excluded. Univariate and multivariate analyses were performed to identify clinicopathologic variables associated with survival and recurrence after resection.From 1984 to 2006, a total of 122 patients with duodenal adenocarcinoma underwent pancreaticoduodenectomy. Overall survival after resection was 48% at 5 years and 41% at 10 years. Five-year survival decreased as the number of lymph nodes involved by metastasis increased from 0 to 1-3 to ≥ 4 (68%, 58%, 17%, respectively, P < 0.01) and as the lymph node ratio increased from 0 to >0-0.2 to >0.2-0.4 to >0.4 (68%, 57%, 14%, 14%, respectively, P < 0.01). Lymph node metastasis was the only independent predictor of decreased survival in multivariate analysis. Recurrence after resection was predominantly distant (81%). Adjuvant chemoradiation did not decrease local recurrence or prolong overall survival; however, patients who received chemoradiation more commonly had nodal metastasis (P = 0.03).The prognostic significance of both the absolute number and ratio of involved lymph nodes emphasizes the need for adequate lymphadenectomy to accurately stage duodenal adenocarcinoma. The mostly distant pattern of recurrence underscores the need for the development of effective systemic therapies.

  View details for DOI 10.1245/s10434-011-2168-3

  View details for Web of Science ID 000304209800029

  View details for PubMedID 22167476

• Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Abelson, J. A., Murphy, J. D., Minn, A. Y., Chung, M., Fisher, G. A., Ford, J. M., Kunz, P., Norton, J. A., Visser, B. C., Poultsides, G. A., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: E595–E601

  Abstract

  To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma.Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively.The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%).Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  View details for DOI 10.1016/j.ijrobp.2011.09.035

  View details for PubMedID 22197234

• Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts BMC GASTROENTEROLOGY Tun, M. T., Pai, R. K., Kwok, S., Dong, A., Gupta, A., Visser, B. C., Norton, J. A., Poultsides, G. A., Banerjee, S., Van Dam, J., Chen, A. M., Friedland, S., Scott, B. A., Verma, R., Lowe, A. W., Park, W. G. 2012; 12

  Abstract

  Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.

  View details for DOI 10.1186/1471-230X-12-15

  View details for PubMedID 22333441

• An HNF4 alpha-miRNA Inflammatory Feedback Circuit Regulates Hepatocellular Oncogenesis CELL Hatziapostolou, M., Polytarchou, C., Aggelidou, E., Drakaki, A., Poultsides, G. A., Jaeger, S. A., Ogata, H., Karin, M., Struhl, K., Hadzopoulou-Cladaras, M., Iliopoulos, D. 2011; 147 (6): 1233-1247

  Abstract

  Hepatocyte nuclear factor 4α (HNF4α) is essential for liver development and hepatocyte function. Here, we show that transient inhibition of HNF4α initiates hepatocellular transformation through a microRNA-inflammatory feedback loop circuit consisting of miR-124, IL6R, STAT3, miR-24, and miR-629. Moreover, we show that, once this circuit is activated, it maintains suppression of HNF4α and sustains oncogenesis. Systemic administration of miR-124, which modulates inflammatory signaling, prevents and suppresses hepatocellular carcinogenesis by inducing tumor-specific apoptosis without toxic side effects. As we also show that this HNF4α circuit is perturbed in human hepatocellular carcinomas, our data raise the possibility that manipulation of this microRNA feedback-inflammatory loop has therapeutic potential for treating liver cancer.

