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We described trends and disparities in utilization of systemic chemotherapy in metastatic hepato-pancreato-biliary (HPB) cancers.We queried the National Cancer Database for metastatic HPB cancers [hepatocellular carcinoma (HCC), biliary tract cancers (BTC), pancreatic adenocarcinoma (PDAC)]. We used multivariable analysis to examine the factors associated with utilization of systemic chemotherapy. We utilized marginal structural logistic models to estimate the effect of health insurance, facility type, or facility volume on utilization of systemic chemotherapy.We identified 162,283 patients with metastatic HPB cancers: 23,923 (14.7%) had HCC, 26,766 (16.5%) had BTC, and 111,594 (68.8%) had PDAC. A total of 37.2% patients with HCC, 55.6% with BTC, and 56.4% with PDAC received chemotherapy. Age ≥70 years and Charlson-Deyo score ≥2 were associated with lower likelihood of receiving chemotherapy across all cancers. Patients with private health insurance had higher receipt of chemotherapy. Receiving treatment at academic facilities had no effect on the receipt of chemotherapy. Treatment of patients with HCC or PDAC at high-volume facilities resulted in higher receipt of chemotherapy.A significant proportion of patients with metastatic HPB cancers do not receive systemic chemotherapy. Several disparities in administration of chemotherapy for metastatic HPB cancers exist.

To examine the average treatment effect of hepato-pancreato-biliary (HPB) cancer volume on survival outcomes of patients with non-resected pancreatic adenocarcinoma (PDAC).We queried the National Cancer Database (2004-2018) for patients with HPB malignancies (PDAC, pancreatic neuroendocrine neoplasms, hepatocellular carcinoma, biliary tract cancers). We determined the 25th, 50th, and 75th percentiles based on the total annual HPB volume. We then identified patients with non-resected PDAC. We utilized inverse probability (IP)-weighted Cox regression to estimate the effect of facility volume on overall survival (OS).We identified 710,988 patients with HPB malignancies. The 25th, 50th, and 75th percentiles of total annual HPB volume were 32, 71, and 177 cases/year, respectively. We included a total of 196,150 patients with non-resected PDAC. Patients treated at ≥25th, ≥50th, and ≥75th percentile facilities had improved median OS compared to those treated at facilities below these thresholds (5.8 vs. 4.2months, 6.5 vs. 4.5months, 7.5 vs. 4.8months, respectively; p 0.001 for all). Treatment at facilities ≥25th, ≥50th, and ≥75th percentile resulted in lower hazards of death than treatment at lower-percentile facilities (HR: 0.87, 95% CI: 0.84-0.90; HR: 0.87, 95% CI: 0.83-0.91; HR: 0.85, 95% CI: 0.79-0.91, respectively).Our data suggest that consolidation of care of patients with PDAC to high-volume centers may be beneficial even in the nonoperative setting.

Consensus guidelines recommend for perioperative chemotherapy and surgery for patients with clinical stage (cT) T2 or greater gastric adenocarcinoma. We compared adherence to guidelines in these patients stratified by race.Non-Hispanic White and Black patients with resected ≥cT2 gastric adenocarcinoma were identified within the National Cancer Database (2008-2017). We compared administration of preoperative chemotherapy by race, adjusting for clinicodemographic variables. We performed marginal standardization of logistic regression to calculate adjusted probabilities of administration of preoperative chemotherapy in patients under the age of 80 years with insurance.A total of 13,850 patients were identified (White = 12,161; Black = 1,689). Black race was associated with lower likelihood of receiving preoperative chemotherapy than White race (odds ratio = 0.46, 95% confidence interval: 0.39-0.54). Other factors associated with lower likelihood of preoperative chemotherapy included age ≥70 years, female sex, treatment at community facilities, non-private or no health insurance, and cT4 disease. Factors associated with higher likelihood of preoperative chemotherapy included treatment at high-volume facilities, longer distance to facility, higher education and income levels, cT3 disease, and cN+ disease. In patients80 years with insurance, marginal standardization models demonstrated that Black race was associated with a lower adjusted probability of receiving preoperative chemotherapy regardless of age, insurance payor, facility type/volume, distance to facility, cT stage, cN stage, sex, and education/income levels.Black race was associated with underutilization of preoperative chemotherapy for cT2 or greater gastric cancer, in discordance to published guidelines. The etiology of these disparities is multifactorial, and correcting the root causes represents a critical area for improvement.

