Publications by authors named "Jashodeep Datta"

70 Publications

Disentangling the obesity paradox in upper gastrointestinal cancers: Weight loss matters more than body mass index.

Cancer Epidemiol 2021 Feb 26;72:101912. Epub 2021 Feb 26.

Division of Gastroenterology and Hepatology, Perelman School of Medicine at the University of Pennsylvania, United States; Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, United States. Electronic address:

Objectives: The obesity paradox, whereby obesity appears to confer protection against cancer-related mortality, remains controversial. This has not yet been evaluated in upper gastrointestinal cancers.

Designs: We identified esophageal, cardia, and non-cardia gastric adenocarcinomas in the Veterans Health Administration between 2006-2016. Multivariable Cox proportional hazard models evaluate the impact of BMI at- and prior to- cancer diagnosis on mortality, adjusting for demographics, clinical characteristics, weight loss, and clinical stage (early: T1B/2N0; locally advanced: ≥T2N+).

Results: We identify 1308 patients: 99 % male, median 66 years. In early disease, relative to BMI 30, BMI 18 and 20 at diagnosis had increased risk of death (HR 1.83, 95 %CI: 1.38-2.44 and HR 1.50, 95 %CI: 1.20-1.87, respectively, p < 0.0001). Patients with BMI > 30 did not. In locally advanced disease, at diagnosis BMI 18 (HR 1.58, 95 %CI: 1.0001-1.48, p = 0.05), BMI 20 (HR 1.46, 95 %CI: 1.01-2.09, p = 0.04), and BMI 25 (HR 1.20, 95 %CI: 1.04-1.38, p = 0.01) had increased risk of death, but BMI > 30 did not. In models assessing premorbid BMI and weight loss, increasing amounts of weight loss were associated with mortality independent of BMI in early cancers. For locally advanced cancers, without weight loss, there was no association with death, regardless of BMI.

Conclusion: The predominant driver of mortality across clinical stages is weight loss. The obesity paradox appears to exist in early stage disease only. Future studies should investigate mechanisms for the obesity paradox, accompanying physiologic changes with weight loss preceding diagnosis, and if patients with low BMI and weight loss benefit from early nutritional support.
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http://dx.doi.org/10.1016/j.canep.2021.101912DOI Listing
February 2021

Contemporary Reappraisal of Intraoperative Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Review.

JAMA Surg 2021 Feb 3. Epub 2021 Feb 3.

Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.

Importance: Although margin-negative (R0) resection is the gold standard for surgical management of localized pancreatic ductal adenocarcinoma (PDAC), the question of how to manage the patient with a microscopically positive intraoperative neck margin (IONM) during pancreaticoduodenectomy remains controversial.

Observations: In the absence of randomized clinical trials, we critically evaluated high-quality retrospective studies examining the oncologic utility of re-resecting positive IONMs during pancreaticoduodenectomy for PDAC (2000-2019). Several studies have concluded that additional pancreatic resection to achieve an R0 margin in IONM-positive cases does not influence survival. The largest is a multi-institutional study of 1399 patients undergoing pancreaticoduodenectomy, which demonstrated that in comparison with patients undergoing R0 resection (n = 1196; median survival, 21 months), those with either final R1 resections (n = 131) or undergoing margin conversion from IONM-positive to R0 resection on permanent section (n = 72) demonstrated similar median survival times (13.7 and 11.9 months, respectively). Conversely, recent reports suggest that the conversion of IONM to R0 resection with additional resection or even total pancreatectomy may be associated with improved survival. The discordance between these conflicting studies could be explained in part by the influence of biologic and physiologic selection on the association of IONM re-resection and survival. Since most studies did not include patients receiving modern combination chemotherapy regimens, the intersection between margin status, tumor biology, and chemoresponsiveness remains unclear. Furthermore, there are no dedicated data to guide surgical management in IONM-positive pancreaticoduodenectomy for patients receiving neoadjuvant chemotherapy.

Conclusions And Relevance: Although data regarding the oncologic utility of additional resection to achieve a tumor-free margin following initial IONM positivity during pancreaticoduodenectomy for PDAC are conflicting, they suggest that IONM positivity may be a surrogate for biologic aggressiveness that is unlikely to be mitigated by the extent of surgical resection. The complex relationship between margin status and chemoresponsiveness warrants exploration in studies including patients receiving increasingly effective neoadjuvant chemotherapy.
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http://dx.doi.org/10.1001/jamasurg.2020.5676DOI Listing
February 2021

Multimodality Therapy in Operable Pancreatic Cancer: Should We Sequence Surgery Last?

Ann Surg Oncol 2021 Jan 16. Epub 2021 Jan 16.

Division of Surgical Oncology, Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.

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http://dx.doi.org/10.1245/s10434-020-09400-xDOI Listing
January 2021

ASO Visual Abstract: Does Major Pancreatic Surgery have Utility for Nonagenarians with Pancreas Cancer?

Ann Surg Oncol 2021 Jan 7. Epub 2021 Jan 7.

Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

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http://dx.doi.org/10.1245/s10434-020-09343-3DOI Listing
January 2021

Distinct Genomic Profiles are Associated With Conversion to Resection and Survival in Patients With Initially Unresectable Colorectal Liver Metastases Treated With Systemic and Hepatic Artery Chemotherapy.

Ann Surg 2020 Nov 17. Epub 2020 Nov 17.

Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Objective: To examine genomic correlates of CTR and overall survival (OS) in patients with IU-CRLM treated with combination systemic and hepatic artery infusion (HAI) chemotherapy.

Background: In patients presenting with IU-CRLM, combination systemic and HAI chemotherapy enables CTR with associated long-term OS in a subset of patients. Genomic correlates of CTR and OS in IU-CRLM have not been previously explored.

Methods: Specimens from IU-CRLM patients receiving systemic/HAI chemotherapy (2003-2017) were submitted for next-generation sequencing. Fisher Exact test assessed associations with CTR, and Kaplan-Meier/Cox methods assessed associations with OS from HAI initiation.

