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Background and Objectives: Pancreatoduodenectomy (PD) has been associated with significant morbidity and mortality. To reduce morbidity, minimally invasive pancreatoduodenectomies (MIPD) have become more prevalent. We aimed to compare short-term survival and complications for open (OPD) versus MIPD and to assess the relationship between operative approach and operative time on outcomes., Methods: Patients undergoing PD between 2017 and 2020 were identified within the National Surgical Quality Improvement Program (NSQIP). The primary outcome was operative time, and the secondary outcomes were death at 30 days, reoperation, readmission, and NSQIP-identified 30-day postoperative complications. A multivariable logistic regression was performed., Results: A total of 14 977 PDs were performed from 2017 to 2020. MIPD increased from less than 8% of pancreatoduodenectomies performed in 2017 to over 10% of PD by 2020. Of the MIPD cohort, 62% were robotic, and 38% were laparoscopic, with robotic surgery becoming most prevalent by the end of the study period. MIPD was associated with significantly longer operative times than OPD (p < 0.01). MIPD was associated with decreased odds of postoperative bleeding and surgical site infection (p < 0.01), but higher odds of death at 30 days., Conclusions: MIPD has been shown to have improved postoperative outcomes compared to OPD but is associated with longer operative times, which can be associated with increased complications., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Purpose: The treatment of gastric adenocarcinoma (GA) continues to evolve. While neoadjuvant chemotherapy (NAC) has demonstrated emerging benefit, the optimal treatment regimen, and sequence remain to be firmly established., Methods: Patients with nonmetastatic GA who underwent resection were identified within the 2020 National Cancer Database. Patients were compared between the mutually exclusive treatment groups of NAC, neoadjuvant chemoradiotherapy (NCRT), adjuvant chemotherapy, adjuvant chemoradiotherapy (CRT), and surgery only. The primary endpoint was receipt of NAC or NCRT. Patients were 1-to-1 propensity score matched for receiving any neoadjuvant therapy. Multivariable logistic regression was used to identify predictors of receipt of any neoadjuvant therapy and receipt of any adjuvant therapy., Results: Twenty-five thousand and seventy-three patients were included in the analysis. Patients were treated with NAC (25.0%), NCRT (31.4%), adjuvant chemotherapy (6.5%), adjuvant CRT (12.6%), and surgery only (24.5%). Compared to 2006-2011, patients diagnosed between 2012 and 2017 experienced the greatest increases in NAC (18.6% vs. 29.0%; p < 0.001) and NCRT (25.0% vs. 35.5%; p < 0.001). Median OS was 44.9 months. OS was longest for patients who received any neoadjuvant therapy compared to those receiving adjuvant or surgery only (51.0 vs. 42.4 vs. 38.0 months, respectively; p < 0.001). Patients who were Black, in the lowest income quartile or treated at lower volume facilities were less likely to receive NAT (all p < 0.001)., Conclusions: There has been significant acceleration in the use of neoadjuvant therapy for GA. Currently, NCRT followed by surgery are the most common treatment sequences in the United States. Additional trials are needed to further define the optimal treatment sequence., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: While frailty has gained attention for its utility in risk stratification, no studies have directly compared them to existing risk calculators. The objective of this study was to compare the risk stratification of the American College of Surgeons Surgical Risk Calculator (ACS-SRC), the Revised Risk Analysis Index (RAI-rev), and the Modified Frailty Index (5-mFI). The primary outcomes were 30-day postoperative morbidity, 30-day postoperative mortality, unplanned readmission, unplanned reoperation, and discharge disposition other than home., Methods: Patients undergoing anatomic lung resection for primary, nonsmall cell lung cancer were identified within the ACS National Quality Improvement Program (ACS NSQIP) database. Tools were compared for discrimination in the primary outcomes., Results: 9663 patients undergoing anatomic lung resection for cancer between 2012 and 2014 were included. The cohort was 53.1% female. Median age at diagnosis was 67 (IQR 59-74) years. Perioperative morbidity and mortality rates were 10.9% (n = 1048) and 1.6% (n = 158). Rates of 30-day postoperative unplanned readmission and reoperation were 7.5% (n = 725) and 4.8% (n = 468). The ACS-SRC had the highest discrimination for all measured outcomes, as measured by the area under the receiver operating curve (AUC) and corresponding confidence interval (95% CI). This included perioperative mortality (AUC 0.74, 95% CI 0.71-0.78), compared to RAI-rev (AUC 0.66, 95% CI 0.62-0.69) and 5-mFI (AUC 0.61, 95% CI 0.57-0.65; p < 0.001). The RAI-rev and 5-mFI had similar discrimination for all measured outcomes., Conclusion: ACS-SRC was the perioperative risk stratification tool with the highest predictive discrimination for adverse, 30-day, postoperative events for patients with cancer treated with anatomic lung resection., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Objectives: The PROSPECT trial showed noninferiority of neoadjuvant chemotherapy (NAC) with selective chemoradiation (CRT) versus CRT alone. However, trial results are often difficult to reproduce with real-world data. Pathologic outcomes and overall survival (OS) were evaluated by neoadjuvant strategy in locally advanced rectal adenocarcinoma patients in a national database., Methods: The 2012-2020 National Cancer Database was queried for clinical T2N1 and T3N0-1 rectal adenocarcinoma patients with definitive resection. Patients were categorized by neoadjuvant treatment with CRT alone, NAC alone, and NAC with CRT. Outcomes included R0 resection, pathologic complete response (PCR), and OS., Results: Of 18 892 patients, 16 126 (85.4%) received CRT, 1018 (5.4%) NAC, and 1748 (9.3%) NAC with CRT. Patients with NAC alone or NAC with CRT were more likely to have stage-III disease, private insurance, and academic facility treatment (all p < 0.001). NAC alone had lower adjusted odds of an R0 resection (OR 0.72; 95%CI 0.54-0.95) and PCR (OR 0.77; 95%CI 0.64-0.93). NAC with CRT demonstrated improved OS (HR 0.71; 95%CI 0.61-0.82), with no difference between NAC and CRT alone. Among patients who received adjuvant chemotherapy, no differences in OS were seen., Conclusions: Patients who received NAC alone had worse pathologic outcomes. NAC had similar OS to CRT and NAC with CRT showed improved OS., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: Regionalizing hepatic resections to high-volume hospitals (HVH) has improved outcomes, yet widened disparities in access. We sought to evaluate the association of hospital volume with quality care outcomes and overall survival (OS) between minor and major hepatectomy for primary liver cancer., Methods: The National Cancer Database identified patients with primary liver cancer who underwent minor/major hepatectomy (2009-2019). HVHs were defined by the top quartile in annual case volume (vs. the bottom three quartiles). Quality care outcomes (time to resection, margin status, length of stay, 30-day readmission, 30-day mortality, 90-day mortality) and OS were assessed using multivariable regression., Results: Overall, 6,988 patients underwent minor hepatectomy and 4880 major hepatectomy. No differences in quality care outcomes or OS based on hospital volume for minor hepatectomy were observed (all p > 0.05). Treatment at HVHs for major hepatectomy was associated with decreased odds of 30-day and 90-day mortality events (all p < 0.05). Median OS was 40.2 months [IQR 21.7-66.6] at HVHs versus 33.5 [IQR 17.0-58.7] at low-volume hospitals which remained independently predictive of improved OS on multivariable analysis (HR 0.86, 95% CI 0.79-0.93)., Conclusion: These results support regionalization to HVHs for major hepatectomy; however, minor hepatectomy can be safely performed at hospitals regardless of volume., (© 2024 Wiley Periodicals LLC.)