  View details for DOI 10.1016/j.cell.2011.10.043

  View details for Web of Science ID 000298148100014

  View details for PubMedID 22153071

• Hybrid Resection of Duodenal Tumors JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Poultsides, G. A., Pappou, E. P., Bloom, G. P., Orlando, R. 2011; 21 (7): 603-608

  Abstract

  The aim of this study was to review our experience with the hand-assisted laparoscopic management of duodenal tumors with no or low malignant potential and to compare this approach with published case reports of purely laparoscopic local duodenal resection.Eight cases of hand-assisted laparoscopic local duodenal resection performed from 2000 to 2008 were retrospectively reviewed. Hand-assistance was utilized for complete duodenal mobilization, and local duodenal resection was accomplished extracorporeally through the hand-access incision. Patient and tumor characteristics, operative time, length of stay, and complications were compared with 18 cases of totally laparoscopic local excision of duodenal tumors published since 1997. Patients with ampullary tumors were excluded.Compared with the purely laparoscopic approach, the hand-assisted technique was associated with shorter operative time (179 versus 131 minutes, P=.03) and was more commonly used for lesions located in the third portion of the duodenum (0% versus 37.5%, P=.02). Tumor size (2.9 cm versus 3.2 cm, P=.61) and length of hospital stay (5.9 versus 5.9 days, P=.96) were similar between the two groups. The rate of complications was also comparable (0% versus 12.5%, P=.31); 1 of 8 patients in the hand-assisted group developed an incisional hernia at the hand-access site.Hand-assisted laparoscopic local duodenal resection is a feasible, safe, and effective alternative to the totally laparoscopic approach. In addition to being associated with comparable length of hospital stay, hand-assistance can shorten operative time by facilitating duodenal mobilization as well as extracorporeal duodenal resection and closure.

  View details for DOI 10.1089/lap.2010.0387

  View details for Web of Science ID 000294059200006

  View details for PubMedID 21774700

• Laparoscopic Duodenojejunostomy for Superior Mesenteric Artery Syndrome DIGESTIVE DISEASES AND SCIENCES Magee, G., Slater, B. J., Lee, J. T., Poultsides, G. A. 2011; 56 (9): 2528-2531

  View details for DOI 10.1007/s10620-011-1757-0

  View details for PubMedID 21643740

• Surgical Management of Neuroendocrine Tumors of the Gastrointestinal Tract ONCOLOGY-NEW YORK Huang, L. C., Poultsides, G. A., Norton, J. A. 2011; 25 (9): 794-803

  Abstract

  Neuroendocrine tumors of the pancreas (islet cell tumors) and of the luminal gastrointestinal tract (carcinoids) are a heterogeneous group of epithelial neoplasms that share certain common characteristics. First, they are similar histologically and are difficult to distinguish under light microscopy. Second, they can be associated with hypersecretory syndromes. Third, they are generally slow-growing and have a better prognosis than adenocarcinomas at the same site; however, they do become incurable when they progress to unresectable metastatic disease. Surgery is the only curative treatment and is recommended for most patients for whom cross-sectional imaging suggests that complete resection is possible. This article reviews the surgical management of gastrointestinal neuroendocrine tumors, including the preoperative control of hormonal symptoms, extent of resection required, postoperative outcomes, and differing management strategies as determined by whether the tumor has arisen sporadically or as part of a familial disorder, such as multiple endocrine neoplasia type 1 (MEN1).

  View details for PubMedID 21936439

• Ruptured Biliary Cystadenoma Managed by Angiographic Embolization and Interval Partial Hepatectomy DIGESTIVE DISEASES AND SCIENCES Ghole, S. A., Bakhtary, S., Staudenmayer, K., Sze, D. Y., Pai, R. K., Visser, B. C., Norton, J. A., Poultsides, G. A. 2011; 56 (7): 1949-1953

  View details for DOI 10.1007/s10620-011-1677-z

  View details for PubMedID 21445579

• Pancreatic Endocrine Tumors With Major Vascular Abutment, Involvement, or Encasement and Indication for Resection ARCHIVES OF SURGERY Norton, J. A., Harris, E. J., Chen, Y., Visser, B. C., Poultsides, G. A., Kunz, P. C., Fisher, G. A., Jensen, R. T. 2011; 146 (6): 724-732

