Search

Background: Whipple pancreaticoduodenectomy (PD) is a complex gastrointestinal surgery that is performed increasingly via minimally invasive approach through robotic platforms. We sought to provide a comparative review of available data regarding robot-assisted vs open PD in terms of cost-effectiveness, overall survival, and other perioperative and long-term oncologic outcomes., Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, PubMed, Scopus, and Web of Science databases were searched from 1980 to April 2024 using designated keywords. English-language studies comparing costs and oncologic outcomes of robotic vs open PDs were considered for inclusion. Reviews, abstracts, case reports, letters to the editor, and non-English articles were excluded., Results: A total of 1733 studies were initially identified throughout the literature search. After the removal of duplicates, title and abstract screening identified 16 studies that were included in the review. No statistically significant differences were detected in terms of short-term complications (95% CI, 0.805-1.096; P = .42), mortality (95% CI, 0.599-1.123; P = .21), and readmission (95% CI, 0.959-1.211; P = .20) among patients undergoing open vs robotic PD. Robotic PDs was associated with a slightly better overall survival (95% CI, 1.020-1.233) and higher costs (95% CI, 0.134-1.139; P = .013). Mean length of stay (LOS) was higher in the open PD group (95% CI, -0.353 to 0.189; P < .001)., Conclusion: Robotic-assisted PD had a slightly shorter LOS and improved overall survival. There were no differences in short-term complications, mortality, or readmission. The use of cohort studies and residual potential selection bias necessitate randomized controlled trials to define the benefit of robotic PD., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Process-based quality metrics are important for improving long-term outcomes after surgical resection. We sought to develop a practical surgical quality score for patients diagnosed with pancreatic ductal adenocarcinoma undergoing curative-intent resection., Methods: Patients who underwent surgical resection for pancreatic ductal adenocarcinoma between 2010 and 2017 were identified using the National Cancer Database. Five surgical quality metrics were defined: minimally invasive approach, adequate lymphadenectomy, negative surgical margins, receipt of adjuvant therapy, and no prolonged hospitalization. Log-rank test and multivariable Cox regression analysis were used to determine the association of quality metrics with overall survival., Results: A total of 38,228 patients underwent curative-intent resection for pancreatic ductal adenocarcinoma. Median age at diagnosis was 68 years (interquartile range = 61-75), and roughly half the cohort was male (n = 19,562; 51.2%). Quality metrics were achieved on a varied basis: minimally invasive approach (n = 5,701; 14.9%), adequate lymphadenectomy (n = 27,122; 80.0%), negative surgical margin (n = 29,248; 76.5%), receipt of adjuvant therapy (n = 26,006; 68.0%), and absence of prolonged hospitalization (n = 26,470; 69.2%). An integer-based surgical quality score from 0 (no quality metrics) to 16 (all quality metrics) was calculated. Patients with higher scores had progressively better overall survival. Median overall survival differed substantially among the score categories (score = 0-4 points, 8.7 [8.0-9.6] months; 5-8 points, 17.5 [16.9-18.2] months; 9-12 points, 22.1 [21.6-22.8] months; and 13-16 points, 30.8 [30.2-31.3] months; P <  .001). On multivariable analysis, risk-adjusted mortality hazards decreased in a stepwise manner with higher scores (0-4 points: reference; 5-8 points: multivariable adjusted hazard ratio = 0.60; 95% CI, 0.57-0.63; 9-12 points: adjusted hazard ratio = 0.49; 95% CI, 0.47-0.52; 13-16 points: and adjusted hazard ratio = 0.37; 95% CI, 0.34-0.40; all P < .001)., Conclusion: Adherence to quality metrics may be associated with improved overall survival. Efforts aimed at increasing compliance with quality metric measures may help optimize long-term outcomes among patients undergoing surgical resection for pancreatic ductal adenocarcinoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The effect of preoperative anemia on clinical outcomes of patients undergoing resection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been previously investigated. This study aimed to characterize how preoperative anemia affected short- and long-term outcomes of patients undergoing curative-intent resection of GEP-NETs., Methods: Patients who underwent curative-intent resection for GEP-NETs between January 1990 and December 2020 were identified from 8 major institutions. The last preoperative hemoglobin level was recorded; anemia was defined as <13.5 g/dL in males or <12.0 g/dL in females based on the guides of the American Society of Hematology. The effect of anemia on postoperative outcomes was assessed on uni- and multivariate analyses., Results: Among 1559 patients, the median age was 58 years (IQR, 48-66), and roughly one-half of the cohort was male (796 [51.1%]). Most patients had a pancreatic tumor (1040 [66.7%]), followed by small bowel (259 [16.6%]), duodenum (103 [6.6%]), stomach (66 [4.2%]), appendix (53 [3.4%]), and other locations (38 [2.6%]). The median preoperative hemoglobin level was 13.4 g/dL (IQR, 12.2-14.5). Overall, 101 (6.7%) and 119 (8.5%) patients received an intra- or postoperative packed red blood cell (pRBC) transfusion, respectively. A total of 972 patients (44.5%) experienced a postoperative complication. Although the overall incidence of complications was no different among patients who did (anemic: 48.7%) vs patients who did not (nonanemic: 47.3%) have anemia (P = .597), patients with preoperative anemia were more likely to develop a major (Clavien-Dindo grade ≥IIIa: 48.9% [anemic] vs 38.0% [nonanemic]; P = .006) and multiple (≥3 types of complications: 32.2% [anemic] vs 19.7% [anemic]; P < .001) complications. Of note, 1-, 3-, and 5-year overall survival (OS) rates were 96.7%, 90.5%, and 86.6%, respectively. On multivariable analysis, anemia (hazard ratio, 2.0; 95% CI, 1.2-3.2; P = .006) remained associated with worse OS; postoperative pRBC transfusion was associated with an OS (5-year OS: 75.0% vs 87.7%; P = .017) and recurrence-free survival (RFS; 5-year RFS: 66.9% vs 76.5%; P = .047)., Conclusion: Preoperative anemia was commonly identified in roughly 1 in 3 patients who underwent curative-intent resection for GEP-NETs. Preoperative anemia was strongly associated with a higher risk of postoperative morbidity and worse long-term outcomes., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: We sought to define the accuracy of preoperative imaging to detect lymph node metastasis (LNM) among patients with pancreatic neuroendocrine tumors (pNETs), as well as characterize the impact of preoperative imaging nodal status on survival., Methods: Patients who underwent curative-intent resection for pNETs between 2000 and 2020 were identified from eight centers. Sensitivity and specificity of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-CT, and OctreoScan for LNM were evaluated. The impact of preoperative lymph node status on lymphadenectomy (LND), as well as overall and recurrence-free survival was defined., Results: Among 852 patients, 235 (27.6%) individuals had LNM on final histologic examination (hN1). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 12.4%, 98.1%, 71.8%, and 74.4% for CT, 6.3%, 100%, 100%, and 80.1% for MRI, 9.5%, 100%, 100%, and 58.7% for PET, 11.3%, 97.5%, 66.7%, and 70.8% for OctreoScan, respectively. Among patients with any combination of these imaging modalities, overall sensitivity, specificity, PPV, and NPV was 14.9%, 97.9%, 72.9%, and 75.1%, respectively. Preoperative N1 on imaging (iN1) was associated with a higher number of LND (iN1 13 vs. iN0 9, p = 0.003) and a higher frequency of final hN1 versus preoperative iN0 (iN1 72.9% vs. iN0 24.9%, p < 0.001). Preoperative iN1 was associated with a higher risk of recurrence versus preoperative iN0 (median recurrence-free survival, iN1→hN1 47.5 vs. iN0→hN1 92.7 months, p = 0.05)., Conclusions: Only 4% of patients with LNM on final pathologic examine had preoperative imaging that was suspicious for LNM. Traditional imaging modalities had low sensitivity to determine nodal status among patients with pNETs., (© 2023. Society of Surgical Oncology.)

Background and Objectives: Pancreatic cancer (PDAC) requires a multimodality approach. We sought to define the association between social determinants of health (SDOH) and delayed or nonreceipt of adjuvant chemotherapy (aCT) among patients undergoing PDAC resection., Methods: Data on patients who underwent PDAC resection between 2014 and 2020 were identified from Medicare Standard Analytic Files and merged with the county-level social vulnerability index (SVI). Mediation analysis defined the association between SVI subthemes and aCT receipt., Results: Among 24 078 patients, 47.7% received timely aCT, 17.7% received delayed aCT, and 34.6% did not receive any aCT. High SVI was associated with delay (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.10-1.34) and nonreceipt of aCT (OR 1.30, 95% CI 1.20-1.41) (both p < 0.05). 73.1% of the variation in timely aCT receipt was directly attributable to SVI, whereas 26.9% of the effect was due to indirect mediators including hospital volume (6.4%), length-of-stay (7.9%) and postoperative complications (12.6%). Socioeconomic status (delayed aCT: OR 1.25, 95% CI 1.13-1.38; nonreceipt aCT: OR 1.25, 95% CI 1.15-1.36) and household composition and disability (delayed aCT: OR 1.30, 95% CI 1.17-1.43; nonreceipt aCT: OR 1.19, 95% CI 1.09-1.29) were associated with receipt of aCT (both p < 0.001)., Conclusions: Most of the disparities in receipt of aCT after PDAC surgery are driven by underlying SDOH such as SVI., (© 2023 Wiley Periodicals LLC.)

Pancreatic adenocarcinoma (PDAC) is disease with a 5-year survival of only 12%. Many patients with PDAC present with late-stage disease and even early-stage disease can often be characterized by an aggressive tumor biology. Standard therapy for metastatic PDAC consists mainly of chemotherapy regimens like FOLFIRINOX, FOLFOX, or gemcitabine and nab-paclitaxel. Research has focused on sequencing PDAC tumors to understand better the mutational landscape and transcriptomics of PDAC with the goal to develop targeted therapies. Targeted therapies may potentially minimize the toxic risks of chemotherapy and provide a long-term survival benefit. We herein review the underlying molecular pathogenesis of PDAC, as well as the classification schema created from current sequencing data, and recent updates related to targeted therapy for PDAC., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Aims: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs., Methods: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL)., Results: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm 2 to 5.7 ± 2.5 cm 2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R 2  = 0.87, p = 0.03) and surface area (R 2  = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX)., Conclusion: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: Neoadjuvant therapy (NT) is increasingly recommended for patients with localized pancreatic ductal adenocarcinoma (PDAC). Recent research has highlighted the significant treatment burden that patients experience during NT, but caregiver well-being during NT is poorly understood., Methods: A cross-sectional mixed-methods analysis of primary caregivers of patients with localized PDAC receiving NT was undertaken. All patients completed the Caregiver Quality of Life Index-Cancer (CQOLC) survey, while semi-structured interviews were conducted among a convenience sample of participants., Results: Among 28 caregivers, the mean age was 60.1 years, and most were patient spouses/significant others (71.4%). Patients had resectable (18%), borderline resectable (46%), or locally advanced (36%) PDAC with a mean treatment duration of 2.9 months at the time of their caregiver's enrollment. Most caregivers felt that they received adequate emotional/psychosocial support (80%) and understood the rationale for NT (93%). A majority (60%) reported that caregiving responsibilities impacted their daily lives and required a decrease in their work hours, leading to financial challenges (47%). While overall QOL was moderate (mean 83 ± 21.1, range 0-140), "emotional burden" (47.3 ± 20.9), and "positive adaption" (57.3 ± 13.9) were the lowest ranked CQOLC subsection scores., Discussion: Caregivers of patients with PDAC undergoing NT experience significant emotional symptoms and impact on their daily lives. Assessing caregiver needs and providing resources during NT should be a priority., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: To investigate the impact of prognostic nutritional index (PNI) on short- and long-term outcomes of patients who underwent curative-intent resection for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs)., Methods: Patients with GET-NETs who underwent curative-intent resection were identified from a multi-center database. The prognostic impact of clinicopathological factors including PNI on post-operative outcomes were evaluated. A novel nomogram was developed and externally validated., Results: A total of 2,099 patients with GEP-NETs were included in the training cohort; 255 patients were in the external validation cohort. Median PNI (n = 973) was 47.4 (IQR 43.1-52.4). At the time of presentation, 1,299 (61.9%) patients presented with some type of clinical symptom. Low-PNI (≤42.2) was associated with gastrointestinal symptoms, as well as nodal metastasis and distant metastasis (all p &lt; 0.05). Patients with a low PNI had a higher incidence of severe (≥Clavien-Dindo grade IIIa: low PNI 24.9% vs. high PNI 15.4%, p = 0.001) and multiple (≥3 types of complications: low PNI 14.5% vs. high PNI 9.2%, p = 0.024) complications, as well as a worse overall survival (OS)(5-year OS, low PNI 73.7% vs. high PNI 88.5%, p &lt; 0.001), and RFS (5-year RFS, low PNI 68.5% vs. high PNI 79.8%, p = 0.008) versus patients with high PNI (&gt;42.2). A nomogram based on PNI, tumor grade and metastatic disease demonstrated excellent discrimination and calibration to predict OS in both the training (C-index 0.748) and two external validation (C-index 0.827, 0.745) cohorts., Conclusions: Low PNI was common and associated with worse short- and long-term outcomes among patients with GEP-NETs., (© 2023 S. Karger AG, Basel.)