Introduction: Perioperative risk stratification is an essential component of preoperative planning for cancer surgery. While frailty has gained attention for its utility in risk stratification, no studies have directly compared it to existing risk calculators. Therefore, the objective of this study was to compare the risk stratification of the American College of Surgeons Surgical Risk Calculator (ACS-SRC), the Revised Risk Analysis Index (RAI-rev), and the Modified Frailty Index (5-mFI). The primary outcomes were 30-day postoperative morbidity, 30-day postoperative mortality, unplanned readmission, unplanned reoperation, and discharge disposition other-than-home., Methods: Patients undergoing anatomic lung resection for primary, non-small cell lung cancer were identified within the American College of Surgeons National Quality Improvement Program (ACS NSQIP) database. The ACS-SRC, RAI-rev, and 5-mFI tools were used to predict adverse postoperative events. Tools were compared for discrimination in the primary outcomes., Results: 9663 patients undergoing anatomic lung resection for cancer between 2012 and 2014 were included. The cohort was 53.1% female. Median age at diagnosis was 67 (interquartile range = 59-74) years. Cardiothoracic surgeons performed 89% and general surgeons performed 11.0% of the operations. Perioperative morbidity and mortality rates were 10.9% (n = 1048) and 1.6% (n = 158). Rates of 30-day postoperative unplanned readmission and reoperation were 7.5% (n = 725) and 4.8% (n = 468). The ACS-SRC had the highest discrimination for all measured outcomes, as measured by the area under the receiver operating curve (AUC) and corresponding confidence interval (95% confidence interval [CI]). This included perioperative mortality (AUC = 0.74, 95% CI = 0.71-0.78), compared to RAI-rev (AUC = 0.66, 95% CI = 0.62-0.69) and 5-mFI (AUC = 0.61, 95% CI = 0.57-0.65; p < 0.001). The RAI-rev and 5-mFI had similar discrimination for all measured outcomes., Conclusion: ACS-SRC was the perioperative risk stratification tool with the highest predictive discrimination for adverse, 30-day, postoperative events for patients with cancer treated with anatomic lung resection., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Objectives: Given increased utilization of neoadjuvant therapy (NAT) for gastric adenocarcinoma, practice patterns deviating from standard of care (upfront resection) remain unknown. We sought to identify factors associated with NAT use and survival outcomes among early-stage gastric cancers., Methods: The National Cancer Database identified patients with early-stage (T1N0M0) gastric cancer (2010-2020). Multivariable logistic regression assessed characteristics associated with NAT utilization compared to upfront surgery. After 1:1 propensity score matching, Kaplan-Meier methods and Cox regression assessed overall survival (OS)., Results: Of 6452 patients with early-stage gastric cancer, 626 (9.7%) received NAT. Patients who received NAT were more likely treated at community hospitals, had moderate to poorly differentiated disease, and tumors located in the cardia (all p < 0.05). After propensity score matching, 1,248 patients remained. Median OS for NAT was 37.1 months (IQR 20.2-64.0) versus 45.6 months (IQR 22.5-72.8) for resection (p < 0.001). Treatment with NAT remained independently predictive of worse OS on Cox regression (hazard ratio 1.19; 95% confidence interval 1.05-1.34)., Conclusions: Although patients who received NAT had more aggressive prognostic features, NAT was associated with worse OS despite accounting for this selection bias. These results highlight the importance of adhering to guidelines, regardless of differing disease characteristics, which has significant implications on outcomes., (© 2024 Wiley Periodicals LLC.)

