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Background Weight changes during neoadjuvant chemotherapy (NAC) for pancreatic cancer (PDAC) are not well studied. We hypothesized that weight loss may predict poor outcomes. Methods Weight change from NAC initiation to pancreatectomy was grouped: gain (≥5%), stable, and loss (≥5%). Pathologic, postoperative, and survival outcomes were compared. Results 95 patients were included: 31.6% lost weight, 58.9% maintained weight, and 9.5% gained weight. There were no differences in chemotherapeutic regimens. Median recurrence-free survival (RFS) and overall survival (OS) were similar between patients with stable weight and those who lost weight (RFS: 9.6vs14.0months; OS: 25.8vs26.7months). Among those who gained weight, RFS (29.5months) and OS (38.4months) were greater relative to the other weight categories. On multivariable regression, weight gain was associated with improved RFS compared to loss (HR = 0.16). Conclusion Most patients maintain or lose weight during NAC, and weight loss does not predict poor outcomes. Weight gain may predict improved RFS.

Most patients with pancreatic adenocarcinoma (PDAC) do not undergo surgical resection. The role of radiotherapy (RT) in non-operatively managed localized pancreatic adenocarcinoma is unclear.The National Cancer Database (2010-2016) was queried for patients with clinical stage II-III PDAC treated with multiagent systemic chemotherapy (CT) +/- RT but not surgery. Factors associated with the receipt of RT and overall survival were compared after adjusting for patient demographics and clinical characteristics.A total of 14,921 patients were included, of whom 9279 received CT and 5382 received CT + RT. Patients treated with CT + RT were more likely to be younger (65vs66yrs), treated at non-academic facilities (48.8%vs46.7%), have private insurance (40.3%vs36.5%), and have clinical T4 tumors (53.6%vs48.7%). Most patients who were treated with RT received external beam radiotherapy (89.3%), and the median dose was 5,000 cGy. Median time to start of RT was 129 days. CT + RT was associated with longer overall survival (15.9vs11.8mos,p 0.001), and remained associated with survival on multivariable analysis (HR 0.74, 95%CI 0.70-0.78). On a 4-month conditional survival analysis, combined CT + RT remained associated with improved survival compared to CT alone (16.0vs13.1mos,p 0.001).In patients with non-operatively managed localized pancreatic adenocarcinoma, combined radiotherapy and multiagent systemic chemotherapy is associated with improved overall survival compared to chemotherapy alone.

Background The Centers for Medicare and Medicaid Services proposed reimbursement cuts for operations in 2021. Literature examining reimbursement for common operations is scarce. Methods Reimbursement rates were abstracted (2011–2021). Trends in reimbursement rates were analyzed using linear regression. Results From 2011 to 2021, the national inflation rate was 16.3%. Unadjusted reimbursement rates for open and laparoscopic inguinal hernia repairs increased by 6.5% and 7.2%, respectively. There was an increase in unadjusted reimbursement for open appendectomies of 5.1% and 6.1% for laparoscopic. Unadjusted reimbursement for open cholecystectomies increased by 4.4%, but decreased by 6.8% for laparoscopic. When adjusted to 2021 values, reimbursement for all six operations decreased. Laparoscopic and open cholecystectomies experienced the largest decreases (19.8%, 10.2%). Conclusion Since 2011, there have been decreases in adjusted reimbursement for three common operations, independent of operative approach. Awareness of trends in reimbursement rates should be a priority to ensure sustainable general surgical care.

Background Guidelines recommend resection of non-functional neuroendocrine tumors of the pancreas (NF-pNETs) that are ≥2 cm in size. We compared utilization of surgery based on race. Methods We identified non-Hispanic White and Black patients with localized NF-pNETs ≥2 cm and Charlson-Deyo score 0–1 in the NCDB (2004–2016). We compared utilization of surgery by race, adjusting for clinicodemographic variables. Overall survival was compared based on management. Results A total of 3459 patients were included (White = 3005; Black = 454). Black patients were younger (58vs63 years) and more often treated at academic facilities (65.3%vs60.3%). Overall, Black and White patients underwent surgery at similar rates (77.3%vs79.6%). When stratified by primary site, Black patients with body/tail tumors were less likely to undergo surgery (78.5%vs84.7%). On multivariable analysis, Black race was associated with a lower likelihood of surgery overall (OR 0.74,p = 0.034) and in patients with body/tail tumors (OR 0.56,p = 0.001). Non-operative management was associated with a higher risk of death (HR 3.19,p Conclusion In a national cohort of patients with NF-pNETs meeting criteria for resection, Black race is associated with lower frequency of surgery. Operative intervention is associated with prolonged survival. Persistent racial disparities in management of a surgically curable disease should be targeted for improvement.