Irreversible electroporation (IRE) is used as a locoregional treatment modality for patients with locally advanced pancreatic cancer (LAPC), but is non-curative and is associated with postoperative morbidity and mortality. We performed a systematic review and meta-analysis comparing survival outcomes of multimodal therapy with or without IRE.Separate searches were performed for multimodal therapy + IRE and multimodal therapy alone given the lack of comparative literature using PubMed, SCOPUS, and Cochrane Library in 3/2021. We determined overall survival (OS) and progression-free survival (PFS) from diagnosis and time of IRE. Treatment-related morbidity and mortality was determined.Of 585 published articles, 48 met inclusion criteria for IRE (n = 27) and without IRE (n = 21) with data for 1420 (IRE) and 1348 (without IRE) patients. The 6/12/24 months OS with IRE was 99%/84%/28%. The 6/12/24 months OS without IRE was 99%/80%/12%. At 12 months from IRE, OS was 55% and PFS was 12%. The mean major complication and 90-day mortality rates for IRE were 17.95% and 2.65%.Multimodal therapy alone is associated with similar OS to multimodal therapy + IRE in patients with LAPC. Most patients progress and nearly half die within 1 year of the IRE procedure. Given the lack of quality prospective data, IRE should remain experimental and be used with caution in LAPC.

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.

Elderly patients with adenocarcinoma of the pancreatic head can achieve reasonable survival with multimodal therapy. An analysis specific to cancers of the pancreatic tail has not been published.We identified patients ≥65 years with localized adenocarcinoma of the pancreatic tail in the National Cancer Database (2011-2017). Patients were grouped by age (65-79 and ≥80 years) and categorized by treatment regimen. Postoperative outcomes and survival were analyzed using propensity score matching and multivariable logistical regression.2168 patients were included: 73.9% were 65-79 years and 26.1% were ≥80 years. 34.1% of octogenarians did not receive any treatment, relative to 15.9% of younger patients (p 0.001). Thirty-day mortality rates were similar in operatively managed patients; however, the 90-day mortality rate among octogenarians was greater (3.0% vs. 7.8%, p 0.001; odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.07-3.19). Age ≥ 80 was not associated with survival on multivariable hazards regression (hazard ratio [HR] = 1.08, 95% CI = 0.95-1.24). After propensity matching, the addition of chemotherapy was not associated with improved survival relative to distal pancreatectomy alone among octogenarians (HR = 1.09, 95% CI = 0.72-1.65).Management of adenocarcinoma of the pancreatic tail varies based on patient age. Resection appears to play a key role in management, but there is substantial upfront risk. Shared decision making should be employed to balance the chance for long-term survival with the risk of early mortality.

