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Introduction: The role of 5-lipoxygenase (5-LO) in colon cancer is unknown. Tumor-infiltrating macrophages, neutrophils, and mast cells have been shown to play important roles in colon tumorigenesis and are dependent on 5-LO for function.Methods and Materials: Utilizing the APC(Δ468) polyposis model, we performed 5-LO gene knockouts and evaluated the subsequent changes in macrophage, neutrophil, and mast cell density at the tumor site. The proliferative and degranulation capacities of 5-LO-deficient mast cells were also measured, quantifying thymidine incorporation and β-hexosaminidase release, respectively.Results: APC(Δ468)/5LO(-/-) mice displayed increased tumor-infiltrating macrophages and decreased neutrophils at the polyp site. In vitro, mast cells deficient for 5-LO proliferated at a diminished rate while mast cell degranulation was unchanged.Discussion: We provide evidence suggesting that 5-LO deficiency has differential effects on the infiltration of macrophages and neutrophils in adenomatous polyps, increasing and decreasing infiltration of these cells, respectively. Our observations are consistent with a protective role for tumor-infiltrating macrophages in the initiation of polyp formation. The mechanisms through which 5-LO deficiency negatively affects these cells are under investigation.Conclusions: These results provide evidence that 5-LO plays an important role in tumorigenesis and further indicate that 5-LO-selective inhibitors can be investigated as potential therapeutic agents for colorectal polyposis and cancer. [ABSTRACT FROM AUTHOR]

Background: Although invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is thought to be more indolent than sporadic pancreatic adenocarcinoma (PAC), the natural history remains poorly defined. The authors compared survival and identify prognostic factors after resection for invasive IPMN versus stage-matched PAC.Methods: The Surveillance, Epidemiology, and End Results database (1991-2005) was used to identify 729 patients with invasive IPMN and 8082 patients with PAC who underwent surgical resection.Results: Patients with resected invasive IPMN experienced improved overall survival when compared with resected PAC (median survival, 21 vs 14 months; P<.001). Stratification by nodal status demonstrated no difference in survival among lymph node-positive patients; however, median survival of resected, lymph node-negative, invasive IPMN was significantly improved compared with lymph node-negative PAC (34 vs 18 months; P<.001). On multivariate analysis, PAC histology was an adverse predictor of overall survival (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.50) compared with invasive IPMN. For patients with invasive IPMN, positive lymph nodes (HR, 1.98; 95% CI, 1.50-2.60), high tumor grade (HR, 1.74; 95% CI, 1.31-2.31), tumor size>2 cm (HR, 1.50; 95% CI, 1.04-2.19), and age>66 years (HR, 1.33; 95% CI, 1.03-1.73) were adverse predictors of survival.Conclusions: Although lymph node-negative invasive IPMN showed improved survival after resection compared with lymph node-negative PAC, the natural history of lymph node-positive invasive IPMN mimicked that of lymph node-positive PAC. The authors also identified adverse predictors of survival in invasive IPMN to guide discussions regarding use of adjuvant therapies and prognosis after resection of invasive IPMN. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows. DESIGN: A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed. RESULTS: Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur. CONCLUSIONS: Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or 'stellate' cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment. [ABSTRACT FROM AUTHOR]

Despite advances in immune checkpoint inhibitors, chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX [5-fluorouracil, F; irinotecan, I; and oxaliplatin, O (FIO)] regimen, and immune checkpoint inhibitors have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in patients with PDAC. In this study, we report that neoadjuvant FOLFIRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of FIO. In addition, we find that the KPC-FIO cells, established from repeated treatment of mouse PDAC cell lines with six to eight cycles of FIO, display enhanced ERK phosphorylation and demonstrate increased sensitivity to MEK inhibition in vitro and in vivo. Significantly, the KPC-FIO cells develop tumors with a proinflammatory immune profile similar to human PDAC tumors after neoadjuvant FOLFIRINOX treatment. Furthermore, we found that the MEK inhibitor trametinib enables additional infiltration of highly functional CD8+ T cells into the KPC-FIO tumors and potentiates the efficacy of anti-PD-1 antibody in syngeneic mouse models. Our findings provide a rationale for combining trametinib and anti-PD-1 antibodies in patients with PDAC after neoadjuvant or short-term FOLFIRINOX treatment to achieve effective antitumor responses., (©2024 American Association for Cancer Research.)

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.)