There is evidence that neoadjuvant therapy is associated with improved survival compared with upfront pancreatectomy for pancreatic adenocarcinoma. Treatment at high-volume pancreatic surgery centers is associated with improved short-term postoperative outcomes compared with low-volume centers. We compared overall survival of patients with early-stage pancreatic adenocarcinoma who received neoadjuvant therapy before resection stratified by facility volume.Patients with clinical T0 to T2 pancreatic adenocarcinoma who received neoadjuvant therapy before pancreatoduodenectomy were identified in the National Cancer Database (2010-2016). High-volume pancreatic surgery centers performed ≥36 pancreatectomies/year. Patients were matched 1:1 by propensity score. Pathologic outcomes, postoperative outcomes, and overall survival were compared.Before matching, 1,449 patients were treated at low-volume centers and 250 at high-volume pancreatic surgery centers. After matching, there were 177 patients per group. High-volume pancreatic surgery centers were more commonly academic/research facilities (99.4% vs 54.0%; P.001), and patients traveled greater distances (65 vs 13 miles; P.001). Time from diagnosis to neoadjuvant therapy and surgery was similar. Treatment at high-volume pancreatic surgery centers was associated with shorter duration of stay (7 vs 8 days; P = .003) and lower 90-day mortality rate after pancreatoduodenectomy (0.0% vs 5.0%; P = .01). Patients treated at high-volume pancreatic surgery centers had improved overall survival (36.3 vs 29.4 months; P = .03; hazard ratio 0.73). On subset analysis of academic/research facilities, high-volume pancreatic surgery centers remained associated with shorter duration of stay, lower 90-day mortality, and greater overall survival.The majority of patients treated with neoadjuvant therapy for early-stage pancreatic adenocarcinoma received care at low-volume centers. Treatment at high-volume pancreatic surgery centers was associated with improved overall survival and short-term postoperative outcomes.

BACKGROUND AND OBJECTIVES This study investigated the impact of treating facility type on guideline-concordant sentinel lymph node biopsy (SLNB) management in T1a* (defined as a Breslow depth

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival of common cancers, partly because there are no reliable early detection tests. Unintentional weight loss (≥ 5% decrease from baseline) has been linked to PDAC, but the frequency and severity of weight loss using objective measures, and its relationship to prognosis, have not been well characterized. We identified 390 patients with PDAC (all stages) and two or more prediagnosis weights in the electronic medical record. Percentage weight loss in the 365 and 180 days preceding diagnosis was calculated. Results were compared with raw weights of age- and sex-matched non-cancer controls (n = 780). Odds ratios for PDAC were calculated using conditional logistic regression. Cox proportional hazards models were used for survival. Within 1 year of diagnosis, more PDAC patients lost ≥ 5% weight relative to controls (74.9% vs. 11.2%; p

Pancreatic ductal adenocarcinoma (PDAC) has historically poor outcomes. Difficult decisions must be made by patients and providers, especially in the elderly for whom treatment morbidities may not be tolerable. Herein, we report treatment-dependent outcomes of octogenarians with localized PDAC. The National Cancer Database identified patients ≥60 years with localized PDAC of the pancreatic head (2011–2016). Patients were grouped by age (60–79 and ≥80 years) and categorized by treatment regimen: no treatment, chemotherapy, pancreaticoduodenectomy, pancreaticoduodenectomy with perioperative chemotherapy, or pancreaticoduodenectomy with adjuvant chemotherapy. Postoperative outcomes and survival were analyzed. A total of 35,409 patients were included, 8745 (24.7%) of which were ≥80 years. Over 52% of octogenarians did not receive any treatment, compared to 19.1% of younger patients (p

Introduction Surgical researchers seek to publish their findings in esteemed surgical journals to advance science and their careers. A detailed investigation of study and manuscript attributes in a specific research area, like pancreatic neoplasia, may yield informative insights for researchers looking to maximize research impact. Objectives We analyzed publications related to pancreatic surgery primarily focused on pancreatic and periampullary tumors in order to identify elements associated with acceptance into high impact journals and a high likelihood of future citations. Methods A comprehensive review of nine surgical journals was performed between 2010-19. Journals were grouped based on impact factor into high (>3), medium (1-3) and low ( Results A total of 1,044 out of 21,536 (4.8%) articles published in the index journals were related to pancreatic tumors. The most common focus of study was perioperative outcomes and complications (46.7%). There was significantly more number of authors, participating institutions, countries, and randomized clinical trials in higher impact journals as well as high-cited articles (p 0.05). Conclusion Pancreatic neoplasia continues to be extensively studied in surgical literature. Specific elements of study methodology and design were identified as potentially key attributes to acceptance in high impact journals and citation success.

Overall survival (OS) has increased in recent adjuvant clinical trials of pancreatic ductal adenocarcinoma (PDAC). Although oncologists have taken notice, the root causes have not been fully examined. All phase 3 adjuvant PDAC clinical trials were screened (n = 13), and eight trials (2007–2019) that met a study requirement of having a gemcitabine monotherapy arm to serve as a uniform comparative anchor across trials were identified. Patient enrollment eligibility criteria were compared across trials and categorized as tumor- or patient-related factors. Disease-free survival (DFS) and OS in the gemcitabine-only and non-gemcitabine arms were plotted and compared over time using linear regression. In the non-gemcitabine arms, OS increased over time, but the slope did not achieve statistical significance (p = 0.0815). Interestingly, OS improved for patients receiving only gemcitabine (slope, 1.99 months; p = 0.0018), whereas DFS remained constant (p = 0.897). Carbohydrate antigen (CA) 19-9 values and pathologic profiles of tumors were only marginally different across all cohorts. Recent adjuvant trials had stricter inclusion criteria (i.e., more patients were excluded for medical reasons; linear regression, p = 0.010). Survival for patients with resected PDAC has roughly doubled in phase 3 adjuvant trials during the past decade. Improved outcomes likely are attributable to improved adjuvant therapeutic regimens, but also reflect healthier patients enrolled in the more recent trials.