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

Surgical volume-outcome relationships have been described for a variety of procedures. There is scant literature on total institutional volume and outcomes in patients who are nonoperatively managed. We examined the average treatment effect of total hepatopancreatobiliary malignancy case volume on survival outcomes of patients with nonresected hepatobiliary malignancies.We identified patients with hepatopancreatobiliary malignancies [pancreatic adenocarcinoma, pancreatic neuroendocrine neoplasms, hepatocellular carcinoma, biliary tract cancers] within the National Cancer Database (2004-2018). We determined percentile thresholds based on the total annual hepatopancreatobiliary malignancy case volume. We then identified nonoperatively managed patients with hepatocellular carcinoma or biliary tract cancers. We used inverse probability-weighted Cox regression to estimate the effect of facility volume on overall survival.We identified 710,988 patients with hepatopancreatobiliary malignancies. Total annual hepatopancreatobiliary malignancy case volume of 32, 71, and 177 cases/year corresponded to the 25th, 50th, and 75th percentiles. A total of 96,420 with hepatocellular carcinoma and 52,627 patients with biliary tract cancers were managed nonoperatively. In patients with hepatocellular carcinoma or biliary tract cancer, treatment at ≥25th, ≥50th, and ≥75th percentile facilities was associated with improved median, 1-, 2-, and 3-year overall survival compared with treatment at lower-percentile facilities. On inverse probability-weighted Cox analysis, treatment at higher-percentile facilities resulted in a lower hazard of death. Consistent findings were observed in patients with early or intermediate/advanced hepatocellular carcinoma or metastatic biliary tract cancers.Patients with nonoperatively managed hepatocellular carcinoma or biliary tract cancer who receive treatment at higher-volume facilities have improved survival outcomes. These data suggest regionalization of care for patients with hepatocellular carcinoma or biliary tract cancer to high-volume centers may improve survival.

To compare rates of venous thromboembolism (VTE) and postpancreatectomy hemorrhage (PPH) in patients with pancreatic or periampullary malignancy preimplementation and postimplementation of routine extended VTE prophylaxis.Guidelines recommend up to 28 days of VTE prophylaxis following major abdominal cancer operations. There is a paucity of data examining rates of VTE and PPH in patients who receive extended VTE prophylaxis following pancreatectomy.Single-institution analysis of patients who underwent pancreatectomy for malignancy (2004-2021). VTE and PPH rates within 90 days of discharge were compared based on receipt of extended VTE prophylaxis with enoxaparin.A total of 478 patients were included. Twenty-two (4.6%) patients developed a postoperative VTE, 12 (2.5%) of which occurred postdischarge. Twenty-five (5.2%) patients experienced PPH, 13 (2.7%) of which occurred postdischarge. There was no associated difference in the development of postdischarge VTE between patients who received extended VTE prophylaxis and those who did not (2.3% vs 2.8%, P=0.99). There was no associated difference in the rate of postdischarge PPH between patients who received extended VTE prophylaxis and those who did not (3.4% vs 1.9%, P=0.43). In the subset of patients on antiplatelet agents, the addition of enoxaparin did not appear to be associated with higher VTE (3.9 vs. 0%, P=0.31) or PPH (3.0 vs. 4.5%, P=0.64) rates.Extended VTE prophylaxis following pancreatectomy for malignancy was not associated with differences in postdischarge VTE and PPH rates. These data suggest extended VTE prophylaxis is safe but may not be necessary for all patients following pancreatectomy.

Resection of locoregional pancreatic neuroendocrine neoplasms (PanNENs) is typically recommended, but there is a paucity of data on the management of elderly patients.The National Cancer Database (2004-2016) was queried for patients 80 years or older with localized PanNENs. Patients were grouped as nonoperative or operative management. Postoperative outcomes and survival were compared.In total, 591 patients were included: 202 underwent resection, and 389 did not. Increasing age and pancreatic head tumors were associated with lower likelihood of resection. The overall 90-day mortality rate was 6.4%, which was higher for pancreatoduodenectomy than distal pancreatectomy (13.6% vs 5.1%, respectively). Operatively managed patients had longer median survival (80.8 vs 45.0 months, P0.001), and this association was independent of tumor location. On multivariable Cox regression, resection remained associated with longer survival (hazard ratio, 0.69; 95% confidence interval, 0.50-0.95). Among operatively managed patients, age and tumor location were not associated with survival; however, greater comorbidity and high-risk tumor-specific features were associated with worse survival.Resection of nonfunctional PanNENs in elderly patients is associated with improved survival compared with nonoperative management. Resection could be considered in appropriate operative candidates, regardless of tumor location, but the perioperative mortality rate must be considered.