Background: Guideline-concordant care (GCC) is associated with improved survival for patients with cancer; however, variations in receipt of GCC remain a concern. The objective of this study was to evaluate the association of Commission on Cancer (CoC) hospital accreditation status with receipt of GCC and survival among patients with colon cancer., Methods: This retrospective observational study identified patients diagnosed with stage I-IV colon cancer from 2018 to 2020 from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program Database. Guideline concordance was defined as receipt of stage-appropriate lymphadenectomy or chemotherapy. Multivariable logistic regression models investigated associations with receipt of GCC. Cox proportional hazards regression models assessed 3-year cancer-specific mortality risk., Results: Of 222,583 patients with colon cancer, 146,629 (91.2%) of eligible patients received guideline-concordant lymphadenectomy and 70,586 (81.9%) of the eligible patients received guideline-concordant chemotherapy. Treatment at CoC-accredited hospitals was the strongest modifiable predictor for receipt of guideline-concordant lymphadenectomy (odds ratio [OR] 1.82; 95% confidence interval [CI] 1.75-1.88) and chemotherapy (OR 2.14; 95% CI 2.06-2.23). Among patients treated at CoC-accredited hospitals, risk adjusted mortality was decreased for patients with stage I-II disease (hazard ratio [HR] 0.94; 95% CI 0.80-0.99), stage III disease (HR 0.93; 95% CI 0.88-0.98), and stage IV disease (HR 0.88; 95% CI 0.84-0.92)., Conclusions: For patients with colon cancer, treatment at CoC-accredited hospitals was associated with increased receipt of GCC and decreased mortality risk. Benchmarking data may serve as a valuable accountability tool for quality assessment to improve cancer treatment and outcomes., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

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.)

Background: Cancer outcome disparities have been reported in highly vulnerable communities. The objective of this study was to evaluate the association of social vulnerability with receipt of guideline-concordant care (GCC) and mortality risk for patients with colorectal cancer., Study Design: This retrospective observational study identified patients with stage I-III colon or stage II-III rectal cancer between 2018 and 2020 from the National Program of Cancer Registries Database. Data were merged with the Centers for Disease Control and Prevention Social Vulnerability Index (SVI) at the county level. GCC was defined as stage-appropriate lymphadenectomy, radiation therapy, or systemic therapy. Multivariable logistic regression and Cox proportional hazards regression investigated associations of SVI, as a continuous and categorical variable stratified into quartiles, with GCC and 3-year cancer-specific mortality risk, respectively., Results: Among 124,950 patients (colon, n=102,399; rectal, n=22,551), median SVI was 60.9 (IQR 35.0 to 79.5). Patients in the highest SVI quartile had 21% decreased odds of receiving GCC (95% CI 0.76 - 0.83). Treatment at Commission on Cancer (CoC) accredited hospitals was associated with increased GCC (OR 1.79; 95% CI 1.72 - 1.85). Although there was an inverse, decreasing association between SVI and probability of GCC, probability at non-CoC-accredited hospitals declined faster than at CoC-accredited hospitals (p<0.05). After adjusting for receipt of GCC, highly vulnerable patients treated at CoC-accredited hospitals had decreased mortality risk (HR 0.91; 95% CI 0.83 - 0.98)., Conclusion: For highly vulnerable patients, treatment at CoC-accredited hospitals was associated with increased receipt of GCC and decreased mortality risk, which may reflect CoC-accreditation requirements for treatment guideline adherence, community engagement, and addressing barriers to care., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatic cancer remains highly lethal and resection represents the only chance for cure. Although patients are counseled regarding short-term (0-3 months) mortality, little is known about mortality 3-6 months (intermediate-term) following surgery. We assessed predictors of intermediate-term mortality, evaluated hospital-level variation, and developed a nomogram to predict intermediate-term mortality risk., Methods: Patients undergoing pancreatic cancer resection were identified from the National Cancer Database (2010-2020). Multivariable logistic regression identified predictors of intermediate-term mortality and assessed differences between short-term and intermediate-term mortality. Multinomial regression grouped by intermediate-term mortality quartiles evaluated hospital-level variation. A neural network model was constructed to predict intermediate-term mortality risk. All statistical tests were 2-sided., Results: Of 45,297 patients, 3,974 (8.9%) died within 6-months of surgery of which 2,216 (5.1%) were intermediate-term. Intermediate-term mortality was associated with increasing T-category, positive nodes, lack of systemic therapy, and positive margins (all p < .05) compared with survival beyond 6-months. Compared with short-term, intermediate-term mortality was associated with treatment at high-volume hospitals, positive nodes, neoadjuvant systemic therapy, adjuvant radiotherapy, and positive margins (all p < .05). Median intermediate-term mortality rate per hospital was 4.5% (IQR 2.6-6.5). Highest quartile hospitals had decreased odds of treatment with neoadjuvant systemic therapy, neoadjuvant radiotherapy, and adjuvant radiotherapy (all p < .05). The neural network nomogram was highly accurate (Accuracy: 0.9499; AUC-ROC of 0.7531) in predicting individualized intermediate-term mortality risk., Conclusion: Nearly 10% of patients undergoing pancreatectomy for cancer died within 6-months of which half occurred in the intermediate-term. These data have real-world implications to improve shared decision-making when discussing curative-intent pancreatectomy., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.)

