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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.

Background Although guidelines recommend open adrenalectomy for most resectable adrenal malignancies, minimally invasive adrenalectomies are performed. Robotic adrenalectomies have become more popular recently, but there is a paucity of literature comparing laparoscopic and robotic resections. Methods Patients who underwent a planned minimally invasive adrenalectomy for adrenal malignancies (adrenocortical carcinoma, malignant pheochromocytoma, other carcinoma) were identified in the National Cancer Database. The primary outcome was the conversion rate from minimally invasive to open. Other post-operative outcomes and survival were compared. Results 416 patients (76.5%) underwent a laparoscopic adrenalectomy and 128 (23.5%) underwent a robotic operation. Demographics and clinical characteristics were similar. Approximately 19% of tumors resected by a minimally invasive approach were > 10 cm. The intra-operative conversion rate was decreased among robotic adrenalectomies relative to laparoscopic on univariate (7.8% vs. 18.3%, p = 0.005) and multivariable (odds ratio 0.39, p = 0.01) analyses. Using marginal standardization, there was a stepwise increase in the conversion rate as tumor size increased ( 10 cm) for laparoscopic (7.5%, 18.0%, 33.2%) and robotic (3.1%, 8.3%, 17.3%) adrenalectomies. Operations which required conversion had a greater margin positivity rate, greater length of stay, and an association with poor overall survival. Conclusion In contrast to most clinical guidelines, minimally invasive adrenalectomies are being performed on large malignant tumors. A laparoscopic approach was associated with a greater conversion rate and subsequent poor outcomes. If a surgeon is not planning an open adrenalectomy, but adrenal malignancy is a possibility, robotic adrenalectomy may be the preferred approach for resectable adrenal tumors.

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

Robotic esophagectomies are increasingly common and are reported to have superior outcomes compared with an open approach; however, it is unclear if all institutions can achieve such outcomes. We hypothesize that early adopters of robotic technique would have improved short-term outcomes.The National Cancer Database (2010-2016) was used to identify robotic esophagectomies. Early adopters were defined as programs which performed robotic esophagectomies in 2010-2011, late adopters in 2012-2013. Outcomes of esophagectomies performed between 2014 and 2016 were compared and included length of stay, number of lymph nodes evaluated, readmission, conversion rate, and 90-day mortality. Multivariable regressions, accounting for robotic esophagectomy volume, were used to control for confounding factors.There were 37 early adopters and 35 late adopters. Between 2014 and 2016, 683 robotic esophagectomies were performed: 446 (65.3%) by early adopters and 237 (34.7%) by late adopters. Early adopters were more likely to be academic programs (96.2 versus 72.8%, P 0.01). Other clinical and demographic variables were similar. Late adopters were found to have decreased a number of lymph nodes evaluated (coefficient -2.407, P = 0.004) compared with early adopters. There were no significant differences in length of stay, readmissions, rate of positive margins, conversion from robotic to open, or 90-day mortality.When accounting for robotic esophagectomy volume, late adoption of robotic esophagectomy was associated with a reduced lymph node harvest, but other postoperative outcomes were similar. These data suggest that programs can safely start new robotic esophagectomy programs, but must ensure an adequate case load.

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

BACKGROUND Adrenocortical carcinoma (ACC) is often a contraindication to minimally invasive adrenalectomy (MIA). We used an administrative data set to analyze postoperative outcomes. We hypothesized that small tumors would have better short- and long-term outcomes, independent of the operative approach. METHODS The National Cancer Database (2010-2016) identified patients with ACC who underwent adrenalectomy. Tumors were grouped: 10 cm (n = 443). The primary and secondary outcomes were margin positivity and overall survival, respectively. RESULTS Nine hundred and ninety-nine patients were analyzed: 37% MIA and 63% open adrenalectomy (OA). As the size increased, the rate of attempted MIA decreased. Larger tumors were associated with conversion to open. Although tumors with local invasion and those which required conversion to open were associated with an increased likelihood of a positive margin, tumor size was not. Although "complete" MIA (vs. OA) and tumor size were not associated with differences in survival, conversion (HR = 1.83, p = .02), positive margins (HR = 1.54, p = .01), and local invasion (HR = 1.84, 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.

