Raja Narayan, MD MPH

All Publications

• Addition of adjuvant hepatic artery infusion to systemic chemotherapy following resection of colorectal liver metastases is associated with reduced liver-related mortality. Journal of surgical oncology Srouji, R., Narayan, R., Boerner, T., Buisman, F., Seier, K., Gonen, M., Balachandran, V. P., Drebin, J., Jarnagin, W. R., Kingham, T. P., Wei, A., Kemeny, N. E., D'Angelica, M. 2020

  Abstract

  BACKGROUND: After resection of colorectal liver metastases (CRLM), recurrent disease in the liver is a major cause of death but may be reduced with the addition of adjuvant hepatic arterial infusion (HAI) chemotherapy to systemic chemotherapy (SYS).OBJECTIVE: This study investigates organ-specific causes of death in patients receiving adjuvant HAI and SYS compared to adjuvant SYS alone.METHODS: Between 2000 and 2007, patients undergoing complete CRLM resection were identified from a prospectively maintained liver resection database and categorized as receiving HAI+SYS or SYS only. Using newly constructed definitions, mortality was attributed to specific organs (liver, lung, peritoneum, and brain) or infection. Univariate models and cumulative incidence functions were generated using competing risk methods.RESULTS: Of 361 eligible patients, 208 (57.6%) received HAI+SYS and 153 (42.4%) received SYS. The median follow up among survivors was 142 months (range=12-217 months). Ten-year overall survival was 50.6% in the HAI+SYS group compared to 30.9% in those receiving SYS (P=.004). The 5-year cumulative incidence of liver-related mortality was 6.8% in the HAI+SYS group compared to 14.3% in the SYS group (P=.007).CONCLUSION: The addition of HAI to SYS after CRLM resection is associated with a 50% reduction in liver-related mortality at 5 years.

  View details for DOI 10.1002/jso.25916

  View details for PubMedID 32236970

• Disease-free interval and tumor functional status can be used to select patients for resection/ablation of liver metastases from adrenocortical carcinoma: insights from a multi-institutional study. HPB : the official journal of the International Hepato Pancreato Biliary Association Ayabe, R. I., Narayan, R. R., Ruff, S. M., Wach, M. M., Lo, W., Nierop, P. M., Steinberg, S. M., Ripley, R. T., Davis, J. L., Koerkamp, B. G., D'Angelica, M. I., Kingham, T. P., Jarnagin, W. R., Hernandez, J. M. 2020; 22 (1): 169?75

  Abstract

  Adrenocortical carcinoma (ACC) is an aggressive malignancy that frequently metastasizes to the liver. Given the limitations of systemic therapy in this setting, we sought to determine characteristics associated with a two-fold increase in survival with resection/ablation compared to that reported with chemotherapy alone (?12 months).Patients who underwent resection/ablation at our institutions for ACC liver metastases were identified. Those who survived 12-24 months after metastasectomy were excluded, as the aim was to characterize patients who most clearly benefited from these procedures. Clinicopathologic and treatment characteristics were assessed for associations with survival.Sixty-two patients met inclusion criteria, of whom 44 survived >24 months and 18 survived <12 months. Patients with extended survival were less likely to have functioning tumors (p = 0.047), had fewer liver metastases (p = 0.047), and a longer disease-free interval (DFI) (median 17.6 vs 2.3 months, p < 0.0001). On multivariable analysis, DFI (OR = 1.33, 95% CI = 1.12-1.58) and non-functioning tumor (OR = 0.13, 95% CI = 0.13-0.56) were independently associated with prolonged survival.Metastasectomy/ablation should be considered for patients with ACC liver metastases. DFI and tumor functional status may be useful in selecting optimal candidates for these procedures.