  Abstract

  Surgery for pancreatic endocrine tumors (PETs) with blood vessel involvement is controversial.Resection of PETs with major blood vessel involvement can be beneficial.The combined databases of the National Institutes of Health and Stanford University hospitals were queried.Operation, pathologic condition, complications, and disease-free and overall survival.Of 273 patients with PETs, 46 (17%) had preoperative computed tomography evidence of major vascular involvement. The mean size for the primary PET was 5.0 cm. The involved major vessel was as follows: portal vein (n = 20), superior mesenteric vein or superior mesenteric artery (n = 16), inferior vena cava (n = 4), splenic vein (n = 4), and heart (n = 2). Forty-two of 46 patients had a PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n = 7) or resection (n = 35). Resections included distal or subtotal pancreatectomy in 23, Whipple in 10, and total in 2. Eighteen patients had concomitant liver resection: 10 wedge resection and 8 anatomic resections. Nine patients had vascular reconstruction: each had reconstruction of the superior mesenteric vein and portal vein, and 1 had concomitant reconstruction of the superior mesenteric artery. There were no deaths, but 12 patients had complications. Eighteen patients (41%) were immediately disease free, and 5 recurred with follow-up, leaving 13 (30%) disease-free long term. The 10-year overall survival was 60%. Functional tumors were associated with a better overall survival (P < .001), and liver metastases decreased overall survival (P < .001).These findings suggest that surgical resection of PETs with vascular abutment/invasion and nodal or distant metastases is indicated.

  View details for PubMedID 21690450

• Colloid Carcinoma of the Pancreas DIGESTIVE DISEASES AND SCIENCES Plerhoples, T. A., Ahdoot, M., DiMaio, M. A., Pai, R. K., Park, W. G., Poultsides, G. A. 2011; 56 (5): 1295-1298

  View details for DOI 10.1007/s10620-011-1573-6

  View details for Web of Science ID 000289899200008

  View details for PubMedID 21253833

• Reassessing the need for primary tumor surgery in unresectable metastatic colorectal cancer: overview and perspective. Therapeutic advances in medical oncology Poultsides, G. A., Paty, P. B. 2011; 3 (1): 35-42

  Abstract

  In the absence of symptoms, primary tumor resection in patients who present with unresectable metastatic colorectal cancer is of uncertain benefit. Prophylactic surgery has been traditionally considered in this setting in order to prevent subsequent complications of perforation, obstruction, or bleeding later during the treatment course, which may require urgent surgery associated with higher mortality. However, recent data have called into question the efficacy of this upfront surgical strategy. We provide a brief overview of how current combinations of systemic chemotherapy including fluorouracil, oxaliplatin, irinotecan, and targeted biologic agents have allowed improved local (in addition to distant) tumor control, significantly decreasing the incidence of late primary-related complications requiring surgery from roughly 20% in the era of single-agent fluoropyrimidine chemotherapy to almost 7% in the era of modern triple-drug chemotherapy. In addition, we attempt to highlight those factors most associated with subsequent primary tumor-related complications in an effort to identify the subset of patients with synchronous metastatic colorectal cancer who might benefit from a surgery-first approach. Finally, we discuss modern nonsurgical options available for palliation of the primary colorectal tumor and review the outcome of patients for which emergent surgery is eventually required to address primary-related symptoms.

  View details for DOI 10.1177/1758834010386283

  View details for PubMedID 21789154

  View details for PubMedCentralID PMC3126037

• Intrahepatic Cholangiocarcinoma SURGICAL CLINICS OF NORTH AMERICA Poultsides, G. A., Zhu, A. X., Choti, M. A., Pawlik, T. M. 2010; 90 (4): 817-?

