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Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF.The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach.A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P.001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone.In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

Background and Aims : EUS-guided needle-based confocal laser endomicroscopy (nCLE) improves the diagnostic accuracy of pancreatic cystic lesions (PCLs) but concerns regarding its expense have limited widespread adoption of this technology. We conducted a cost-benefit analysis to assess the healthcare resource implications of adding EUS-nCLE to the standard of care (SOC) management of PCLs. Methods : A post-hoc analysis of a prospective study (2015-2018) evaluating EUS-nCLE for the diagnosis of PCLs was performed. The SOC diagnosis was based on clinical history, PCL morphology, and cyst fluid analysis. A minimum of 5-years of surveillance was included, the cost of EUS and MRI/MRCP was derived from institutional billing data (US$), and the total hospital costs (adjusted for inflation) for pancreatic operations were derived from the National (US) Readmission Database. Results : A reference diagnosis was available in 93 subjects (mean cyst size=36.4±15.7 mm; surgical histopathology, n=67 and diagnostic molecular markers in cyst fluid, n=26). SOC and nCLE were discordant in 13 (14%) subjects. The addition of nCLE led to 11 subjects being clinically downstaged from mucinous to non-mucinous not warranting surgery (total cost savings= $1,080,418), 1 subject upstaged from non-mucinous to mucinous, warranting surgical resection (cost savings of 5-years surveillance: $46,200), and 1 subject incorrectly classified as non-mucinous (cost excess of 5-years surveillance: $46,200). Overall, the addition of nCLE led to a net savings of $ 442,438 (mean: $ 4,757.40 /patient) for this cohort. Conclusions : EUS-nCLE is potentially cost-beneficial in the management of PCLs (≥ 3 cm) by preventing at least one unnecessary pancreatic surgery for every ten subjects undergoing evaluation by current practices. ClinicalTrials.gov number: NCT02516488.

Pancreatic diseases have long been associated with impaired glucose control. This study sought to identify the incidence of new insulin-dependent diabetes mellitus (IDDM) after pancreatectomy and the predictive accuracy of hemoglobin A1c (HbA1c) or blood glucose. Patients who underwent partial pancreatectomy and had preoperative HbA1c available at two academic institutions were assessed for new IDDM on discharge in relation to complication rates and survival. Of the 267 patients analyzed, 67% had abnormal HbA1c levels prior to surgery (mean 6.8%, glucose 135 mg/dL). Two hundred eight (77.9%) were not insulin-dependent prior to surgery, and 35 (16.8%) developed new IDDM after resection. On multivariable regression, increasing HbA1c and preoperative glucose were the only significant predictors for new IDDM. Optimal predictive cutoffs (HbA1c of 6.25% and glucose of 121 mg/dL) were determined in a discovery group (n = 143) and confirmed in a validation group (n = 124) with a diagnostic sensitivity of 72.7% and specificity of 84.8%. Patients with new IDDM after resection had higher rates of severe complications (OR 3.39), increased TPN at discharge (OR 4.32), and increased rates of discharge to nursing facilities (OR 2.57) (all P < 0.05). New IDDM was also associated with a decreased cancer-specific survival. Preoperative HbA1c ≥ 6.25% and blood glucose ≥ 121 mg/dL can accurately identify patients at increased risk of IDDM. These diagnostics may help identify patients in a preoperative setting that may benefit from interventions such as diabetes education or enhanced glucose control preoperatively.

Neutrophil-to-lymphocyte ratio has been correlated with clinical outcomes in many cancers. We investigated whether the delta-NLR (ΔNLR) following radiation therapy (RT) could predict achieving surgical resection and the overall survival (OS) of patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC), and whether the splenic radiation dose impacted ΔNLR.101 patients with biopsy-proven BRPC or LAPC who received induction chemotherapy followed by RT were retrospectively enrolled. Following contouring of spleens, dose-volume histograms (DVHs) for splenic dosimetric parameters were calculated. Pre- and post-RT complete blood counts (CBC) within two weeks were recorded. Delta (Δ) values were calculated by subtracting the post-RT value from the pre-RT value. Cox regression survival analysis for pre and postradiation CBC values and OS was performed. Receiver operating curves (ROC) were generated and optimal cutoff points for highest sensitivity and specificity were identified. Kaplan-Meier curves for OS were generated.On univariate Cox regression analysis, the only significant CBC value associated with OS was ΔNLR (HR 1.06, CI 1.03-1.09, p 0.001). On multivariate analysis, ΔNLR, age, and completed resection all significantly predicted for worse OS (p 0.05). ΔNLR significantly predicted achieving surgical resection (p = 0.04) and the optimal cutoff point for ΔNLR was 2.5. Patients with ΔNLR 2.5 had significantly longer OS (log rank p = 0.046). Spleen radiation dose parameters were all significantly higher in patients with a ΔNLR ≥ 2.5. Optimal radiation cutoff points to predict a ΔNLR ≥ 2.5 were splenic Dmean of 308 cGy and V5 of 10.3%.Among patients with BRPC or LAPC who have received induction chemotherapy, elevated ΔNLR after RT significantly predicts worse OS and decreased odds of achieving resection. Furthermore, ΔNLR is correlated with higher splenic doses, suggesting the spleen may be an important organ at risk.

The effect of community-level factors on surgical outcomes has not been well examined. We sought to characterize differences in "textbook outcomes" (TO) relative to social vulnerability among Medicare beneficiaries who underwent operations for cancer.Individuals who underwent operations for lung, esophageal, colon, or rectal cancer between 2013 and 2017 were identified using the Medicare database, which was merged with the CDC's Social Vulnerability Index (SVI). TO was defined as surgical episodes with the absence of complications, extended length of stay, readmission, and mortality. The association of SVI and TO was assessed using mixed-effects logistic regression.Among 203,800 patients (colon, n = 113,929; lung, n = 70,642; rectal, n = 14,849; and esophageal, n = 4,380), median age was 75 years (interquartile range 70 to 80 years) and the overwhelming majority of patients was White (n = 184,989 [90.8%]). The overall incidence of TO was 56.1% (n = 114,393). The incidence of complications (low SVI: 21.5% vs high SVI: 24.0%) and 90-day mortality (low SVI: 7.0% vs high SVI: 8.4%) were higher among patients from highly vulnerable neighborhoods (both, p0.05). In turn, there were lower odds of achieving TO among high-vs low-SVI patients (odds ratio 0.83; 95% CI, 0.78 to 0.87). Although high-SVI White patients had 10% lower odds (95% CI, 0.87 to 0.93) of achieving TO, high-SVI non-White patients were at 22% lower odds (95% CI, 0.71 to 0.85) of postoperative TO. Compared with low-SVI White patients, high-SVI minority patients had 47% increased odds of an extended length of stay, 40% increased odds of a complication, and 23% increased odds of 90-day mortality (all, p0.05).Only roughly one-half of Medicare beneficiaries achieved the composite optimal TO quality metric. Social vulnerability was associated with lower attainment of TO and an increased risk of adverse postoperative surgical outcomes after several common oncologic procedures. The effect of high SVI was most pronounced among minority patients.

We sought to determine the impact of payer-mix on post-operative outcomes among Medicare beneficiaries following hepatopancreatic surgery.Medicare beneficiaries who underwent hepatopancreatic surgery were identified. Hospital quality markers were obtained from the Hospital General Information dataset. Hospitals were dichotomized (low/average vs. high) based on Medicare patient days versus all patient days irrespective of payer type.High Medicare patient-mix hospitals were more likely to be ranked higher than the national average relative to safety of care (29.4% vs. 38.1%) and timeliness of care (15.4% vs. 26.3%) versus low burden Medicare hospitals (both p 0.001). However, Medicare beneficiaries who had hepatopancreatic surgery at a high Medicare patient-mix hospital were at higher risk of a complication (OR = 1.13, 95%CI 1.04-1.22), and death within 30-days (OR = 1.37, 95%CI 1.23-1.53) following surgery.While hospitals caring for higher numbers of Medicare beneficiaries generally performed better on CMS quality indicators, these rankings did not equate to improved post-operative outcomes.