  View details for DOI 10.1016/j.hpb.2019.07.002

  View details for PubMedID 31447392

• ASO Author Reflections: Perioperative Genomic Profiles and Prognosis of Peripheral and Perihepatic Circulating Tumor DNA in Patients with Colorectal Liver Metastases ANNALS OF SURGICAL ONCOLOGY Narayan, R. R., Kingham, T. 2019; 26: S583?S584

  View details for DOI 10.1245/s10434-019-07360-5

  View details for Web of Science ID 000509110700031

• Quantification of Donor Liver Steatosis Using an Unsupervised Artificial Intelligence Platform Narayan, R., Abadilla, N., Yang, L., Hsu, C., Jensen, C., Chen, S. B., Higgins, J. P., Melcher, M. L. ELSEVIER SCIENCE INC. 2019: E151

  View details for Web of Science ID 000492749600360

• 10-Year Experience of Kasai Hepatoportoenterostomy in Biliary Atresia: High-Dose Adjuvant Steroids Improve Outcomes Taylor, J., Abadilla, N., Narayan, R., Pickering, J. M., Bruzoni, M. ELSEVIER SCIENCE INC. 2019: E164

  View details for Web of Science ID 000492749600386

• Peripheral Circulating Tumor DNA Detection Predicts Poor Outcomes After Liver Resection for Metastatic Colorectal Cancer Narayan, R. R., Goldman, D. A., Gonen, M., Reichel, J., Huberman, K. H., Raj, S., Viale, A., Kemeny, N. E., Allen, P. J., Balachandran, V. P., D'Angelica, M. I., DeMatteo, R. P., Drebin, J. A., Jarnagin, W. R., Kingham, T. SPRINGER. 2019: 1824?32

  View details for DOI 10.1245/s10434-019-07201-5

  View details for Web of Science ID 000467643800036

• ASO Author Reflections: Perioperative Genomic Profiles and Prognosis of Peripheral and Perihepatic Circulating Tumor DNA in Patients with Colorectal Liver Metastases. Annals of surgical oncology Narayan, R. R., Kingham, T. P. 2019

  View details for PubMedID 30989499

• Predicting Pathology From Imaging in Children Undergoing Resection of Congenital Lung Lesions Narayan, R. R., Abadilla, N., Greenberg, D. R., Sylvester, K. G., Hintz, S. R., Barth, R. A., Bruzoni, M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2019: 68?73

  View details for DOI 10.1016/j.jss.2018.10.042

  View details for Web of Science ID 000458498300010

• Regional differences in gallbladder cancer pathogenesis: Insights from a multi-institutional comparison of tumor mutations CANCER Narayan, R. R., Creasy, J. M., Goldman, D. A., Gonen, M., Kandoth, C., Kundra, R., Solit, D. B., Askan, G., Klimstra, D. S., Basturk, O., Allen, P. J., Balachandran, V. P., D'Angelica, M., DeMatteo, R. P., Drebin, J. A., Kingham, T., Simpson, A. L., Abou-Alfa, G. K., Harding, J. J., O'Reilly, E. M., Butte, J. M., Matsuyama, R., Endo, I., Jarnagin, W. R. 2019; 125 (4): 575?85

  View details for DOI 10.1002/cncr.31850

  View details for Web of Science ID 000457532800009

• Lost in translation: Informed consent in the medical mission setting Sceats, L. A., Morris, A. M., Narayan, R. R., Mezynski, A., Woo, R. K., Yang, G. P. MOSBY-ELSEVIER. 2019: 438?43

  View details for DOI 10.1016/j.surg.2018.06.010

  View details for Web of Science ID 000455970900030

• Peripheral Circulating Tumor DNA Detection Predicts Poor Outcomes After Liver Resection for Metastatic Colorectal Cancer. Annals of surgical oncology Narayan, R. R., Goldman, D. A., Gonen, M., Reichel, J., Huberman, K. H., Raj, S., Viale, A., Kemeny, N. E., Allen, P. J., Balachandran, V. P., D'Angelica, M. I., DeMatteo, R. P., Drebin, J. A., Jarnagin, W. R., Kingham, T. P. 2019