  Abstract

  Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the bile ducts, arising from malignant transformation of the epithelial cells that line the biliary apparatus. ICC is relatively uncommon, but its incidence is on the increase. ICC is frequently discovered as an incidental, indeterminate liver mass. Surgical resection of ICC represents the only potentially curative therapeutic option. The role of routine hilar lymphadenectomy is controversial, but should be considered to optimize staging. Although adjuvant chemotherapy and radiotherapy is probably not supported by current data, each should strongly be considered in patients with lymph node metastasis or an R1 resection. For those patients with inoperable disease, locoregional therapy with transarterial chemoembolization can be considered.

  View details for DOI 10.1016/j.suc.2010.04.011

  View details for Web of Science ID 000280985500015

  View details for PubMedID 20637950

• Histopathologic Basis for the Favorable Survival after Resection of Intraductal Papillary Mucinous Neoplasm-Associated Invasive Adenocarcinoma of the Pancreas ANNALS OF SURGERY Poultsides, G. A., Reddy, S., Cameron, J. L., Hruban, R. H., Pawlik, T. M., Ahuja, N., Jain, A., Edil, B. H., Iacobuzio-Donahue, C. A., Schulick, R. D., Wolfgang, C. L. 2010; 251 (3): 470-476

  Abstract

  To identify pathologic features that may account for the favorable survival after resection of invasive pancreatic adenocarcinoma arising in the setting of intraductal papillary mucinous neoplasm (IPMN) compared with standard pancreatic ductal adenocarcinoma (PDA) in the absence of IPMN.The 5-year survival after resection of IPMN-associated invasive adenocarcinoma is reported to be between 40% and 60%, which is superior to the 10-25%, typically cited after resection of standard PDA. It remains unclear whether this represents distinct biology or simply a tendency for earlier presentation of IPMN-associated invasive adenocarcinoma.A single institution's prospective pancreatic resection database was retrospectively reviewed to identify patients with invasive pancreatic adenocarcinoma who underwent pancreatectomy with curative intent. Log rank and Cox regression analysis were used to identify factors associated with survival.From 1995 to 2006, 1260 consecutive patients were identified, 132 (10%) with IPMN-associated invasive adenocarcinoma and 1128 (90%) with standard PDA. Actuarial 5-year survival was 42% after resection for IPMN-associated versus 19% for standard PDA (P < 0.001). However, compared with standard PDA, invasive adenocarcinoma arising within an IPMN was associated with a lower incidence of (1) advanced T stage (T2-T4, 96% vs. 73%, P < 0.001); (2) regional lymph node metastasis (78% vs. 51%, P < 0.001); (3) poor tumor differentiation (44% vs. 26%, P < 0.001); (4) vascular invasion (54% vs. 33%, P < 0.001); (5) perineural invasion (92% vs. 63%, P < 0.001); and (6) microscopic margin involvement (28% vs. 14%, P < 0.001). Specifically, in the presence of any one of the aforementioned adverse pathologic characteristics, outcomes after resection for IPMN-associated and standard PDA were not significantly different.The favorable biologic behavior of IPMN-associated compared with standard PDA is based on its lower rate of advanced T stage, lymph node metastasis, high tumor grade, positive resection margin, perineural, and vascular invasion. In the presence of any one of the aforementioned adverse pathologic characteristics, however, survival outcomes after resection of IPMN-associated and after resection of standard pancreatic adenocarcinoma are similar.

  View details for DOI 10.1097/SLA.0b013e3181cf8a19

  View details for Web of Science ID 000275060800014

  View details for PubMedID 20142731

• Hepatic resection for colorectal metastases: the impact of surgical margin status on outcome HPB Poultsides, G. A., Schulick, R. D., Pawlik, T. M. 2010; 12 (1): 43-49

  Abstract

  An R0 margin width of 1 cm has traditionally been considered a prerequisite to minimize local recurrence and optimize survival following hepatic resection for metastatic colorectal cancer. However, recent data have called into question the prognostic importance of the '1-cm rule'. Specifically, several studies have noted that, although an R0 resection is important, the actual margin width may not be as critical. We provide a brief overview of the impact of an R1 vs. an R0 resection on local recurrence and overall survival. In addition, we specifically review the impact of margin width in patients who have undergone an R0 resection. Finally, we highlight those factors most associated with an increased likelihood of an R1 resection and provide recommendations for avoiding and dealing with microscopic carcinoma discovered intraoperatively at the cut parenchymal transection margin.