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

We examined the association between Medicaid expansion (ME) and the diagnosis, treatment, and survival of patients with hepatocellular carcinoma (HCC).We identified patients with HCC65yrs with Medicaid or without insurance within the National Cancer Database before (2010-2013) or after (2015-2017) ME with early (cT1) or intermediate/advanced (cT2-T4 or M1) disease.We identified 4848 patients with HCC before and 4526 after ME. Prior to ME, there was no association between future ME status and diagnosis of early HCC (34.5% vs. 32.9%). There was no association between future ME status and treating early HCC with ablation, resection, or transplantation. Patients with early HCC in future ME states were less likely to die (HR = 0.81, 95% CI: 0.67-0.98). After ME, patients in ME states were more likely to be diagnosed with early HCC (39.2% vs. 32.1%). Patients with early disease in ME states were more likely to undergo resection (OR=1.78, 95% CI: 1.16-2.75) or transplantation (OR=3.20, 95% CI: 1.40-7.33). There was a further associated decrease in the hazard of death (HR=0.68, 95% CI: 0.54-0.86).ME was associated with early diagnosis of HCC. For early HCC, ME was associated with increased utilization of resection and transplantation and improvement in survival.

We describe factors associated with trial enrollment for patients with hepato-pancreato-biliary (HPB) malignancies. We analyzed the association and effect of trial enrollment on overall survival (OS).The National Cancer Database (2004-2017) was queried for common HPB malignancies (pancreatic adenocarcinoma [PDAC]neuroendocrine tumors, hepatocellular carcinoma [HCC], biliary tract cancers [BTC]). Multivariable logistic regression was used to identify factors associated with trial enrollment. OS was analyzed by multivariable Cox regression. Inverse-probability-weighted Cox regression was utilized to determine the effect of trial enrollment on OS.A total of 1573 (0.3%) of 511,639 patients were enrolled in trials; pancreatic malignancy: 1214 (0.4%); HCC: 217 (0.14%); BTC: 106 (0.15%). HCC and BTC were associated with lower likelihood of enrollment compared with pancreatic malignancy. Black and Hispanic patients were less likely to be enrolled compared to White patients. Treatment at academic facilities and metastatic disease were associated with higher likelihood of enrollment. Enrollment was associated with higher OS for PDAC, metastatic HCC, and metastatic BTC. Trial enrollment exhibited an OS advantage for PDAC and metastatic HCC.Nationally, fewer than 1% of patients with HPB malignancies were enrolled in clinical trials. There are racial, sociodemographic, and facility-based disparities in trial enrollment.

Objective measures of post-pancreatectomy weight change for pancreatic ductal adenocarcinoma (PDAC) have not been extensively studied for long-term outcomes. We used weight measurements in our institutional medical record to analyze trends in post-pancreatectomy weight and determine the association with disease status.Pancreatectomies for PDAC (n = 315) and benign indications (n = 111) were identified. Preoperative baseline, minimum postoperative (Min #1), and subsequent postoperative maximum (Max) weights were abstracted. Multivariable Cox hazards regression was conducted to analyze the association between weight change and survival.Median weight loss postoperatively in each group was 20 lbs. PDAC patients gained 10 lbs after Min #1 compared to 15 lbs in the benign cohort (p 0.001). Few patients returned to their preoperative weight (29.8% PDAC vs. 40.5% benign, p = 0.04). Patients with early PDAC recurrence ( 13 months) lost more weight (18.0% vs. 13.3% vs. 10.9%, p 0.001) and gained less weight (2.1% vs. 12.0% vs. 7.9%, p 0.001) compared with those with late cancer recurrence (≥ 13 months) or no evidence of active disease, respectively. PDAC patients lost 11.2 lbs in the year preceding recurrence diagnosis. Weight loss was not associated with survival; however, weight gain was associated with improved survival.Resections for PDAC are complicated by a similar degree of weight loss as patients with benign disease, and there is no association with survival. However, failure to gain weight is especially ominous. Weight loss after weight recovery foreshadows disease recurrence. These data suggest that rigorous weight tracking is an untapped surveillance strategy in patients with PDAC.