Introduction: While Medicaid Expansion (ME) has improved healthcare access, disparities in outcomes after volume-dependent surgical care persist. We sought to characterize the impact of ME on postoperative outcomes among patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC) at high-volume (HVF) versus low-volume (LVF) facilities., Methods: Patients who underwent resection for PDAC were identified from the National Cancer Database (NCDB; 2011-2018). HVF was defined as ≥20 resections/year. Patients were divided into pre- and post-ME cohorts, and the primary outcome was textbook oncologic outcomes (TOO). Difference-in-difference (DID) analysis was used to assess changes in TOO achievement among patients living in ME versus non-ME states., Results: Among 33,764 patients who underwent resection of PDAC, 19.1% (n = 6461) were treated at HVF. Rates of TOO achievement were higher at HVF (HVF: 45.7% vs. LVF: 32.8%; p < 0.001). On multivariable analysis, undergoing surgery at HVF was associated with higher odds of achieving TOO (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.49-1.72) and improved overall survival (OS) [hazard ratio (HR) 0.96, 95% CI 0.92-0.99]. Compared with patients living in non-ME states, individuals living in ME states were more likely to achieve TOO on adjusted DID analysis (5.4%, p = 0.041). Although rates of TOO achievement did not improve after ME at HVF (3.7%, p = 0.574), ME contributed to markedly higher rates of TOO among patients treated at LVF (6.7%, p = 0.022)., Conclusions: Although outcomes for PDAC remain volume-dependent, ME has contributed to significant improvement in TOO achievement among patients treated at LVF. These data highlight the impact of ME on reducing disparities in surgical outcomes relative to site of care., (© 2023. Society of Surgical Oncology.)

Purpose: The purpose of this study was to examine the impact of early versus late palliative care referral (PCR) following pancreatic cancer diagnosis., Methods: Patients diagnosed with PDAC who received a PCR between 2014 and 2020 at a major academic institution were identified. PCR was classified as early (< 30 days) or late (≥ 30 days) based on time from definitive diagnosis. Data were obtained on number of emergency department (ED) visits, intensive care unit (ICU) admissions, and hospital admissions., Results: Among 1458 patients with PDAC, 419 (28.7%) received PCR, among which 67.3% (n = 282) received a late PCR. Of those who received PCR, the majority were White (85%) and male (54.8%), with a median age of 62 years at time of diagnosis. Patients who received an early PCR more commonly presented with stage 4 disease at diagnosis (early: n = 91, 69% vs. late: n = 132, 47%), whereas patients who received a late PCR more commonly presented with stage 1, 2, or 3 disease (early: n = 40, 30.5% vs. late: n = 150, 53.2%) (p < 0.001). Patients who received early PCR had fewer median ED visits (1 vs. 2, p < 0.001) and hospital admissions (1 vs. 2, p < 0.001) compared with patients who received late PCR. However, after performing recurrent-event Cox-proportional hazards models, the timing of PCR did not impact hospital admission (HR 0.88, 95% CI 0.68, 1.14; p = 0.3)., Conclusion: Timing of PCR for patients with PDAC was not associated with healthcare utilization. Further prospective trials are needed to study the patient-centered impact of early integration of palliative care services into multidisciplinary pancreatic cancer teams., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Access to high-quality cancer care is affected by environmental exposures and structural inequities. This study sought to investigate the association between the environmental quality index (EQI) and achievement of textbook outcomes (TO) among Medicare beneficiaries over the age of 65 who underwent surgical resection for early-stage pancreatic adenocarcinoma (PDAC)., Methods: Patients diagnosed with early-stage PDAC from 2004 to 2015 were identified using the SEER-Medicare database and combined with the US Environmental Protection Agency's EQI data. High EQI category indicated poor environmental quality, whereas low EQI indicated better environmental conditions., Results: A total of 5,310 patients were included, of which 45.0% (n = 2,387) patients achieved TO. Median age was 73 years and more than half were female (n = 2,807, 52.9%), married (n = 3,280, 61.8%), and resided in the Western region of the US (n = 2,712, 51.1%). On multivariable analysis, patients residing in moderate and high EQI counties were less likely to achieve a TO (referent: low EQI; moderate EQI: OR 0.66, 95% CI 0.46-0.95; high EQI: OR 0.65, 95% CI 0.45-0.94; p < 0.05). Increasing age (OR 0.98, 95%CI 0.97-0.99), racial minorities (OR 0.73, 95% CI 0.63-0.85), having a Charlson co-morbidity index > 2 (OR 0.54, 95%CI 0.47-0.61) and stage II disease (OR 0.82, 95%CI 0.71-0.96) were also associated with not achieving a TO (all p < 0.001)., Conclusion: Older Medicare patients residing in moderate or high EQI counties were less likely to achieve an "optimal" TO after surgery. These results demonstrate that environmental factors may drive post-operative outcomes among patients with PDAC., (© 2023. The Society for Surgery of the Alimentary Tract.)