BACKGROUND AND OBJECTIVES Current data are conflicting as to whether the outcomes of octogenarians undergoing resection for esophagogastric adenocarcinoma are comparable to younger patients. This study aims to compare perioperative outcomes and survival of patients ≥80 years old with younger patients undergoing curative resection for esophagogastric adenocarcinoma. METHODS Retrospective data were collected on 190 patients who underwent resection with curative intent for adenocarcinomas found in the stomach and esophagogastric junction from 2004 to 2015 at a single institution. RESULTS Of the 190 patients, 34 (18%) were ≥80 years old. Octogenarians were more likely to have chronic kidney disease (CKD) and were less likely to have received neoadjuvant chemotherapy. Pathologic features were similar between groups. Octogenarians' tumors were more likely to be located in the gastric body as compared to the esophagogastric junction in younger patients. Although the length of stay was comparable, octogenarians were significantly less likely to be discharged home (P

Background While adjuvant chemotherapy benefits patients with pancreatic ductal adenocarcinoma (PDAC), the importance of the time to initiation of adjuvant therapy remains unclear. Aim This study seeks to better understand whether the timing of postoperative chemotherapy initiation affects long‐term outcomes in PDAC. Methods and Results A systematic literature search was performed in Medline, Embase, and Cochrane Library in March 2020. Studies focused on the association between the timing of adjuvant therapy on long‐term outcomes in resected PDAC patients were included. The impact of early and delayed therapy as defined by the respective studies was evaluated using forest plot analysis. Overall survival (OS) and disease‐free survival (DFS) served as primary endpoints. Out of 3099 published articles, 10 retrospective studies met inclusion criteria. Combined, these studies included clinical data of 13 344 patients. The cut off used to define “early” and “delayed” treatment groups varied in the included studies ranging from 3 to 12 weeks. Due to this heterogeneity, a sub‐group analysis of three time cut offs was performed: 3 to 5 weeks, 6 to 8 weeks, and 9 to 12 weeks. There was a significant decrease in OS and DFS when adjuvant therapy was delayed by 3 to 5 weeks after surgery (OS, pooled hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.25‐2.78; DFS, pooled HR = 1.62, 95% CI = 1.12‐2.34). However, due to small sample size and limited studies in this subgroup analysis, the results may be indeterminate. There was no significant decrease in OS with delayed initiation of adjuvant therapy by 6 to 8 weeks and 9 to 12 weeks. Similarly, delay in adjuvant therapy beyond 3‐5 weeks. Conclusions There was no conclusive evidence suggesting improved survival in patients starting treatment at various time cut offs. Studies investigating the extreme ends of the time‐to‐treatment spectrum may prove more informative.

Our research group recently surveyed the clinical trial landscape in pancreatic adenocarcinoma and identified 430 active trials. These represent an opportunity to expand treatment options for patients with pancreatic adenocarcinoma. Our primary objective was to detail clinical trial participation among patients with pancreatic adenocarcinoma. Our secondary objective was to evaluate survival.We queried the National Cancer Database (2004-2016) for patients with pancreatic adenocarcinoma. Patients were stratified by trial participation: clinical trial or non-trial. Multivariable logistic regression was used to identify variables associated with trial participation. The Kaplan-Meier method and multivariable Cox hazards regression were used to analyze survival.In total, 261,483 patients were included: 1,110 (0.4%) were enrolled in a clinical trial. A total of 57 Black patients participated in a clinical trial (0.19% of Black patients). This was lower compared to White patients (n = 955, 0.49% of White patients, P.001). After adjusting for demographic and clinical factors, Black patients were less likely to be enrolled in a clinical trial (odds ratio = 0.387, P.001). Patients treated at nonacademic medical centers were less likely to be in a clinical trial. Trial participation was associated with an increased median survival relative to non-trial patients (stage IV: 9.0 vs 3.8 months, P.001), and this association remained on multivariable regression (hazard ratio = 0.779, P.001).Fewer than 1% of patients with pancreatic adenocarcinoma participated in a clinical trial. There are racial and sociodemographic disparities in clinical trial enrollment. An association was observed between clinical trial participants and prolonged survival.

The timing of inpatient discharges can impact hospital throughput with later discharges leading to decreased patient satisfaction, increased length of stay (LOS), and longer boarding times.A 12-month targeted intervention that included both pre-operative and inpatient components was implemented across all surgical inpatient services to increase the proportion of patients discharged by noon.Discharge by noon rates increased from 14.3% to 21.5% during the 12-month initiative (p 0.01). The case mix index adjusted LOS (aLOS) decreased from 2.17 to 2.02 days (p 0.01). ED, PACU, and ICU boarding times were all significantly lower during the initiative (p 0.01, p 0.01, p = 0.03 respectively).A targeted initiative to discharge surgical patients earlier resulted in a 50% increase in the proportion of patients discharged by noon. Associated with this finding were improvements in hospital throughput as measured by aLOS and boarding times in the ED, ICUs, and PACU.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. Operative management of early disease includes ablation, resection, and transplantation. We compared the operative management of early-stage HCC in patients stratified by race.We identified patients with cT1 HCC and Charlson-Deyo score 0-1 in the National Cancer Database (2004-2016). We compared operative/non-operative management by race, adjusting for clinicodemographic variables. We performed marginal standardization of logistic regression to ascertain adjusted probabilities of resection or transplantation in patients under 70 years of age with insurance.A total of 25,029 patients were included (White = 20,410; Black = 4619). After adjusting for clinico demographic variables, Black race was associated with a lower likelihood of undergoing operative intervention (OR 0.89,p = 0.009). Black patients were more likely to undergo resection (OR 1.23,p 0.001) and less likely to undergo transplantation (OR 0.60,p 0.001). Marginal standardization models demonstrated Black race was associated with increased probability of resection in patients50yrs, with private insurance/Medicare, and lower probability of transplantation regardless of age or insurance payor.Black race is associated with lower rates of hepatic transplantation and higher rates of hepatic resection for early HCC regardless of age or insurance payor. The etiology of these disparities is multifactorial and correcting the root causes represents a critical area for improvement.

Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients’ advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.