Importance: Hospital-level factors, such as hospital type or volume, have been demonstrated to play a role in treatment disparities for Black patients with cancer. However, data evaluating the association of hospital accreditation status with differences in treatment among Black patients with cancer are lacking., Objective: To evaluate the association of Commission on Cancer (CoC) hospital accreditation status with receipt of guideline-concordant care and mortality among non-Hispanic Black patients with colon cancer., Design, Setting, and Participants: This population-based cohort study used the National Program of Cancer Registries, which is a multicenter database with data from all 50 states and the District of Columbia, and covers 97% of the cancer population in the US. The participants included non-Hispanic Black patients aged 18 years or older diagnosed with colon cancer between January 1, 2018, and December 31, 2020. Race and ethnicity were abstracted from medical records as recorded by health care facilities and practitioners. The data were analyzed from December 7, 2023, to January 17, 2024., Exposure: CoC hospital accreditation., Main Outcome and Measures: Guideline-concordant care was defined as adequate lymphadenectomy during surgery for patients with stages I to III disease or chemotherapy administration for patients with stage III disease. Multivariable logistic regression models investigated associations with receipt of guideline-concordant care and Cox proportional hazards regression models assessed associations with 3-year cancer-specific mortality., Results: Of 17 249 non-Hispanic Black patients with colon cancer (mean [SD] age, 64.8 [12.8] years; 8724 females [50.6%]), 12 756 (74.0%; mean [SD] age, 64.7 [12.8] years) were treated at a CoC-accredited hospital and 4493 (26.0%; mean [SD] age, 65.1 [12.5] years) at a non-CoC-accredited hospital. Patients treated at CoC-accredited hospitals compared with those treated at non-CoC-accredited hospitals had higher odds of receiving guideline-concordant lymphadenectomy (adjusted odds ratio [AOR], 1.89; 95% CI, 1.69-2.11) and chemotherapy (AOR, 2.31; 95% CI, 1.97-2.72). Treatment at CoC-accredited hospitals was associated with lower cancer-specific mortality for patients with stages I to III disease who received surgery (adjusted hazard ratio [AHR], 0.87; 95% CI, 0.76-0.98) and for patients with stage III disease eligible for chemotherapy (AHR, 0.75; 95% CI, 0.59-0.96)., Conclusions and Relevance: In this cohort study of non-Hispanic Black patients with colon cancer, patients treated at CoC-accredited hospitals compared with those treated at non-CoC-accredited hospitals were more likely to receive guideline-concordant care and have lower mortality risk. These findings suggest that increasing access to high-quality guideline-concordant care at CoC-accredited hospitals may reduce variations in cancer treatment and outcomes for underserved populations.