Early detection is a valued strategy to decrease cancer mortality rates; however, new strategies are needed. Unintentional weight loss (UWL) is experienced by patients across the cancer spectrum, but often goes unnoticed. Patient-centered weight tracking may be a useful early detection marker. Fifty patients were enrolled in a prospective patient-centered weight tracking trial. Patients received a scale and monetary compensation to participate. A reminder to measure and record weight was texted to participants for 26 consecutive weeks. Most patients were black (86.0%) and female (68.0%). The median age was 47 years (range: 22-84 years). Many participants had Medicaid (42.0%) and the median household income by home zip code was $31,046. After 26 weeks, 90% of patients had recorded at least one weight. Among all patients, 73.7% of all possible weights were recorded and the median response rate per patient was 92.3% (24 of 26 weights). There was no difference in the response rates during the first and second halves of the study (77.7% vs. 69.7%, P = 0.53). The range of weight change over the study period was 16.1% loss to 25.0% gain, with 56% of patients maintaining stable weight. Seven patients (14.0%) lost more than 5% weight and 11 patients (22.0%) gained over 5%. Of the seven patients with weight loss, two (4.0% of the cohort) were determined to have UWL. Patient-centered weight tracking is feasible and inexpensive, and has potential as an early detector of UWL. Further studies are needed to apply this strategy to detect underlying malignancies.

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.

Weight loss has long been known to be associated with multiple chronic conditions, including heart failure, COPD, depression, and cancer. Recent reports have suggested that unintentional weight loss (UWL) could be leveraged as an early marker of malignancy. Most studies use standardized cutoff values of ≥5% weight loss to define UWL; however, this threshold has not been validated in different body weight classifications (underweight, overweight, etc.). The purpose of this review was to describe the association between a patient’s weight category, the severity of UWL prior to cancer diagnosis, cancer stage at diagnosis, and cancer-specific mortality. Obesity has been identified as a risk factor for many malignancies. Current data are conflicting about whether patients with obesity are more or less likely to experience UWL prior to diagnosis of a malignancy. Similarly, data analyzing the association between baseline BMI and cancer stage at diagnosis or cancer-specific mortality are mixed. UWL has been associated with an increased risk of all-cause mortality, independent of baseline BMI. Unfortunately, reliable body weight measurements are infrequently obtained, decreasing the likelihood that UWL would be detected clinically. Weight loss, when unintentional, is a serious condition which requires prompt clinical evaluation. Future studies are needed to objectively quantify UWL among patients with varying baseline BMI.

Neoadjuvant chemotherapy (NAC) downstages breast cancer and provides prognostic information. Males with breast cancer are known to receive less treatment overall and have poorer outcomes relative to females. We hypothesized that males would be less likely to receive NAC. Patients with a primary diagnosis of cN1–3 breast cancer were identified in the National Cancer Database (2004–2016). Multivariable logistic regression determined the association between NAC utilization and sex, and the relationship between sex and NAC response, controlling for demographic and tumor factors. Overall survival was analyzed using a multivariable Cox model. In total, 196,027 patients (194,010 females, 2017 males) met inclusion criteria. A significantly greater proportion of males underwent mastectomy (80% vs. 60%, P < 0.001), and axillary lymph node dissection (76% vs. 74%, P = 0.022). Overall fewer men received chemotherapy than women (73% vs. 84%, P < 0.001); men also received NAC at a significantly lower rate (26% men vs. 45% women, P < 0.001). After accounting for demographic and oncologic factors including hormone receptor (HR) subtype, females remained more likely to undergo NAC (OR 1.84, P < 0.001). On multivariable analysis, sex was not associated with pathologic response or overall survival after NAC. Although oncologic outcomes after NAC were similar, males with node-positive breast cancer received less NAC and more aggressive surgery than females. These data suggest men achieve outcomes comparable to women with cN1–3 disease, and NAC should be used in appropriate male patients to downstage the breast and axilla.

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.

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.