Background: Immunotherapy (IT) has led to improved survival in several common cancers but success in pancreatic ductal adenocarcinoma (PDAC) has been limited. We analyzed if combination IT–chemotherapy (IT-CT) is associated with improved survival compared with chemotherapy alone (CT) in patients with metastatic PDAC. Methods: The National Cancer Database (2004–2016) was queried for patients who were diagnosed with metastatic PDAC. Patients were categorized by treatment group: CT only and IT-CT. Patients were excluded if they received radiation or a surgical procedure. The primary outcome was overall survival. Results: A total of 59,289 patients were identified, of whom 58,947 (99.4%) received CT and 342 (0.6%) received IT-CT. The IT-CT group was younger, had fewer comorbidities, and was more often treated at an academic center. The utilization of multiagent CT was similar between the groups. Median survival of patients treated with IT-CT was longer than CT alone (7.9 months vs. 6.3 months, p = 0.005). On multivariable analysis, receipt of IT-CT was associated with a survival advantage as compared with CT (hazard ratio = 0.86, 95% confidence intervals 0.76–0.97) when adjusting for demographics and type of CT regimen. Conclusion: In patients with metastatic PDAC, it appears that combination IT-CT may perhaps be associated with a survival advantage compared with CT alone.

Background Adenosquamous carcinoma of the pancreas has historically poor survival. We analyzed survival outcomes stratified by treatment regimen and sequence using an administrative dataset. Methods Adult patients with nonmetastatic adenosquamous carcinoma of the pancreas were identified using the National Cancer Database (2010−2016). Multivariable analyses were used to determine factors associated with receipt of neoadjuvant or adjuvant chemotherapy. Overall survival was estimated by Kaplan-Meier analysis and a multivariable Cox model was used to evaluate factors associated with survival. Results A total of 838 patients with adenosquamous carcinoma of the pancreas were included in the analysis. The median age was 69 years and 64.7% of patients underwent pancreatectomy. Among patients who underwent pancreatectomy, 60.5% received adjuvant chemotherapy, 14.8% received neoadjuvant chemotherapy, and 24.7% underwent surgery alone. Older age and increasing comorbidity index were associated with a reduced likelihood of receiving neoadjuvant or adjuvant chemotherapy. Median survival of patients who received chemotherapy alone was similar compared with patients who underwent pancreatectomy alone (9.2 vs 7.2 months, P = .504). Survival was improved if patients received both chemotherapy and pancreatectomy (neoadjuvant = 19.6 months, hazard ratio = 0.58; adjuvant = 19.4 months, hazard ratio = 0.64) compared with pancreatectomy alone. Conclusion Patients with adenosquamous carcinoma of the pancreas who do not receive multimodal therapy have poor survival. The sequence of chemotherapy and pancreatectomy is not associated with survival, but 25% of patients who undergo surgery do not receive chemotherapy. Given that there is no difference in median survival between patients who undergo pancreatectomy alone or receive chemotherapy alone, our data question whether neoadjuvant chemotherapy should be considered in patients with potentially resectable adenosquamous carcinoma of the pancreas.

The use of minimally invasive approaches to hepatectomy has increased in recent years, but the risk of postoperative venous thromboembolism (VTE) is undefined. We aimed to compare VTE rates after open hepatectomy and minimally invasive hepatectomy using an administrative dataset. Patients with primary or metastatic liver tumors were identified in the National Surgical Quality Improvement Program-targeted hepatectomy database (2016–2018). VTE was compared between patients who underwent open or minimally invasive hepatectomy after a propensity score matching of 1:1 for demographics, comorbidities, and operative factors. A total of 6935 patients underwent open hepatectomy and 2237 underwent minimally invasive hepatectomy. After matching, there were 1968 patients per group without differences in demographics, comorbidities, or operative variables. Prior to matching, the VTE rate was higher among patients who underwent open hepatectomy (2.8% vs. 1.1%, p < 0.001), and open hepatectomy was independently associated with VTE (OR = 1.90, p = 0.006). The VTE rate remained higher among open hepatectomy compared to minimally invasive hepatectomy after matching (2.4% vs. 1.1%, p = 0.003). Open hepatectomy was associated with a higher VTE rate in patients undergoing minor (1.9 vs. 1.0%, p = 0.028) and major hepatectomy (5.0 vs. 1.9%, p = 0.045). Patients who undergo an open hepatectomy for malignancy have a higher incidence of postoperative VTE compared to minimally invasive hepatectomy for both minor and major hepatectomy.

BACKGROUND Most data on postoperative outcomes among patients with proximal extrahepatic cholangiocarcinoma are reported by single institutions. The purpose of this study was to analyze postoperative outcomes stratified by age and comorbidities. METHODS Patients with proximal extrahepatic cholangiocarcinoma who underwent a resection were identified in the National Cancer Database. Pathologic, postoperative, and survival outcomes were compared based on age and Charlson-Deyo comorbidity index. RESULTS Among the 1,579 patients, the average age was 66 years, and 9.4% of patients were older than 80 years. Most patients had a Charlson-Deyo score of 0 (72.4%), with the minority having scores of 1 (20.5%) or ≥2 (7.1%). Patients ≥80 years had a higher 90-day mortality rate compared with patients 65 to 79 and