The role of neoadjuvant therapy (NT) for ampullary carcinoma (AC) has not been clearly established.Patients who underwent pancreatoduodenectomy for AC between 2004 and 2016 were identified in the National Cancer Database. Overall survival (OS) was compared between those who received NT before resection and those who underwent surgery first (SF). Propensity score matching (PSM) was performed using age, pathologic T and N stage, and tumor differentiation.Among 8688 patients with AC, 175 (2.0%) received NT before surgery. While patients who received NT were younger (p = .022) and more likely to have nodal metastasis (43.3% vs. 35.1%, p .001), there was no difference in OS on univariate (43 vs. 33 months; hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.88-1.37, p = .401) or multivariate (HR: 1.09, 95% CI: 0.88-1.36, p = .416) analysis between groups. After PSM, there remained no difference in OS between NT or SF groups on univariate (37 vs. 32 months; HR: 1.20, 95% CI: 0.87-1.64, p = .350) or multivariate (HR: 0.99, 95% CI: 0.71-1.38, p = .943) analysis.NT followed by surgery was not associated with improved survival outcomes compared with SF among patients with localized AC. While NT is an acceptable alternative for patients with advanced disease, SF should remain the standard of care.

The objective of this study was to analyze whether primary tumor resection (PTR) among patients with stage IV gastrointestinal neuroendocrine tumor (GI-NET) and unresected metastases was associated with improved outcomes. Patients diagnosed with stage IV GI-NETs were identified in the linked SEER-Medicare database from 2004 to 2015. Overall survival (OS) of patients who did versus did not undergo PTR was examined using bivariate and multivariable cox regression analysis as well as propensity score matching (PSM). Among 2219 patients with metastatic GI-NETs, 632 (28.5%) underwent PTR, whereas 1587 (71.5%) did not. The majority of individuals had a NET in the pancreas (n = 969, 43.6%); the most common site of metastatic disease was the liver (n = 1064, 47.9%). Patients with stage IV small intestinal NETs most frequently underwent PTR (62.6%) followed by individuals with colon NETs (56.5%). After adjusting for all competing factors, PTR remained independently associated with improved OS (HR = 0.65, 95% CI: 0.56–0.76). Following PSM (n = 236 per group), patients who underwent PTR had improved OS (median OS: 1.3 years vs 0.8 years, p = 0.016). While PTR of NETs originating from stomach, small intestine, colon, and pancreas was associated with improved OS, PTR of rectal NET did not yield a survival benefit. Primary GI-NET resection was associated with a survival benefit among individuals presenting with metastatic GI-NET with unresected metastases. Resection of primary GI-NET among patients with stage IV disease and unresected metastases should only be performed in selected cases following multi-disciplinary evaluation.

Pancreatic cancer is a lethal disease, and, even with modern therapies, the mortality has not decreased significantly in decades. The prognostic importance of lymph node status is well defined; however, the role of extended lymphadenectomy to improve local recurrence and overall survival remains debated. Six randomized controlled trials have evaluated the extent of lymph node dissection in pancreaticoduodenectomy for pancreatic cancer. We sought to review the current literature to evaluate the role of lymphadenectomy in pancreatic cancer. The impact of each trial and its contribution to the literature is discussed. Multiple randomized trials have failed to note an improvement in overall survival with extended lymphadenectomy for pancreatic cancer. Rather, extended lymphadenectomy was associated with increased morbidity, operating room time, and length of stay.

Geographic variations in access to care exist in the USA. We sought to characterize county-level disparities relative to access to surgery among patients with early-stage hepatopancreatic (HP) cancer. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked database from 2004 to 2015 to identify patients undergoing surgery for early-stage HP cancer . County-level information was acquired from the Area Health Resources Files (AHRF). Multivariable logistic regression analysis was performed to assess factors associated with utilization of HP surgery on the county level. Among 13,639 patients who met inclusion criteria, 66.9% (n = 9125) were diagnosed with pancreatic cancer and 33.1% (n = 4514) of patients had liver cancer. Among patients diagnosed with early-stage liver and pancreas malignancy, two-thirds (n = 8878, 65%) underwent surgery. Marked county-level variation in the utilization of surgery was noted among patients with early-stage HP cancer ranging from 57.1% to more than 83.3% depending on which county a patient resided. After controlling for patient and tumor-related characteristics, counties with the highest quartile of patients living below the poverty level had 35% lower odds of receiving surgery for early stage HP cancer compared patients who lived in a county with the lowest proportion of patients below the poverty line (OR 0.65, 95% CI 0.55–0.77). In addition, patients residing in counties with the highest surgeon-to-population ratio (OR 2.01, 95% CI 1.52–2.65), as well as the highest hospital bed-to-population ratio (OR 1.29, 95% CI 1.07–1.54), were more likely to undergo surgical treatment for an early-stage HP malignancy. Area-level variations among patients undergoing surgery for early-stage HP cancer were mainly due to differences in structural measures and county-level factors. Policies targeting high-poverty counties and improvement in structural measures may reduce variations in utilization of surgery among patients diagnosed with early-stage HP cancer.

The current study aimed to define the relationship between patient satisfaction, hospital-level factors, and clinical outcomes among patients undergoing major surgery for cancer. The Medicare Inpatient Standard Analytic Files were used to identify patients undergoing lung, esophageal, colorectal, hepatic, or pancreatic surgery between 2016 and 2017, and Hospital Consumer Assessment of Healthcare Providers and Systems survey data were used to assess performance in terms of patient satisfaction. Among 60,446 patients, half were female (n = 31,244, 52%) with a median age of 73 years (interquartile range [IQR] 69–78 years). Patients who underwent surgery for esophageal resection (odds ratio [OR] 2.44; 95% confidence interval [CI] 1.10–5.40) and were Caucasian (OR 2.43; 95% CI 2.11–2.81) had optimal patient satisfaction. Hospital level factors such as urban location (OR 3.69; 95% CI 3.16–4.29), 200 + beds (OR 3.58; 95% CI 3.09–4.13), greater inpatient surgical volume (OR 3.03; 95% CI 2.82–3.25), higher nurse-to-bed ratio (OR 4.57; 95% CI 4.25–4.92), non-profit hospital status (OR 1.14; 95% CI 1.01–1.29), and non-teaching hospital status (OR 1.52; 95% CI 1.39–1.65) were related to optimal patient satisfaction. In adjusted analysis, patients undergoing surgery at hospitals reporting poor or average patient satisfaction had 22% higher odds of 90-day mortality than patients undergoing surgery at optimal-satisfaction hospitals (OR 1.22; 95% CI 1.09–1.36). In addition, hospitals with the highest patient satisfaction scores also had the highest proportion of surgical cases that achieved the composite textbook outcome (TO) quality metric (OR 1.12; 95% CI 1.05–1.20). Higher patient satisfaction was strongly associated with hospital structural measures such as bed number, urban location, nurse-to-bed ratio, and “optimal” TO after cancer surgery. These data highlight how high quality of care can directly lead to improved patient satisfaction among surgical patients with cancer.