  View details for DOI 10.1111/j.1477-2574.2009.00121.x

  View details for Web of Science ID 000286434900007

  View details for PubMedID 20495644

• Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment JOURNAL OF CLINICAL ONCOLOGY Poultsides, G. A., Servais, E. L., Saltz, L. B., Patil, S., Kemeny, N. E., Guillem, J. G., Weiser, M., Temple, L. K., Wong, W. D., Paty, P. B. 2009; 27 (20): 3379-3384

  Abstract

  The purpose of this study was to describe the frequency of interventions necessary to palliate the intact primary tumor in patients who present with synchronous, stage IV colorectal cancer (CRC) and who receive up-front modern combination chemotherapy without prophylactic surgery.By using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin; bolus fluorouracil, leucovorin, and irinotecan; or fluorouracil, leucovorin, and irinotecan) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded.Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (ie, stent or radiotherapy), and 213 (89%) never required any direct symptomatic management for their intact primary tumor. Of those 213 patients, 47 patients (20%) ultimately underwent elective colon resection at the time of metastasectomy, and eight patients (3%) underwent this resection during laparotomy for hepatic artery infusion pump placement. Use of bevacizumab, location of the primary tumor in the rectum, and metastatic disease burden were not associated with increased intervention rate.Most patients with synchronous, stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary tumor. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

  View details for DOI 10.1200/JCO.2008.20.9817

  View details for Web of Science ID 000267821400019

  View details for PubMedID 19487380

• Image of the Month Left Paraduodenal Hernia ARCHIVES OF SURGERY Poultsides, G. A., Zani, S., Bloom, P., Tishler, D. S. 2009; 144 (3): 287-288

  View details for Web of Science ID 000264218700021

  View details for PubMedID 19289672

• Epigenetic regulation of hTERT promoter in hepatocellular carcinomas INTERNATIONAL JOURNAL OF ONCOLOGY Iliopoulos, D., Satra, M., Drakaki, A., Poultsides, G. A., Tsezou, A. 2009; 34 (2): 391-399

  Abstract

  Although hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, the molecular pathogenesis of the disease has not been elucidated. Several studies have shown that telomerase activity and hTERT expression are increased in HCCs. In the present study we tried to elucidate hTERT transcriptional and epigenetic regulatory mechanisms in HCC. hTERT expression was tested by real-time PCR and DNA methylation status was assessed by MethyLight and DNA bisulfite sequencing analyses in 106 tissues (64 with HCC and 42 without liver disorders) and also in 7 hepatocarcinoma cell lines (HepG2, HepG3B2, C3A, SNU-182, SNU-398, SBU-449 and SNU-475). hTERT expression levels were inversely correlated with DNA methylation levels in HCC and normal tissues (r=-0.859). hTERT expression was found to be regulated by DNA methylation and histone H3-K9 modifications, affecting the ability of c-myc binding in E-box 1 site in hTERT promoter. Additionally, c-myc siRNA liposomal down-regulation inhibited significantly hTERT expression (p<0.05). Thus, we propose that hTERT is regulated by a combination of epigenetic mechanisms (DNA methylation and histone modifications) and by the transcription factor c-myc in HCC.