BACKGROUND Neoadjuvant chemotherapy is used infrequently in the management of distal pancreatic cancers. We investigated outcomes associated with neoadjuvant chemotherapy or up-front surgery in patients undergoing distal pancreatectomy. METHODS The National Cancer Database (2004-2016) was queried for patients with pancreas cancer who underwent distal pancreatectomy. Demographics, clinical characteristics, postoperative outcomes, pathologic outcomes, and overall survival were analyzed by univariate and multivariate analysis. RESULTS Six thousand five-hundred and twenty-three patients were included, including 5,643 who underwent up-front distal pancreatectomy and 880 who received neoadjuvant therapy. Factors associated with receipt of neoadjuvant chemotherapy included care at academic/research programs, higher education level, higher clinical T stage, higher clinical N stage, and elevated carbohydrate antigen 19-9 level. Patients who received neoadjuvant therapy had fewer positive lymph nodes, higher margin-negative resection rate, lower 30-day readmission rate, and lower 90-day mortality rate. Patients who received neoadjuvant therapy had longer median overall survival (28.8 vs 22.0 months; P

Background Neoadjuvant therapy is increasingly utilized in the management of pancreatic adenocarcinoma. The type of neoadjuvant therapy and its effect on pathologic response remains understudied. Methods A retrospective review was performed on patients who underwent neoadjuvant therapy followed by pancreatectomy. Multivariable regressions were used to determine associations between neoadjuvant therapy regimens and pathologic response. Results Seventy-five patients with pathologic responses available for review received FOLFIRINOX (61%) or gemcitabine with nab-paclitaxel (39%). Demographics, histologic differentiation, and utilization of chemoradiation were similar between the groups. Multivariable logistic regression demonstrated that chemoradiation was associated with an increased likelihood of a complete or near-complete pathologic response and a decreased rate of lymphovascular invasion and lymph node positivity. Neither chemotherapy regimen nor number of cycles administered were associated with pathologic response. Conclusions Neoadjuvant chemoradiation may be associated with complete or near-complete pathologic response regardless of chemotherapy regimen in pancreatic cancer patients.

Objective: Pancreatic cancer is the most aggressive common cancer and is desperately in need of novel therapies. Unlike many other common cancers, there have been no new paradigm-changing therapies in the past 40 years beyond multi-agent chemotherapy. In this study, we perform the first comprehensive analysis of the current clinical trial landscape in pancreatic cancer to better understand the pipeline of new therapies. Materials and Methods: We queried https://clinicaltrials.gov/ for registered pancreatic cancer clinical trials. Studies were curated and categorized according to phase of study, clinical stage of the study population, type of the intervention under investigation, and biologic mechanism targeted by the therapy under study. Results: As of May 18, 2019, there were 430 total active therapeutic interventional trials testing 590 interventions. The vast minority of trials (n = 37, 8.6%) are in phase III testing. 189 (31%) interventions are immunotherapies, 69 (11%) target cell signaling pathways, 154 (26%) target cell cycle or DNA biology, and 35 (6%) target metabolic pathways. Of the late phase trials, only 14 are currently testing novel interventions. Rather, 23 phase III trials examine new ways to deliver existing FDA-approved drugs, procedures, or pain management. Conclusions: A large number of novel therapeutic strategies are currently under investigation. They include a broad range of therapies targeting diverse biologic processes. However, only a small number of novel therapies are in late-stage testing, suggesting that future progress is likely several years away, and dependent on the success of early-stage trials.

Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are uncommon. Consensus guidelines have conflicting recommendations. We performed a nationwide analysis of patterns in management and outcomes based on facility type and tumor size.The National Cancer Database (2004-2016) was queried for patients with localized NF-pNETs (1 cm, 1-2 cm,2 cm) stratified by facility type. Management decisions, operative outcomes, and survival were compared.A total of 7170 patients were included in the analysis (1 cm = 916; 1-2 cm = 2180;2 cm = 4074). Most patients were treated at academic facilities (62.8%). Over 67% of patients with tumors1 cm underwent resection, independent of facility type (p = 0.443). There was no association between facility type and operative vs non-operative management of patients with NF-pNETs 1-2 cm in size. Patients treated at academic facilities were more likely to undergo resection for tumors2 cm compared to other facility types. Resection was associated with improved survival among patients with tumors 1-2 cm (HR = 0.43,p 0.001) and2 cm (HR = 0.32,p 0.001), but not1 cm (HR = 0.64,p = 0.054), as compared to non-operative management.There is heterogeneity in management of NF-pNETs across facility types. Treatment at academic facilities appears to be associated with higher resection rates for tumors2 cm. There appears to be an independent association between operative management and improved survival for tumors ≥1 cm in size.

The use of minimally invasive approaches for pancreatoduodenectomy has increased in recent years, but the risk of postoperative VTE is undefined. We aimed to compare venous thromboembolism (VTE) rates after open and minimally invasive pancreatoduodenectomy using an administrative dataset. Patients who underwent pancreatoduodenectomy within the National Surgical Quality Improvement Program targeted pancreatectomy database (2016–2018) were identified. VTE was compared between patients who underwent open or minimally invasive pancreatoduodenectomy directly and after propensity score matching 1:1 for demographics, comorbidities, and peri-/intra-operative factors. A total of 12,227 patients underwent pancreatoduodenectomy during the study period (open: n = 11,217; minimally invasive: n = 1010). Before matching, the VTE rate was higher among patients who underwent minimally invasive pancreatoduodenectomy (5.2% vs. 3.8%, p = 0.033), and minimally invasive resection was independently associated with VTE (OR = 1.46, 95%CI = 1.09–2.06). After matching, there were 916 patients per group without differences in demographics or comorbidities. Patients who underwent minimally invasive pancreatoduodenectomy had longer median operative times (422 vs. 348 min). The VTE rate remained higher following minimally invasive pancreatoduodenectomy after matching (5.1% vs. 2.9%, p = 0.018), mainly driven by a higher DVT rate (3.9% vs. 1.7%, p = 0.005). Minimally invasive pancreatoduodenectomy is associated with a higher postoperative VTE rate compared to open pancreatoduodenectomy.