Results: Of 128 IU-CRLM patients, 51 (40%) underwent CTR at median 6 months (range: 3-35) from HAI initiation. CTR and persistently unresectable cohorts differed significantly in preoperative systemic chemotherapy exposure, node-positive primary status, and size of largest liver metastasis. Median and 5-year OS was 66 months and 51%. CTR was associated with prolonged survival (time-dependent HR 0.23, 95% CI: 0.12-0.46, P < 0.001). The most frequently altered genes were APC (81%), TP53 (77%), and KRAS (37%). Oncogenic mutations in SOX9 and BRAF were associated with CTR. BRAF mutations, any RAS pathway alterations, and co-altered RAS/RAF-TP53 mutations were associated with worse survival. Classification and regression tree analysis defined prognostically relevant clusters of genomic risk to reveal co-altered RAS/RAF-TP53 as the highest risk subgroup. Co-altered RAS/RAF-TP53 remained independently associated with worse survival (HR 2.52, 95% CI: 1.37-4.64, P = 0.003) after controlling for CTR, number of liver metastases, and preoperative extrahepatic disease.

Conclusions: Distinct genomic profiles are associated with CTR and survival in patients with IU-CRLM treated with HAI/systemic chemotherapy. Presence of SOX9, BRAF, and co-altered RAS/RAF-TP53 mutations are promising biomarkers that, when validated in larger datasets, may impact treatment of IU-CRLM patients.
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http://dx.doi.org/10.1097/SLA.0000000000004613DOI Listing
November 2020

Does Major Pancreatic Surgery Have Utility in Nonagenarians with Pancreas Cancer?

Ann Surg Oncol 2020 Nov 3. Epub 2020 Nov 3.

Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, Georgia.

Objective: This study aims to define the role of surgery and assess different therapies for nonagenarians with localized, nonmetastatic pancreatic adenocarcinoma (PDAC).

Methods: The National Cancer Database (NCDB) was queried for patients ≥ 90 years of age with nonmetastatic, localized PDAC from 2004-2016. Postoperative mortality was assessed at 30 and 90 days in patients receiving pancreatoduodenectomy or total pancreatectomy. Overall survival (OS) was compared between three treatment groups: surgery alone, chemotherapy alone, and chemoradiation (chemoRT) alone.

Results: Of 380,524 patients with PDAC, 98 patients ≥ 90 years of age underwent curative-intent resection; 55% were female and 75% had a Charlson-Deyo comorbidity score of 0. A total of 17% received postoperative chemotherapy, 51.1% had poorly differentiated tumors with a median tumor size of 3 cm, 55.1% had positive lymph nodes, and 19.4% had positive resection margins. Postoperative median length of stay was 11 days. Postoperative 30- and 90-day mortality was 10.0% and 18.9%, respectively. Median OS for the surgery alone group was 11.6 months compared with 20.4 months in those receiving adjuvant therapy (p = 0.01). Among nonoperative PDAC patients, median OS in patients receiving chemotherapy only (n = 207) was 7.2 months, while chemoRT only (n = 100) was similar to surgery only (11 versus 11.6 months, p = 0.97).

Conclusions: Even in well-selected nonagenarians, pancreatoduodenectomy or total pancreatectomy carries a high mortality rate. While adjuvant therapy after resection provides the best survival, it is seldom achieved, and chemoRT alone affords identical survival statistics as surgery alone. These data suggest it is reasonable to consider chemoRT as initial therapy, then reassess candidacy for resection if performance status allows.
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http://dx.doi.org/10.1245/s10434-020-09279-8DOI Listing
November 2020

Surgical management of hepatocellular carcinoma patients with portal vein thrombosis: The United States Safety Net and Academic Center Collaborative Analysis.

J Surg Oncol 2021 Feb 30;123(2):407-415. Epub 2020 Oct 30.

Division of Surgical Oncology, Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: Although consensus guidelines generally discourage any surgical management (ASM; i.e., resection and/or transplantation) in patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT), recent series from Asia have challenged this paradigm.

Methods: Patients from the US Safety Net Collaborative database (2012-2014) with localized HCC and radiographically confirmed PVT were propensity-score matched based on demographic and clinicopathologic factors associated with receipt of ASM and overall survival (OS). OS was compared between patients undergoing ASM and those not selected for surgery.

Results: Of 1910 HCC patients, 207 (14.5%) had localized disease and PVT. The majority received either liver-directed therapies (LDTs; 34%) and/or targeted systemic therapies (36%). Twenty-one patients (10.1%) underwent ASM (resection [n = 11], transplantation [n = 10]); a third experienced any complication with no 30-day mortalities. Independent predictors of undergoing ASM were younger age, recent hepatology consultation, and lower model of end-stage liver disease (MELD) score. After matching for age, comorbidities, MELD, tumor size, receipt of LDT, or systemic therapy, OS was significantly longer for patients selected for ASM versus non-ASM patients (median not reached vs. 5.8 months, p < .001).

Conclusion: In a large North American multi-institutional cohort, a minority of HCC patients with PVT were selected for ASM. Resection or transplantation was associated with improved survival and may have a role in the multimodality management in selected patients.
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http://dx.doi.org/10.1002/jso.26282DOI Listing
February 2021

A Call for Caution in Overinterpreting Exceptional Outcomes Following Radical Surgery for Pancreatic Cancer: Let the Data Speak.

Ann Surg 2020 Oct 19. Epub 2020 Oct 19.

Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine.

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http://dx.doi.org/10.1097/SLA.0000000000004471DOI Listing
October 2020

Deciphering high risk molecular alterations in gastrointestinal malignancy utilizing an extreme outlier strategy.

Oncoscience 2020 May 5;7(5-6):26-29. Epub 2020 May 5.

Division of Surgical Oncology, Dewitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA.

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http://dx.doi.org/10.18632/oncoscience.503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343576PMC
May 2020

Less may be more: shifting paradigm toward minimally invasive gastrectomy for locally advanced gastric cancer.

Transl Gastroenterol Hepatol 2019 26;4:79. Epub 2019 Nov 26.

Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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http://dx.doi.org/10.21037/tgh.2019.09.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917539PMC
November 2019

Coaltered and Is Associated with Extremes of Survivorship and Distinct Patterns of Metastasis in Patients with Metastatic Colorectal Cancer.

Clin Cancer Res 2020 03 12;26(5):1077-1085. Epub 2019 Nov 12.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: We aimed to investigate genomic correlates underlying extremes of survivorship in metastatic colorectal cancer and their applicability in informing survival in distinct subsets of patients with metastatic colorectal cancer.

Experimental Design: We examined differences in oncogenic somatic alterations between metastatic colorectal cancer cohorts demonstrating extremes of survivorship following complete metastasectomy: ≤2-year ( = 17) and ≥10-year ( = 18) survivors. Relevant genomic findings, and their association with overall survival (OS), were validated in two independent datasets of 935 stage IV and 443 resected stage I-IV patients.

Results: In the extremes-of-survivorship cohort, significant co-occurrence of hotspot mutations and alterations was observed in ≤2-year survivors ( < 0.001). When validating these findings in the independent cohort of 935 stage IV patients, incorporation of the cumulative effect of any oncogenic (i.e., either , or ) and alteration generated three prognostic clusters: (i) -altered alone (median OS, 132 months); (ii) -altered alone (65 months) or - and pan-wild-type (60 months); and (iii) coaltered - (40 months; < 0.0001). Coaltered - was independently associated with mortality (HR, 2.47; 95% confidence interval, 1.91-3.21; < 0.001). This molecular profile predicted survival in the second independent cohort of 443 resected stage I-IV patients. Coaltered - was associated with worse OS in patients with liver ( = 490) and lung ( = 172) but not peritoneal surface ( = 149) metastases. Moreover, coaltered - tumors were significantly more likely to involve extrahepatic metastatic sites with limited salvage options.

Conclusions: Genomic analysis of extremes of survivorship following colorectal cancer metastasectomy identifies a prognostic role for coaltered - and its association with distinct patterns of colorectal cancer metastasis.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056517PMC
March 2020

Genomic stratification beyond Ras/B-Raf in colorectal liver metastasis patients treated with hepatic arterial infusion.

Cancer Med 2019 11 10;8(15):6538-6548. Epub 2019 Sep 10.

Department of Medicine, MSKCC, New York City, New York, USA.

Background: Resection of colorectal liver metastases (CLM) can cure disease, but many patients with extensive disease cannot be fully resected and others recur following surgery. Hepatic arterial infusion (HAI) chemotherapy can convert extensive liver disease to a resectable state or decrease recurrence risk, but response varies and no biomarkers currently exist to identify patients most likely to benefit.

Methods: We performed a retrospective cohort study of CLM patients receiving HAI chemotherapy whose tumors underwent MSK-IMPACT sequencing. The frequency of oncogenic alterations and their association with overall survival (OS) and objective response rate were analyzed at the individual gene and signaling pathway levels.

Results: Three hundred and seventy patients met inclusion criteria: 189 (51.1%) who underwent colorectal liver metastasectomy followed by HAI + systemic therapy (Adjuvant cohort), and 181 (48.9%) with unresectable CLM (Metastatic cohort) who received HAI + systemic therapy, consisting of 63 (34.8%) with extrahepatic disease and 118 (65.2%) with liver-restricted disease. Genomic alterations were similar in each cohort, and no individual gene or pathway was significantly associated with objective response. Patients in the adjuvant cohort with concurrent Ras/B-Raf alteration and SMAD4 inactivation had worse prognosis while in the metastatic cohort patients with co-alteration of Ras/B-Raf and TP53 had worse OS. Similar findings were observed in a validation cohort.

Conclusions: Concurrently altered Ras/B-Raf and SMAD4 mutations were associated with worse survival in resectable patients, while concurrent Ras/B-Raf and TP53 alterations were associated with worse survival in unresectable patients. The mutual exclusivity of Ras/B-Raf, SMAD4, and TP53 may have prognostic value for CLM patients receiving HAI.
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http://dx.doi.org/10.1002/cam4.2415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825986PMC
November 2019

Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review.

JAMA Surg 2019 08;154(8):768-776

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: 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.

Observations: 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.

Conclusions And Relevance: 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.
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http://dx.doi.org/10.1001/jamasurg.2019.1694DOI Listing
August 2019

Toward More Accurate Understanding of Lymph Node Metastasis Risk in Early Gastric Cancer.

JAMA Surg 2019 03 20;154(3):e185250. Epub 2019 Mar 20.

Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York.

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http://dx.doi.org/10.1001/jamasurg.2018.5250DOI Listing
March 2019

SMAD4 Loss in Colorectal Cancer Patients Correlates with Recurrence, Loss of Immune Infiltrate, and Chemoresistance.

Clin Cancer Res 2019 03 26;25(6):1948-1956. Epub 2018 Dec 26.

Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: SMAD4 has shown promise in identifying patients with colorectal cancer at high risk of recurrence or death. A discovery cohort and independent validation cohort were classified by SMAD4 status. SMAD4 status and immune infiltrate measurements were tested for association with recurrence-free survival (RFS). Patient-derived xenografts from SMAD4-deficient and SMAD4-retained tumors were used to examine chemoresistance.

Results: The discovery cohort consisted of 364 patients with stage I-IV colorectal cancer. Median age at diagnosis was 53 years. The cohort consisted of 61% left-sided tumors and 62% stage II/III patients. Median follow-up was 5.4 years (interquartile range, 2.3-8.2). SMAD4 loss, noted in 13% of tumors, was associated with higher tumor and nodal stage, adjuvant therapy use, fewer tumor-infiltrating lymphocytes (TIL), and lower peritumoral lymphocyte aggregate (PLA) scores (all < 0.04). SMAD4 loss was associated with worse RFS ( = 0.02). When stratified by SMAD4 and immune infiltrate status, patients with SMAD4 loss and low TIL or PLA had worse RFS ( = 0.002 and = 0.006, respectively). Among patients receiving 5-fluorouracil (5-FU)-based systemic chemotherapy, those with SMAD4 loss had a median RFS of 3.8 years compared with 13 years for patients with SMAD4 retained. In xenografted mice, the SMAD4-lost tumors displayed resistance to 5-FU. An independent cohort replicated our findings, in particular, the association of SMAD4 loss with decreased immune infiltrate, as well as worse disease-specific survival.