Assessing composite measures of quality such as textbook outcome may be superior to focusing on individual parameters when evaluating hospital performance. The aim of the current study was to assess the impact of teaching hospital status on the occurrence of a textbook outcome after hepatopancreatic surgery.The Medicare Inpatient Standard Analytic Files were used to identify patients undergoing hepatopancreatic surgery from 2013 to 2015 for a malignant indication. Stratified and multivariable regression analyses were performed to determine the relationship between teaching hospital status, hospital surgical volume and textbook outcome.Among 8,035 Medicare patients (hepatectomy; 41.8%, pancreatectomy; 58.2%), 6,196 (77.1%) patients underwent surgery at a major teaching hospital, whereas 1,839 (22.9%) patients underwent surgery at a minor teaching hospital. Patients undergoing surgery for pancreatic cancer at a major teaching hospital had a greater likelihood of achieving a textbook outcome compared with patients treated at a minor teaching hospital (minor teaching hospital: 456, 40% versus major teaching hospital: 1,606, 45.4%; P = .002). The likelihood of textbook outcome was also greater among patients undergoing hepatopancreatic surgery at high-volume centers (pancreas, low volume: 875, 40.5% versus high volume: 1,187, 47.1% P.001; liver, low volume: 608, 41.8% versus high volume: 886, 46.6%; P = .005). When examining only major teaching hospitals, patients undergoing a pancreatectomy at a high-volume center had 29% greater odds of achieving a textbook outcome (odds ratio 1.29, 95% confidence interval 1.12-1.49). In contrast, among patients undergoing pancreatic resection at high-volume centers, the odds of achieving a textbook outcome was comparable among major versus minor teaching hospital (odds ratio 1.17, 95% confidence interval 0.89-1.53).The odds of achieving a textbook outcome after pancreatic and hepatic surgery was greater at major versus minor teaching hospitals; however, this effect was largely mediated by hepatopancreatic procedural volume. Patients and payers should focus on regionalization of pancreatic and liver resection to high-volume centers in an effort to optimize the chances of achieving a textbook outcome.

Better outcomes at high-volume surgical centers have driven regionalization of complex surgical care. In turn, access to high-volume centers often requires travel over longer distances. We sought to characterize travel patterns among patients who underwent a hepatectomy. The California Office of Statewide Health Planning database was used to identify patients who underwent hepatectomy between 2005 and 2016. Total distance traveled and whether a patient bypassed the nearest hospital that performed hepatectomy to get to a higher-volume center were assessed. Multivariate analyses were used to identify factors associated with bypassing a local hospital for a higher-volume center. Overall, 13,379 adults underwent a hepatectomy in 229 hospitals; only 26 hospitals were high volume (> 15 cases/year). Median travel time to a hospital that performed hepatectomy was 25.2 min (IQR: 13.1–52.0). The overwhelming majority of patients (91.6%) bypassed the nearest providing hospital to seek care at a destination hospital. Among patients who bypassed a closer hospital, 75.5% went to a high-volume hospital. Outcomes at destination hospitals were improved compared with nearest hospitals (incidence of complications: 20.4% vs. 22.9% %; failure-to-rescue: 7.1% vs 10.9%; mortality 1.5% vs. 2.6%). Medicaid beneficiaries (OR 0.69, 95%CI 0.56–0.85) were less likely to bypass the nearest hospital to go to a high-volume hospital; additionally, Medicaid patients were less likely to undergo hepatectomy at a high-volume hospital independent of bypassing the nearest hospital (OR 0.60, 95%CI 0.48–0.76). Among the 3703 patients who underwent hepatectomy at a low-volume center, 2126 patients had actually bypassed a high-volume hospital. Among the remaining 1577 patients, 95% of individuals would have needed to travel less than 1 additional hour to reach a high-volume center. Roughly, one-quarter of patients undergoing hepatectomy received care at a low-volume center; nearly all of these patients either bypassed a high-volume hospital or would have needed to travel less than an additional hour to reach a high-volume center. Travel distance needs to be considered in policies and healthcare delivery design to improve care of patients undergoing hepatic resection.

We conducted an institutional study to compare the clinical and pathological efficacy between the neoadjuvant therapy (NAT)‐modified FOLFIRINOX (mFOLF) vs nanoparticle albumin–bound paclitaxel plus gemcitabine (nab‐P/G) for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients who completed resection. The study retrospectively enrolled patients with pathologically confirmed BRPC or LAPC from 2010 to 2018 at our institution. The survival rates were determined by the Kaplan‐Meier method and log‐rank test was used to test differences. Cox's proportional hazard model was used to assess survival with respect to covariates. Seventy‐two patients who completed at least two cycles of neoadjuvant chemotherapy and surgical resection were included, with 52 (72.2%) patients receiving mFOLF and 20 (27.8%) receiving nab‐P/G. Patients treated with mFOLF had statistically higher rates of RECIST 1.1 partial or complete response (16/52 vs 1/20, P = .028). Additionally, mFOLF patients had greater pathological tumor size reduction, fewer positive lymph nodes, and higher treatment response grade compared to the nab‐P/G patients (all P, Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with poor survival rates. For borderline resectable or unresectable disease, intensive multi‐drug chemotherapy regimens with either modified FOLFIRINOX (mFOLF) or nab‐paclitaxel plus gemcitabine are preferred. We retrospectively compared these two chemotherapy regimens in patients who completed resection and found the mFOLF group had better overall clinical and pathological response rates. Randomized clinical trials are needed, and this study provides valuable information in the interim.

Background The objective of the current study was to define and compare rates of textbook outcomes (TO) among patients undergoing colorectal, lung, esophagus, liver, and pancreatic surgery for cancer at U.S. News & World Report (USNWR) ranked hospitals. Methods Medicare Inpatient Standard Analytic Files 2013-2015 were utilized to examine the relationship of TO and USNWR hospital ratings following surgery for colorectal, lung, esophageal, pancreatic, and liver cancer. TO was defined as no postoperative surgical complications, no prolonged length of hospital stay, no readmission within 90 days after discharge, and no postoperative mortality within 90 days after surgery. Results Among the 35,352 Medicare patients included in the cohort, 16,820 (47.6%) underwent surgery at honor roll hospitals, whereas 18 532 (52.4%) underwent surgery at non-honor roll hospitals. The overall proportion of patients who achieved TO was 50.1%. In examining the clinical outcomes of patients who underwent surgery, there was no difference in the odds of achieving TO at honor roll vs non-honor roll hospitals (colorectal: odds ratio [OR], 0.87; 95% confidence interval [CI], 0.69-1.10; lung: OR, 1.07; 95% CI, 0.87-1.32; esophagus: OR, 1.44; 95% CI, 0.72-2.89; liver: OR, 1.27; 95% CI, 0.87-1.84; pancreas: OR, 1.04; 95% CI, 0.67-1.62). Conclusion and relevance Patients undergoing surgery for lung, esophageal, liver, pancreatic, and colorectal cancer had comparable rates of TO at honor roll vs non-honor roll hospitals. No linear association was observed between hospital position in the rank and postoperative outcomes such as TO indicating that patients should not overly focus on the exact position within USNWR ranked hospitals. These data highlight to patients and physicians that up to one-half of patients undergoing surgery for cancer should anticipate at least one adverse outcome.