Background: Social conditions and dietary behaviors have been implicated in the rising burden of gastrointestinal cancers (GIC). The "food environment" reflects influences on a community level relative to food availability, nutritional assistance, and social determinants of health. Using the US Department of Agriculture-Food Environment Atlas (FEA), we sought to characterize the association of food environment on GIC presenting stage and long-term survival., Methods: Patients diagnosed with GIC between 2013 and 2017 were identified using the SEER database. FEA-scores were based on 282 county-level food security variables, store-restaurant availability, SNAP/WIC enrollment, pricing/taxes, and producer vicinity adjusted-for factors of socioeconomic status, race-ethnicity, transportation access, and comorbidities. Relative FEA rankings across US counties were averaged into a composite score and assigned to patients by county-of-residence. The association of FEA, cancer stage, and survival were analyzed using multiple logistic regression and cox-proportional hazard models relative to White/non-White race/ethnicity., Results: Among 287,148 patients, the most common GIC-sites were colon (n = 97,942, 34%), pancreas (n = 49,785, 17.3%), liver (n = 31,098, 11.0%) and esophagus (n = 16,271, 5.7%). A worse food environment was independently associated with increased odds of late-stage diagnosis (esophageal odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05; hepatic OR: 1.06, 95% CI: 1.03-1.08; pancreatic OR: 1.04, 95% CI: 1.01-1.06) among all patients; in contrast, food environment was associated with colorectal cancer stage among non-White patients only (OR: 1.04, 95% CI: 1.03-1.06). Worse food environment was associated with worse 3-year survival (colon OR: 1.03, 95% CI: 1.01-1.04; hepatic OR: 1.12, 95% CI: 1.08-1.17; gastric OR: 1.07, 95% CI: 1.01-1.13). Similar associations were noted relative to overall survival among the entire cohort (biliary tract hazard ratio [HR]: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.02, 95% CI: 1.01-1.04; hepatic HR: 1.07, 95% CI: 1.06-1.09; pancreatic HR: 1.04, 95% CI: 1.02-1.05; rectum HR: 1.03, 95% CI: 1.01-1.04; gastric HR: 1.05, 95% CI: 1.03-1.07), as well as among non-White patients (biliary HR: 1.04, 95% CI: 1.01-1.07; colon HR: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.05, 95% CI: 1.02-1.08; hepatic HR: 1.08, 95% CI: 1.06-1.10) (all p < 0.003)., Conclusions: Food environment was independently associated with late-stage tumor presentation and worse 3-year and overall survival among GIC patients. Interventions to address inequities across communities relative to food environments are needed to alleviate disparities in cancer care., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: The International Study Group of Liver Surgery's criteria stratifies post-hepatectomy liver failure (PHLF) into grades A, B, and C. The clinical significance of these grades has not been fully established., Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) hepatectomy-targeted database was analyzed. Outcomes between patients without PHLF, with grade A PHLF, and grade B or C PHLF were compared. Univariate and multivariable logistic regression were performed., Results: Six thousand two hundred seventy-four adults undergoing elective major hepatectomy were included in the analysis. The incidence of grade A PHLF was 4.3% and grade B or C was 5.3%. Mortality was similar between patients without PHLF (1.2%) and with grade A PHLF (1.1%), but higher in those with grades B or C PHLF (25.4%). Overall morbidities rates were 19.3%, 41.7%, and 72.8% in patients without PHLF, with grade A PHLF, and with grade B or C PHLF, respectively (p < 0.001). Grade A PHLF was associated with increased morbidity (grade A: odds ratios [OR] 2.7 [95% CI: 2.0-3.5]), unplanned reoperation (grade A: OR 3.4 [95% CI: 2.2-5.1]), nonoperative intervention (grade A: OR 2.6 [95% CI: 1.9-3.6]), length of stay (grade A: OR 3.1 [95% CI: 2.3-4.1]), and readmission (grade A: OR 1.8 [95% CI: 1.3-2.5]) compared to patients without PHLF., Conclusions: Although mortality was similar between patients without PHLF and with grade A PHLF, other postoperative outcomes were notably inferior. Grade A PHLF is a clinically distinct entity with relevant associated postoperative morbidity., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Prior studies in social determinants (SDoH) of truncal-extremity melanomas (TEM) have analyzed race, income, and environmental factors relative to their effect on health disparities. However, they are limited by the narrow scopes of SDoH and study population, while lacking analyses of interrelational contribution of SDoH on TEM disparities., Methods: This retrospective cohort study of adult TEM patients (1975-2017) assessed linear regression trends in months of survival, as well as logistic regression trends in advanced presenting stage, surgery, and chemotherapy receipt across TEM subtypes with increasing overall social vulnerability and vulnerability in 15 SDoH variables grouped into socioeconomic status (SES), minority-language status (ML), household composition (HH), and housing-transportation (HT) themes measured by the SVI. SVI measures are ranked/compared across all US counties for relative vulnerability in a specific SDH and their total composite while accounting for sociodemographic-regional differences., Results: Across 325 760 TEM patients, increasing overall social vulnerability demonstrated significant decreases in the survival period for 7/13 TEM histology types (p < 0.001), with relative decreases in the survival period as high as 44.0% (67.0-37.5 months) for epithelioid cell. SES and HH were the highest-magnitude contributors to these overall trends. For many patients with TEM, increased odds of advanced presenting stage (highest with acral-lentiginous: odds ratio [OR], -1.18; 95% confidence interval [CI], 1.02-1.36), decreased odds of indicated surgery receipt (lowest with amelanotic, 0.79; 0.71-0.87), and increased odds of indicated chemotherapy (highest with melanoma in giant nevi: 1.50; 1.01-2.44) were observed; SES and ML followed by HH and HT contributed to these trends., Conclusions: There were detriments in TEM care & prognosis in the United States with increasing social vulnerability. Identifying which SDH quantifiably are associated more with disparities in interrelational, real-world contexts is important to provide nuance to inform future research and initiatives to address TEM disparity., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) and chemoradiation (NCRT) have demonstrated improved survival for gastric cancer. However, the optimal neoadjuvant treatment remains unclear. We sought to evaluate perioperative and histopathologic outcomes among neoadjuvant treatments for locoregional gastric cancer., Methods: The National Cancer Database queried patients who received NAC or NCRT followed by resection for T2-T4 and/or node-positive gastric cancer (2006-2018). Logistic and Poisson regression assessed perioperative (30-day readmission, 30- and 90-day mortality, length of stay [LOS]) and histopathologic outcomes (pathologic complete response [PCR], margin status, and negative pathologic lymph nodes [ypN0]). Kaplan-Meier methods and Cox regression assessed overall survival (OS)., Results: Of 9831 patients, 4221 (42.9%) received NAC and 5610 (57.1%) NCRT. There were no differences in perioperative outcomes, apart from patients treated with NCRT exhibiting increased LOS (incidence rate ratio 1.09, 95% confidence interval [CI] 1.03-1.16). Patients who received NCRT were more likely to achieve PCR, margin-negative resection, and ypN0 (all p < 0.05). Median OS was 36.8 months for NAC and 33.6 months for NCRT (p < 0.001). NCRT independently predicted worse OS (vs. NAC, hazard ratio 1.10, 95% CI 1.03-1.18)., Conclusion: NCRT was associated with better histologic tumor response although NAC was associated with improved OS. Better understanding prognostication through histologic assessment following neoadjuvant therapy is needed., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Objectives: Regionalization of care is associated with improved perioperative outcomes after adrenalectomy. However, the relationship between travel distance and treatment of adrenocortical carcinoma (ACC) is unknown. We investigated the association between travel distance, treatment, and overall survival (OS) among patients with ACC., Methods: Patients diagnosed with ACC between 2004 and 2017 were identified with the National Cancer Database. Long distance was defined as the highest quintile of travel (≥42.2 miles). The likelihood of surgical management and adjuvant chemotherapy (AC) were determined. The association between travel distance, treatment, and OS was evaluated., Results: Of 3492 patients with ACC included, 2337 (66.9%) received surgery. Rural residents were more likely to travel long distances for surgery than metropolitan residents (65.8% vs. 15.5%, p < 0.001), and surgery was associated with improved OS (HR 0.43, 95% CI 0.34-0.54). Overall, 807 (23.1%) patients received AC with rates decreasing approximately 1% per 4-mile travel distance increase. Also, long distance travel was associated with worse OS among surgically treated patients (HR 1.21, 95% CI 1.05-1.40)., Conclusions: Surgery was associated with improved overall survival for patients with ACC. However, increased travel distance was associated with lower likelihood to receive adjuvant chemotherapy and decreased overall survival., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Most radical prostatectomies are completed with robotic assistance. While studies have previously evaluated perioperative outcomes of robot-assisted radical prostatectomy (RARP), this study investigates disparities in access and clinical outcomes of RARP., Study Design: The National Cancer Database (NCDB) was used to identify patients who received radical prostatectomy for cancer between 2010 and 2017 with outcomes through 2018. RARP was compared to open radical prostatectomy (ORP). Odds of receiving RARP were evaluated while adjusting for covariates. Overall survival was evaluated using a propensity-score matched cohort., Results: Overall, 354 752 patients were included with 297 676 (83.9%) receiving RARP. Patients who were non-Hispanic Black (82.8%) or Hispanic (81.3%) had lower rates of RARP than non-Hispanic White (84.0%) or Asian patients (87.7%, p < 0.001). Medicaid or uninsured patients were less likely to receive RARP (75.5%) compared to patients with Medicare or private insurance (84.4%, p < 0.001). Medicaid or uninsured status was associated with decreased odds of RARP in adjusted multivariable analysis (OR 0.61, 95% CI 0.49-0.76). RARP was associated with decreased perioperative mortality and improved overall survival compared to ORP., Conclusion: Patients who were underinsured were less likely to receive RARP. Improved access to RARP may lead to decreased disparities in perioperative outcomes for prostate cancer., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Objectives: Emergency department (ED) utilization after gastrointestinal cancer operations is poorly characterized. Our study objectives were to determine the incidence of, reasons for, and predictors of ED treat-and-release encounters after gastrointestinal cancer operations., Methods: Patients who underwent elective esophageal, hepatobiliary, gastric, pancreatic, small intestinal, or colorectal operations for cancer were identified in the 2015-2017 Healthcare Cost and Utilization Project State Inpatient and State Emergency Department Databases for New York, Maryland, and Florida. The primary outcomes were the incidence of ED treat-and-release encounters and readmissions within 30 days of discharge., Results: Among 51 527 patients at 406 hospitals, 4047 (7.9%) had an ED treat-and-release encounter, and 5573 (10.8%) had an ED encounter with readmission. In total, 40.7% of ED encounters were treat-and-release encounters. ED treat-and-release encounters were most frequently for pain (12.0%), device/ostomy complaints (11.7%), or wound complaints (11.4%). ED treat-and-release encounters predictors included non-Hispanic Black race/ethnicity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.12-1.37) and Medicare (OR 1.27, 95% CI 1.16-1.40) or Medicaid (OR 1.82, 95% CI 1.62-2.40) coverage., Conclusions: ED treat-and-release encounters are common after major gastrointestinal operations, making up nearly half of postdischarge ED encounters. The reasons for ED treat-and-release encounters differ from those for ED encounters with readmissions., (© 2023 Wiley Periodicals LLC.)