Conclusions: Our data show SMAD4 loss correlates with worse clinical outcome, resistance to chemotherapy, and decreased immune infiltrate, supporting its use as a prognostic marker in patients with colorectal cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-1726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421131PMC
March 2019

Oncodriver inhibition and CD4 Th1 cytokines cooperate through Stat1 activation to induce tumor senescence and apoptosis in HER2+ and triple negative breast cancer: implications for combining immune and targeted therapies.

Oncotarget 2018 May 1;9(33):23058-23077. Epub 2018 May 1.

Harrison Department of Surgical Research, Department of Surgery, University Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

In patients with HER2-expressing breast cancer many develop resistance to HER2 targeted therapies. We show that high and intermediate HER2-expressing cancer cell lines are driven toward apoptosis and tumor senescence when treated with either CD4 Th1 cells, or Th1 cytokines TNF-α and IFN-γ, in a dose dependent manner. Depletion of HER2 activity by either siRNA or trastuzumab and pertuzumab, and subsequent treatment with either anti-HER2 Th1 cells or TNF-α and IFN-γ resulted in synergistic increased tumor senescence and apoptosis in cells both sensitive and cells resistant to trastuzumab which was inhibited by neutralizing anti-TNF-α and IFN-γ. Th1 cytokines induced minimal senescence or apoptosis in triple negative breast cancer cells (TNBC); however, inhibition of EGFR in combination with Th1 cytokines sensitized those cells causing both senescence and apoptosis. TNF-α and IFN-γ led to increased Stat1 phosphorylation through serine and tyrosine sites and a compensatory reduction in Stat3 activation. Single agent IFN-γ enhanced Stat1 phosphorylation on tyrosine 701 and similar effects were observed in combination with TNF-α and EGFR inhibition. These results demonstrate Th1 cytokines and anti-oncodriver blockade cooperate in causing tumor senescence and apoptosis in TNBC and HER2-expressing breast cancer, suggesting these combinations could be explored as non-cross-reactive therapy preventing recurrence in breast cancer.
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http://dx.doi.org/10.18632/oncotarget.25208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955413PMC
May 2018

Laparoscopic Heller Myotomy vs Per Oral Endoscopic Myotomy: Patient-Reported Outcomes at a Single Institution.

J Am Coll Surg 2018 04 2;226(4):465-472.e1. Epub 2018 Feb 2.

Department of General Surgery, University of Pennsylvania, Philadelphia, PA. Electronic address:

Background: Although laparoscopic Heller myotomy (LHM) has been the standard of care for achalasia, per oral endoscopic myotomy (POEM) has gained popularity as a viable alternative. This retrospective study aimed to compare patient-reported outcomes between LHM and POEM in a consecutive series of achalasia patients with more than 1 year of follow-up.

Study Design: We reviewed demographic and procedure-related data for patients who underwent either LHM or POEM for achalasia between January 2011 and May 2016. Phone interviews were conducted assessing post-procedure achalasia symptoms via the Eckardt score and achalasia severity questionnaire (ASQ). Demographics, disease factors, and survey results were compared between LHM and POEM patients using univariate analysis. Significant predictors of procedure failure were analyzed using univariate and multivariate analysis.

Results: There were no serious complications in 110 consecutive patients who underwent LHM or POEM during the study period, and 96 (87%) patients completed phone surveys. There was a nonsignificant trend toward better patient-reported outcomes with POEM. There were significant differences in patient characteristics including sex, achalasia type, mean residual lower esophageal pressure (rLESP), and follow-up time. The only univariate predictors of an unsatisfactory Eckardt score or ASQ were longer follow-up and lower rLESP, with follow-up length being the only predictor on multivariate analysis.

Conclusions: There were significant demographic and clinical differences in patient selection for POEM vs LHM in our group. Although the 2 procedures have similar patient-reported effectiveness, subjective outcomes seem to decline as a result of time rather than procedure type.
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http://dx.doi.org/10.1016/j.jamcollsurg.2017.12.050DOI Listing
April 2018

Identification of Patients for Adjuvant Therapy After Resection of Carcinoma of the Extrahepatic Bile Ducts: A Propensity Score-Matched Analysis.

Ann Surg Oncol 2017 Dec 26;24(13):3926-3933. Epub 2017 Sep 26.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Background: Resectability rates for extrahepatic cholangiocarcinoma have increased over time, but long-term survival after resection alone with curative intent remains poor. Recent series suggest improved survival with adjuvant therapy. Patient subsets benefiting most from adjuvant therapy have not been clearly defined.

Methods: Patients with extrahepatic cholangiocarcinoma who underwent resection with curative intent and received adjuvant therapy (chemotherapy ± radiotherapy) or surgery alone (SA) were identified in the U.S. National Cancer Data Base (2004-2014). Cox regression identified covariates associated with overall survival (OS). Adjuvant therapy and SA cohorts were matched (1:1) by propensity scores based on the survival hazard in Cox modeling. Overall survival was compared by Kaplan-Meier estimates.

Results: Of 4872 patients, adjuvant chemotherapy was used frequently for 2416 (49.6%), often in conjunction with radiotherapy (RT) (n = 1555, 64.4%). Adjuvant chemotherapy with or without RT was used increasingly for cases with higher T classification [reference: T1-2; T3: 1.36; 95% confidence interval (CI), 1.19-1.55; T4: 1.77; 95% CI 1.38-2.26], nodal positivity [odds ratio (OR), 1.26; 95% CI 1.01-1.56], lymphovascular invasion (OR 1.21; 95% CI 1.01-1.46), or margin-positive resection (OR 1.85; 95% CI 1.61-2.12), and was associated with significant improvements in OS for each high-risk subset in the propensity score-matched cohort. Adjuvant therapy was associated with improved median OS for hilar tumors (40.0 vs 30.6 months; p = 0.025) but not distal tumors (33.0 vs 30.3 months; p = 0.123). Chemoradiotherapy was associated with superior outcomes compared with chemotherapy alone in the subset of margin-positive resection [hazard ratio (HR), 0.63; 95% CI 0.42-0.94].