BACKGROUND Composite outcomes may more accurately reflect patient and provider expectations around optimal care. We sought to determine the impact of achieving a so-called "textbook oncologic outcome" (TOO) among patients undergoing resection of pancreatic adenocarcinoma (PDAC). METHODS Patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2006 and 2016 were identified in the National Cancer Database (NCDB). TOO was defined by: margin negative resection, compliant lymph node evaluation, no prolonged length-of-stay, no 30-day readmission/mortality, and receipt of adjuvant chemotherapy. Factors associated with TOO and overall survival (OS) were evaluated using multivariable logistic and Cox regression models, respectively. RESULTS Among 18 608 patients who underwent PD at 782 hospitals, many patients successfully achieved certain TOO factors such as R0 margin (77.9%) and no 30-day mortality (96.9%), while other TOO criteria such as receipt of adjuvant therapy (48.2%) were achieved less frequently. Overall, only 3124 (16.8%) patients achieved a TOO. Factors associated with lower odds of TOO included: older age, Black race, Medicaid insurance, Community facility, and low PD facility (

Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown.A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers. Postoperative morbidity, radiographic response according to response evaluation criteria in solid tumors (RECIST) criteria, and long-term outcomes were compared between patients who underwent TACE vs TARE.Among 248 patients with NELM, 197 (79%) received TACE and 51 (21%) received TARE. While patients who underwent TACE were more likely to have carcinoid syndrome, larger tumors, and higher chromogranin A levels, there was no difference in tumor differentiation, primary site, bilobar disease, or synchronous presentation. Nearly all TARE treatments (92%) were performed as outpatient procedures, while 99% of TACE patients spent at least 1 night in the hospital. There were no differences in overall morbidity (TARE 13.7% vs TACE 22.6%, p = 0.17), grade III/IV complication (5.9% vs 9.2%, p = 0.58), or 90-day mortality. The disease control rate (DCR) on first post-treatment imaging (RECIST partial/complete response or stable disease) was greater for TACE compared with TARE (96% vs 83%, p0.01). However, there was no difference in median overall survival (OS, 35.9 months vs 50.1 months, p = 0.3) or progression-free survival (PFS, 15.9 months vs 19.9 months, p = 0.37).In this retrospective multi-institutional analysis, both TACE and TARE with Y-90 were safe and effective liver-directed therapies for unresectable NELM. Although TARE was associated with a shorter length of hospital stay, TACE demonstrated improved short-term DCR, and both resulted in comparable long term outcomes.

BACKGROUND. Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS. A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000–2016). Demographic and clinical factors were compared by insurance status. Patients C 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan–Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS. The USNETSG database included 2022 patients. Of those, 1425 were aged 18–64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32–5.48, p = 0.006]. CONCLUSIONS. Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

Objectives The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established. Methods The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed. Results Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%. Conclusions Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

// Adam R. Wolfe 1 , * , Patrick Wald 1 , * , Amy Webb 1 , Nikhil Sebastian 1 , Steve Walston 1 , Ryan Robb 1 , Wei Chen 1 , Marall Vedaie 1 , Mary Dillhoff 1 , Wendy L. Frankel 1 , Wooil Kwon 2 , Jin-Young Jang 2 and Terence M. Williams 1 1 The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA 2 Department of Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea * Co-first authors Correspondence to: Terence M. Williams, email: terence.williams@osumc.edu Keywords: pancreatic cancer; miRNA; non-coding RNA; prognostic biomarker; local-regional recurrence Received: November 12, 2019 Accepted: January 29, 2020 Published: March 10, 2020 ABSTRACT Resectable pancreatic adenocarcinoma (PC) is generally managed with surgery followed by chemotherapy, but the role of postoperative chemoradiation (pCRT) is controversial. We sought to identify a microRNA (miRNA) expression profile associated with higher risk for local-regional recurrence (LRR), which might help identify patients that may benefit from pCRT. Total RNA was isolated from viable tumor from 88 patients who underwent PC resection with or without chemotherapy, but did not receive radiation. Digital miRNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated miRNAs, and dichotomized about the median to detect correlations between risk group, LRR and overall survival (OS). Two cohorts from The Cancer Genome Atlas (TCGA) and Seoul National University (SNU) were used for validation. Patients with high-risk scores had significantly worse LRR ( p = 0.001) and worse OS ( p = 0.034). Two-year OS rates for the high- and low-risk groups were 27.7% and 52.2%, respectively. On multivariable analysis, the risk score remained significantly associated with LRR ( p = 0.018). When validated on TCGA data, a high-risk score was associated with worse OS on univariate ( p = 0.03) and multivariable analysis ( p = 0.017). When validated on the SNU cohort, a high-risk score was likewise associated with worse OS ( p = 0.042). We have developed a 4-miRNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts. This signature has the potential to select patients most likely to benefit from pCRT, and should be tested further.

The aim of the current study is to assess rates of textbook outcome (TO) among Medicare beneficiaries undergoing hepatopancreatic (HP) surgery for cancer at dedicated cancer centers (DCCs) and National Cancer Institute affiliated cancer centers (NCI-CCs) versus non-DCC non-NCI hospitals. Medicare Inpatient Standard Analytic Files were utilized to identify patients undergoing HP surgery between 2013 and 2017. TO was defined as no postoperative surgical complications, no 90-day mortality, no prolonged length of hospital stay, and no 90-day readmission after discharge. Among 21,234 Medicare patients, 8.2% patients underwent surgery at DCCs whereas 32.1% underwent surgery at NCI-CCs and 59.7% underwent an operation at neither DCCs nor NCI-CCs. Although DCCs more often cared for patients with severe comorbidities [Charlson score > 5: DCCs, 1195 (68.9%), NCI-CCs, 3687 (54.1%), others, 3970 (31.3%); p

Background: The adoption of spleen-preserving distal pancreatectomy (SPDP) for malignant disease such as pancreatic neuroendocrine tumors (pNETs) has been controversial. The objective of the current study was to assess the impact of SPDP on outcomes of patients with pNETs. Methods: Patients undergoing a distal pancreatectomy for pNET between 2002 and 2016 were identified in the US Neuroendocrine Tumor Study Group database. Propensity score matching (PSM) was used to compare short- and long-term outcomes of patients undergoing SPDP versus distal pancreatectomy with splenectomy (DPS). Results: Among 621 patients, 103 patients (16.6%) underwent an SPDP. Patients who underwent SPDP were more likely to have lower BMI (median, 27.5 [IQR 24.0–31.2] vs. 28.7 [IQR 25.7–33.6]; p = 0.005) and have undergone minimally invasive surgery (n = 56, 54.4% vs. n = 185, 35.7%; p < 0.001). After PSM, while the median total number of lymph nodes examined among patients who underwent an SPDP was lower compared with DPS (3 [IQR 1–8] vs. 9 [5–13]; p < 0.001), 5-year overall survival (OS) and recurrence-free survival (RFS) were comparable (OS: 96.8 vs. 92.0%, log-rank p = 0.21, RFS: 91.1 vs. 84.7%, log-rank p = 0.93). In addition, patients undergoing SPDP had less intraoperative blood loss (median, 100 mL [IQR 10–250] vs. 150 mL [IQR 100–400]; p = 0.001), lower incidence of serious complications (n = 13, 12.8% vs. n = 28, 27.5%; p = 0.014), and shorter length of stay (median: 5 days [IQR 4–7] vs. 6 days [IQR 5–13]; p = 0.049) compared with patients undergoing DPS. Conclusion: SPDP for pNET was associated with acceptable perioperative and long-term outcomes that were comparable to DPS. SPDP should be considered for patients with pNET.