Background: Modern-day internet access and technology usage substantially impacts aspects of surgical care but remain ill-defined for their associations with gastrointestinal-cancer (GIC) outcomes. We sought to develop the Digital Inequity Index (DII), a novel, a self-adapted tool to quantify access to digital resources, to assess the impact of "digital inequity" on GIC care and prognosis., Methods: Adult (20+) patients with gastrointestinal malignancies between 2013 and 2017 were identified from the Surveillance, Epidemiology, and End Results Program database. DII was calculated based on 17 census-tract level variables derived from the American Community Survey and Federal Communications Commission. Variables were categorized as infrastructure-access (i.e., electronic device ownership, broadband type, internet provider availability, income-broadband subscription ratio) or sociodemographic (i.e., education, income, disability status), ranked relative across all US counties, and then averaged into a composite score. The association between DII and surgery receipt, staging, surveillance period, and survival time were assessed with multiple logistic and linear regressions., Results: Among 287 228 patients, increasing DII was associated with increased odds of late-stage disease (highest odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.05-1.10 for hepatic) and decreased odds of receiving surgery (lowest OR: 0.94, 95% CI: 0.93-0.96 for hepatic). Higher DII was associated with shorter postoperative surveillance length (largest decrease -20.4% for hepatic) and overall survival length (largest decrease -16.0% for pancreatic). Sociodemographic and infrastructure-access factors contributed equivalently to surveillance time disparities, while infrastructure-access factors contributed more to survival disparities across GIC types., Conclusions: As technology dependence has increased, inequities in digital access should be targeted as a contributor to surgical oncologic disparities., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: Accurate clinical staging (CS) of gastric adenocarcinoma is important to guide treatment planning. Our objectives were to (1) assess clinical to pathologic stage migration patterns for patients with gastric adenocarcinoma, (2) identify factors associated with inaccurate CS, and (3) evaluate the association of understaging with survival., Methods: The National Cancer Database was queried for patients who underwent upfront resection for stage I-III gastric adenocarcinoma. Multivariable logistic regression was used to detect factors associated with inaccurate understaging. Kaplan-Meier analyses and cox proportional hazards regression were performed to assess overall survival (OS) for patients with inaccurate CS., Results: Of 14 425 analyzed patients, 5781 (40.1%) patients were inaccurately staged. Factors associated with understaging included treatment at a Comprehensive Community Cancer Program, presence of lymphovascular invasion, moderate to poor differentiation, large tumor size, and T2 disease. Based on overall CS, median OS was 51.0 months for accurately staged patients and 29.5 months for understaged patients (<0.001)., Conclusion: Clinical T-category, large tumor size, and worse histologic features lead to inaccurate CS for gastric adenocarcinoma, impacting OS. Improvements to staging parameters and diagnostic modalities focusing on these factors may improve prognostication., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Objectives: Evidence for neoadjuvant therapy (NAT) in extrahepatic cholangiocarcinoma (eCCA) is limited. Our objectives were to: (1) characterize treatment trends, (2) identify factors associated with receipt of NAT, and (3) evaluate associations between NAT and postoperative outcomes., Methods: Retrospective cohort study of the National Cancer Database (2004-2017). Multivariable logistic regression assessed associations between NAT and postoperative outcomes. Stratified analysis evaluated differences between surgery first, neoadjuvant chemotherapy, and neoadjuvant chemoradiation (CRT)., Results: Among 8040 patients, 417 (5.2%) received NAT. NAT increased during the study period 2.9%-8.4% (p < 0.001). Factors associated with receipt of NAT included age <50 (vs. >75, odds ratio [OR] 4.32, p < 0.001) and stage 3 disease (vs. 1, OR 1.68, p = 0.01). Compared with surgery first, patients who received NAT had higher odds of R0 resection (OR 1.49, p = 0.01) and lower 30-day mortality (OR 0.51, p = 0.04). On stratified analysis, neoadjuvant chemotherapy was not associated with differences in any outcomes. However, neoadjuvant CRT was associated with improvement in R0 resection (OR 3.52, <0.001) and median survival (47.8 vs. 25.3 months, log-rank < 0.001) compared to surgery first., Conclusions: NAT, particularly neoadjuvant CRT, was associated with improved postoperative outcomes. These data suggest expanding the use of neoadjuvant CRT for eCCA., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: Low-grade appendiceal mucinous neoplasms (LAMNs) are generally treated by surgical resection, but posttreatment surveillance protocols are not well-established. The objectives of this study were to characterize posttreatment surveillance and determine the risk of recurrence following surgical resection of LAMN., Methods: Patients who underwent surgical resection of localized LAMNs in an 11-hospital regional healthcare system from 2000 to 2019 were identified. Posttreatment surveillance regimens were characterized, and rates of disease recurrence were evaluated., Results: A total of 114 patients with LAMNs were identified. T-category was pTis for 92 patients (80.7%), pT3 for 7 (6.1%), pT4a for 14 (12.3%), and pT4b for 1 (0.9%). Two patients (1.8%) had a positive resection margin. Posttreatment surveillance was performed for 39 (34.2%) patients and consisted of office visits for 32 (82%) patients, computerized tomography imaging for 30 (77%), magnetic resonance imaging for 5 (13%), colonoscopy for 15 (38%), and serum tumor marker measurement for 12 (31%). After a mean follow-up duration of 4.7 years, no patients experienced tumor recurrence., Conclusions: Posttreatment surveillance is common among patients with LAMNs. However, no patients experienced tumor recurrence, regardless of T-category or margin status, suggesting that routine surveillance following surgical resection of LAMN may be unnecessary., (© 2021 Wiley Periodicals LLC.)