Conclusions: Adjuvant multimodality therapy is associated with improved survival for patients with resected extrahepatic cholangiocarcinoma and high-risk features.
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http://dx.doi.org/10.1245/s10434-017-6095-9DOI Listing
December 2017

Contemporary reappraisal of the efficacy of adjuvant chemotherapy in resected retroperitoneal sarcoma: Evidence from a nationwide clinical oncology database and review of the literature.

Surg Oncol 2017 Jun 2;26(2):117-124. Epub 2017 Feb 2.

Division of Endocrine and Oncologic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Background: While margin-negative resection remains the cornerstone of therapy for retroperitoneal sarcoma (RPS), the impact of adjuvant chemotherapy (AC) on overall survival (OS) remains poorly understood.

Methods: The National Cancer Data Base was queried for patients undergoing curative-intent resection of primary non-metastatic RPS (2004-2013). Multivariable modeling identified factors associated with AC receipt. Cox regression identified covariates associated with OS, and AC and surgery alone (SA) cohorts were matched 1:1 by propensity scores based on these covariates. In the propensity-score matched cohort, OS was compared by Kaplan-Meier estimates. Results from this analysis were presented in the context of a review of the existing literature on the impact of AC in resected RPS.

Results: Of 3892 resected RPS patients, 90.0% and 10.0% received SA and AC, respectively. Predictors of AC receipt included younger age, non-Caucasian race, hospital location, histologic grade, adjacent organ invasion, and histologic subtype. The propensity score-matched cohort comprised 767 patients (SA n = 377; AC n = 390); at a median follow-up of 59.2 (IQR 35.0-85.3) months, median OS of the propensity-matched cohort was 53.6 (IQR 22.4-119.5) months. Utilization of AC was associated with significantly worse long-term survival (median OS: 47.8 vs. 68.9 months, p = 0.017; HR 1.30, 95% CI 1.05-1.61). AC was not associated with improved OS in margin-positive (R1/R2) resection, high-grade (G2/G3) and larger (>10 cm) tumors, or in any histologic subtype. Albeit not statistically significant, there was a trend toward improved OS with AC in spindle cell (HR 0.37, 95% CI 0.10-1.38), giant cell (HR 0.82, 95% CI 0.32-2.13), and synovial (HR 0.26, 95% CI 0.05-1.33) sarcoma.

Conclusions: Data from a large nationwide oncology database and review of the existing literature do not support adjuvant chemotherapy regimens following curative-intent resection of RPS, even in subgroups at high risk of failure (e.g., R1/R2 resection, high-grade or large tumors). The possible benefit of conventional adjuvant regimens in spindle cell, giant cell, and synovial sarcoma should be explored in prospective studies.
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http://dx.doi.org/10.1016/j.suronc.2017.01.008DOI Listing
June 2017

Adjuvant chemotherapy versus chemoradiotherapy in the management of patients with surgically resected duodenal adenocarcinoma: A propensity score-matched analysis of a nationwide clinical oncology database.

Cancer 2017 05 7;123(6):967-976. Epub 2016 Nov 7.

Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: To the authors' knowledge, optimal adjuvant approaches for resected duodenal adenocarcinoma are not well established. Given the significant risk of locoregional disease recurrence, there may be a subset of patients who demonstrate an improvement in overall survival (OS) from the addition of radiotherapy (chemoradiotherapy [CRT]) to an adjuvant chemotherapy regimen.

Methods: Patients with resected, nonmetastatic duodenal adenocarcinoma who received chemotherapy (694 patients) or CRT (550 patients) were identified in the National Cancer Data Base (1998-2012). Cox regression identified covariates associated with OS. The chemotherapy and CRT cohorts were matched (1:1) by propensity scores based on the likelihood of receiving CRT or the survival hazard from Cox modeling. OS was compared using Kaplan-Meier estimates.

Results: CRT was more frequently used for patients who underwent positive-margin surgical resection (15.9% vs 9.1%; P<.001). At a median follow-up of 79.2 months (interquartile range, 52.9-114.9 months), the median OS of the propensity score-matched cohort was 46.7 months (interquartile range, 18.9 months to not reached). No survival advantage was observed for patients who were treated with adjuvant CRT compared with those treated with adjuvant chemotherapy (median OS: 48.9 months vs 43.5 months [HR, 1.04; 95% confidence interval, 0.88-1.22 (P = .669)]). CRT was not found to be associated with a significant improvement in the median OS after positive-margin surgical resection (133 patients; 27.6 months vs 18.5 months [P = .210]) or in the presence of T4 classification (461 patients; 30.6 months vs 30.4 months [P = .844]) inadequate lymph node staging (584 patients; 40.5 months vs 43.2 months [P = .707]), lymph node positivity (647 patients; 38.3 months vs 34.1 months [P = .622]), or poorly differentiated histology (429 patients; 46.6 months vs 35.7 months [P = .434]).

Conclusions: The addition of radiation to adjuvant therapy does not appear to significantly improve survival, even in high-risk cases. Cancer 2017;123:967-76. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30439DOI Listing
May 2017

Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2 DCIS Independent of Route: Results of Randomized Selection Design Trial.