Purpose: Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Patients with cancer have high information needs and the Internet has materialized as a leading source of information for many patients. Nevertheless, little is known about the availability, accessibility, quality, and readability of online information regarding NT for PDAC., Methods: A search of online patient informational materials (PIMs) pertaining to NT for PDAC was conducted using a combination of common search engines and browsers. Two independent researchers evaluated the readability, quality, and availability of unique PIMs from the top 25 websites from each search using validated measures., Results: Among the 130 websites retrieved, 46 (35.4%) unique PIMs focused on treatment of PDAC. Only 30 (23%) mentioned NT as a possible treatment option. Downstaging was the rationale for NT mentioned in the majority (90%) of websites. The mean quality and reliability of the 30 PIMs, assessed using the DISCERN instrument, was 3.3 ± 0.7, suggesting moderate quality/reliability. The mean readability score, assessed using the SMOG Grade tool, was 10.96 ± 1.49, which is equivalent to an 11th grade reading level., Conclusion: The low availability, poor readability, and moderate quality of online informational materials regarding NT for PDAC highlight the need for new patient-centered resources to educate patients and caregivers on an increasingly utilized treatment strategy for localized PDAC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Pancreatic ductal adenocarcinoma has the lowest 5-y relative survival of all solid tumor malignancies. Palliative care can improve the quality of life of both patients and their caregivers. However, the utilization patterns of palliative care in patients with pancreatic cancer are unclear., Methods: Pancreatic cancer patients who were diagnosed between October 2014 and December 2020 at the Ohio State University were identified. Palliative care and hospice utilization and referral patterns were assessed., Results: Of the 1458 pancreatic cancer patients, 55% (n = 799) were male, median age at diagnosis was 65 y (interquartile range [IQR]: 58, 73), and most were Caucasian (n = 1302, 89%). Palliative care was utilized by 29% (n = 424) of the cohort, with the initial consultation obtained after an average of 6 ± 9 mo from diagnosis. Patients who received palliative care were younger (62 y, IQR: 55, 70 versus 67 y, IQR: 59, 73; P < 0.001) and more frequently members of racial and ethnic minorities (15% versus 9%; P < 0.001) versus those who did not receive palliative care. Among the 344 (24%) patients who received hospice care, 153 (44%) had no prior palliative care consultation. Patients referred to hospice care survived a median of 14 d (95% CI, 12-16) after hospice referral., Conclusions: Only 3 out of 10 patients with pancreatic cancer received palliative care at an average of 6 mo from initial diagnosis. More than two out of every five patients referred to hospice had no previous palliative care consultation. Efforts to understand the impact of improved integration of palliative care into pancreatic cancer programs are needed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Racial/ethnic disparities in pancreatic adenocarcinoma (PDAC) outcomes may relate to receipt of National Comprehensive Cancer Network (NCCN) guideline-compliant care. We assessed the association between treatment at minority-serving hospitals (MSH) and receipt of NCCN-compliant care., Patients and Methods: Patients who underwent resection of early-stage PDAC between 2006 and 2019 were identified from the National Cancer Database (NCDB). MSH was defined as the top decile of facilities treating minority ethnicities (Black and/or Hispanic). Factors associated with receipt of NCCN-compliant care and its impact on overall survival (OS) were assessed., Results: Among 44,873 patients who underwent resection of PDAC, most were treated at non-MSH (n = 42,571, 94.9%), while a smaller subset were treated at MSH (n = 2302, 5.1%). Patients treated at MSH were more likely to be at a younger median age (MSH 66 years versus non-MSH 67 years), Black or Hispanic (MSH 58.4% versus non-MSH 12.0%), and not insured (MSH 7.8% versus non-MSH 1.6%). While 71.7% (n = 31,182) of patients were compliant with NCCN care, guideline-compliant care was lower at MSH (MSH 62.5% versus non-MSH 72.2%). On multivariable analysis, receiving care at MSH was associated with not receiving guideline-compliant care [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.74]. At non-MSH, non-white patients had lower odds of receiving guideline-compliant PDCA care (OR 0.85, 95% CI 0.78-0.91). Failure to comply was associated with worse overall survival (OS) [hazard ratio (HR) 1.50, 95% CI 1.46-1.54, all p < 0.001]., Conclusions: Patients with PDAC treated at MSH and minorities treated at non-MSH were less likely to receive NCCN-compliant care. Failure to comply with guideline-based PDAC treatment was associated with worse OS., (© 2023. Society of Surgical Oncology.)

Background: Pancreatic cancer is a lethal proliferative disease driven by multiple genetic and epigenetic alterations. Microarrays and omics-based sequencing techniques are potent tools that have facilitated a broader understanding of the complex biological processes that drive pancreatic ductal adenocarcinoma (PDAC). In turn, these tools have resulted in the identification of novel disease markers, prognostic factors, and therapeutic targets. Herein, we provide a review of the genetic and epigenetic drivers of PDAC relative to recent discoveries that impact patient management., Methods: A review of PubMed, Medline, Clinical Key, and Index Medicus was conducted to identify literature from January 1995 to July 2022 that is related to PDAC genetics and epigenetics. Articles in Spanish and English were considered during selection., Results: Molecular, genetic, and epigenetic diagnostic tools, novel biomarkers, and promising therapeutic targets have emerged in the treatment of pancreatic cancer. The implementation of microarray technology and application of large omics-based data repositories have facilitated recent discoveries in PDAC. Multiple molecular analyses based on RNA interference have been instrumental in the identification of novel therapeutic targets for patients with PDAC. Moreover, microarrays and next-generation omics-based discoveries have been instrumental in the characterization of subtypes of pancreatic cancer, thereby improving prognostication and refining patient selection for available targeted therapies., Conclusion: Advances in molecular biology, genetics, and epigenetics have ushered in a new era of discovery in the pathobiology of PDAC. Current efforts are underway to translate these findings into clinical tools and therapies to improve outcomes in patients with PDAC., (© 2023. The Society for Surgery of the Alimentary Tract.)