Despite overall advances in cancer therapy, patients with pancreatic ductal adenocarcinoma continue to have a poor prognosis. While adjuvant therapy is still considered standard, there is mounting evidence that neoadjuvant therapy confers similar benefits in patients with locally advanced disease. The primary measures of response are radiographic, biochemical, margin status, and pathologic. Given overall low response rates and the need for new treatment strategies, standard metrics remain important to the investigation of new systemic agents., (© 2021 Wiley Periodicals LLC.)

Background and Objectives: Extended chemoprophylaxis is recommended for high-risk patients following pancreatectomy for malignancy. However, quantifying risk remains difficult. We sought to (a) identify factors associated with post-discharge venous thromboembolism (VTE) following pancreatectomy for malignancy and (b) develop a post-discharge VTE risk calculator to identify high-risk patients., Methods: Patients who underwent pancreatectomy for malignant histology from 2014 to 2018 were identified from the ACS NSQIP pancreatectomy procedure targeted dataset. Preoperative, intraoperative, and postoperative factors known at hospital discharge were evaluated for association with post-discharge VTE via multivariable logistic regression. A post-discharge VTE risk calculator was developed and validated., Results: Of 19 340 analyzed patients, 280 (1.5%) developed post-discharge VTE. Post-discharge VTE was associated with increasing body mass index (BMI; eg, morbidly obese BMI odds ratio [OR]: 1.99 [95% confidence interval {CI}: 1.30-3.02] vs normal BMI), procedure type (distal pancreatectomy OR: 1.47 [95% CI: 1.02-2.12] vs pancreaticoduodenectomy), pancreatic fistula (OR: 1.59 [95% CI: 1.19-2.13]) and delayed gastric emptying (OR: 1.81 [95% CI: 1.29-2.52]). Patients' predicted probability of post-discharge VTE ranged from 0.7% to 9.0%. Twenty iterations of 10-fold cross-validation demonstrated internal validity., Conclusions: Preoperative, intraoperative, and postoperative factors were associated with post-discharge VTE following pancreatectomy for malignancy. This post-discharge VTE risk calculator allows for quantification of individual post-discharge VTE risk, which ranged from 0.7% to 9.0%., (© 2020 Wiley Periodicals LLC.)

Palliative care, unlike hospice, can be utilized concurrently with disease-modifying or curative therapies. Some of the benefits of palliative care include improved quality of life, less end-of-life treatment, and decreased medical costs. Furthermore, palliative care can help guide treatment decisions to be in line with patients' physical, psychological, and spiritual needs. On the basis of these benefits, we advocate for palliative care involvement early in the course of advanced malignancy and other terminal diagnoses., (© 2019 Wiley Periodicals, Inc.)