Clin Cancer Res 2017 Jun 13;23(12):2961-2971. Epub 2016 Dec 13.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Vaccination with HER2 peptide-pulsed DC1s stimulates a HER2-specific T-cell response. This randomized trial aimed to establish safety and evaluate immune and clinical responses to vaccination via intralesional (IL), intranodal (IN), or both intralesional and intranodal (ILN) injection. Fifty-four HER2 patients [42 pure ductal carcinoma (DCIS), 12 early invasive breast cancer (IBC)] were enrolled in a neoadjuvant HER2 peptide-pulsed DC1 vaccine trial. Patients were randomized to IL ( = 19), IN ( = 19), or ILN ( = 16) injection. Immune responses were measured in peripheral blood and sentinel lymph nodes by ELISPOT or sensitization assay. Pathologic response was assessed in resected surgical specimens. Vaccination by all injection routes was well tolerated. There was no significant difference in immune response rates by vaccination route (IL 84.2% vs. IN 89.5% vs. ILN 66.7%; = 0.30). The pathologic complete response (pCR) rate was higher in DCIS patients compared with IBC patients (28.6% vs. 8.3%). DCIS patients who achieved pCR ( = 12) and who did not achieve pCR ( = 30) had similar peripheral blood anti-HER2 immune responses. All patients who achieved pCR had an anti-HER2 CD4 immune response in the sentinel lymph node, and the quantified response was higher by response repertoire ( = 0.03) and cumulative response ( = 0.04). Anti-HER2 DC1 vaccination is a safe and immunogenic treatment to induce tumor-specific T-cell responses in HER2 patients; immune and clinical responses were similar independent of vaccination route. The immune response in the sentinel lymph nodes, rather than in the peripheral blood, may serve as an endpoint more reflective of antitumor activity. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-1924DOI Listing
June 2017

Anti-HER2 CD4 T-Helper Type 1 Immune Response is Superior to Breast MRI for Assessing Response to Neoadjuvant Therapy in Patients with HER2-Positive Breast Cancer.

Ann Surg Oncol 2017 Apr 8;24(4):1057-1063. Epub 2016 Nov 8.

Department of Breast Oncology, H Lee Moffitt Cancer Center, Tampa, FL, USA.

Background: In human epidermal growth factor 2-positive breast cancer (HER2BC), neoadjuvant chemotherapy and anti-HER2-targeted therapy (nCT) achieves a complete pathologic response (pCR) in 40-67% of patients. Posttreatment magnetic resonance imaging (pMRI) is considered the gold standard, with high specificity but lower sensitivity for assessing response. The authors previously determined that anti-HER2Th1 immune response is associated with pathologic response after nCT in HER2BC patients. This study contrasted pMRI with anti-HER2Th1 response for assessing pCR in HER2BC.

Methods: A retrospective review of HER2BC patients at the authors' institution was performed. Original pMRI reports were collected, and images were reviewed by a breast radiologist blinded to pCR and immune response. The post-nCT imaging-based tumor response was assessed by Response Evaluation Criteria in Solid Tumors. The anti-HER2Th1 response was determined by ex vivo stimulation of peripheral blood mononuclear cells with six major histocompatibility complex (MHC) class 2-derived HER2 peptides via enzyme-linked immunospot (ELISPOT). Posttreatment MRI and anti-HER2Th1 responses were cross-tabulated with pCR. Standard diagnostic metrics were computed.

Results: For 30 patients, pMRI and anti-HER2Th1 immune response were measured, with 13 patients (43.3%) achieving pCR. The mean anti-HER2Th1 response in pCR was 167 (range 53-418), and
Conclusion: The presence of a high anti-HER2Th1 response is superior to pMRI for the assessment of pCR in HER2BC. This assay has considerable promise, and validation in a large-scale study is warranted.
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http://dx.doi.org/10.1245/s10434-016-5651-zDOI Listing
April 2017

Loss of Anti-HER-3 CD4+ T-Helper Type 1 Immunity Occurs in Breast Tumorigenesis and is Negatively Associated with Outcomes.

Ann Surg Oncol 2017 Feb 23;24(2):407-417. Epub 2016 Sep 23.

Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Background: We previously demonstrated a progressive loss of the anti-human epidermal growth factor receptor 2 (HER2) CD4+ T-helper type 1 (Th1) response during HER2 breast tumorigenesis. This loss is associated with residual disease following neoadjuvant therapy and increased risk of recurrence. In this study, we assessed the fate of anti-HER3 Th1 immunity during breast tumorigenesis.

Methods: Peripheral blood from 131 subjects, including healthy donors (HDs), patients with benign breast disease (BD), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC), was collected. Interferon (IFN)-γ immune responses to four HER3-derived major histocompatibility complex (MHC) class II promiscuous peptides were tested via enzyme-linked immunosorbent (ELISPOT) assays, and three immune response parameters were compared: anti-HER3 (i) responsivity, or proportion of subjects responding to at least one peptide; (ii) repertoire, or number of responding peptides; and (iii) cumulative response, or summed peptide response.

Results: A significant decline in anti-HER3 Th1 response was observed going from HDs to IBC patients; patients with triple-negative breast cancer (TNBC) demonstrated the lowest responses. HDs had significantly higher Th1 responses versus estrogen receptor (ER) IBC and TNBC patients across all three immune parameters; HER2 IBC patients displayed responses similar to HDs and BDs. Patients with recurrent breast cancer and residual disease following neoadjuvant therapy demonstrated significantly lower anti-HER3 Th1 immunity compared with patients without recurrence or with a pathologic complete response to neoadjuvant therapy.

Conclusions: Anti-HER3 CD4+ Th1 responses decline during breast tumorigenesis, particularly in TNBC. Attempts to immunologically restore depressed responses in vulnerable subgroups may help mitigate recurrence.
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http://dx.doi.org/10.1245/s10434-016-5584-6DOI Listing
February 2017

HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction.

PLoS One 2016 25;11(8):e0161781. Epub 2016 Aug 25.

Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States of America.

Overexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissue samples of esophageal biopsy specimens from 73 patients with Barrett's esophagus with either low-grade dysplasia (LGD) (n = 32) or high-grade dysplasia (HGD) (n = 59) were analyzed for HER1, HER2, HER3 and CMET expression by immunohistochemistry (IHC). Immunophenotype was correlated with histologic and clinical features. High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD). There was a significant association of HER2 (20.0% vs. 2.1%, p = 0.022) and HER3 (80.0% vs. 40.4%, p = 0.023) overexpression in HGD lesions associated with foci of invasive carcinoma compared to those without invasive foci. Overexpression of CMET was observed in 42.9% of specimens, was increasingly observed with HGD compared to LGD (58.3% vs. 36.7%, p = 0.200), and was most often co-expressed with HER3 (62.5% of HER3-positive specimens vs. 38.2% of HER3-negative specimens, p = 0.212). In summary, HER3 is frequently overexpressed in high-grade dysplastic lesions of the gastroesophageal junction and may be a marker of invasive progression. These data provide rationale for targeting HER2 and HER3 pathways in an early disease setting to prevent disease progression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161781PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999185PMC
July 2017

Comparing International and United States Undergraduate Medical Education and Surgical Outcomes Using a Refined Balance Matching Methodology.

Ann Surg 2017 05;265(5):916-922

*University of Pennsylvania, Perelman School of Medicine, Department of Surgery, Philadelphia, PA †Hospital of the University of Pennsylvania, Department of Surgery, Center for Surgery and Health Economics, Philadelphia, PA ‡University of Pennsylvania, Wharton School, Department of Statistics, Philadelphia, PA.

Objective: The aim of this study is to compare surgical outcomes of international medical graduates (IMGs) and United States medical graduates (USMGs).

Summary Of Background Data: IMGs represent 15% of practicing surgeons in the United States (US), and their training pathways often differ substantially from USMGs. To date, differences in the clinical outcomes between the 2 cohorts have not been examined.

Methods: Using a unique dataset linking AMA Physician Masterfile data with hospital discharge claims from Florida and New York (2008-2011), patients who underwent 1 of 32 general surgical operations were stratified by IMG and USMG surgeon status. Mortality, complications, and prolonged length of stay were compared between IMG and USMG surgeon status using optimal sparse network matching with balance.

Results: We identified 972,718 operations performed by 4581 surgeons (72% USMG, 28% IMG). IMG and USMG surgeons differed significantly in demographic (age, gender) and baseline training (years of training, university affiliation of training hospital) characteristics. USMG surgeons performed complex procedures (13.7% vs 11.1%, P < 0.01) and practiced in urban settings (79.4% vs 75.6%, P < 0.01) more frequently, while IMG surgeons performed a higher volume of studied operations (50.7 ± 5.1 vs 57.8 ± 8.4, P < 0.01). In the matched cohort analysis of 396,810 patients treated by IMG and USMG surgeons, rates of mortality (USMG: 2.2%, IMG: 2.1%; P < 0.001), complications (USMG: 14.5%, IMG: 14.3%; P = 0.032), and prolonged length of stay (pLOS) (USMG: 22.7%, IMG: 22.8%; P = 0.352) were clinically equivalent.

Conclusion: Despite considerable differences in educational background, surgical training characteristics, and practice patterns, IMG and USMG-surgeons deliver equivalent surgical care to the patients whom they treat.
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http://dx.doi.org/10.1097/SLA.0000000000001878DOI Listing
May 2017

Addition of anti-estrogen therapy to anti-HER2 dendritic cell vaccination improves regional nodal immune response and pathologic complete response rate in patients with ER/HER2 early breast cancer.

Oncoimmunology 2017;6(9):e1207032. Epub 2016 Jul 1.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

HER2-directed therapies are less effective in patients with ER compared to ER breast cancer, possibly reflecting bidirectional activation between HER2 and estrogen signaling pathways. We investigated dual blockade using anti-HER2 vaccination and anti-estrogen therapy in HER2/ER early breast cancer patients. In pre-clinical studies of HER2 breast cancer cell lines, ER cells were partially resistant to CD4 Th1 cytokine-induced metabolic suppression compared with ER cells. The addition of anti-estrogen treatment significantly enhanced cytokine sensitivity in ER, but not ER, cell lines. In two pooled phase-I clinical trials, patients with HER2 early breast cancer were treated with neoadjuvant anti-HER2 dendritic cell vaccination; HER2/ER patients were treated with or without concurrent anti-estrogen therapy. The anti-HER2 Th1 immune response measured in the peripheral blood significantly increased following vaccination, but was similar across the three treatment groups (ER vaccination alone, ER vaccination alone, ER vaccination + anti-estrogen therapy). In the sentinel lymph nodes, however, the anti-HER2 Th1 immune response was significantly higher in ER patients treated with combination anti-HER2 vaccination plus anti-estrogen therapy compared to those treated with anti-HER2 vaccination alone. Similar rates of pathologic complete response (pCR) were observed in vaccinated ER patients and vaccinated ER patients treated with concurrent anti-estrogen therapy (31.4% vs. 28.6%); both were significantly higher than the pCR rate in vaccinated ER patients who did not receive anti-estrogen therapy (4.0%, = 0.03). Since pCR portends long-term favorable outcomes, these results support additional clinical investigations using HER2-directed vaccines in combination with anti-estrogen treatments for ER/HER2 DCIS and invasive breast cancer.
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http://dx.doi.org/10.1080/2162402X.2016.1207032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599079PMC
July 2016

Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study.

PLoS Med 2016 Apr 26;13(4):e1002007. Epub 2016 Apr 26.

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Background: Several prior studies have found an association between statin use and reduced risk of colorectal cancer. We hypothesized that these findings may be due to systematic bias and examined the independent association of colorectal cancer risk with statin use, serum cholesterol, and change in cholesterol concentration.

Methods And Findings: 22,163 colorectal cancer cases and 86,538 matched controls between 1995 and 2013 were identified within The Health Improvement Network (THIN) a population-representative database. Conditional logistic regression models estimated colorectal cancer risk with statin use, serum total cholesterol (mmol/L), and change in total cholesterol level. We confirmed a decreased risk of colorectal cancer with statin use (long-term: odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91-0.99; short-term: OR, 0.92; 95% CI, 0.85-0.99). However, to assess whether the observed association may result from indication bias, a subgroup analysis was conducted among patients prescribed a statin. In this subgroup (n = 5,102 cases, n = 19,032 controls), 3.1% of case subjects and 3.1% of controls discontinued therapy. The risk of colorectal cancer was not significantly different among those who continued statin therapy and those who discontinued (OR, 0.98; 95% CI, 0.79-1.22). Increased serum cholesterol was independently associated with decreased risk of colorectal cancer (OR, 0.89 per mmol/L increase; 95% CI, 0.87-0.91); the association was only present if serum cholesterol was measured near the cancer diagnosis (<6 mo: OR, 0.76; 95% CI, 0.47-0.61; >24 mo: OR, 0.98; 95% CI, 0.93-1.03). Decreases in serum total cholesterol >1 mmol/L ≥1 year prior to cancer diagnosis were associated with subsequent colorectal cancer (statin users: OR, 1.25; 95 CI%, 1.03-1.53; nonusers: OR, 2.36; 95 CI%, 1.78-3.12). As an observational study, limitations included incomplete data and residual confounding.