Objective: Determining the impact of county-level upward economic mobility on stage at diagnosis and receipt of treatment among Medicare beneficiaries with pancreatic adenocarcinoma., Summary Background Data: The extent to which economic mobility contributes to socioeconomic disparities in health outcomes remains largely unknown., Methods: Pancreatic adenocarcinoma patients diagnosed in 2004-2015 were identified from the SEER-Medicare linked database. Information on countylevel upward economic mobility was obtained from the Opportunity Atlas. Its impact on early-stage diagnosis (stage I or II), as well as receipt of chemotherapy or surgery was analyzed, stratified by patient race/ethnicity., Results: Among 25,233 patients with pancreatic adenocarcinoma, 37.1% (n = 9349) were diagnosed at an early stage; only 16.7% (n = 4218) underwent resection, whereas 31.7% (n = 7996) received chemotherapy. In turn, 10,073 (39.9%) patients received any treatment. Individuals from counties with high upward economic mobility were more likely to be diagnosed at an earlier stage (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.25), as well as to receive surgery (OR 1.58, 95% CI 1.41-1.77) or chemotherapy (OR 1.51, 95% CI 1.39-1.63). White patients and patients who identified as neither White or Black had increased odds of being diagnosed at an early stage (OR 1.12, 95% CI 1.02-1.22 and OR 1.35, 95% CI 1.02-1.80, respectively) and of receiving treatment (OR 1.73, 95% CI 1.59-1.88 and OR 1.49, 95% CI 1.13-1.98, respectively) when they resided in a county of high vs low upward economic mobility. The impact of economic mobility on stage at diagnosis and receipt of treatment was much less pronounced among Black patients (high vs low, OR 1.28, 95% CI 0.96-1.71 and OR 1.30, 95% CI 0.99-1.72, respectively)., Conclusions: Pancreatic adenocarcinoma patients from higher upward mobility areas were more likely to be diagnosed at an earlier stage, as well as to receive surgery or chemotherapy. The impact of county-level upward mobility was less pronounced among Black patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neoadjuvant therapy is increasingly being used before surgery for localized pancreatic cancer. Given the importance of completing multimodal therapy, the aim of this study was to characterize surgical resection rates after neoadjuvant therapy as well as the reasons for, and long-term prognostic impact of, not undergoing resection., Methods: A systematic review and meta-analysis of prospective trials and high-quality retrospective studies since 2010 was performed to calculate pooled resection rates using a generalized random-effects model for potentially resectable, borderline resectable, and locally advanced pancreatic cancer. Median survival times were calculated using random-effects models for patients who did and did not undergo resection., Results: In 125 studies that met the inclusion criteria, neoadjuvant therapy consisted of chemotherapy (36.8 per cent), chemoradiation (15.2 per cent), or chemotherapy and radiation (48.0 per cent). Among 11 713 patients, the pooled resection rates were 77.4 (95 per cent c.i. 71.3 to 82.5), 60.6 (54.8 to 66.1), and 22.2 (16.7 to 29.0) per cent for potentially resectable, borderline resectable, and locally advanced pancreatic cancer respectively. The most common reasons for not undergoing resection were distant progression for resectable and borderline resectable cancers, and local unresectability for locally advanced disease. Among 42 studies with survival data available, achieving surgical resection after neoadjuvant therapy was associated with improved survival for patients with potentially resectable (median 38.5 versus 13.3 months), borderline resectable (32.3 versus 13.9 months), and locally advanced (30.0 versus 14.6 months) pancreatic cancer (P < 0.001 for all)., Conclusion: Although rates of surgical resection after neoadjuvant therapy vary based on anatomical stage, surgery is associated with improved survival for all patients with localized pancreatic cancer. These pooled resection and survival rates may inform patient-provider decision-making and serve as important benchmarks for future prospective trials., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Partial pancreatic resection is a known risk factor for new-onset pancreatogenic diabetes mellitus (P-DM). The long-term incidence of P-DM and its clinical impact after partial pancreatic resection remains unknown. The primary objective of this study is to determine the long-term incidence of P-DM and its clinical impact after partial pancreatic resection., Study Design: The Medicare 100% Standard Analytic File (2013 to 2017) was queried for all patients who underwent partial pancreatic resection (pancreaticoduodenectomy, distal pancreatectomy). The primary outcome was the development of postoperative P-DM after surgery., Results: Among 4,255 patients who underwent a pancreaticoduodenectomy or distal pancreatectomy, with a median follow-up of 10.8 months, the incidence of P-DM was 20.3% (n=863) and occurred at a median of 3.6 months after surgery. For patients with at least a 3-year follow-up, 32.2% of patients developed P-DM. Risk factors for developing P-DM included male sex (odds ratio [OR] 1.32, 95% CI 1.13 to 1.54), undergoing a distal pancreatectomy (OR 1.98, 95% CI 1.68 to 2.35), having a malignant diagnosis (OR 1.65, 95% CI 1.34 to 2.04), a family history of diabetes (OR 2.06, 95% CI 1.43 to 2.97; all p < 0.001), and being classified as prediabetic in the preoperative setting (OR 1.57, 95% CI 1.18 to 2.08; p = 0.002). Patients who developed P-DM were more commonly readmitted within 90 days of surgery and had higher postoperative healthcare expenditures in the year after surgery ($24,440 US dollars vs $16,130 US dollars; both p < 0.001) vs patients without P-DM., Conclusions: Approximately 1 in 5 Medicare beneficiaries who undergo a pancreatic resection develop P-DM after pancreatic resection. Appropriate screening and improved patient education should be conducted for these patients, in particular, for those with identified risk factors.