Background: Venous thromboembolism (VTE) chemoprophylaxis is the standard of care after gastrointestinal (GI) cancer surgery; however, variation in risk based on pathologic factors (eg, stage and histology) is unclear. This study aimed to evaluate the association of pathologic factors with VTE after GI cancer surgery., Methods: The American College of Surgeons National Surgical Quality Improvement Program procedure targeted datasets were queried for patients who underwent colorectal, pancreatic, primary hepatic, and esophageal cancer surgery between 2017 and 2020. Disease-specific and pathologic factors associated with postoperative VTE were evaluated using multivariable logistic regression., Results: Among 70,934 patients who underwent GI cancer surgery, the incidence rates of 30-day postoperative VTE were 3.3% for pancreatic cancer, 3.2% for esophageal cancer, 2.7% for primary hepatic, and 1.3% for colorectal cancer. T stage was associated with VTE for colorectal cancer (T4 vs T1; odds ratio [OR], 1.79; 95% CI, 1.24-2.60), pancreatic cancer (all T stages vs T1; P < .05), and primary hepatic cancer (T4 vs T1; OR, 2.80; 95% CI, 1.55-5.08). N stage was associated with VTE for colorectal cancer (N2 vs N0; OR, 1.33; 95% CI, 1.04-1.68) and pancreatic cancer (N2 vs N0; OR, 1.36; 95% CI, 1.03-1.81). M stage was associated with VTE for colorectal cancer (OR, 1.47; 95% CI, 1.17-1.85) and esophageal cancer (OR, 2.54; 95% CI, 1.24-5.19). Histologic subtype was not associated with VTE, except for pancreatic neuroendocrine tumors vs adenocarcinoma (OR, 1.34; 95% CI, 1.03-1.74)., Conclusion: Pathologic factors were associated with higher 30-day VTE risk after GI cancer surgery. Acknowledging the association of pathologic factors on VTE is an important first step to considering a more tailored approach to chemoprophylaxis., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

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.)

Background: Hepatic artery infusion (HAI) is less frequently used in the adjuvant setting for resectable colorectal liver metastasis (CRLM) due to concerns regarding toxicity. Our objective was to evaluate the safety and feasibility of establishing an adjuvant HAI program., Methods: Patients who underwent HAI pump placement between January 2019 and February 2023 for CRLM were identified. Complications and HAI delivery were compared between patients who received HAI in the unresectable and adjuvant settings., Results: Of 51 patients, 23 received HAI for unresectable CRLM and 28 in the adjuvant setting. Patients with unresectable CRLM more commonly had bilobar disease (n = 23/23 vs n = 18/28, p < 0.01) and more preoperative liver metastases (median 10 [IQR 6-15] vs 4 [IQR 3-7], p < 0.01). Biliary sclerosis was the most common complication (n = 2/23 vs n = 4/28); however, there were no differences in postoperative or HAI-specific complications. In the most recent two years, 0 patients in the unresectable group vs 2 patients in the adjuvant group developed biliary sclerosis. All patients were initiated on HAI with no difference in treatment times or dose reductions., Conclusion: Adjuvant HAI is safe and feasible for patients with resectable CRLM. HAI programs can carefully consider including patients with resectable CRLM if managed by an experienced multidisciplinary team with quality assurance controls in place., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Prior works have studied the impact of social determinants on various cancers but there is limited analysis on eye-orbit cancers. Current literature tends to focus on socioeconomic status and race, with sparse analysis of interdisciplinary contributions. We examined social determinants as measured by the Centers for Disease Control and Prevention (CDC) Social Vulnerability Index (SVI), quantifying eye and orbit melanoma disparities across the United States., Methods: A retrospective review of 15,157 patients diagnosed with eye-orbit cancers in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017 was performed, extracting 6139 ocular melanomas. SVI scores were abstracted and matched to SEER patient data, with scores generated by weighted averages per population density of county's census tracts. Primary outcome was months survived, while secondary outcomes were advanced staging, high grading, and primary surgery receipt., Results: With increased total SVI score, indicating more vulnerability, we observed significant decreases of 23.1% in months survival for melanoma histology (p < 0.001) and 19.6-39.7% by primary site. Increasing total SVI showed increased odds of higher grading (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.43) and decreased odds of surgical intervention (OR 0.94, 95% CI 0.92-0.96). Of the four themes, higher magnitude contributions were observed with socioeconomic status (26.0%) and housing transportation (14.4%), while lesser magnitude contributions were observed with minority language status (13.5%) and household composition (9.0%)., Conclusions: Increasing social vulnerability, as measured by the CDC SVI and its subscores, displayed significant detrimental trends in prognostic and treatment factors for adult eye-orbit melanoma. Subscores quantified which social determinants contributed most to disparities. This lays groundwork for providers to target the highest-impact social determinant for non-clinical factors in patient care., (© 2024. Society of Surgical Oncology.)