Background: Previous research has demonstrated that specific radiographic criteria, including the presence of calcifications and the enhancement pattern on computed tomography (CT) imaging, correlates with clinicopathologic features and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (NET). We sought to investigate whether these radiographic characteristics were prognostic among patients with neuroendocrine liver metastases (NELM) undergoing surgical resection. Methods: The preoperative contrast-enhanced CT scans of all patients who underwent resection of NELM at a single institution between 2000–2015 were retrospectively reviewed. The presence of calcifications was determined on non-contrast phase imaging. Enhancement on the arterial phase scan was categorized as hyperenhancing, hypoenhancing, or mixed. Relevant clinicopathologic characteristics as well as recurrence-free survival (RFS) and overall survival (OS) were compared between groups. Results: Among 82 patients who underwent resection of NELM, 57 had available data on calcifications while 51 had data available on arterial enhancement patterns. Among all patients, median age was 58 (IQR: 47–63) and the majority were female (N=48, 59.5%). The most common primary tumor locations were pancreas (N=25, 30.5%) and small bowel (N=27, 32.9%). The most commonly performed operations were right hepatectomy (N=29, 35.4%), bisegmentectomy (N=15, 18.3%), and segmentectomy (N=14, 17.1%). Median tumor number was 4 (IQR: 2–9), median Ki-67 was 5% (IQR: 2–10%), and median size of the largest liver metastasis was 4.5 (IQR: 2.8–7.7) cm. Twelve (21%) patients had tumor calcifications. Among patients with and without calcifications there were no differences in demographics, clinicopathologic characteristics, RFS (P=0.772) or OS (P=0.095). Arterial enhancement was hypoenhancing in 23 (45.1%), hyperenhancing in 10 (19.6%), and mixed in 18 (35.3%). Similarly, there were no differences between arterial enhancement groups in demographics, clinicopathologic characteristics, RFS (P=0.618) or OS (P=0.268). Conclusions: Radiographic characteristics on contrast-enhanced CT are not associated with the outcomes of patients undergoing resection of NELM. Future investigations should evaluate the prognostic impact of functional neuroendocrine imaging.

Background To define recurrence patterns and time course, as well as risk factors associated with recurrence following curative resection of pNETs. Method Patients who underwent curative-intent resection for pNET between 1997 and 2016 were identified from the US Neuroendocrine Tumor Study Group. Data on baseline and tumor-specific characteristics, overall survival (OS), timing and first-site of recurrence, predictors and recurrence management were analyzed. Results Among 1020 patients, 154 (15.1%) patients developed recurrence. Among patients who experienced recurrence, 76 (49.4%) had liver-only recurrence, while 35 (22.7%) had pancreas-only recurrence. The proportion of liver-only recurrence increased from 54.3% within one-year after surgery to 61.5% from four-to-six years after surgery; whereas the proportion of pancreas-only recurrence decreased from 26.1% to 7.7% over these time periods. While liver-only recurrence was associated with tumor characteristics, pancreas-only recurrence was only associated with surgical margin status. Patients undergoing curative resection of recurrence had comparable OS with patients who had no recurrence (median OS, pancreas-only recurrence, 133.9 months; liver-only recurrence, not attained; no recurrence, 143.0 months, p = 0.499) Conclusions Different recurrence patterns and timing course, as well as risk factors suggest biological heterogeneity of pNET recurrence. A personalized approach to postoperative surveillance and treatment of recurrence disease should be considered.

The relationship of volume and travel distance to patient outcomes after resection of gallbladder cancer (GBC) remains poorly defined.The 2004-2015 National Cancer Database was used to identify GBC resection patients and examine the impact of travel distance, hospital volume and both on overall survival (OS) and quality of care indicators.Among 10,174 patients undergoing surgery for GBC, the majority of patients were Caucasian (N = 8,175, 80%) and had a Charlson-Deyo comorbidity score of 0 (N = 6,785, 67%). On unadjusted survival analysis increasing travel distance and hospital volume were associated with improved OS (both p0.001). After controlling for competing risk factors, the 4th quartile of hospital volume was associated with a decreased hazard of death (HR 0.831, 95% CI 0.751-0.920, p0.001). When both hospital volume and travel distance were included, the association with improved OS persisted only for hospital volume (4th quartile HR 0.835, 95% CI 0.753-0.925, p0.001), whereas there was no independent association of increasing travel distance with OS.Both increasing travel distance and hospital volume were associated with improved OS; however, adjusted models demonstrated that the impact of travel distance was mediated through hospital volume.

Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34, 95%CI 1.27–11.38, p = 0.017) and OS (HR = 2.89, 95%CI 1.10–4.76, p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39, 95%CI 1.03–5.54, p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71, 95%CI 1.14–6.48, p = 0.025), DR (HR = 1.93, 95%CI 1.10–3.38, p = 0.022), and OS (HR = 1.97, 95%CI 1.17–3.34, p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p &lt, 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.

The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality. Our objective was to assess the accuracy of the ACS-NSQIP calculator for estimating risk after curative intent resection for primary GI neuroendocrine tumors (GI-NETs). Adult patients with GI-NET who underwent complete resection from 2000 to 2017 were identified using a multi-institutional database, including data from eight academic medical centers. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using receiver operating characteristic curves and the area under the curve (AUC). Seven hundred three patients were identified who met inclusion criteria. The most commonly performed procedures were resection of the small intestine with anastomosis (N = 193, 26%) and partial colectomy with anastomosis (N = 136, 18%). The majority of patients were younger than 65 years (N = 482, 37%) and ASA Class III (N = 337, 48%). The most common comorbidities were diabetes (N = 128, 18%) and hypertension (N = 395, 56%). Complications among these patients based on ACS NSQIP definitions included any complication (N = 132, 19%), serious complication (N = 118, 17%), pneumonia (N = 7, 1.0%), cardiac complication (N = 1, 0.01%), SSI (N = 80, 11.4%), UTI (N = 17, 2.4%), venous thromboembolism (N = 18, 2.5%), renal failure (N = 16, 2.3%), return to the operating room (N = 27, 3.8%), discharge to nursing/rehabilitation (N = 22, 3.1%), and 30-day mortality (N = 9, 1.3%). The calculator provided reasonable estimates of risk for pneumonia (AUC = 0.721), cardiac complication (AUC = 0.773), UTI (AUC = 0.716), and discharge to nursing/ rehabilitation (AUC = 0.779) and performed poorly (AUC < 0.7) for all other complications Fig. 1). The ACS-NSQIP risk calculator estimates a similar proportion of risk to actual events in patients with GI-NET but has low specificity for identifying the correct patients for many types of complications. The risk calculator may require modification for some patient populations.

BACKGROUND: Appendiceal neuroendocrine tumors (A-NETs) are rare neoplasms of the GI tract. They are typically managed according to tumor size; however, the impact of surgical strategy on the short- and long-term outcomes is unknown. METHODS: All patients who underwent resection of A-NET at 8 institutions from 2000 to 2016 were analyzed retrospectively. Patient clinicopathologic features and outcomes were stratified according to resection type. RESULTS: Of 61 patients identified with A-NET, mean age of presentation was 44.7 ± 16.0 years and patients were predominantly Caucasian (77%) and female (56%). Mean tumor size was 1.2 ± 1.3 cm with a median of 0.8 cm. Thirty-one patients (51%) underwent appendectomy and 30 (49%) underwent colonic resection. The appendectomy group had more T1 tumors (87% vs 42%, p < 0.01) than the colon resection group. Of patients in the colon resection group, 27% had positive lymph nodes and 3% had M1 disease. R0 resections were achieved in 90% of appendectomy patients and 97% of colon resection patients. Complications occurred with a higher frequency in the colon resection group (30%) compared with those in the appendectomy group (6%, p = 0.02). The colon resection group also had a longer length of stay, higher average blood loss, and longer average OR time. Median RFS and OS were similar between groups. CONCLUSION: A-NET RFS and OS are equivalent regardless of surgical strategy. Formal colon resection is associated with increased length of stay, OR time, higher blood loss, and more complications. Further study is warranted to identify patients that are likely to benefit from more aggressive surgery.