Purpose: In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes., Methods and Materials: This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between 2012 and 2015 at a high-volume pancreatic cancer center. For induction CTX, most received modified FOLFIRINOX (mFFX), or gemcitabine and nab-paclitaxel (GnP) followed by 5-fraction SBRT for all. During fiducial placement, biopsies were obtained with DNA extracted for targeted sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform., Results: Median induction CTX duration was ≥4 months, and 31 patients received mFFX (65%). Among 44 LAPC patients, 17 (39%) were surgically explored, and 12 of 16 (75%) achieved a R0 resection. Median overall survival (mOS) was 20.2 and 14.6 months from diagnosis and SBRT, respectively. One- and 2-year OS from SBRT was 58% and 28%. The mOS after resection was 28.6 and 22.4 months from diagnosis and SBRT, respectively. Median local progression-free survival was 23.9 and 15.8 months from diagnosis and SBRT, respectively. The mOS for pre-SBRT CA 19-9 ≤180 U/mL versus >180 was 23.1 and 11.3 months, respectively (hazard ratio, 0.53; P = .04). Only 1 patient (2.1%) had late grade ≥2 gastrointestinal toxic effects attributable to SBRT. Despite significant pretreatment with chemotherapy, 88% of tumor specimens were effectively sequenced; survival outcomes were not significantly associated with specific mutational patterns. Quality of life was prospectively collected pre- and post-SBRT with the EORTC QLQ-C30 and PAN26 questionnaires showing no significant change., Conclusions: SBRT was safely administered with MA-CTX with minimal toxicity. A high proportion of LAPC patients underwent R0 resection with favorable survival outcomes., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is highly variable and there is a paucity of effective treatment options for patients with PDAC. Genome-wide analyses may allow for potential drugs to be identified using differentially expressed genes, as well as constructing protein interaction networks and molecule-gene connectivity mapping., Methods: Microarray data of RNA expression profiling of PDAC and normal pancreas tissues were downloaded from the Gene Expression Omnibus (GEO). Functional and pathway enrichment information of the DEGs was obtained using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Corresponding homologous proteins were analyzed by protein-protein interaction analysis. Survival-related hub genes were screened and potential therapeutic drugs for PDAC were identified using the connectivity mapping (cMap)., Results: Of 18,229 PDAC genes assessed using RNA expression profiling from 118 PDAC tumor samples and 13 normal pancreatic tissue samples, 1502 and 744 genes were upregulated and downregulated, respectively, versus normal pancreas tissue. Protein-protein interaction analysis revealed 10 upregulated hub genes (ITGB1, ITGAV, SDC1, KRAS, CCNB2, COL1A2, AURKA, CDC20, COL1A1, COL3A1) and 10 downregulated hub genes (CPB1, CPA1, CPA2, CTRB2, CTRC, CELA3A, CELA2B, PRSS3, CELA2A, REG1A). The connectivity mapping score related to this hub gene list was used to generate the candidate drugs for PDAC treatment, which includes tyrosine kinase inhibitors (lucitanib, lapatinib, ceritinib and CYT-387), serine/threonine protein kinase inhibitors (roscovitine, BS-181, purvalanol-a, MK-2206 and palomid-529) and other small molecules., Conclusion: Using available genetic atlas data, potential drug candidates for treatment of PDAC were identified based on differentially expressed genes, protein interaction analysis and connectivity mapping. These results may help focus efforts on identifying targeted agents with potential therapeutic efficacy for evaluation in prospective clinical trials of patients with PDAC., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: To define surgical outcomes of patients with high-grade gastro-entero-pancreatic neuroendocrine neoplasm grade G3 (GEP-NEN G3)., Methods: Patients who underwent surgical resection between 2000 and 2016 were identified. The overall survival (OS) and recurrence-free survival (RFS) of patients with gastro-entero-pancreatic neuroendocrine tumors grade G3 (GEP-NET G3) versus neuroendocrine carcinoma (NEC) were evaluated., Results: Fifty-one out of 2182 (2.3%) patients who underwent surgical resection were diagnosed as GEP-NEN G3. The pancreas was the most common primary site (n = 3772.5%). A majority of patients had lymph node metastasis (n = 3262.7%); one in three (n = 1631.4%) had distant metastasis. The median OS and RFS of the entire cohort were 56.4 and 34.5 months, respectively. Perineural invasion was a strong prognostic factor associate with OS after surgical resection. Patients with NEC had a worse survival outcome versus patients with NET G3 (median OS: 33.1 months vs. not attained, p = 0.088). In contrast, among patients who underwent curative-intent resection, patients with NEC had comparable RFS versus patients with NET G3 (median RFS: 35.6 vs. 33.9 months, p = 0.774)., Conclusions: Surgical resection provided acceptable short- and long-outcomes for well-selected patients with resectable GEP-NEN G3. NEC was associated with a worse OS versus NET G3., (© 2022 Wiley Periodicals LLC.)