Importance: Prior reports demonstrated that patients with cancer experienced worse outcomes from pandemic-related stressors and COVID-19 infection. Patients with certain malignant neoplasms, such as high-risk gastrointestinal (HRGI) cancers, may have been particularly affected., Objective: To evaluate disruptions in care and outcomes among patients with HRGI cancers during the COVID-19 pandemic, assessing for signs of long-term changes in populations and survival., Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database to identify patients with HRGI cancer (esophageal, gastric, primary liver, or pancreatic) diagnosed between January 1, 2018, and December 31, 2020. Data were analyzed between August 23 and September 4, 2023., Main Outcome and Measures: Trends in monthly new cases and proportions by stage in 2020 were compared with the prior 2 years. Kaplan-Meier curves and Cox regression were used to assess 1-year mortality in 2020 compared with 2018 to 2019. Proportional monthly trends and multivariable logistic regression were used to evaluate 30-day and 90-day mortality in 2020 compared with prior years., Results: Of the 156 937 patients included in this study, 54 994 (35.0%) were aged 60 to 69 years and 100 050 (63.8%) were men. There was a substantial decrease in newly diagnosed HRGI cancers in March to May 2020, which returned to prepandemic levels by July 2020. For stage, there was a proportional decrease in the diagnosis of stage I (-3.9%) and stage II (-2.3%) disease, with an increase in stage IV disease (7.1%) during the early months of the pandemic. Despite a slight decrease in 1-year survival rates in 2020 (50.7% in 2018 and 2019 vs 47.4% in 2020), survival curves remained unchanged between years (all P > .05). After adjusting for confounders, diagnosis in 2020 was not associated with increased 1-year mortality compared with 2018 to 2019 (hazard ratio, 0.99; 95% CI, 0.97-1.01). The rates of 30-day (2.1% in 2018, 2.0% in 2019, and 2.1% in 2020) and 90-day (4.3% in 2018, 4.4% in 2019, and 4.6% in 2020) operative mortality also remained similar., Conclusions and Relevance: In this retrospective cohort study, a period of underdiagnosis and increase in stage IV disease was observed for HRGI cancers during the pandemic; however, there was no change in 1-year survival or operative mortality. These results demonstrate the risks associated with gaps in care and the tremendous efforts of the cancer community to ensure quality care delivery during the pandemic. Future research should investigate long-term survival changes among all cancer types as additional follow-up data are accrued.

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: Little is known about surgery for malignancy among people experiencing homelessness (PEH). Poor healthcare access may lead to delayed diagnosis and need for unplanned surgery. This study aimed to (1) characterize access to care among PEH, (2) evaluate postoperative outcomes, and (3) assess costs associated with surgery for malignancy among PEH., Methods: This was a retrospective cohort study of patients in the Healthcare Cost and Utilization Project (HCUP) who underwent surgery in Florida, New York, or Massachusetts for gastrointestinal or lung cancer from 2016 to 2017. PEH were identified using HCUP's "Homeless" variable and ICD-10 code Z59. Multivariable regression models controlling patient and hospital variables evaluated associations between homelessness and postoperative morbidity, length of stay (LOS), 30-day readmission, and hospitalization costs., Results: Of 67,034 patients at 566 hospitals, 98 (0.2%) were PEH. Most PEH (44.9%) underwent surgery for colorectal cancer. PEH more frequently underwent unplanned surgery than housed patients (65.3% vs 23.7%, odds ratio (OR) 5.17, 95% confidence interval (CI) 3.00-8.92) and less often were treated at cancer centers (66.0% vs 76.2%, p=0.02). Morbidity rates were similar between groups (20.4% vs 14.5%, p=0.10). However, PEH demonstrated higher odds of facility discharge (OR 5.89, 95% CI 3.50-9.78) and readmission (OR 1.81, 95% CI 1.07-3.05) as well as 67.7% longer adjusted LOS (95% CI 42.0-98.2%). Adjusted costs were 32.7% higher (95% CI 14.5-53.9%) among PEH., Conclusions: PEH demonstrated increased odds of unplanned surgery, longer LOS, and increased costs. These results underscore a need for improved access to oncologic care for PEH., (© 2023. Society of Surgical Oncology.)