Background and Objectives: Delayed gastric emptying (DGE) occurs commonly following pancreaticoduodenectomy (PD), but the rate of DGE in the absence of other intra-abdominal complications is poorly understood. The objectives of this study were to define the incidence of DGE and identify risk factors for DGE in patients without pancreatic fistula or other intra-abdominal infections., Methods: Retrospective cohort study utilizing the American College of Surgeons National Surgical Quality Improvement Program pancreatectomy variables to identify patients with DGE following PD without evidence of fistula or intra-abdominal infection. Multivariable models were developed to assess preoperative, intraoperative, and technical factors associated with DGE., Results: The rate of DGE was 11.7% in 10502 cases without pancreatic fistula or intra-abdominal infection. Patients were more likely to develop DGE if age ≥75 (odds ratio [OR], 1.22; P = 0.003), male (OR, 1.29; P < 0.001), underwent pylorus-sparing PD (OR, 1.27; P = 0.004), or had a prolonged operative time (OR, 1.38 if greater than seven vs less than 5 hours; P = 0.005). Factors not associated with DGE included BMI, pathologic indication, and surgical approach., Conclusion: The incidence of DGE after PD is notable even in patients without other abdominal complications. Identification of patients at increased risk for DGE may aid patient counseling as well as decisions regarding surgical technique, enteral feeding access, and enhanced-recovery pathways., (© 2019 Wiley Periodicals, Inc.)

Background: Pancreatic fistula remains common, with limited ability to risk stratify patients preoperatively. The objective of this study was to identify risk factors for clinically-relevant postoperative pancreatic fistula (CR-POPF) that are routinely available in the preoperative setting., Methods: Preoperatively available variables for all pancreaticoduodenectomies from 2014-2017 were examined using a national clinical registry. The cohort was separated into risk factor identification and internal validation subgroups., Results: Among 15 033 pancreaticoduodenectomies, the CR-POPF rate was 16.7%. CR-POPF was more likely in patients that were male (odds ratio [OR], 1.51), obese (body mass index [BMI] > 30, OR, 1.97), had minimal preoperative weight loss (OR, 1.25), had a nondilated pancreatic duct (OR, 1.81), did not have diabetes, (OR, 1.80), did not receive neoadjuvant therapy (OR, 1.78), had no evidence of biliary obstruction (OR, 1.18), or had nonadenocarcinoma pathology (OR, 1.96; all P < 0.01). Patients with three or fewer risk factors had a CR-POPF rate of 7.1%, while those with six or more risk factors had a CR-POPF rate of 26.3% (P < 0.001)., Conclusion: Preoperative CR-POPF risk evaluation could be a useful tool in patient counseling and surgical planning, and risk may allow for more well-informed decisions regarding perioperative management, including enhanced recovery protocols and use of somatostatin analogs., (© 2019 Wiley Periodicals, Inc.)

The liver is the second leading site of colorectal cancer metastases, following the lymph nodes. Although metastatic resection for colorectal cancer liver metastases has been shown to improve survival, many patients cannot undergo surgery. Several nonsurgical therapies are available in these situations, however high-quality evidence comparing the effectiveness of these therapies is sparse. Here, we review the currently available evidence in support of nonresectional regional therapies for colorectal metastases to the liver., (© 2019 Wiley Periodicals, Inc.)

Objective: The aim of this study was to identify if prolonged length of hospital stay was protective for certain post-discharge complications requiring readmission after pancreatectomy., Methods: Patients undergoing elective pancreatectomy from 2012 to 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Multivariate regression analyses were conducted to elucidate the association of length of hospital stay (LOS), in-hospital complications, and post-discharge complications with 30-day hospital readmission., Results: Mean LOS for the readmitted versus not readmitted cohort was 9.01 and 10.36, respectively (P < 0.001). Approximately half of hospital readmissions occur within 7 days of discharge from the hospital. The readmission rate (after hospital discharge) for patients with any in-hospital complication was 13.2%. On the other hand, the readmission rate for patients with any post-discharge complication was 70.8%. Readmission rates were above 85% for patients with the following post-discharge complications: organ/space surgical site infection (SSI), pneumonia, ventilator dependence greater than 48 h, progressive renal insufficiency, sepsis, and septic shock. In a multivariate logistic regression model, prolonged LOS reduced the odds of any post-discharge complication requiring readmission (OR = 0.68, P = 0.01). Specifically, prolonged LOS reduced the odds of a post-discharge organ/space SSI requiring readmission (OR = 0.72, P = 0.02)., Conclusion: Readmission after pancreatectomy primarily occurs due to a new post-discharge event. Furthermore, increased LOS is protective for readmission for post-pancreatectomy complications, particularly those due to post-discharge organ space SSIs. Our findings suggest that solely focusing on reducing LOS in pancreatectomy may lead to the unintended consequence of increasing readmission rates., (© 2018 Wiley Periodicals, Inc.)