Hepatic, pancreatic, and biliary (HPB) cancers, including hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), and cholangiocarcinoma (CCA) cause a disproportionate amount of the global cancer-related mortality. Despite advances in surgical technique and improved systemic therapies, overall 5-year survival remains dismal, especially for patients with pancreatic and biliary cancer. Historically, systemic therapies for patients with HPB cancers were administered in a "one-size-fits-all" approach due to limited reliable data on efficacy for specific patient populations. However, recent advances in genetic testing techniques have greatly improved our understanding of HPB oncogenesis, shedding light on specific genetic mutations responsible for progression from physiologic cellular regulation to uninhibited cellular replication and invasive cancer. Investigations into the oncogenesis of HPB cancers have revealed multiple actionable genetic variants, as well as increased susceptibilities to currently available systemic therapies. For example, patients with PDAC and a known BRCA mutation are more likely to benefit from FOLFIRINOX or gemcitabine plus cisplatin. While patients with CCA and a IDH1 mutation may benefit from ivosidenib. As a result, many national and societal guidelines now recommend some form of genetic testing in the workup of patients with HPB cancers. We herein review the role of genetic testing in these aggressive cancers including DNA sequencing techniques, clinically relevant mutations, therapeutic implications, and current clinical recommendations., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The seventh leading cause of cancer-related death globally, pancreatic ductal adenocarcinoma (PDAC) involves the exocrine pancreas and constitutes greater than 90% of all pancreatic cancers. Surgical resection in combination with systemic chemotherapy with or without radiation remains the mainstay of treatment and the only potentially curative treatment option. While there has been improvement in systemic chemotherapy, long-term survival among patients with PDAC remains poor. Improvement in the understanding of tumorigenesis, genetic mutations, the tumor microenvironment (TME), immunotherapies, as well as targeted therapies continued to drive advances in PDAC treatment. We herein review the TME, genetic landscape, as well as various metabolic pathways associated with PDAC tumorigenesis relative to emerging therapies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Despite its rising adoption, the use of minimally invasive (MIS) pancreaticoduodenectomy (PD) in the treatment of pancreatic cancer remains controversial. We sought to compare MIS and open PD for pancreatic cancer resection in terms of short-term, long-term, and oncologic outcomes using the win ratio, a novel statistical approach., Methods: Patients undergoing PD for pancreatic adenocarcinoma 2010-2016 were identified from the National Cancer Database (NCDB). Patients were paired based on age, sex, race, tumor size, Charlson-Deyo score, and receipt of neoadjuvant chemotherapy. The win ratio was calculated based on 30-day and 3-year mortality, receipt of adjuvant chemotherapy, surgical margin status, examination of at least 11 lymph nodes, extended length of stay, and 30-day readmission., Results: Among 18,936 patients, median age was 67 (IQR: 60-74); most patients had stage II disease at diagnosis (n = 16,530, 87.3%) and tumor size ≥ 2 cm (n = 15,880, 83.9%). The majority of patients underwent open PD (n = 16,409, 86.7%) versus MIS PD (n = 2527, 13.3%). For every matched patient-patient pair, the odds of the patient undergoing MIS PD "winning" were 1.14 (95%CI 1.13-1.15) higher versus open PD. The benefits of MIS PD were most pronounced among patients with tumor size < 2 cm (WR 1.21, 95%CI 1.13-1.30 versus ≥ 2 cm, WR 1.13, 95%CI 1.12-1.14) and patients who received neoadjuvant chemotherapy prior to resection (WR 1.28, 95%CI 1.23-1.32 versus no neoadjuvant chemotherapy, WR 1.13, 95%CI 1.11-1.14)., Conclusions: MIS PD may be preferable to open PD based on a hierarchical composite outcome that considered short-term, long-term, and oncologic outcomes., (© 2022. The Society for Surgery of the Alimentary Tract.)

Introduction: There is a paucity of effective treatment options for advanced pancreatic neuroendocrine tumors (pNETs). Genome-wide analyses may allow for potential drugs to be identified based on differentially expressed genes (DEGs)., Methods: Oligo microarray data of RNA expression profiling of pNETs and normal pancreas tissues were downloaded from the Gene Expression Omnibus. Functional and pathway enrichment information of the DEGs was obtained using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Corresponding homologous proteins were analyzed and potential therapeutic drugs for pNETs were identified using the Connectivity Map and Drug-Gene Interaction Database., Results: Assessment of raw data from 12,610 pNET genes demonstrated that 1082 and 380 genes were upregulated and downregulated, respectively, compared with normal pancreas tissue. Upregulated pathways were associated with nitrogen metabolism (i.e., GABAergic synapse, and graft-versus-host disease), whereas downregulated pathways included C-type leptin receptor signaling pathway, pertussis and AMPK signaling pathway. In particular, the protein-protein interaction analysis revealed 10 upregulated hub genes (DYNLL1, GNB5, GNB2, GNG4, GNAI2, GNAI1, HIST2H2BE, NUP107, NUP133, and SNAP25) and 10 downregulated hub genes (CXCL8, F2, CXCL2, GCG, SST, INS, GALR3, CCL20, ADRA2B, and CXCL6). Using the Drug-Gene Interaction Database, candidate drugs for pNETs treatment included 3 EGFR inhibitors (canertinib, erlotinib, WZ-4-145), as well as other cell-signaling pathway inhibitors such as AG-592, acarbose, lonidamine, azacytidine, rottlerin, and HU-211., Conclusion: Using available genetic atlas data, potential drug candidates for treatment of pNETs were identified based on differentially expressed genes. These results may help focus efforts on identifying targeted agents with therapeutic efficacy to treat patients with pNETs., (© 2022. The Society for Surgery of the Alimentary Tract.)

Importance: The identification of incidental pancreas cystic lesions (PCLs) has increased in recent decades with the expanded use and improved sensitivity of cross-sectional imaging. Because the overall risk of malignancy associated with PCLs is low, yet the relative morbidity of pancreatic surgery is high, evidence-based guidelines are necessary for appropriate surveillance and management. Therefore, this article provides a review of existing guidelines regarding surveillance and management of PCLs and highlights recent advances in the diagnostic evaluation of cysts and the postresection management of mucinous lesions., Observations: There are 5 main guidelines related to the management of PCLs: the American Gastrointestinal Association (AGA) guidelines, the American College of Gastroenterology (ACG) guidelines, the American College of Radiology (ACR) recommendations, the European evidence-based guidelines, and the International Association of Pancreatology (IAP)/Fukuoka guidelines. These guidelines are based on retrospective studies that do not account or control for most tumor- and patient-specific factors. These guidelines also vary in scope, recommendations for surgical resection vs surveillance, as well as duration and type of follow-up., Conclusions and Relevance: PCL guidelines should be viewed within the context of the data limitations on which they are based. PCL subtype-specific guidelines on surveillance and treatment are needed. In the future, the integration of cyst-specific genomic analysis, as well as evolutions in advanced diagnostic tools, such as cyst fluid next-generation sequencing and EUS-guided confocal laser endomicroscopy, may also better inform treatment guidelines. Owing to the current low-quality evidence on which many guidelines are based and the inherent morbidity of pancreas surgery, it is imperative that patients with PCLs are referred to institutions with advanced diagnostics and a multidisciplinary approach to patient surveillance and management.