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: Disparities in colon cancer care and outcomes by race/ethnicity, socioeconomic status (SES), and insurance are well recognized; however, the extent to which inequalities are driven by patient factors versus variation in hospital performance remains unclear. We sought to compare disparities in care delivery and outcomes at low- and high-performing hospitals., Methods: We identified patients with stage I-III colon adenocarcinoma from the 2012-2017 National Cancer Database. Adequate lymphadenectomy and timely adjuvant chemotherapy administration defined hospital performance. Multilevel regression models evaluated disparities by race/ethnicity, SES, and insurance at the lowest- and highest-performance quartile hospitals., Results: Of 92,573 patients from 704 hospitals, 45,982 (49.7%) were treated at 404 low-performing hospitals and 46,591 (50.3%) were treated at 300 high-performing hospitals. Low-performing hospitals treated more non-Hispanic (NH) Black, Hispanic, low SES, and Medicaid patients (all p < 0.01). Among low-performing hospitals, patients with low versus high SES (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82-0.92), and Medicare (OR 0.90, 95% CI 0.85-0.96) and Medicaid (OR 0.88, 95% CI 0.80-0.96) versus private insurance, had decreased odds of receiving high-quality care. At high-performing hospitals, NH Black versus NH White patients (OR 0.83, 95% CI 0.72-0.95) had decreased odds of receiving high-quality care. Low SES, Medicare, Medicaid, and uninsured patients had worse overall survival at low- and high-performing hospitals (all p < 0.01)., Conclusion: Disparities in receipt of high-quality colon cancer care occurred by SES and insurance at low-performing hospitals, and by race at high-performing hospitals. However, survival disparities by SES and insurance exist irrespective of hospital performance. Future steps include improving low-performing hospitals and identifying mechanisms affecting survival disparities., (© 2023. Society of Surgical Oncology.)

Introduction: Surgical resection is the primary curative treatment for localized gastric cancer. A multitude of research supports surgical nodal sampling guidelines. Though there are known disparities in adherence to nodal sampling, it is unclear how hospital program-level disparities have changed over time. The purpose of this study is to evaluate trends in program-level disparities in adherence to gastric cancer nodal sampling guidelines., Methods: Patients who underwent resection of gastric cancer from 2005 to 2017 were identified in the National Cancer Database. Patients treated at academic programs were compared to those treated at nonacademic programs, and rates and trends of adherence to nodal sampling guidelines (defined as ≥15 lymph nodes) were determined. Adjusted multivariable analysis was used to determine likelihood of nodal sampling adherence while controlling for sociodemographic, clinical, hospital, and travel distance characteristics., Results: A total of 55,421 patients were included with 27,201 (49.1%) of patients meeting adherence criteria for lymph node sampling. Academic programs treated 44.4% of the total cohort. Overall, lymph node sampling criteria were met in 59.2% of patients treated at high-volume academic programs and 37.0% of patients treated at low-volume nonacademic programs (incidence rate ratios 0.67, 95% confidence interval 0.63-0.72 versus high-volume academic programs). Adherence rates improved from 2005 to 2017 for both low-volume nonacademic programs (27.8% in 2005 to 50.1% in 2017) and high-volume academic programs (46.0% in 2005 to 69.8% in 2017, P < 0.001)., Conclusions: Though adherence rates have improved from 2005 to 2017, high-volume academic programs were more likely to adhere to lymph node sampling guidelines for gastric cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.)

Importance: Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA)., Objective: To determine VTE rates after cancer surgery, as well as rates of inpatient and outpatient (posthospital discharge) chemoprophylaxis adherence within the VHA., Design, Setting, and Participants: This retrospective cohort study within 101 hospitals of the VHA health system included patients aged 41 years or older without preexisting bleeding disorders or anticoagulation usage who underwent surgical treatment for cancer with general surgery, thoracic surgery, or urology between January 1, 2015, and December 31, 2022. The VHA Corporate Data Warehouse, Pharmacy Benefits Management database, and the Veterans Affairs Surgical Quality Improvement Program database were used to identify eligible patients. Data analysis was conducted between January 2022 and July 2023., Exposures: Inpatient surgery for cancer with general surgery, thoracic surgery, or urology., Main Outcomes and Measures: Rates of postoperative VTE events within 30 days of surgery and VTE chemoprophylaxis adherence were determined. Multivariable Poisson regression was used to determine incidence-rate ratios of inpatient and postdischarge chemoprophylaxis adherence by surgical specialty., Results: Overall, 30 039 veterans (median [IQR] age, 67 [62-71] years; 29 386 men [97.8%]; 7771 African American or Black patients [25.9%]) who underwent surgery for cancer and were at highest risk for VTE were included. The overall postoperative VTE rate was 1.3% (385 patients) with 199 patients (0.7%) receiving a diagnosis during inpatient hospitalization and 186 patients (0.6%) receiving a diagnosis postdischarge. Inpatient chemoprophylaxis was ordered for 24 139 patients (80.4%). Inpatient chemoprophylaxis ordering rates were highest for patients who underwent procedures with general surgery (10 102 of 10 301 patients [98.1%]) and lowest for patients who underwent procedures with urology (11 471 of 17 089 patients [67.1%]). Overall, 3142 patients (10.5%) received postdischarge chemoprophylaxis, with notable variation by specialty., Conclusions and Relevance: These findings indicate the overall VTE rate after cancer surgery within the VHA is low, VHA inpatient chemoprophylaxis rates are high, and postdischarge VTE chemoprophylaxis prescribing is similar to that of non-VHA health systems. Specialty and procedure variation exists for chemoprophylaxis and may be justified given the low risks of overall and postdischarge VTE.