Background and Objectives: Patient selection remains paramount when developing and adopting quality-based assessment and reimbursement models, and enhanced recovery protocols. Gender is a patient characteristic known before surgery which can inform risk stratification. Our aim was to evaluate the effect of gender on intraoperative blood transfusions, operative time, length of hospital stay, estimated blood loss (EBL) as well as postoperative surgical site infections (SSIs), and mortality., Methods: Patients undergoing elective pancreatectomy from 2005 to 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and Northwestern institutional databases. Multivariable analyses were conducted to identify the association between gender and these outcomes., Results: Analyses demonstrated that male gender was independently associated with blood transfusion (OR 1.23), operative time >6 hr (OR 1.76), length of stay greater than 11 days (OR 1.17), and all-type SSIs (OR 1.17), especially superficial SSIs (OR 1.15) and organ space SSIs (OR 1.18). Analysis of the institutional cohort found that male gender was independently associated with increased odds of EBL > 1 L for Whipple procedures (OR 2.85)., Conclusions: Male gender is a significant predictor of increased operative time, length of stay, transfusions, EBL > 1L, as well as postoperative organ space surgical site infections in these patients. J. Surg. Oncol. 2017;115:131-136. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background and Objectives: ERCP prior to pancreaticoduodenectomy is unnecessary in select patients. When performed, it should be in conjunction with endoscopic ultrasound (EUS) to increase diagnostic sensitivity and allow for metal stent placement. The aim of this study was to determine differences in endoscopic practice patterns at community medical centers (CMC) and a comprehensive pancreaticobiliary referral center (PBRC)., Methods: Retrospective cohort study of all patients seen at a PBRC for endoscopic and/or surgical management of potentially resectable malignant distal biliary obstruction from 1/2011 to 6/2014., Results: Of 75 patients, 30 underwent endoscopic management at a CMC and 45 were initially managed at our PBRC. ERCP was attempted in 92% of patients. EUS was performed more frequently (100% vs. 13.3 %, P < 0.0001), ERCP was more successful (93% vs. 69%, P = 0.02), and metal stent placement more likely (41% vs. 5%, P = 0.005) at our PBRC compared to a CMC. The majority (81%) of patients undergoing initial endoscopy at a CMC required repeat endoscopy at our PBRC., Conclusions: Patients who are candidates for pancreaticoduodenectomy frequently undergo ERCP. At a CMC, ERCP is often unsuccessful, is rarely accompanied by EUS, and often requires repeat endoscopy. Our findings support regionalizing the management of suspected pancreatic malignancy into dedicated specialty centers. J. Surg. Oncol. 2016;113:647-651. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Localized hepatocellular carcinoma (HCC) in patients with adequate liver function is typically treated with resection. Non-surgical modalities including trans-arterial embolization have emerged as options for intermediate/advanced HCC. Hypothesizing that non-surgical techniques have expanded to localized disease, we examined treatment patterns, factors associated with surgical therapy, and the impact of modality on survival., Methods: Non-cirrhotic, localized HCC patients were identified from the National Cancer Data Base (2003-2011). Trends were examined using average annual percent change (AAPC). Regression models were developed to determine factors associated with treatment and assess the association of modality with survival., Results: Of 10,187 patients (median tumor size: 3.7 cm), 6,387 (62.7%) underwent surgery and 3,800 (37.3%) non-surgical therapy. Surgery declined from 61.6% to 44.5% (AAPC, -3.7%; 95%CI, -4.9% to -2.6%, P < 0.001). Non-surgical therapies increased from 17.2% to 39.2% (AAPC 11.4%; 95%CI, 8.8-14.1%, P < 0.001). White race, higher income, and treatment in an academic center (OR = 1.37, 95%CI 1.13-1.66) were associated with surgery. Patients selected for non-surgical therapy had worse adjusted 5-year survival (HR=2.05, 95%CI 1.85-2.26)., Conclusions: Non-surgical therapy has become as common as surgery in the treatment of non-cirrhotic, localized HCC. Randomized studies are needed to compare the effectiveness of treatments for this disease., (© 2015 Wiley Periodicals, Inc.)

Background: The Clavien-Dindo system (CD) does not change the grade assigned a complication when multiple readmissions or interventions are required to manage a complication. We apply a modification of CD accounting for readmissions and interventions to pancreaticoduodenectomy (PD)., Methods: PDs done between 1999 and 2009 were reviewed. CD grade IIIa complications requiring more than one intervention and II and IIIa complications requiring significantly prolonged lengths of stay including all 90-day readmissions were classified severe-adverse-postoperative-outcomes (SAPO). CD IIIb, IV, and V complications were also classified SAPOs. All other complications were considered minor-adverse-postoperative-outcomes (MAPO)., Results: Four-hundred forty three of 490 PD patients (90.4%) had either no complication or a complication of low to moderate CD grade (I, II, IIIa). When reclassified by the new metric, 92 patient-outcomes (19%) were upgraded from CD II or IIIa to SAPO. One-hundred thirty nine patients (28.4%) had a SAPO. Multivariable regression identified age >75 years, pylorus preservation and operative blood loss >1,500 ml as predictors of SAPO. Age was not associated with poor outcome using the unmodified CD system., Conclusions: Established systems may under-grade the severity of some complications following PD. We define a procedure-specific modification of CD accounting for readmissions and multiple interventions. Using this modification, advanced age, pylorus preservation, and significant blood loss are associated with poor outcome., (© 2014 Wiley Periodicals, Inc.)

Background: Extremity sarcoma national guidelines offer several stage-specific treatment options; therefore, treatment approaches are not standardized. Our objectives were to examine multimodality treatment trends, practice patterns, and factors associated with neoadjuvant or postoperative adjuvant therapy utilization., Methods: Using the National Cancer Data Base (2000-2009), treatment of non-metastatic extremity sarcoma was examined. Regression models were developed to identify factors associated with neoadjuvant or postoperative adjuvant therapy receipt and treatment sequence., Results: Twenty-two thousand fifty-one patients underwent resection (stage I: 45.2%, stage II: 27.7%, stage III: 27.1%). Over 10 years, neoadjuvant radiation (6.4-11.6%, P < 0.001) and chemotherapy utilization (1.4-1.8%, P = 0.037) increased, while postoperative radiation (34.3-29.2%, P = 0.023) and trimodality therapy decreased (10.5-9.6%, P = 0.002). After adjusting for age, comorbidities, and histology, patients with large high-grade tumors treated at high-volume academic centers were more likely to receive neoadjuvant therapy (all P < 0.001). Postoperative chemotherapy utilization was associated with younger age, synovial histology, high grade, and surgical margins (all P < 0.001)., Conclusions: Utilization of neoadjuvant therapy for extremity sarcoma has increased over time. Practice patterns are not only related to tumor size, grade, histology, and margins but also hospital type. Opportunities remain to better define the most effective multimodality treatment for extremity sarcoma., (© 2013 Wiley Periodicals, Inc.)

Background and Objectives: Recommendations to refer pancreatic procedures to high-volume centers have been in place for a decade. We sought to determine whether regionalization of pancreatic procedures to high-volume centers is occurring in Illinois., Methods: We compared pancreatic procedures performed in Illinois hospitals from 2000 to 2004 [time period (TP) 1] versus 2005-2009 (TP2) for changes in inpatient mortality and hospital volume. Hospitals were categorized into low- (LVH), intermediate- (IVH), or high-volume (HVH)., Results: From TP1 to TP2, there was a 23% increase in absolute case volume (2,232-2,737), despite fewer hospitals performing pancreatic procedures (114-95). In hospital mortality decreased (5.5-3.3%, P < 0.01) and was lowest at HVHs. LVHs and IVHs were associated with a 4.7 and 3.0 higher odds of mortality, respectively (both P < 0.001). Overall, HVHs performed 659 (+73%) more procedures, whereas cumulative procedure volume dropped by 154 cases at LVHs (+1%) and IVHs (-18%)., Conclusions: We observed limited evidence of regionalization of pancreatic procedures in Illinois. The increase in HVH case volume cannot be solely attributed to regionalization, given the corresponding modest decrease seen at non-HVHs. There is opportunity for Illinois hospitals to implement strategies such as selective referral to improve mortality after pancreatic resection., (Copyright © 2013 Wiley Periodicals, Inc.)