  Abstract

  BACKGROUND: Liver resection can be curative for well-selected metastatic colorectal cancer (CRC) patients. Circulating tumor DNA (ctDNA) has shown promise as a biomarker for tumor dynamics and recurrence following CRC resection. This prospective pilot study investigated the use of ctDNA to predict disease outcome in resected CRC patients.METHODS: Between November 2014 and November 2015, 60 patients with CRC were identified and prospectively enrolled. During liver resection, blood was drawn from peripheral (PERIPH), portal (PV), and hepatic (HV) veins, and 3-4weeks postoperatively from a peripheral vein (POSTOP). Kappa statistics were used to compare mutated (mt) genes in tissue and ctDNA. Disease-specific and disease-free survival (DSS and DFS) were assessed from surgery with Kaplan-Meier and Cox methods.RESULTS: For the 59 eligible patients, the most commonly mutated genes were TP53 (mtTP53: 47.5%) and APC (mtAPC: 50.8%). Substantial to almost-perfect agreement was seen between ctDNA from PERIPH and PV (mtTP53: 89.8%, kappa=0.73, 95% confidence interval [CI] 0.53-0.93; mtAPC: 94.9%, kappa=0.83, 95% CI 0.64-1.00), as well as HV (mtTP53: 91.5%, kappa=0.78, 95% CI 0.60-0.96; mtAPC: 91.5%, kappa=0.73, 95% CI 0.51-0.95). Tumor mutations and PERIPH ctDNA had fair-to-moderate agreement (mtTP53:72.9%, kappa=0.44, 95% CI 0.23-0.66; mtAPC: 61.0%, kappa=0.23, 95% CI 0.04-0.42). Detection of PERIPH mtTP53 was associated with worse 2-year DSS (mt+ 79% vs. mt- 90%, P=0.024).CONCLUSIONS: Peripheral blood reflects the perihepatic ctDNA signature. Disagreement between tissue and ctDNA mutations may reflect the true natural history of tumor genes or an assay limitation. Peripheral ctDNA detection before liver resection is associated with worse DSS.

  View details for PubMedID 30706231

• Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review. JAMA surgery Datta, J., Narayan, R. R., Kemeny, N. E., D'Angelica, M. I. 2019

  Abstract

  Although liver metastasis develops in more than half of patients with colorectal cancer, only 15% to 20% of these patients have resectable liver metastasis at presentation. Moreover, patients with initially unresectable colorectal liver metastasis (IU-CRLM) who progress on first-line systemic chemotherapy have limited treatment options. Hepatic arterial infusion chemotherapy (HAIC), in combination with systemic chemotherapy, leverages a multimodality approach to achieving control of hepatic disease and/or expanding resectability in patients with liver-only disease or liver-dominant disease.Intra-arterial delivery of agents with high first-pass hepatic extraction (eg, floxuridine) limits systemic toxic effects and allows for administration of systemic chemotherapy at near-full doses. Hepatic arterial infusion chemotherapy in conjunction with systemic chemotherapy augments response rates up to 92% in patients who are chemotherapy naive, and up to 85% in pretreated patients with IU-CRLM. In turn, these responses translate into encouraging rates of conversion to resectability (CTR). Prospective trials have reported CTR rates as high as 52% in heavily pretreated patients with IU-CRLM who have an extensive hepatic disease burden. As such, CTR remains a compelling indication for liver-directed chemotherapy in this subset of patients. This review discusses the biological rationale for HAIC, evolution of rational combinations with systemic chemotherapy, contemporary evidence for CTR using HAIC and systemic chemotherapy, juxtaposition with rates of CTR using systemic chemotherapy alone, and morbidity and toxic effect profiles of HAIC.The argument is made for consideration of earlier initiation of HAIC in patients with IU-CRLM who are chemotherapy naive and for adoption of HAIC strategies to augment rates of resectability in patients who have failed first-line systemic chemotherapy before proceeding to second-line or third-line regimens.