Background The focus of the current Medicare payment reform is to increase value – i.e. improve health care quality while lowering costs. This study sought to define cost variation and surgical quality among hospitals within small geographic areas typical of work commute patterns. Methods Medicare Provider Analysis and Review (MEDPAR) Inpatient Files was used to identify patients undergoing elective liver and pancreatic surgery between 2013 and 2015. Hospitals were assigned to combined statistical areas (CSAs) based on zip codes. Average price-standardized Medicare payments were used to identify highest- and lowest-cost hospitals within CSAs, and clinical outcomes were compared. Results The study included 12,016 patients. Medicare payments for index hospitalization were 45% ($12,580), 42% ($16,831), 44% ($12,901) and 50% ($18,605) higher for the highest-vs. lowest-cost hospitals for non-complex pancreatic procedures, complex pancreatic procedures, non-complex liver procedures, and complex liver procedures, respectively. Surgical quality was worse at highest-vs. lowest-cost hospitals, demonstrated by higher rates of complications, prolonged LOS and 90-day mortality. Conclusion There was a significant variation in surgical cost for each procedure between CSAs, and within CSAs. Highest-cost hospitals demonstrated worse quality metrics than the lowest-cost hospitals. Local referrals to low-cost hospitals represent an opportunity for increasing value of surgical care.

Recent studies on postoperative pancreatic fistula (POPF) prevention following pancreatoduodenectomy (PD) have proposed omission of perioperative drains for negligible/low-risk patients and early drain removal (≤POD3) for intermediate/high-risk patients with POD1 drain amylase levels of ≤5000 U/L, though this has not been validated using a nationwide cohort.The ACS-NSQIP targeted pancreatectomy database from 2014 to 2016 was queried to identify patients who underwent PD. Patients with POD1 drain amylase levels of ≤5000 U/L were initially stratified as negligible/low- or intermediate/high-risk based on a previously validated modified fistula risk score (mFRS). Differences in relevant postoperative outcomes were then compared among patients who underwent early (≤POD3) vs. late (≥POD4) drain removal.Among 1825 patients who underwent PD, 1540 (84%) had POD1 drain amylase of ≤5000 U/L: 719 (47%) high-risk and 821 (53%) low-risk. Among high-risk patients, early drain removal (n = 205, 29%) was associated with lower rates of POPF (3% vs. 18%, p 0.001), clinically relevant (CR)-POPF (2% vs. 15%, p 0.001), overall morbidity (27% vs. 47%, p 0.001), serious morbidity (15% vs. 24%, p = 0.007) and hospital length of stay (LOS, 7 vs. 8 days, p 0.001). Similarly, early drain removal in low-risk patients (n = 273, 33%) was associated with decreased rates of POPF (1% vs. 6%, p = 0.003), CR-POPF (1% vs. 5%, p = 0.014), overall morbidity (28% vs. 41%, p = 0.0003), serious morbidity (8% vs. 14%, p = 0.015) and LOS (6 vs. 8 days, p 0.001). On multivariate logistic regression analysis, early drain removal remained associated with significantly decreased odds of POPF, CR-POPF, overall and serious morbidity as well as LOS among both high- and low-risk patients (all p 0.05).Among patients with POD1 drain amylase ≤5000 U/L following PD, early drain removal (≤POD3) is associated with improved postoperative outcomes among both high- and low-risk patients. Early drain removal based on POD1 drain amylase is indicated regardless of mFRS.

Background Despite recent enthusiasm for the use of laparoscopic liver resection, data evaluating costs associated with laparoscopic liver resections are lacking. We sought to examine the use of laparoscopic liver surgery, and investigate variations in cost among hospitals performing these procedures. Methods A nationally representative sample of 12,560 patients who underwent a liver resection in 2012 was identified. Multivariable analyses were performed to compare outcomes associated with liver resection. Results Among the 12,560 patients who underwent liver resection, 685 (5.4%) underwent a laparoscopic liver resection. The proportion of liver resections performed laparoscopically varied among hospitals ranging from 4.6% to 20.0%; the median volume of laparoscopic liver resections was 10 operations/year. Although laparoscopic surgery was associated with lower postoperative morbidity (aOR = 0.60, 95%CI: 0.36–0.99) and shorter lengths of stay [(LOS) aIRR = 0.83, 95%CI: 0.70–0.97], it was not associated with inpatient mortality (p = 0.971) or hospital costs (p = 0.863). Costs associated with laparoscopic liver resection varied ranging from $5,907 (95%CI: $5,140-$6,674) to $67,178 (95%CI: $66,271-$68,083). The observed variations between hospitals were due to differences in morbidity (coefficient: $20,415, 95%CI: $16,000-$24,830) and LOS (coefficient: $24,690, 95%CI: $21,688-$27,692). Conclusions Although laparoscopic liver resection was associated with improved short-term perioperative clinical outcomes, utilization of laparoscopic liver resection remains low.

Objective:Despite heterogeneous biology, similar surveillance schemas are utilized after resection of all pancreatic neuroendocrine tumors (PanNETs). Given concerns regarding excess radiation exposure and financial burden, our aim was to develop a prognostic score for disease recurrence to guide individually tailored surveillance strategies.Methods:All patients with primary nonfunctioning, nonmetastatic well/moderately differentiated PanNETs who underwent curative-intent resection at 9-institutions from 2000 to 2016 were included (n = 1006). A Recurrence Risk Score (RRS) was developed from a randomly selected derivation cohort comprised of 67% of patients and verified on the validation-cohort comprised of the remaining 33%.Results:On multivariable analysis, patients within the derivation cohort (n = 681) with symptomatic tumors (jaundice, pain, bleeding), tumors >2cm, Ki67 >3%, and lymph node (LN) (+) disease had increased recurrence. Each factor was assigned a score based on their weighted odds ratio that formed a RRS of 0 to 10: symptomatic = 1, tumor >2cm = 2, Ki67 3% to 20% = 1, Ki67 >20% = 6, LN (+) = 1. Patients were grouped into low-(RRS = 0-2; n = 247), intermediate-(RRS = 3-5; n = 204), or high (RRS = 6-10; n = 9)-risk groups. At 24 months, 33% of high RRS recurred, whereas only 2% of low and 14% of intermediate RRS recurred. This persisted in the validation cohort (n = 325).Conclusions:This international, novel, internally validated RRS accurately stratifies recurrence-free survival for patients with resected PanNETs. Given their unique recurrence patterns, surveillance intervals of 12, 6, and 3 months are proposed for low, intermediate, and high RRS patients, respectively, to minimize radiation exposure and optimize cost/resource utilization.

Formal gastrectomy is occasionally required to achieve complete cytoreduction for patients with peritoneal surface malignancies. In addition, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer is increasingly being explored. Nevertheless, data on the safety of gastrectomy at the time of CRS-HIPEC are limited.The American College of Surgeons-National Surgical Quality Improvement Program databases from 2005 to 2016 were used to identify patients who underwent CRS-HIPEC. Demographic, clinical, and perioperative outcomes were compared between patients who underwent CRS-HIPEC with and without gastrectomy.Among 1168 patients who underwent CRS-HIPEC, 43 (4%) underwent partial (n = 20) or total (n = 23) gastrectomy. Patients who underwent gastrectomy at the time of CRS-HIPEC had a longer operative time (529.3 versus 457.6 min, P = 0.004), were more likely to need an intraoperative transfusion (32.6% versus 14.3%, P = 0.001), experienced a longer length of stay (19.0 versus 11.3 d, P 0.001), and had a significantly greater complication rate (60.5% versus 27.9%, P 0.001), whereas postoperative mortality was not statistically significantly different (4.7% versus 1.4%, P = 0.09). On multivariate logistic regression, gastrectomy (odds ratio [OR] 3.52, P 0.001) was the strongest predictor of postoperative morbidity, in addition to American Society of Anesthesiologists class 4 (OR 2.82, P = 0.001), malnutrition (OR 1.63, P = 0.01), liver resection (OR 1.88, P = 0.01), and colectomy (OR 2.04, P 0.001).Patients undergoing gastrectomy at the time of CRS-HIPEC experience a substantial postoperative complication rate (60%) and extended length of stay (mean 19 d). These findings highlight the need for cautious patient selection and preoperative counseling before performing concomitant gastrectomy and CRS-HIPEC.