Not all patients with pancreatic adenocarcinoma (PDAC) tolerate multiagent neoadjuvant chemotherapy (NAC). We utilized institutional data and the National Cancer Database (NCDB) to investigate if time from diagnosis to NAC initiation is associated with survival.Patients who received NAC and underwent pancreatectomy at our institution (2010-2021) or within the NCDB (2010-2016) were identified. Time from diagnosis to NAC was grouped:21, 21-35, and35 d. Recurrence-free (RFS) and overall survival (OS) was compared.At our institution, 122 patients received NAC before pancreatectomy (21 d: n = 36; 21-35 d: n = 61;35 d: n = 25). Demographics, performance status, and anatomic resectability were similar. There was no difference in RFS (13.3 versus 12.4 versus 11.9 mo) or OS (26.7 versus 25.8 versus 26.1 mo) based on NAC timing. Patients who received FOLFIRINOX had an improvement in RFS (14.4 versus 12.2 versus 6.8 mo, P = 0.05) and OS (39.2 versus 21.4 versus 17.3 mo, P = 0.01) compared to gemcitabine with nab-paclitaxel or other regimens. Within the NCDB, 6713 patients were included (21 d: n = 2087; 21-35 d: n = 2656;35 d: n = 1970). There was no difference in OS (21.6 versus 20.9 versus 22.2 mo). Multiagent NAC was associated with improved OS compared to single-agent (22.6 versus 18.8 mo, P 0.001).Delay in NAC initiation for PDAC is not associated with survival. Patient optimization could be considered with the goal of improving tolerance of multiagent chemotherapy.

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.

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.We analyzed publications related to pancreatic surgery primarily focused on pancreatic and periampullary tumors to identify elements associated with acceptance into high impact journals and a high likelihood of future citations.A comprehensive review of nine surgical journals was performed between 2010 and 2019. Journals were grouped based on impact factor into high (3), medium (1-3), and low (1) impact categories. Each publication was annotated to identify study topic, methodology, and statistical approach. Findings were compared according to journal impact and number of citations to identify predictors of success across these 2 domains.A total of 1044 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 (P0.05). Although advanced statistical analysis was used more commonly in high-impact journals (P0.05), it did not translate to higher citations (P0.05).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.

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 to 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 multi-agent chemotherapy was similar between the groups. Median survival of patients treated with IT-CT was longer than CT alone (7.9 vs 6.3 months, p=0.005). On multivariable analysis, receipt of IT-CT was associated with a survival advantage as compared to CT (HR=0.86, 95% CI 0.76-0.97) when adjusting for demographics and type of chemotherapy regimen.Conclusions: In patients with metastatic PDAC, it appears that combination IT-CT may be associated with a survival advantage compared to CT alone.

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 0.001), with a median weight loss of 14.2 versus 2.9 lbs. The odds ratio for PDAC comparing weight loss within 1 year of 5 to 10% was 10.30 (p 0.001) and 77.82 for ≥ 10% (p 0.001), compared with stable weight. Weight loss prior to diagnosis was also associated with early-stage PDAC. PDAC cases with ≥ 10% prediagnosis weight loss had worse survival compared with stable weights (hazard ratio [HR] 1.60; p = 0.01). Greater prediagnosis weight loss was associated with poor survival after pancreatectomy (5 to 10% vs. 5%, HR 2.40, p = 0.03; ≥ 10% vs. 5%, HR 2.59, p = 0.03).Diagnosis of PDAC is preceded by unintentional weight loss in the majority of patients, even at an early stage. Greater prediagnosis weight loss severity is also associated with poor postoperative survival.

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.