Pretherapy serum neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have both been identified as prognostic in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to identify the prognostic implication of pretherapy NLR and PLR in patients with resectable PDAC.Data were collected retrospectively on patients operated at our institution between 2004 and 2014. A Cox proportional hazards model was used to investigate the relationship between clinical and pathological parameters, NLR and PLR to overall survival (OS). Survival data were analyzed using the Kaplan-Meier method.217 patients were analyzed with a median overall survival (OS) of 17.5 months. Factors identified as being predictive of OS by univariate analysis included age, receipt of adjuvant therapy, margin positivity, pathologic angiolymphatic invasion, T-stage, and N-stage (P0.05). Factors identified as being independently predictive of OS by multivariate analysis included age and angiolymphatic invasion (P0.05). NLR and PLR were not predictive of OS. Survival analysis demonstrated no difference in OS in patients who had high or low NLR or PLR.Pretherapy NLR and PLR do not predict survival in patients who underwent pancreatectomy for PDAC at our institution.

Surgery is the key component of treatment for pancreatic and periampullary cancers. Pancreatectomy is complex, and there are numerous perioperative and intraoperative factors that are important for achieving optimal outcomes. This article focuses specifically on key aspects of the surgical management of periampullary and pancreatic cancers.

Gallbladder cancer (GC) is a rare malignancy with a high mortality rate. Surgery is the only potentially curative treatment. Presentation can vary however with most cases being diagnosed incidentally on routine pathologic exam after a cholecystectomy done for seemingly benign indications. Clinical symptoms secondary to GC typically indicates advanced disease. Treatment decisions are based upon tumor stage. Incidentally discovered T1a cancers are adequately treated with cholecystectomy. T1b to T3 cancers with no evidence of distant metastatic spread are treated with an extended cholecystectomy, regional lymphadenectomy, and bile duct excision if necessary. In the adjuvant setting, treatment options include various chemoradiation and chemotherapy regimens which emphasize the need for multidisciplinary cancer teams in the treatment of GC.

TPS4176 Background: For patients with locally advanced pancreatic cancer, neoadjuvant trials are the preferred strategy. The goals of neoadjuvant treatment are to diminish the size of the primary tumor to allow for safe surgical resection and to limit the chance of developing metastatic disease. mFOLFIRINOX is the gold-standard for treatment in the adjuvant setting and an acceptable regimen in the neoadjuvant setting with many ongoing neoadjuvant trials using it as a chemotherapeutic backbone. CPI-613 (devimistat) is a small-molecule inhibitor of pyruvate dehydrogenase and alpha-ketogluterate dehydrogenase that has been studied in combination with mFOLFIRINOX in a phase I trial of patients with metastatic pancreas cancer and shown to be safe at the proposed phase II dose. Methods: This is a single-center, single-arm phase II trial for patients with locally advanced pancreatic cancer; defined as either borderline resectable or unresectable according to NCCN guidelines and interpreted by the primary investigator. Patients with metastatic disease are excluded. Patients will receive treatment with CPI-613 and mFOLFIRINOX per the table below. The primary endpoint is overall survival. Secondary endpoints are progression free survival and resection rate. At the time of submission this study has completed initial accrual with 37 patients enrolled. Clinical trial information: NCT03699319. [Table: see text]

408 Background: Multi-agent chemotherapy (CT) with or without radiotherapy (RT) is the standard of care for non-metastatic Type B locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) has been described as a treatment modality in patients with LAPC but published postoperative morbidity and mortality rates are high for a non-curative procedure. There have been few studies that have compared directly IRE with standard of care CT ± RT. We performed a meta-analysis of the available literature to compare the outcomes between these treatment groups in LAPC. Methods: A systematic literature search was performed in Medline, Embase, and the Cochrane Library in September 2020. Studies that focused on comparing outcomes between IRE and CT ± RT for LAPC were selected for further study. The impact of IRE versus CT ± RT was evaluated using forest plot analysis. Overall survival (OS) and progression free survival (PFS) served as the primary endpoints. As a secondary objective, short term morbidity and mortality data in both groups was evaluated. Results: Our search yielded 326 papers. After excluding duplicates, 3 studies met inclusion criteria. All were retrospective. Combined, these studies included clinical data on 3,862 patients. The meta-analysis indicated that patients with LAPC who underwent IRE had better OS (HR = 0.46, 95% CI: 0.28-0.74) and PFS (HR = 0.38, 95% CI: 0.24-0.60) compared to patients who received CT ± RT. Due to incomplete morbidity, 30-, and 90- day mortality information reported in the included studies, further analysis was not performed for the same. Conclusions: There is a striking paucity of studies comparing IRE with the standard of care treatment approaches for LAPC. Our meta-analysis reveals that IRE has been associated with longer OS and PFS compared to CT ± RT. However, these studies are limited by retrospective study design, heterogeneity of population and chemotherapy regimens, and incomplete morbidity data, precluding any conclusions. Until higher quality, comparative retrospective studies, or more importantly, prospective studies with standardized indications are conducted, IRE should be used with caution and remains experimental in the treatment of PDAC.