Given the need to increase female representation in hepatopancreatobiliary (HPB) surgery, as well as the need to increase the academic pipeline of women in this subspecialty, we sought to characterize the prevalence of female authorship in the HPB literature. In particular, the objective of the current study was to determine the proportion of women who published HPB research articles as first, second, or last author over the last decade. All articles pertaining to hepatopancreaticobiliary (HPB) surgery appearing in seven surgical journals (Annals of Surgery, British Journal of Surgery, JAMA Surgery, Annals of Surgical Oncology, HPB (Oxford), Surgery, and Journal of Gastrointestinal Surgery) were reviewed for the years 2008 and 2018. Information on sex of author, country of author’s institution, and article type was collected and entered into a computerized database. Among the 1473 index articles included in the final analytic cohort, 414 (28%) publications had a woman as the first or last author, while the vast majority (n = 1,059, 72%) had a man as the first or last author. The number of female first authors increased from 15.6% (n = 92/591) in 2008 to 25.7% (n = 227/882) in 2018 (p

INTRODUCTION: Disparities in health and healthcare access remain a major problem in the United States. The current study sought to investigate the relationship between patient insurance status and hospital selection for surgical care. METHODS: Patients who underwent liver or pancreatic resection for cancer between 2004 and 2014 were identified in the National Inpatient Sample. The association of insurance status and hospital type was examined. RESULTS: In total, 22,254 patients were included in the study. Compared with patients with private insurance, Medicaid patients were less likely to undergo surgery at urban non-teaching hospitals (OR=0.36, 95%CI 0.22–0.59) and urban teaching hospitals (OR=0.54, 95%CI 0.34–0.84) than rural hospitals. Medicaid patients were less likely to undergo surgery at private investor-owned hospitals (OR=0.53, 95%CI 0.38– 0.73) than private non-profit hospitals. In contrast, uninsured patients were 2.2-fold more likely to go to government funded hospitals rather than private non-profit hospitals (OR=2.19, 95%CI 1.76–2.71). CONCLUSION: Insurance status was strongly associated with the type of hospital in which patients underwent surgery for liver and pancreatic cancers. Addressing the reasons for inequitable access to different hospital settings relative to insurance status is essential to ensure that all patients undergoing pancreatic or liver surgery receive high quality surgical care.

Background The burden of health care spending in the United States is a major concern, as health care costs have exponentially increased during the last three decades. The objective of the current study was to investigate the degree of cost-concentration among Medicare patients undergoing liver and pancreatic surgery. Methods Medicare claims data from 2013 to 2015 were used to identify patients undergoing elective liver and pancreatic resections. Patients were divided into four groups: 1) non-complex pancreatic procedures; 2) complex pancreatic procedures; 3) non-complex liver procedures; and 4) complex liver procedures. Unadjusted price-standardized Medicare payments were calculated and payments were divided into quintiles. Patient-level factors associated with payments were analyzed by multivariable linear regression. Results A total of 17,125 patients were included in the study. Patients in the top quintile of spending accounted for over 40% of payments for all liver and pancreatic procedures. Patients with comorbidity scores ≥5, male sex, open surgical approach and a diagnosis of congestive heart failure were associated with higher costs. Conclusion Patients undergoing liver and pancreatic resections on the top 20% of payments were responsible for a disproportionate share of Medicare payments – over 40% of total expenditures. Overall hospital surgical volume was lower among the highest quintile of payments.

Gastric carcinoids are rare neuroendocrine tumors of the gastrointestinal tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients.All patients who underwent resection of gastric carcinoids at 8 institutions from 2000 to 2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection, LR or formal gastrectomy, FG). Clinicopathological parameters, recurrence-free (RFS) and overall survival (OS) were compared between groups.Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p 0.04 and p 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p 0.017). This trend persisted when type II and type IV groups were excluded (p 0.045).Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.

Early drain removal when postoperative day (POD) one drain fluid amylase (DFA) was ≤5000 U/L reduced complications in a previous randomized controlled trial. We hypothesized that most surgeons continue to remove drains late and this is associated with inferior outcomes.We assessed the practice of surgeons in a prospectively maintained pancreas surgery registry to determine the association between timing of drain removal with demographics, comorbidities, and complications. We selected patients with POD1 DFA ≤5000 U/L and excluded those without drains, and subjects without data on POD1 DFA or timing of drain removal. Early drain removal was defined as ≤ POD5.Two hundred and forty four patients met inclusion criteria. Only 90 (37%) had drains removed early. Estimated blood loss was greater in the late removal group (190 mL versus 100 mL, P = 0.005) and pathological findings associated with soft gland texture were more frequent (97 [63%] versus 35 [39%], P 0.0001). Patients in the late drain removal group had more complications (84 [55%] versus 30 [33%], P = 0.001) including pancreatic fistula (55 [36%] versus 4 [4%], P 0.0001), delayed gastric emptying (27 [18%] versus 3 [3%], P = 0.002), and longer length of stay (7 d versus 5 d, P 0.0001). In subset analysis for procedure type, complications and pancreatic fistula remained significant for both pancreatoduodenectomy and distal pancreatectomy.Despite level one data suggesting improved outcomes with early removal when POD1 DFA is ≤ 5000 U/L, experienced pancreas surgeons more frequently removed drains late. This practice was associated with known risk factors (estimated blood loss, soft pancreas) and may be associated with inferior outcomes suggesting potential for improvement.

An understanding of the overall routine intensive care unit utilization, and characterization of the factors associated with a routine intensive care unit stay, may help identify ways to decrease overutilization of this resource after pancreatic surgery.Patients undergoing major pancreatic resection were identified in the Truven Health Analytics (Ann Arbor, MI) MarketScan Commercial Claims and Encounters Database from 2010 to 2014. Routine postoperative intensive care unit admission was defined as an admission to the intensive care unit of 24 hours or less on postoperative day zero. The association between routine intensive care unit admission and postoperative outcomes, including extended length of stay, failure to rescue, and total inpatient costs were evaluated.Of 3,280 patients who underwent a major pancreatic resection, 1,715 patients (52.3%) had a routine intensive care unit admission, which trended down over time (2010, n = 349; 53.0% versus 2014, n = 299; 47.5%; P = .019). The incidence of failure to rescue among patients who were routinely admitted to the intensive care unit (3.7%) was comparable to those admitted to the floor (1.7%, P = .098). Patients who were routinely admitted to the intensive care unit after major pancreatic resection had a median length of stay of 10 days (IQR: 7-15 days) versus 8 days (IQR: 7-12 days) for patients who were not admitted to the ICU (P.001). Routine intensive care unit admission was not associated with higher overall payments (ratio of adjusted total payments: 1.02, 95% CI: 0.98-1.06, P = .297).Routine intensive care unit admission was associated with a longer length of stay but did not translate into lower failure to rescue among patients.