Malignant pheochromocytoma is often managed with adrenalectomy. Most literature focusing on postoperative outcomes are from single institutions. This study aimed to describe outcomes of adrenalectomy for malignant pheochromocytoma using a national database. We hypothesized that minimally invasive approaches might be associated with improved short-term outcomes but potentially inferior oncologic efficacy.Patients who underwent adrenalectomy for malignant pheochromocytoma were identified in the National Cancer Database (2010-2016). Patients were categorized as minimally invasive adrenalectomy or open adrenalectomy. Short- and long-term outcomes were compared.A total of 276 patients underwent adrenalectomy for malignant pheochromocytoma: 50.7% open adrenalectomy and 49.3% minimally invasive adrenalectomy. Demographics were similar, except those who underwent open adrenalectomy had larger tumors compared to minimally invasive adrenalectomy (8.2 cm vs 4.7 cm; P.001). Tumor size ≥6 cm was associated with a reduced likelihood of minimally invasive adrenalectomy (relative to open adrenalectomy) on multivariable regression (odds ratio = 0.23; P.001). Open adrenalectomy was associated with longer duration of stay relative to minimally invasive adrenalectomy (6 vs 3 days; P.001). Rates of positive margins, unplanned readmissions, or 30-/90-day mortalities were similar based on operative approach. Five-year survival rates were similar (open adrenalectomy 74.3%, minimally invasive adrenalectomy 79.1%). There was no association between overall survival and operative approach on multivariable Cox analysis when controlling for tumor size, laterality, and clinicodemographic variables.Patients with larger malignant pheochromocytomas were more likely to undergo an open adrenalectomy. With the exception of an increased duration of stay, there was no difference in short- or long-term postoperative outcomes. These data suggest that minimally invasive adrenalectomy appears safe among tumors6 cm.

Pancreatic cancer cells alter their metabolism to survive cancer-associated stress (1-4). For example, cancer cells must adapt to steep nutrient gradients that characterize the natural tumor microenvironment (TME) (5-7). In the absence of adaptive strategies, harsh metabolic conditions promote the generation of free radicals (8) and impair energy production in tumor cells. Towards this end, wild-type isocitrate dehydrogenase 1 (IDH1) activity is a metabolic requirement for cancer cells living in a harsh metabolic milieu. The cytosolic enzyme interconverts isocitrate and alpha-ketoglutarate, and uses NADP(H) as a cofactor. We show that under low nutrient conditions, the enzymatic reaction favors oxidative decarboxylation to yield NADPH and alpha-ketoglutarate. Metabolic studies showed that the IDH1 products directly support antioxidant defense and mitochondrial function in stressed cancer cells. Genetic IDH1 suppression reduced growth of pancreatic cancer cells in vitro under low nutrient conditions and in mouse models of pancreatic cancer. Surprisingly, allosteric inhibitors of mutant IDH1 proved to be potent wild-type IDH1 inhibitors under conditions specific to the TME, highlighting a natural therapeutic window. The presence of low magnesium enhanced allosteric inhibition by the drug, and ambient low glucose levels enhanced cancer cells’ dependence on wild-type IDH1. Thus, intrinsic TME conditions sensitized wild-type IDH1 to FDA-approved AG-120 (ivosidenib), and revealed the drug to be a potent single-agent therapeutic in cell culture and diverse in vivo cancer models. This work identified a potentially new repertoire of safe cancer therapies, including a clinically available compound, for the treatment of multiple wild-type IDH1 cancers (e.g., pancreatic).

Cardiovascular disease is the leading cause of death in the United States. Obese patients are at an increased risk of cardiovascular disease and weight loss can attenuate the risk. Cancer is the second leading cause of death and commonly associated with weight loss. This review focuses on the complex interaction between body weight, cardiovascular disease, and a cancer diagnosis. The cancer-associated mortality rate has steadily decreased over the last decade. Patients are living longer. Therefore, nonmalignant conditions, such as cardiovascular disease, have assumed an increased importance in cancer survivors. Moreover, patients with cancer are at an especially high risk for cardiovascular disease, due to side effects of various treatments and overlapping risk factors for both malignancy and heart disease. In cancers with a high likelihood of survival or cure, cardiovascular screening, risk factor modification, and attentive treatment of cardiovascular problems should be vigilantly pursued. Like all individuals, patients with cancer should strive to maintain a healthy weight and participate in regular physical activity, with a goal to optimize cardiac health and health span. Weight loss has a cardioprotective effect in cancer survivors without obvious cancer progression. The notion that cardiac health is a low priority for cancer survivors, particularly for patients with a favorable prognosis, is not true. However, in advanced stages of cancer or with highly lethal cancers, weight loss is associated with poor outcomes and nutritional support to optimize nutritional status and maintain body weight should be prioritized.

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 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.