416 Background: Over the last decade, various landmark trials have demonstrated the impact of multi-agent chemotherapy in the treatment of PDAC. However, the impact in the ‘real world’ has been less clear. The ACCORD trial (2011) was a phase III trial comparing combination chemotherapy (FOLFIRINOX) and single agent (gemcitabine) for advanced disease. The MPACT trial introduced another beneficial regimen (nab-paclitaxel and gemcitabine) in 2013. Subsequently, multi-agent chemotherapy became standard of care for medically appropriate patients. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with PDAC between 1998 and 2017. The cohort was divided into two groups: 1998-2011 (pre-ACCORD) and 2012-2017 (post-ACCORD). We analyzed all patients with metastatic PDAC for overall survival and compared results in the two groups using Kaplan Meier analysis and multivariate Cox proportional hazards models. An interrupted time series analysis was also used to compare the temporal trends in 2-year survival between 1998 and 2017. Results: A total of 47,134 patients were diagnosed with PDAC between 1998 and 2017. Nearly two-third of patients (26,438; 57%) had distant disease. On univariate survival analysis, there was a significant increased overall survival probability in the 2012-17 group compared to the 1998-2011 group (p

e16730 Background: Pancreatic cancer is the most aggressive of common cancers and desperately in need of novel therapies. Unlike many other common cancers, there have been no new paradigm-changing therapies in the past 40 years beyond chemotherapy. The most urgent question in the field then is what is coming down the pike? In this study, we perform the first comprehensive analysis of the current clinical trial landscape in pancreatic cancer to better understand the pipeline of new therapies. Methods: We queried clinicaltrials.gov for registered pancreatic cancer clinical trials. Studies were curated and categorized according to the phase of study, the clinical stage of the study population, the type of the intervention under investigation, and the biologic mechanism targeted by the therapy. This compendium revealed the full landscape of investigational therapeutic trials. Results: As of May 18, 2019, there were 440 total trials testing 600 distinct interventions. 104 of these trials spanned multiple phases, yielding 544 trials across phases. These included 38 trials (8.6%) in phase III testing, 269 (61%) in phase II, and 237 (54%) in phase I. With respect to therapeutic category, 186 (31%) were investigating immunotherapies, 66 (11%) targeted cell signaling pathways, 140 (23%) targeted cell cycle or DNA biology, and 32 (5%) targeted metabolic pathways. Of the 38 phase III trials, only 10 are currently testing novel drugs that are not already FDA approved or routinely used in patients for another indication. Conclusions: A large number of novel therapeutic strategies are currently under investigation. They include a broad range of therapies targeting diverse biologic processes. However, only a small number of novel therapies are in late-stage testing, suggesting that future progress is likely several years away, and dependent on the success of early-stage trials. [Table: see text]

4623 Background: The role of neoadjuvant chemotherapy (NAC) for resectable pancreatic cancer (RPC) remains controversial. We sought to compare the outcomes of NAC with upfront surgery (UFS). Methods: The study retrospectively enrolled patients with RPC who had UFS or received neoadjuvant FOLFIRINOX (FFX) or gemcitabine plus albumin-bound paclitaxel (GA). Between-group differences were assessed with T-test for continuous variables, and Chi-square / Fisher’s exact test for categorical variables. The overall survival (OS) and recurrence-free survival (RFS) were determined by the Kaplan-Meier method with Wilcoxon test for the difference between groups. The effects of NAC vs. UFS on OS and RFS were further estimated using Cox regression controlling the effects of age and CA 19-9. Results: Between 2011 and 2019, 131 patients with RPC underwent UFS followed by adjuvant chemotherapy (gemcitabine, n = 65; gemcitabine/capecitabine, n = 18; FFX, n = 9). Up to 32 patients (24.4%) could not receive adjuvant chemotherapy due to surgical complications or poor recovery. Total 50 patients with RPC received NAC (FFX, n = 32; GA, n = 18). Median of 5.5 cycles of FFX or 3 cycles of GA were given prior to surgery. Resection rate was 72% (FFX 62.5%; GA 88.9%). The rest (28%) were no longer surgical candidates due to disease progression rather than toxicities from NAC. On surgical pathological review, complete resection (R0) was achieved in 83.3% of resected cases after NAC (FFX 90%; GA 75%) and 79.4% with UFS. The tumor size distribution was: pT1 11.1%, pT2 41.7%, pT3 44.4% with NAC; pT1 5.4%, pT2 18.3%, pT3 76.3% with UFS. The nodal status distribution was: pN0 27.8%, pN1 55.5%, pN2 16.7% with NAC; pN0 23.7%, pN1 71.0%, pN2 5.3% with UFS. Median pre-treatment CA 19-9 was 321.95 unit/mL in the NAC group and 79.99 unit/mL in the UFS group (p = 0.009). Median age was 70.5 in the NAC group and 72 in the UFS group (p = 0.374). There was no significant difference in the performance status between the two groups. In Kaplan-Meier analysis, there was a significant difference of OS between UFS and NAC with median OS of 648 days under UFS versus 884 days under NAC (p = 0.029); the median of RFS was 390 days under UFS versus 392 days under NAC (p = 0.953). The hazard ratio (NAC vs UFS) adjusted for CA19-9 and age was 0.7 (p = 0.176) for OS and 0.98 (p = 0.918) for RFS. Conclusions: We observed a signal of tumor downstaging, higher R0 rate, and improved OS with NAC compared with UFS. Further prospective trials are needed to validate these results.

Background: Recurrent pancreatic cancer may represent a true local recurrence or a second intrapancreatic primary. Resection of recurrent pancreatic cancer is uncommon. Case Presentation: A 68-year-old woman underwent a distal pancreatectomy/splenectomy for pancreatic adenocarcinoma after presenting with acute pancreatitis. She received 6 months of adjuvant gemcitabine. Nearly 5 years later, she presented with acute pancreatitis. Endoscopic ultrasonography suggested malignant degeneration of an uncinate intraductal papillary mucinous neoplasm (IPMN), but the cytology was negative. She subsequently underwent a completion pancreaticoduodenectomy for what proved to be a second pancreatic adenocarcinoma. Conclusion: Although uncommon, repeat resection for a second pancreatic cancer may be appropriate in select patients. Careful attention to the remnant pancreas must be maintained on surveillance imaging.

Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

Background Etiologies contributing to failure to wean from mechanical ventilation (MV) are multiple, resulting in morbid and costly outcomes. Diaphragm pacing (DP) is used in spinal cord injury to replace MV. Temporary DP could be utilized in acute respiratory failure to reduce MV. Methods A prospective FDA feasibility trial evaluated temporary DP electrodes implanted in each hemi-diaphragm during a subject's primary procedure. Objectives included: ability to provide ventilation, stability analysis with diaphragm electromyography, and adverse event monitoring. Results Twelve patients underwent successful implantation via median sternotomy, laparoscopy or laparotomy. Electrode stimulation exceeded ideal tidal volumes by an average of 37% (0%–95%) confirming ability to prevent atrophy. Daily electromyography confirmed stability of placement and was useful in evaluating hypoventilation. There were no complications and all 48 study electrodes remained intact until complete removal. Conclusion This trial demonstrates ease of placement, removal, functionality and safety of temporary DP electrodes which therapeutically decreases diaphragm atrophy.

Background Patients with altered anatomy due to Roux-en-Y gastric bypass (RYGB) present unique diagnostic and therapeutic challenges when they present with periampullary pathology. We describe a series of patients who underwent pancreatoduodenectomy (PD) after gastric surgery with Roux-en-Y reconstruction and review the literature to highlight technical considerations and outcomes. Methods Patients from two institutions were identified and data regarding preoperative workup, operative conduct, and pathologic and clinical outcomes were collected. Results Eleven patients were included in the institutional series. At the time of periampullary pathology, the median age was 64 years and time since RYGB was 10 years. Median operative time was 361 minutes, estimated blood loss was 500 mLs, and length of stay was 6 days. Remnant gastrectomy was performed in nine patients and reconstruction was performed using the biliopancreatic limb (BP) without revision of the jejuno-jejunostomy in ten patients. Pathology revealed pancreatic cancer (8), chronic pancreatitis (2), and duodenal cancer (1). Three patients experienced major complications and there were no 90-day mortalities. Conclusion Pancreatic surgeons will see an increasing number of patients with Roux-en-Y anatomy who will require evaluation and resection for periampullary diseases. For PD after RYGB, we recommend remnant gastrectomy with reconstruction using the BP limb.

In successfully treated human immunodeficiency virus (HIV) infection, chronic inflammation often persists and has been identified as a major predictor of morbidity and mortality [1, 2]. Moreover, in treated patients with controlled viremia, immune activation and elevated plasma markers of inflammation have been associated with poor CD4+ T-cell restoration [3, 4]; yet the mechanistic link between persistent immune activation, inflammation, and CD4+ T-cell restoration failure is unknown. Earlier studies of patients with immune restoration failure found a link between higher indices of inflammation with morbidities and mortalities despite antiretroviral therapy (ART)–induced viral suppression [1, 5, 6]. It is not clear, however, whether the relationship between inflammation and immune failure is causal, and if it is, the mechanisms whereby inflammation might promote persistent CD4+ T-cell restoration failure (or vice versa) are not defined. An increase in T-cell turnover is characteristic of untreated HIV infection [5–7], and recent data demonstrate elevated frequencies of cycling CD4+ (but not CD8+) T cells in treated HIV-infected patients with immune restoration failure [3, 8]. Loss of CD127, the interleukin 7 receptor α chain (IL-7Rα), and an imputed failure of homeostatic CD4+ T-cell expansion in response to IL-7 have also been identified in treated HIV infection [9, 10] and may contribute to CD4+ T-cell restoration failure [11]. This work asked whether inflammatory cytokines might contribute to CD4+ T-cell restoration failure in treated HIV infection. By treating peripheral blood mononuclear cells (PBMCs) from healthy subjects with the inflammatory cytokines interleukin 6 (IL-6) or interleukin 1β (IL-1β), we could recapitulate much of the immunophenotype seen in patients with immune restoration failure­—decreased expression of CD127 [11, 12] and increased T-cell cycling, especially of memory CD4+ T cells [3, 6, 8, 13]. Importantly, IL-1β is expressed throughout all lymph node (LN) compartments in HIV-infected viremic patients and, while reduced with ART, still remains elevated, compared with levels in uninfected controls, providing in vivo support for our in vitro findings.

In past decade, the treatment of gastric adenocarcinoma has evolved as a result of the publication of two seminal randomized controlled trials. We aimed to examine treatment trends for resectable gastric cancer (stage I–III) using the National Cancer Data Base (NCDB). Our hypothesis was that the use of chemotherapy and chemoradiotherapy in addition to surgery for the treatment of gastric adenocarcinoma has increased from 2000 to 2009. Patients diagnosed with stage I–III gastric adenocarcinoma between 2000 and 2009 were selected from the NCDB Hospital Comparison Benchmark Reports. Attention was paid to the initial treatment regimen and data on hospital setting were collected and analyzed. The Cochran–Armitage test for trend was used to assess changes in treatment over time. A total of 50,778 patients with stage I–III gastric adenocarcinoma were included in the analysis. Between 2000 and 2009, the use of surgery alone decreased significantly across all three stages at both teaching hospitals and community hospitals (p

The management of pancreatic fistulas can be complex and mandates a multidisciplinary approach. Basic principles of fistula control/patient stabilization, delineation of ductal anatomy, and definitive therapy remain of paramount importance.