  View details for DOI 10.1001/jamasurg.2019.1694

  View details for PubMedID 31188415

• Prediction of Recurrence Patterns from Hepatic Parenchymal Disease After Resection of Colorectal Liver Metastases. Annals of surgical oncology Narayan, R. R., Harris, J. W., Chou, J. F., Gönen, M., Bao, F., Shia, J., Allen, P. J., Balachandran, V. P., Drebin, J. A., Jarnagin, W. R., Kemeny, N. E., Kingham, T. P., D'Angelica, M. I. 2019

  Abstract

  Obesity and metabolic syndrome are associated with inflammatory hepatic parenchymal disease (HPD) and increased risk for recurrence after resection of colorectal liver metastases (CRLM). The independent impact of HPD on recurrence patterns has not been well defined.The nonalcoholic fatty liver disease activity score (NAS) was used to quantify HPD including steatosis and fibrosis for all patients with completely resected CRLM between April 2003 and March 2007. Clinicopathologic factors, perioperative history, and outcomes were compared with the NAS. Fisher's exact test was used to examine the association between severe HPD (NAS???3) with clinical and perioperative characteristics. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS). The cumulative incidences of recurrence [any intrahepatic recurrence (IHR), extrahepatic recurrence only (EHR), and death without recurrence (DWR)] were estimated using competing risks methods.Among the 357 patients included in this study, microsteatosis was noted in 124 (35%) patients, severe HPD in 31 (9%), steatohepatitis in 14 (4%), and sinusoidal injury in 36 (10%). After median follow-up of 127 months (range 4-175 months), 10-year RFS was 22% [95% confidence interval (CI) 17-27%]. Ten-year cumulative incidence for IHR, EHR, and DWR was 37%, 30%, and 12%, respectively. After controlling for confounders, NAS???3 was independently associated with higher risk of IHR [hazard ratio (HR) 1.76, 95% CI 1.07-2.90, p?=?0.027] and lower risk of EHR (HR 0.18, 95% CI 0.04-0.75, p?=?0.019) on multivariable analysis.Severe HPD was associated with increased IHR risk and decreased EHR risk. Future investigation into whether improving HPD from reversible etiologies can reduce the risk for IHR is warranted.

  View details for DOI 10.1245/s10434-019-07934-3

  View details for PubMedID 31617122

• Predicting Pathology From Imaging in Children Undergoing Resection of Congenital Lung Lesions. The Journal of surgical research Narayan, R. R., Abadilla, N., Greenberg, D. R., Sylvester, K. G., Hintz, S. R., Barth, R. A., Bruzoni, M. 2018; 236: 68?73

  Abstract

  BACKGROUND: Prenatal magnetic resonance imaging (MRI) is increasingly obtained to define congenital lung lesions (CLL) for surgical management. Postnatal, preoperative computed tomography (CT) provides further clarity at the cost of radiation. Depending on the lesion identified, the indication for resection remains controversial. We investigated the differences in detail found on prenatal MRI and postnatal CT compared with final pathology to determine their utility in preoperative decision-making.MATERIALS AND METHODS: All children undergoing resection of CLLs at a single institution between July 2009 and February 2018 were retrospectively identified. Their imaging, operative, and pathology reports were compared. All imaging studies were examined by pediatric radiologists with experience in prenatal CLL diagnosis.RESULTS: Fifty-five patients underwent CLL resection during the study period with 31 undergoing prenatal MRI, 45 postnatal CT, and 22 both. Resection was performed before 6 mo of age in 62% of patients. In the cohort undergoing both imaging studies, pathologic CLL diagnosis correlated with prenatal MRI and CT in 82% and 100% of patients, respectively (P=0.13). Eight patients had systemic feeding vessels, of which 38% were identified on MRI, and 88% on CT (P=0.13). Both studies had a specificity of 100% for detecting systemic feeding vessels.CONCLUSIONS: For children where prenatal MRI detected a systemic feeding vessel, CT was redundant for preoperative planning but had greater sensitivity. Ultimately, the CLL type predicted from postnatal CT was not significantly different from that predicted by prenatal MRI; however, both imaging modalities had some level of discrepancy with pathology.