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: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of dense stroma that is enriched in hyaluronan (HA), with increased HA levels associated with more aggressive disease. Increased levels of the HA-degrading enzymes hyaluronidases (HYALs) are also associated with tumor progression. In this study, we evaluate the regulation of HYALs in PDAC., Methods: Using siRNA and small molecule inhibitors, we evaluated the regulation of HYALs using quantitative real-time PCR (qRT-PCR), Western blot analysis, and ELISA. The binding of BRD2 protein on the HYAL1 promoter was evaluated by chromatin immunoprecipitation (ChIP) assay. Proliferation was evaluated by WST-1 assay. Mice with xenograft tumors were treated with BET inhibitors. The expression of HYALs in tumors was analyzed by immunohistochemistry and by qRT-PCR., Results: We show that HYAL1, HYAL2, and HYAL3 are expressed in PDAC tumors and in PDAC and pancreatic stellate cell lines. We demonstrate that inhibitors targeting bromodomain and extra-terminal domain (BET) proteins, which are readers of histone acetylation marks, primarily decrease HYAL1 expression. We show that the BET family protein BRD2 regulates HYAL1 expression by binding to its promoter region and that HYAL1 downregulation decreases proliferation and enhances apoptosis of PDAC and stellate cell lines. Notably, BET inhibitors decrease the levels of HYAL1 expression in vivo without affecting the levels of HYAL2 or HYAL3., Conclusions: Our results demonstrate the pro-tumorigenic role of HYAL1 and identify the role of BRD2 in the regulation of HYAL1 in PDAC. Overall, these data enhance our understanding of the role and regulation of HYAL1 and provide the rationale for targeting HYAL1 in PDAC., Competing Interests: The authors declare that they have no competing interests.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood., Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics., Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment., Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care)., Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program., Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32)., Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy., Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

Introduction: Access to cancer care, especially surgery, is limited in rural areas. However, the specific reasons rural patient populations do not receive surgery for non-small cell lung cancer (NSCLC) is unknown. We investigated geographic disparities in reasons for failure to receive guideline-indicated surgical treatment for patients with potentially resectable NSCLC., Methods: The National Cancer Database was used to identify patients with clinical stage I-IIIA (N0-N1) NSCLC between 2004 and 2018. Patients from rural areas were compared to urban areas, and the reason for nonreceipt of surgery was evaluated. Adjusted odds of (1) primary nonsurgical management, (2) surgery being deemed contraindicated due to risk, (3) surgery being recommended but not performed, and (4) overall failure to receive surgery were determined., Results: The study included 324,785 patients with NSCLC with 42,361 (13.0%) from rural areas. Overall, 62.4% of patients from urban areas and 58.8% of patients from rural areas underwent surgery (P < 0.001). Patients from rural areas had increased odds of (1) being recommended primary nonsurgical management (adjusted odds ratio [aOR]: 1.14, 95% confidence interval [CI]: 1.05-1.23), (2) surgery being deemed contraindicated due to risk (aOR: 1.19, 95% CI: 1.07-1.33), (3) surgery being recommended but not performed (aOR: 1.13, 95% CI: 1.01-1.26), and (4) overall failure to receive surgery (aOR: 1.21, 95% CI: 1.13-1.29; all P < 0.001)., Conclusions: There are geographic disparities in the management of NSCLC. Rural patient populations are more likely to fail to undergo surgery for potentially resectable disease for every reason examined., (Copyright © 2022. Published by Elsevier Inc.)

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.)