  View details for DOI 10.3892/ijo_00000162

  View details for Web of Science ID 000262619500012

  View details for PubMedID 19148473

• Angiographic embolization for gastroduodenal hemorrhage 88th Annual Meeting of the New-England-Surgical-Society Poultsides, G. A., Kim, C. J., Orlando, R., Peros, G., Halliscy, M. J., Vignati, P. V. AMER MEDICAL ASSOC. 2008: 457–61

  Abstract

  To examine the safety, efficacy, and predictors of outcome of angiographic embolization in the management of gastroduodenal hemorrhage.Retrospective record review.University-affiliated tertiary care center.All of the patients were referred after endoscopic treatment failure. Surgery was not immediately considered because of poor surgical risk, refusal to consent, or endoscopist's decision. Patients with coagulopathy, hemobilia, and variceal or traumatic upper gastrointestinal tract bleeding were excluded from review.Between January 1, 1996, and December 31, 2006, 70 embolization procedures were performed in 57 patients.Technical success rate (target vessel devascularization), clinical success rate (in-hospital cessation of bleeding without further endoscopic, radiologic, or surgical intervention), and complications.The technical success rate was 94% (66 of 70 angiographies). The primary clinical success rate was 51% (29 of 57 patients), and the clinical success rate after repeat embolization was 56% (32 of 57 patients). Two factors were found to be independent predictors of poor outcome by multivariate analysis: recent duodenal ulcer suture ligation (P = .03) and blood transfusion of more than 6 units prior to the procedure (P = .04). There was no predictive value for angiographic failure based on age, sex, prior coagulopathy, renal failure at presentation, immunocompromised status, multiple organ system failure, empirical (blind) embolization, and use of permanent vs temporary embolic agents. Repeat embolizations were helpful for postsphincterotomy bleeding. Major ischemic complications (4 patients [7%]) were associated with previous foregut surgery.Angiographic embolization for gastroduodenal hemorrhage was associated with in-hospital rebleeding in almost half of the patients. Angiographic failure can be predicted if embolization is performed late, following blood transfusion of more than 6 units, or for rehemorrhage from a previously suture-ligated duodenal ulcer.

  View details for Web of Science ID 000255691800004

  View details for PubMedID 18490553

• Hand-assisted laparoscopic management of liver tumors SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Poultsides, G., Brown, M., Orlando, R. 2007; 21 (8): 1275-1279

  Abstract

  Laparoscopy has clearly advanced the treatment of many diseases related to the liver and biliary tree. The addition of hand assistance can further facilitate minimally invasive liver surgery by providing tactile feedback, atraumatic and versatile retraction, finger-fracture parenchyma dissection, and more precise placement of probes and staplers.Over a 7-year period, 28 patients with liver tumors underwent 31 hand-assisted laparoscopic operations at a tertiary care center. The candidates for hand-assisted laparoscopic resection were patients with lesions involving two hepatic segments or fewer located at the inferior edge of the liver (segments 5 and 6), or confined to the left lateral segment (segments 2 and 3). Ablation was reserved for patients with poor functional status or limited hepatic reserve, and hand-assistance was added for laparoscopic ablation of centrally located tumors (segments 7, 8, and 4a).The selection criteria were met by 52 patients, 6 of whom had benign lesions. The remaining 46 patients had malignant disease, and 15 of these patients (33%) were found to have extrahepatic disease: 11 at initial laparoscopy and 4 at hand-assisted abdominal exploration. Manual exploration also detected additional intrahepatic treatable lesions in two cases. A total of 19 patients (68%) had metastatic disease, and 3 (11%) had primary liver cancer. The most extensive resections were five left lateral segmentectomies. All margins were negative. The mean operative time was 2.75 h, and the mean blood loss was 230 ml. Two diaphragmatic injuries occurred during ablation of segment 8 lesions. Three cases were converted to open surgery because of adhesions. The mean hospital stay was 3.7 days. A group of 15 patients who had metastatic colorectal cancer treated with resection and/or ablation had a mean follow-up period of 24 months (range, 2-61 months) and a mean survival time of 36 months.For selected patients, the hand-assisted technique can be applied safely and effectively to laparoscopic liver surgery and may identify the presence of previously undetectable intrahepatic or extrahepatic disease.