Diets containing omega-6 (ω-6) fat have been associated with increased tumor development in carcinogen-induced pancreatic cancer models. However, the effects of ω-6 fatty acids and background strain on the development of genetically-induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω-6 fat on the development of pancreatic neoplasia in elastase (EL)-Kras(G12D) (EL-Kras) mice in two different backgrounds. EL-Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL-Kras FVB6 F1 (or EL-Kras F1) and EL-Kras B6 congenic mice. Age-matched EL-Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL-Kras FVB and EL-Kras F1 mice were fed a 23% corn oil diet and compared to age-matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL-Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL-Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL-Kras F1 mice were increased in mice fed a high ω-6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL-Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL-Kras F1 mice. The phenotype in EL-Kras F1 and FVB mice is promoted by a diet rich in ω-6 fatty acid., (Copyright © 2010 UICC.)

Background: Though sentinel lymph node biopsy (SLNB) is an integral component of melanoma staging, little is known about its use in children., Methods: Patients (0-18 years) with melanoma diagnosed from 2003 to 2007 in the National Cancer Data Base were assessed. Logistic regression models were used to identify clinicopathologic, socioeconomic, and hospital factors associated with SLNB use and lymph node metastases (LNM)., Results: Of 671 children, 68.7% underwent SLNB. SLNB utilization rates were 39.9% for T1a patients and 87.6% for T1b-T3 patients. T1b-T3 patients were more likely to undergo SLNB if they were older (OR 4.86 95% CI: 1.88-12.59) or cared for at Children's hospitals (OR 2.43 95% CI: 1.09-5.40). T1b-T3 patients were less likely to undergo SLNB if uninsured (OR 0.25 95% CI: 0.08-0.76). Of those with SLNB, 118 (25.6%) had pathologically confirmed LNM. Patients were more likely to have LNM if younger (OR 3.19 95% CI: 1.20-8.51) or having higher T stage (OR 10.38 95% CI: 4.59-23.47)., Conclusions: SLNB use for children with melanoma was associated with clinicopathologic, socioeconomic, and hospital factors. Younger patients have a higher likelihood of LNM but are the least likely to undergo SLNB. Though overall adherence appears high, there remains an opportunity for improved care for children with melanoma.

Bevacizumab (Avastin™; rhuMab VEGF), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has seen increased use in the perioperative treatment of colorectal and pancreatic cancer. Little is known, however, regarding its impact on surgical outcomes in patients undergoing resection. The objective of this review was to examine if the addition of bevacizumab to existing neoadjuvant regimens increases morbidity after cancer resection., (J. Surg. Oncol. 2010;102:539-542. © 2010 Wiley-Liss, Inc.)

Improving the quality of cancer care requires high-quality data, mechanisms to feed back information to hospitals, systems to act on the data, and participation of providers. The purpose of this review is to describe how the National Cancer Database (NCDB) can be utilized to improve the quality of cancer care in the United States through a variety of benchmarking reports and data feedback mechanisms available to hospitals approved by the Commission on Cancer (CoC).

Background and Objectives: Detection of pancreatic cancer by blood-based test may improve outcomes. We sought to establish the feasibility of a blood-based detection of pancreatic cancer through multiplexed array-mediated analysis of DNA methylation., Methods: Methylation was assessed in each plasma sample using a panel of 56 frequently methylated genes. Methylation profiles in patients with ductal cell adenocarcinoma of the pancreas (n = 30) and healthy gender and age-matched controls (n = 30) were compared. Methylation was determined as described previously; a composite biomarker was developed for classification of cancer and normal samples. Sensitivity and specificity of the biomarker were estimated using 25 rounds of fivefold cross-validation., Results: Five promoters were consistently selected for the classifier during cross-validation and comprised the final composite biomarker Five-fold cross-validation results indicate 76% sensitivity and 59% specificity of the biomarker, which included promoters of CCND2, SOCS1, THBS1, PLAU, and VHL., Conclusion: Differential methylation profiling of plasma DNA can detect ductal adenocarcinoma of the pancreas with significant accuracy and should be explored further. While additional improvement of biomarkers is necessary, the blood-based biomarker may be already useful as a first-line detection tool.

Pancreatic adeniocarcinoma is among the deadliest of human cancers. Apigenin, an antitumor flavonoid, inhibits pancreatic cancer cell proliferation in vitro. Geminin is a recently identified novel protein that plays a critical role in preventing abnormal DNA replication by binding to and inhibiting the essential replication factor Cdt1. Microarray analysis identified geminin to be downregulated in pancreatic cancer cells treated with apigenin. Therefore, we investigated the effects of apigenin on geminin expression and other proteins involved in replication (Cdc6, Cdt1, and MCM7) in pancreatic cancer cell lines CD18 and S2013. Real time RT-PCR and western blotting analysis showed that geminin expression is downregulated by apigenin at both mRNA and protein levels. Furthermore, treatment of cells with proteosome inhibitor MG132 reversed the downregulation of geminin by apigenin, supporting our hypothesis that the degradation pathway is another mechanism by which apigenin affects geminin expression. Apigenin treatment also resulted in downregulation of Cdc6 at both mRNA and protein levels. However, Cdt1 and MCM7 expression was not affected in apigenin-treated cells. The effect of apigenin treatment on geminin promoter activity was measured by transient transfection of Hela cells with a reporter gene, demonstrating that apigenin inhibited geminin promoter activity. Geminin expression was also evaluated in human pancreatic tissue (n = 15) by immunohistochemistry and showed that geminin is overexpressed in human pancreatic cancer compared to normal adjacent pancreatic tissue. In conclusion, our studies demonstrated that geminin is overexpressed in human pancreatic cancer and downregulated by apigenin which may contribute to the antitumor effect of this natural flavonoid.