Objective: Regionalization of surgery for non-small cell lung cancer (NSCLC) to high-volume centers (HVCs) improves perioperative outcomes but frequently increases patient travel distance. Travel might decrease rates of adjuvant chemotherapy (AC) use, however, the relationship of distance, volume, and receipt of AC with outcomes is unknown. Our objective was to evaluate the association of distance, volume, and receipt of AC with overall survival among patients with NSCLC., Methods: Patients with stage I to IIIA (N0-N1) NSCLC were identified between 2004 and 2018 using the National Cancer Database. Distance to surgical facility was categorized into quartiles (<5.1, 5.1 to <11.5, 11.5 to <28.1, and ≥28.1 miles), and HVCs were defined as those that perform ≥40 annual resections. Patient characteristics and likelihood of receiving AC anywhere were determined. Propensity score-matched survival analysis was performed using Cox models and Kaplan-Meier curves., Results: Of the 131,982 patients included, 35,658 (27.0%) were stage II to IIIA. Of the stage II to IIIA cohort, 49.6% received AC, 13.1% traveled <5.1 miles to low-volume centers (LVCs), and 18.1% traveled ≥28.1 miles to HVCs ( P  < .001). Among stage II to IIIA patients who traveled ≥28.1 miles to HVCs, 45% received AC versus 51.5% who traveled <5.1 miles to LVCs (incidence rate ratio, 0.88; 95% CI, 0.83-0.94; <5.1 miles to LVC reference). Patients with stage II to IIIA NSCLC who traveled ≥28.1 miles to HVCs and did not receive AC had higher mortality rates than those who traveled <5.1 miles to LVCs and received AC (median overall survival, 52.3 vs 36.7 months; adjusted hazard ratio, 1.41; 95% CI, 1.26-1.57)., Conclusions: Increasing travel distance to surgical treatment is associated with decreased likelihood of receiving AC for patients with stage II to IIIA (N0-N1) NSCLC., (© 2022 The Author(s).)

Purpose: Unresectable intrahepatic cholangiocarcinoma (ICC) signifies a poor prognosis with limited treatment options beyond systemic chemotherapy. This study's purpose was to evaluate the safety, efficacy, and potential for downstaging to resection of yttrium-90 (Y90) radioembolization for treatment of unresectable ICC., Materials and Methods: From 2004 to 2020, 136 patients with unresectable ICC were treated with radioembolization at a single institution. Retrospective review was performed of a prospectively collected database. Outcomes were (1) biochemical and clinical toxicities, (2) local tumor response, (3) time to progression, and (4) overall survival (OS) after Y90. Univariate/multivariate survival analyses were performed. A subgroup analysis was performed to calculate post-resection recurrence and OS in patients downstaged to resection after Y90., Results: Grade 3+ clinical and biochemical toxicities were 7.6% (n = 10) and 4.9% (n = 6), respectively. Best index lesion response was complete response in 2 (1.5%), partial response in 42 (32.1%), stable disease in 82 (62.6%), and progressive disease in 5 (3.8%) patients. Median OS was 14.2 months. Solitary tumor (P < 0.001), absence of vascular involvement (P = 0.009), and higher serum albumin (P < 0.001) were independently associated with improved OS. Eleven patients (8.1%) were downstaged to resection and 2 patients (1.5%) were bridged to transplant. R0-resection was achieved in 8/11 (72.7%). Post-resection median recurrence and OS were 26.3 months and 39.9 months, respectively., Conclusion: Y90 has an acceptable safety profile and high local disease control rates for the treatment of unresectable ICC. Downstaging to resection with > 3 years survival supports the therapeutic role of Y90 for unresectable ICC., Level of Evidence: Level 3, single-arm single-center cohort study., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

To elicit effective antitumor responses, CD8+ T cells need to infiltrate tumors and sustain their effector function within the immunosuppressive tumor microenvironment (TME). Here, we evaluate the role of MNK activity in regulating CD8+ T cell infiltration and antitumor activity in pancreatic and thyroid tumors. We first show that human pancreatic and thyroid tumors with increased MNK activity are associated with decreased infiltration by CD8+ T cells. We then show that, while MNK inhibitors increase CD8+ T cells in these tumors, they induce a T cell exhaustion phenotype in the tumor microenvironment. Mechanistically, we show that the exhaustion phenotype is not caused by upregulation of programmed cell death ligand 1 (PD-L1) but is caused by tumor-associated macrophages (TAMs) becoming more immunosuppressive following MNK inhibitor treatment. Reversal of CD8+ T cell exhaustion by an anti-PD-1 antibody or TAM depletion synergizes with MNK inhibitors to control tumor growth and prolong animal survival. Importantly, we show in ex vivo human pancreatic tumor slice cultures that MNK inhibitors increase the expression of markers associated with immunosuppressive TAMs. Together, these findings demonstrate a role of MNKs modulating a protumoral phenotype in macrophages and identify combination regimens involving MNK inhibitors to enhance antitumor immune responses.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.