  View details for PubMedID 30694781

• Pancreaticoduodenectomy with right gastric vessels preservation: impact on intraoperative and postoperative outcomes. ANZ journal of surgery Gagniere, J., Le Roy, B., Veziant, J., Pereira, B., Narayan, R. R., Pezet, D., Buc, E., Dupre, A. 2018

  Abstract

  BACKGROUND: Sympathetic denervation of the antropyloric area combined with relative devascularization from division of the right gastric vessels (RGV) during pancreaticoduodenectomy (PD) could predispose to delayed gastric emptying (DGE). Therefore, some authors advocated for RGV preservation (RGVP), where feasibility and utility for the prevention of post-operative DGE have never been investigated.METHODS: From 2011 to 2014, patients who underwent classic Whipple PD (CWPD, n=34), standard pylorus-preserving PD (PPPD, n=44) or PPPD with RGVP (n=22) were retrospectively analysed.RESULTS: RGVP was not possible in 12% of the cases because of an intraoperative injury of the RGV. There was no difference between CWPD, standard PPPD and PPPD with RGVP in terms of intraoperative blood loss, operative time, number of lymph node harvested and resection margins. Post-operative morbidity and mortality were comparable between the three groups, including rate (27%, 34% and 32%, P=0.77) and severity of DGE, delay in removing nasogastric tube and use of prokinetics. Hospital stay was similar in all the compared groups.CONCLUSION: This is the first study comparing post-operative outcomes after PPPD with RGVP, standard PPPD and CWPD. Although feasible and safe, RGVP during PPPD appeared to offer no obvious clinical benefit in terms of preventing post-operative complications, especially DGE.

  View details for PubMedID 30497109

• Regional differences in gallbladder cancer pathogenesis: Insights from a multi-institutional comparison of tumor mutations. Cancer Narayan, R. R., Creasy, J. M., Goldman, D. A., Gonen, M., Kandoth, C., Kundra, R., Solit, D. B., Askan, G., Klimstra, D. S., Basturk, O., Allen, P. J., Balachandran, V. P., D'Angelica, M. I., DeMatteo, R. P., Drebin, J. A., Kingham, T. P., Simpson, A. L., Abou-Alfa, G. K., Harding, J. J., O'Reilly, E. M., Butte, J. M., Matsuyama, R., Endo, I., Jarnagin, W. R. 2018

  Abstract

  BACKGROUND: Although rare in the United States, gallbladder cancer (GBCA) is a common cause of cancer death in some parts of the world. To investigate regional differences in pathogenesis and outcomes for GBCA, tumor mutations were analyzed from a sampling of specimens.METHODS: Primary tumors from patients with GBCA who were treated in Chile, Japan, and the United States between 1999 and 2016 underwent targeted sequencing of known cancer-associated genes. Fisher exact and Kruskal-Wallis tests assessed differences in clinicopathologic and genetic factors. Kaplan-Meier methods evaluated differences in overall survival from the time of surgery between mutations.RESULTS: A total of 81 patients were included. Japanese patients (11 patients) were older (median age, 72 years [range, 54-81 years]) compared with patients from Chile (21 patients; median age, 59 years [range, 32-73 years]) and the United States (49 patients; median age, 66 years [range, 46-87 years]) (P=.002) and had more well-differentiated tumors (46% vs 0% for Chile/United States; P<.001) and fewer gallstone-associated cancers (36% vs 67% for Chile and 69% for the United States; P=.13). Japanese patients had a median mutation burden of 6 (range, 1-23) compared with Chile (median mutation burden, 7 [range, 3-20]) and the United States (median mutation burden, 4 [range, 0-27]) (P=.006). Tumors from Japanese patients lacked AT-rich interaction domain 1A (ARID1A) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations, whereas Chilean tumors lacked Erb-B2 receptor tyrosine kinase 3 (ERBB3) and AT-rich interaction domain 2 (ARID2) mutations. SMAD family member 4 (SMAD4) was found to be mutated similarly across centers (38% in Chile, 36% in Japan, and 27% in the United States; P=.68) and was univariately associated with worse overall survival (median, 10 months vs 25 months; P=.039). At least one potentially actionable gene was found to be altered in 80% of tumors.CONCLUSIONS: Differences in clinicopathologic variables suggest the possibility of distinct GBCA pathogenesis in Japanese patients, which may be supported by differences in mutation pattern. Among all centers, SMAD4 mutations were detected in approximately one-third of patients and may represent a converging factor associated with worse survival. The majority of patients carried mutations in actionable gene targets, which may inform the design of future trials.