  View details for DOI 10.1007/s00464-006-9174-8

  View details for Web of Science ID 000248737700003

  View details for PubMedID 17479339

• Carcinoid of the ampulla of Vater: Morpholdgic features and clinical implications WORLD JOURNAL OF GASTROENTEROLOGY Poultsides, G. A., Frederick, W. A. 2006; 12 (43): 7058-7060

  Abstract

  Carcinoids involving the ampulla of Vater are rare lesions that may produce painless jaundice. The published data indicate that these tumors, in contrast to their midgut counterparts, metastasize in approximately half of cases irrespective of primary tumor size. Therefore, radical excision in the form of pancreaticoduodenectomy is recommended regardless of tumor size. As with other gastrointestinal carcinoid tumors, biological treatment with octreotide analogues can be applied to symptomatic patients. Tumor-targeted radioactive therapy is a newly emerging treatment option. We here report case of a carcinoid tumor of the ampulla of Vater presenting as painless jaundice in a 65-year old man and review the relevant literature, giving special attention to the morphologic features, clinical characteristics, and treatment modalities associated with this disease process.

  View details for Web of Science ID 000242299300026

  View details for PubMedID 17109507

• Range of movement in the wrist as a diagnostic tool in radial-sided wrist pain SCANDINAVIAN JOURNAL OF PLASTIC AND RECONSTRUCTIVE SURGERY AND HAND SURGERY Wollstein, R., Watson, H. K., Poultsides, G., Wear-Maggitti, K., Carlson, L. 2006; 40 (4): 230-233

  Abstract

  Kienböck disease is diagnosed by imaging studies, and is often difficult to diagnose in its early stages. Our clinical impression is that wrist movement is more limited in Kienböck disease than when radial-sided wrist pain is caused by other conditions. The purpose of this study was to determine the use of wrist movement in differentiating between early Kienböck disease and radial-sided sprained wrist. We retrospectively reviewed 62 cases of Kienböck disease and 49 patients with radial-sided wrist sprain. Wrist movement at presentation was recorded. The two groups differed significantly in flexion and extension (p<0.001). The ability of movement of the affected wrist relative to the normal side to distinguish between the groups was excellent (AUC = 0.96, 0.97, respectively). The ability of wrist movement measurements to differentiate between early Kienböck disease and radial-sided wrist sprain emphasises that wrist movement should be measured prior to invasive or expensive testing.

  View details for DOI 10.1080/02844310600679590

  View details for Web of Science ID 000239816700007

  View details for PubMedID 16911997

• Portal vein thrombosis after laparoscopic colectomy: Thrombolytic therapy via the superior mesenteric vein AMERICAN SURGEON Poultsides, G. A., Lewis, W. C., Feld, R., Walters, D. L., Cherry, D. A., Ruby, S. T. 2005; 71 (10): 856-860

  Abstract

  Portal vein thrombosis is a rare but well-reported complication after laparoscopic surgery. We present a case of portomesenteric venous thrombosis that occurred 8 days after a laparoscopic-assisted right hemicolectomy. Systemic anticoagulation failed to improve symptoms. The early postoperative state precluded the use of transarterial thrombolytic therapy. Transjugular intrahepatic catheter-directed infusion of urokinase into the superior mesenteric vein resulted in clearance of thrombus and resolution of symptoms. The published data on laparoscopy-induced splanchnic venous thrombosis and transjugular intrahepatic intramesenteric thrombolysis are discussed.