Recent studies on postoperative pancreatic fistula (POPF) prevention suggest that omission of perioperative drains is safe for negligible- or low-risk patients undergoing pancreatoduodenectomy (PD). However, this proposed pathway has not been validated in a nationwide cohort.The ACS-NSQIP-targeted pancreatectomy database from 2014 to 2016 was queried to identify patients who underwent PD. Using a previously validated modified Fistula Risk Score (mFRS), patients were stratified as negligible/low- or intermediate/high-risk. Multivariate regression models were used to analyze the effect of intraoperative drain placement on relevant perioperative outcomes in both high- and low-risk patients.Among 6,730 patients undergoing PD, 3,375 (50%) were high-risk; 3,355 (50%) were low-risk. Among high-risk patients, drain placement (n = 3,093, 92%) was associated with a higher rate of POPF (26% vs 16%, p = 0.0003), clinically relevant (CR) POPF (20% vs 12%, p = 0.0015), and extended hospital length of stay (LOS, 9 vs 7 days, p0.0001), but decreased serious morbidity (29% vs 35%, p = 0.0330). Similarly, drain placement in low-risk patients (n = 2,785, 83%) was associated with a higher rate of POPF (11% vs 6%, p = 0.0006) and extended LOS (8 vs 7 days, p0.0001), yet lower serious morbidity (18% vs 23%, p = 0.0037). On multivariate logistic regression, drain placement was associated with significantly increased odds of CR-POPF and a significantly reduced incidence of serious morbidity among both high-risk (odds ratio [OR] 0.72, 95% CI 0.55 to 0.94, p = 0.0155) and low-risk patients (OR 0.71, 95% CI 0.57 to 0.89, p = 0.0027).In this population-based cohort, the mFRS was unable to stratify patients relative to the need for selective drain placement during PD. For both high- and low-risk patients, perioperative drain placement was associated with increased rates of POPF, CR-POPF, and extended LOS, but decreased incidence of serious morbidity.

OBJECTIVE The aim of the study was to estimate the cost of major complications after liver resection and determine whether high-volume (HV) centers are cost-effective. METHODS From 2002 to 2011, 96,107 cases of liver resection performed in the United States were identified using Nationwide Inpatient Sample. Hospitals were categorized as HV (150+ cases/yr), medium-volume (51-149 cases/yr), and low-volume (LV) (1-50 cases/yr) centers. Multivariable regression analysis identified predictors of cost. Propensity score matching comparing cases with versus without complications and costs of specific complications were estimated. Cost-effectiveness of HV centers was determined by calculating the incremental cost-effectiveness ratio. RESULTS After propensity score matching, the occurrence of a major complication added $33,855 extra cost, increased mean length of stay by 8.7 [95% confidence interval (CI), 8.4-9] days and increased risk of death by 9.3% (all P < 0.001). The cost of most common complications was wound infection (3.8%, $21,995), renal failure (2.8%, $19,201), respiratory failure (2.7%, $25,169), and hemorrhage (3.3%, $9,180), whereas sepsis (0.8%, $33,009), gastrointestinal bleeding (0.5%, $32,835), fistula (0.2%, $27,079), and foreign body removal (0.1%, $29,404) were most costly, but less frequent. Compared with LV centers, liver resection at HV centers was associated with $5109 (95% CI, 4409-5809, P < 0.001) more cost per case, yet on average 0.54 years (95% CI, 0.23-0.86) longer survival for an incremental cost-effectiveness ratio of $9392. CONCLUSIONS HV centers were cost-effective at performing liver resection compared with LV centers. After liver resection, complications such as surgical site infection, respiratory failure, and renal failure contributed the most to annual cost burden.

Background The impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long-term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin. Methods Patients who underwent curative-intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence-free survival were analyzed relative to surgical margin status using univariable and multivariable analyses. Results Among 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence-free survival (10-year recurrence-free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2–2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0–3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0–1.7, P = .060). In contrast, margin status was not associated with overall survival (10-year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6–6.2, P = .001) and recurrence-free survival (hazard ratio 2.6, 95% confidence interval 1.4–5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor-specific factors, such as cellular differentiation, perineural invasion, Ki-67 index, and major vascular invasion, rather than surgical margin, were associated with long-term outcomes. Conclusion Margin status was not associated with long-term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.

BACKGROUND: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized. METHODS: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome. RESULTS: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64–1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis. CONCLUSION: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.

Background The relationship of expenditures related to rescuing patients from complications and hospital quality has not been well characterized. We sought to examine the relationship between payments for treating post-operative complications after liver and pancreas surgery and hospital quality. Methods A retrospective cohort study of patients who underwent hepatopancreatic surgery was performed using claims data from 2013 to 2015 in the Medicare Provider Analysis and Review (MEDPAR) database. Medicare payments for index hospitalization and readmissions, as well as perioperative clinical outcomes were analyzed. Hospitals were stratified using average payments for patients who were rescued from complications (cost-of-rescue). Results A total of 13,873 patients and 737 hospitals were included in the analyses. Patient characteristics were similar across hospitals. Risk-adjusted rates of overall complications were higher at the highest cost-of-rescue hospitals (relative risk [RR], 1.35, 95% confidence interval [CI] 1.16–1.58), as well as rates of serious complications (RR, 1.78, 95% CI 1.51–2.09), 30-day readmission (RR 1.21 95% CI 1.06–1.39), 90-day mortality (RR, 1.29, 95% CI 1.01–1.64), and rates of failure-to-rescue (RR, 1.50, 95% CI 1.14–1.97). Conclusion Highest cost-of-rescue hospitals demonstrated worse quality metrics, including higher rates of serious complications, failure-to-rescue, 30-day readmission, and 90-day mortality.

INTRO: Chromogranin A (CgA) may be prognostic for patients with neuroendocrine tumors; however, the clinical utility of this test is unclear. METHODS: Patients undergoing resection for pancreatic neuroendocrine tumors (pNET) were selected from the eight institutions of the US Neuroendocrine Tumor Study Group database. Cox regression was used to identify pre-operative variables that predicted recurrence-free survival (RFS), and those with p < 0.1 were included in a risk score. The risk score was tested in a unique subset of the overall cohort. RESULTS: In the entire cohort of 287 patients, median follow-up time was 37 months, and 5-year RFS was 73%. Cox regression analysis identified four variables for inclusion in the risk score: CgA > 5x ULN (HR 4.3, p = 0.01), tumor grade 2/3 (HR 3.7, p = 0.01), resection for recurrent disease (HR 6.2, p < 0.01), and tumor size > 4 cm (HR 4.5, p = 0.1). Each variable was assigned 1 point. Risk-score testing in the unique validation cohort of 63 patients revealed a 95% negative predictive value for recurrence in patients with zero points. DISCUSSION: This simple pre-operative risk scoring system resulted in a high degree of specificity for identifying patients at low-risk for tumor recurrence. This test can be utilized pre-operatively to aid informed decision-making.

Background FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

BACKGROUND: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression. METHODS: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and plasma IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models. RESULTS: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was. CONCLUSION: Circulating IL-6 levels do not correlate with weight loss (i.e., cachexia), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia.

Background Care patterns among patients diagnosed with pancreatic adenocarcinoma remain poorly defined. Methods Cluster analysis was performed on patients with pancreatic adenocarcinoma to assess time from diagnosis to death spent in different care settings (home self-care-dominant[HSC], acute in-hospital care-dominant[ACS], hospice care-dominant[HC] or mixed home and hospice care[MHH]). Results Among 32,816 patients, most belonged to the HSC group (n = 13,459, 41%), followed by MHH (n = 9,091, 28%), ACS (n = 5,737, 18%) and HC (n = 4,529, 14%). Only about 1 in 3 patients in the HSC (n = 4,028, 30%) or ACS (n = 2,206, 35%) received hospice services for at least one week before death. 16% of patients (n = 5,188) died in the hospital, which was most common among ACS patients (n = 1,640, 29%). Median daily expenditures varied according to health care utilization (HSC, $44.6, IQR 12.3–130.1 vs MHH, $162.3, IQR 60.5–351.9 vs ACS, $489.7, IQR 243.2–856.8 vs HC, $306.1, IQR 132.3–580.0; p Conclusions Pancreatic adenocarcinoma patients differed with regards to health care utilization, hospice use and expenditures following diagnosis.

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.