  View details for PubMedID 30427539

• Lost in translation: Informed consent in the medical mission setting. Surgery Sceats, L. A., Morris, A. M., Narayan, R. R., Mezynski, A., Woo, R. K., Yang, G. P. 2018

  Abstract

  BACKGROUND: Informed consent is a fundamental tenet of ethical care, but even under favorable conditions, patient comprehension of consent conversations may be limited. Little is known about providing informed consent in more uncertain situations such as medical missions. We sought to examine the informed consent process in the medical mission setting.METHODS: We studied informed consent for adult patients undergoing inguinal herniorrhaphy during a medical mission to Guatemala using a convergent mixed-methods design. We audiotaped informed consents during preoperative visits and immediately conducted separate surveys to elicit comprehension of risks. Informed consent conversations and survey responses were translated and transcribed. We used descriptive statistics to examine informed consent content, including information provided by surgeon, the translation of information, and patient comprehension, and used thematic analysis to examine the consent process.RESULTS: Thirteen adult patients (median age 53 years, 69% male) participated. Surgeons conveyed 4 standard risks in 10 out of 13 encounters (77%); all 4 risks were translated to patients in 10 out of 13 encounters (77%). No patient could recall all 4 risks. Qualitative themes regarding the informed consent process included limited physician language skills, verbal domination by physicians and interpreters, and mistranslation of risks. Patients relied on faith and prior or vicarious experiences to qualify surgical risks instead of consent conversations. Many patients restated surgical instructions when asked about risks.CONCLUSION: Despite physicians' attempts to provide informed consent, medical mission patients did not comprehend surgical risks. Our data reveal a critical need to develop more effective methods for communicating surgical risks during medical missions.

  View details for PubMedID 30061041

• Robotic-Assisted Lobectomies in the National Cancer Database JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Arnold, B. N., Thomas, D. C., Narayan, R., Blasberg, J. D., Detterbeck, F. C., Boffa, D. J., Kim, A. W. 2018; 226 (6): 1052?62

  Abstract

  Robotic-assisted thoracoscopic surgery (RobATS) lobectomy is becoming more common for the treatment of lung cancer. As with any relatively new technology, there is the assumption that greater experience leads to greater proficiency. The objective of this study was to analyze outcomes of patients undergoing RobATS lobectomy as hospitals gain experience, and to describe outcomes after conversion to open procedures.The National Cancer Database (NCDB) was used to analyze robotic lobectomies for lung cancer from 2010 to 2014. Individual hospitals were categorized by the year they began reporting robotic lobectomies to the NCDB. Primary outcomes were perioperative morbidity and mortality and rate of conversion to open lobectomy.There were 7,645 robotic lobectomies identified from 465 hospitals. The overall conversion rate was 9.2% (n = 702). A propensity-matched analysis showed no significant difference between experienced and inexperienced hospitals with respect to 30-day mortality (1.07% vs 2.03%, p = 0.092) or 90-day mortality (2.35% vs 3.63%, p = 0.104). Conversion to open was a predictor of 30-day mortality (odds ratio [OR] 2.54, CI 1.56 to 4.14) and 90-day mortality (OR 2.68, CI 1.83 to 3.91). Patients who underwent conversion had higher 90-day mortality compared with patients not undergoing conversion, in years of experience: 2 (p = 0.043), 3 (p = 0.002), and 4 (p = 0.003).Mortality after RobATS lobectomy at experienced hospitals is not significantly different than at inexperienced hospitals. Though conversion rates decrease with experience, patients who undergo conversion have higher mortality than those who do not, particularly in hospitals with more experience. This suggests that a deliberate effort to increase experience with and improve patient selection for RobATS lobectomies may ameliorate the conversions and their attendant sequelae.

  View details for DOI 10.1016/j.jamcollsurg.2018.03.023

  View details for Web of Science ID 000433087400025

  View details for PubMedID 29574177

• Predicting Pathology from Imaging in Children Undergoing Resection of Congenital Pulmonary Malformations Narayan, R. R., Abadilla, N., Greenberg, D. R., Bruzoni, M. ELSEVIER SCIENCE INC. 2017: S154

  View details for DOI 10.1016/j.jamcollsurg.2017.07.347

  View details for Web of Science ID 000413315300327