George A. Poultsides, MD

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

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 Web of Science ID 000329763900008

View details for PubMedID 24321190

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

View details for PubMedID 23633157

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

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

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 Web of Science ID 000317308200032

View details for PubMedID 23149854

View details for DOI 10.1016/j.jvs.2012.01.048

View details for Web of Science ID 000315944400045

View details for PubMedID 23446129

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 Web of Science ID 000313548400009

View details for PubMedID 23297725

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

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

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 Web of Science ID 000308883700011

View details for PubMedID 22987171

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

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 Web of Science ID 000305993800007

View details for PubMedID 22762402

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 Web of Science ID 000305558000030

View details for PubMedID 22396008

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

View details for Web of Science ID 000305746100009

View details for PubMedID 22212729

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

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 Web of Science ID 000301923400002

View details for PubMedID 22333441

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

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

View details for DOI 10.1007/s10620-011-1757-0

View details for Web of Science ID 000294800100005

View details for PubMedID 21643740

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 Web of Science ID 000293651000002

View details for PubMedID 21936439

View details for DOI 10.1007/s10620-011-1677-z

View details for Web of Science ID 000291481800006

View details for PubMedID 21445579

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 Web of Science ID 000291851500018

View details for PubMedID 21690450

View details for DOI 10.1007/s10620-011-1573-6

View details for Web of Science ID 000289899200008

View details for PubMedID 21253833

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

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

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

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

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

View details for Web of Science ID 000264218700021

View details for PubMedID 19289672

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

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

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

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

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

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

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

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

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

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