Conclusions: Although the risk of colorectal cancer was lower in statin users versus nonusers, no difference was observed among those who continued versus discontinued statin therapy, suggesting the potential for indication bias. The association between decreased serum cholesterol and colorectal cancer risk suggests a cholesterol-lowering effect of undiagnosed malignancy. Clinical judgment should be used when considering causes of cholesterol reduction in patients, including those on statin therapy.
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http://dx.doi.org/10.1371/journal.pmed.1002007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846028PMC
April 2016

Multimodality Therapy Improves Survival in Resected Early Stage Gastric Cancer in the United States.

Ann Surg Oncol 2016 09 18;23(9):2936-45. Epub 2016 Apr 18.

Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Background: National guidelines endorse adjuvant chemotherapy ± radiotherapy (C ± RT) for early-stage gastric cancer (ESGC). Compliance with these guidelines and the specific impact of adjuvant C ± RT on overall survival (OS) in ESGC have not been extensively explored.

Methods: The National Cancer Data Base was queried for stage IB-II gastric adenocarcinoma patients undergoing gastrectomy (1998-2011). Multivariable modeling identified factors associated with adjuvant C ± RT receipt and compared risk-adjusted OS by treatment type (i.e., adjuvant therapy versus surgery alone).

Results: Of 23,461 ESGC patients (1998-2011), 79.4 % and 20.6 % received surgery alone and adjuvant C ± RT (chemoradiotherapy 17.7 %; chemotherapy alone 2.9 %), respectively. Predictors of adjuvant C ± RT receipt included age <67 years, pathologic nodal positivity, and adequate lymph node staging (LNS; ≥15 nodes examined; all p < 0.001). Survival analyses included 15,748 patients (1998-2006); median, 1-, and 5-year survival were 63.5 months, 86.0 %, and 27.0 % respectively. Omission of adjuvant C ± RT conferred an increased hazard of risk-adjusted mortality in the overall cohort, and stage IB and II subgroups (all p ≤ 0.001). The benefit of adjuvant C ± RT was most pronounced in stage II and node-positive patients-regardless of LNS adequacy (all p < 0.001)-and inadequately staged IB patients (p = 0.003). While associated with a trend toward improved OS in node-negative patients overall (p = 0.051), adjuvant C ± RT did not improve OS if surgical LNS was adequate in this subgroup (p = 0.960).

Conclusions: Adoption of adjuvant C ± RT in ESGC remains incomplete nationally. Receipt of adjuvant therapy is associated with improved risk-adjusted survival relative to surgery alone; however, in adequately staged patients without lymph node metastasis, this benefit is less certain.
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http://dx.doi.org/10.1245/s10434-016-5224-1DOI Listing
September 2016

Advances in Surgical Management of Pancreatic Diseases.

Gastroenterol Clin North Am 2016 Mar;45(1):129-44

Division of Gastrointestinal Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, USA. Electronic address:

The surgical management of pancreatic diseases is rapidly evolving, encompassing advances in evidence-driven selection of patients amenable for surgical therapy, preoperative risk stratification, refinements in the technical conduct of pancreatic operations, and quantification of postoperative morbidity. These advances have resulted in dramatic reductions in mortality following pancreatic surgery, particularly at high-volume pancreatic centers. Surgical decision making is complex, and requires an intimate understanding of disease pathobiology, host physiology, technical considerations, and evolving trends. This article highlights key developments in the contemporary surgical management of pancreatic diseases.
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http://dx.doi.org/10.1016/j.gtc.2015.10.002DOI Listing
March 2016

Outcomes of 157 V-Patch(TM) Implants in the Repair of Umbilical, Epigastric, and Incisional Hernias.

Am Surg 2016 Jan;82(1):6-10

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Umbilical, epigastric, and incisional hernias have traditionally been repaired using a Mayo or tensioned suture technique, with recurrence rates of approximately 50 per cent. Recent studies have shown that a tension-free repair using mesh can drastically decrease recurrence rates. Reinforced deployment prostheses are preferred because they enable retrofascial placement through a small incision, thus avoiding the potential morbidity of a larger incision and the costs associated with a laparoscopic approach. A retrospective chart review was performed of all umbilical, epigastric and incisional hernias repaired with V-Patch, a reinforced deployment prosthesis, by a single surgeon. Data analysis included patient characteristics, operative and postoperative metrics, hernia recurrence, and complication rates. Between 2009 and 2012, 157 implantations were performed in 152 patients during 156 procedures. Patient age ranged from 20 to 85 (mean 48). There were 88 females (57.9%) and 64 males (42.1%) with average body mass index of 30.6. Patch size distribution was 78 small (49.7%), 55 medium (35.0%), and 24 large (15.3%). There were 81 umbilical hernias (51.6%), 36 epigastric hernias (22.9%), 39 incisional hernias (24.8%), and 1 multiple recurrent inguinal hernia (0.6%) repaired. Follow-up time ranged from 18 months to 4.3 years. There were six hernia recurrences (3.2%). Complications included three patients (1.9%) with mesh infection, one with an enterocutaneous fistula (0.6%), and one patient with a postoperative small bowel obstruction (0.6%). Four patients required patch explantation (2.5%). The V-Patch reinforced deployment prosthesis is effective in the treatment of umbilical, epigastric, and incisional hernias, and has a low rate of complications.
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January 2016