Thoracoscopic pneumonectomy commonly requires conversion to thoracotomy. We hypothesize that conversion would lead to worse short- and long-term outcomes compared with operations completed thoracoscopically.The National Cancer Database identified patients who underwent a pneumonectomy from 2010 to 2016. Trends in conversion were described using linear regression. Multivariable regression of factors associated with conversion was performed. Short-term outcomes included duration of stay, number of lymph nodes harvested, margin status, readmission, and 90-day mortality. Long-term outcome was evaluated as overall survival.A total of 8,037 patients underwent a pneumonectomy. The rate of attempted thoracoscopic pneumonectomies increased from 11% to 22% (P.001) and the rate of conversion decreased from 39% to 33% (P = .011). On multivariable analysis, a greater patient comorbidity index and pathologic nodal-stage 2 disease were associated with an increased rate of conversion. The mean number of lymph nodes evaluated was greater as was the duration of stay in the conversion group, but conversion to open thoracotomy was not associated with positive surgical margins, readmission rate, 90-day mortality, or survival.Thoracoscopic pneumonectomy is performed with increasing frequency and decreasing conversion rate. Conversion is associated with a greater duration of stay but other short- and long-term outcomes are similar. This observation suggests minimal harm in conversion from minimally invasive to open pneumonectomy.

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.

Background Pancreatectomy is a complex operation with a historic readmission rate of approximately 20%. Hospital readmissions lead to increased patient and health system costs, morbidity, and mortality making them a topic of great interest. The objective of this study was to identify factors associated with readmission after pancreatectomy in order to target areas for improvement. Methods Pancreatectomy procedures for malignancy in adults from 2005 to 2011 were identified in the California State Inpatient Database. Descriptive analysis was conducted to evaluate the association between baseline variables and readmission status. Logistic regression models were developed to determine whether the bivariate associations identified persisted after adjusting for patient characteristics. Results Of the 4262 patients who underwent a pancreatectomy, 843 (19.8%) were readmitted within 30 days. Readmission rates by year did not vary over the study period. Results from multivariable analysis showed that males, Hispanics, Medicare recipients, patients with an initial length of stay >11 days, patients who were discharged to a skilled nursing facility, and those with chronic anemia were more likely to be readmitted compared to those without these characteristics. The majority of readmissions occurred within 15 days after discharge. Conclusions Readmissions after pancreatectomy are multifactorial. Preoperative optimization, minimizing postoperative complications, and assuring patients have been evaluated by a multidisciplinary team may reduce the readmission rate.

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]

643 Background: Pancreatic cancer has the worst survival of common cancers and there are no reliable early detection tests. While prior reports link unintentional weight loss (>5% decrease from baseline) to pancreatic cancer, there has never been a study documenting the frequency of this presenting sign using raw patient weight data. Methods: Patients at our institution with a pancreatic neoplasm (n=288) were queried using ICD-9 code 157.9 and ICD-10 code C25.9. Retrospective review identified 95 patients with pancreatic ductal adenocarcinoma and two or more prediagnosis weights (>7 days apart). Date of diagnosis was defined by the date of positive biopsy or encounter with surgical or medical oncology. Standard statistical analysis was performed. Results: Among the 95 patients, there was a slight preponderance of female (65.3%) and Caucasian (54.7%) patients. The median age at diagnosis was 71 (range: 41-90) and the median BMI was 25.6 kg/m2 (range: 15.4-49.5). 9.5% presented with clinical stage I disease, 27.3% with stage II, 9.5% with stage III, and 53.7% with stage IV. Within 1 year of diagnosis (range: 9-365 days), median weight loss was 7.1% of body weight (range: 0.2-34.5%). In this period, 71.6% of patients lost greater than 5% body weight and 32.6% lost over 10% (Table). In the 6 months before diagnosis (range: 9-180 days), median weight loss was 6.4% (range: 0.2-24.2%). A subgroup analysis of early (I, II) and late stage (III, IV) patients showed that those with late stage at presentation lost significantly more prediagnosis weight compared to the early stage patients (median 8.2% vs 5.6%, p=0.02) in a median of 175 days. Prior to diagnosis of late stage patients, 80.0% lost over 5% body weight and 38.3% lost over 10%. Conclusions: Diagnosis of pancreatic cancer is preceded by weight loss in the majority of cases, even at an early stage. Monitoring unintentional weight loss in otherwise asymptomatic patients may be an inexpensive and practical way to detect pancreatic cancer. [Table: see text]