  View details for Web of Science ID 000232812000013

  View details for PubMedID 16468535

• Common origins of carotid and subclavian arterial systems: Report of a rare aortic arch variant ANNALS OF VASCULAR SURGERY Poultsides, G. A., Lolis, E. D., VASQUEZ, J., Drezner, A. D., Venieratos, D. 2004; 18 (5): 597-600

  Abstract

  An aberrant right subclavian artery (aSA) arising from the proximal descending aorta is one of the most common anomalies of the aortic arch. We present our experience with an asymptomatic atypical aSA variant found during routine anatomic dissection. This aortic arch variant had two branches, the first being a bicarotid trunk and the second being a common trunk for both subclavian arteries. The right subclavian artery traveled behind the esophagus to reach the right upper extremity, thus forming an incomplete vascular ring around the trachea and the esophagus. The literature has been silent about the existence of this exact aSA variation. A plausible embryologic explanation is provided. An aSA is rarely symptomatic, but when symptoms do occur and intervention is warranted, it is important for surgeons and radiologists alike to be aware of the vascular anomalies that may potentially coexist with this entity. The surgical and endovascular options associated with this unique vascular anomaly are also discussed.

  View details for DOI 10.1007/s10016-004-0060-3

  View details for Web of Science ID 000223785100014

  View details for PubMedID 15534741

• Double trisomy (48,XXY,+21) in monozygotic twins: case report and review of the literature ANNALES DE GENETIQUE Iliopoulos, D., Poultsides, G., Peristeri, V., KOURI, G., Andreou, A., Voyiatzis, N. 2004; 47 (1): 95-98

  Abstract

  The occurrence of double aneuploidy in the same individual is a relatively rare phenomenon. We describe twin newborns with typical clinical features of Down's syndrome, of which one revealed 48,XXY,+21 GTG-band karyotype. The second newborn died 2 days after its birth, and was clinically diagnosed having Down syndrome. Due to the same clinical features of the twins, the common placenta and amniotic sac, we speculate that they were monozygotics and as a result the second newborn should also be a Klinefelter. The purpose of this report is to present a rare case of possible coincidence of double aneuploidy in newborn twins. A review of the literature showed that double trisomy (48,XXY,+21) in a twin newborn infant has never occurred.

  View details for DOI 10.1016/j.anngen.2003.08.025

  View details for Web of Science ID 000221069400010

  View details for PubMedID 15050879

• Endovascular stent-graft placement for nonaneurysmal infrarenal aortic rupture: A case report and review of the literature JOURNAL OF VASCULAR SURGERY VASQUEZ, J., Poultsides, G. A., Lorenzo, A. C., Foster, J. E., Drezner, A. D., Gallagher, J. 2003; 38 (4): 836-839

  Abstract

  Penetrating atheromatous ulceration of the infrarenal aorta is a rare entity. There are few reported cases of this lesion, and most of the published data is in regards to the thoracic aorta. Spontaneous rupture of a nonaneurysmal noninfected atherosclerotic infrarenal aorta is a rare event. We report the eleventh case of this occurrence and present the first reported case of endovascular stent-graft placement in treating this entity. We review the literature regarding ulcerative disease of the aorta and specifically discuss the published data on spontaneous rupture of the nondilated, noninfected infrarenal aorta secondary to penetrating atheromatous ulceration.

  View details for DOI 10.1016/S0741-5214(03)00557-3

  View details for Web of Science ID 000185858700035

  View details for PubMedID 14560239

• Distal trapezius musculocutaneous flap for upper thoracic back wounds associated with spinal instrumentation and radiation ANNALS OF PLASTIC SURGERY Chun, J. K., Lynch, M. J., Poultsides, G. A. 2003; 51 (1): 17-22

  Abstract

  Upper thoracic wounds with exposed hardware from spinal instrumentation and previous radiation presents a subset of back wound coverage problems that lend themselves to a unique opportunity to use the distal trapezius musculocutaneous flap. The unradiated, healthy skin paddle can be transposed between the radiated skin edges to seal and cover the exposed hardware and achieve early primary healing of the back wound without the need for a skin graft. The authors review their series of the upper back radiated wounds reconstructed with the trapezius musculocutaneous flaps, immediately at the time of the spinal surgery and secondarily after the incisional wound breakdown, to cover the exposed hardware. Their contiguous skin flap design strategy, results, and complications are discussed.

  View details for Web of Science ID 000184132000004

  View details for PubMedID 12838120