Objectives: Physicians are increasingly recommending neoadjuvant therapy (NT) before surgery for pancreatic ductal adenocarcinoma (PDAC). However, patient preferences for and opinions regarding NT are poorly understood., Methods: Survivors and caregivers from a national PDAC patient advocacy organization completed an online survey assessing preferences for NT versus surgery first (SF) and factors influencing their decision making., Results: Among 54 participants, 74.1% had a personal history of PDAC. While most patients preferred SF for resectable disease, NT was the preferred treatment approach for borderline resectable, locally advanced, and resectable cancers with high carbohydrate antigen 19-9. The most important factor influencing patient decision making regarding NT was its impact on overall survival while the least important was published national guidelines. The most preferred rationale for NT was ability to downstage to surgical resection and early treatment of micrometastatic disease., Conclusions: Among a national cohort of PDAC survivors and caregivers, the majority preferred SF for resectable PDAC, whereas NT was preferred when the resectability of a tumor was in question. The impact of NT on quantity and quality of life, as well as the likelihood of achieving surgical resection, was most highly valued by participants., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with liver-only metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone. Recent studies have explored the role of surgical resection among patients with limited metastatic disease. National practice patterns and the impact of surgery among these patients remains unknown., Methods: The National Cancer Database was queried for all patients with pancreatic adenocarcinoma between 2010 and 2015. The primary outcome was overall survival from the time of diagnosis. Patients with liver-only metastatic disease were included. Univariable and multivariable logistic regression models were constructed to determine the association of patient, hospital, and regional factors with receipt of surgical resection. A propensity score-matched cohort (1:1) was generated by matching patient- and tumor-related factors (age, sex, race, comorbidity burden, primary tumor site, primary tumor size) among patients with liver-only stage IV pancreatic adenocarcinoma who received chemotherapy alone compared to those who received chemotherapy and underwent pancreatectomy and liver metastatectomy., Results: Among 312,426 patients who met the study criteria, one half (n = 140,043, 50.4%) had stage IV disease; metastatic sites included bone (n = 5493, 3.1%), brain (n = 620, 0.4%), lung (n = 16,580, 9.5%), and liver (n = 62,444, 35.7%). Patients with stage IV disease were more likely to be younger (odds ratio: 1.10, 95% confidence interval: 1.0-1.2; P = .03) and have poorly (odds ratio: 2.1, 95% confidence interval: 1.8-2.5; P < .001) or undifferentiated (odds ratio: 3.1, 95% confidence interval: 2.3-4.1; P < .001) tumors. Among stage IV patients with liver-only disease (n = 47,785, 14.9%), 891 patients (1.9%) underwent pancreatic resection. Patients who underwent resection were more likely to be younger (odds ratio 1.4, 95% confidence interval: 1.0-1.8; P = .03) and treated at an academic/research center (odds ratio 2.1, 95% confidence interval: 1.2-3.5; P = .006). Median overall survival among patients who underwent resection was 10.74 months versus 3.4 months among patients who did not undergo resection. After controlling for patient and disease-related factors, patients who underwent surgical resection had a lower risk of death versus patients who did not undergo surgery (hazard ratio: 0.5, 95% confidence interval: 0.4-0.6; P < .001). After propensity score matching, patients who received multimodality treatment for liver-only metastatic pancreatic adenocarcinoma (surgery, chemotherapy) had a longer median overall survival (15.6 months vs 8.1 months) compared to those who received chemotherapy alone (P < .001)., Conclusion: This study suggests that pancreatic resection in patients with liver metastases, in combination with chemotherapy and/or chemoradiation, may be associated with improved survival in well-selected patients. However, attempts at an aggressive surgical approach for patients with liver-only stage IV pancreatic adenocarcinoma patients should only be performed only under a well-designed prospective clinical trial., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system., Background: Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial., Methods: Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification., Results: The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts., Conclusion: A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Given the importance of completing multimodality therapy, the purpose of this qualitative study was to characterize physician perspectives on barriers and facilitators to delivering NT., Methods: A purposive sample of surgical, medical, and radiation oncologists participated in semi-structured interviews. Interviews were transcribed and coded by 3 independent researchers, iteratively identifying themes until saturation was achieved., Results: Participants (n = 27) were heterogeneous in specialty, years of experience, practice setting, gender, and geography. The most commonly cited advantage of NT was the ability to downstage patients. The most commonly cited barriers included lack of access and limited evidence. Patient preference for immediate surgery was frequently cited as a barrier, but most participants felt that patients eventually understood the treatment recommendation after informed discussion. Recommendations to enhance the delivery of NT included improved patient education, communication, and better evidence., Conclusion: In this qualitative study, indications for, barriers to, and opportunities to improve the delivery of NT for localized PDAC were identified. These results highlight the need for better evidence and protocol standardization for NT as well as methods of improving care coordination, communication, and education to improve patient-centered outcomes., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Few empiric studies evaluate the effects of regionalization on pancreatic cancer care., Methods: We queried the National Cancer Database to identify patients undergoing pancreaticoduodenectomy for clinical stage I/II pancreatic adenocarcinoma between 2006 and 2015. Facilities were categorized by annual pancreatectomy volume. Textbook oncologic outcome was defined as a margin negative resection, appropriate lymph node assessment, no prolonged hospitalization, no 30-day readmission, no 90-day mortality, and timely receipt of adjuvant chemotherapy. Multivariable regression adjusted for comorbid disease, pathologic stage, and facility characteristics was used to evaluate the relationship between facility volume and textbook outcome., Results: Sixteen thousand six hundred and two patients underwent pancreaticoduodenectomy; 3566 (21.5%) had a textbook outcome. Operations performed at high volume centers increased each year (45.8% in 2006 to 64.2% in 2015, p < 0.001) as did textbook outcome rates (14.3%-26.2%, p < 0.001). Surgical volume was associated with textbook outcome. High volume centers demonstrated higher unadjusted rates of textbook outcome (25.4% vs. 11.8% p < 0.01) and increased adjusted odds of textbook outcome relative to low volume centers (odds ratio: 2.39, [2.02, 2.85], p < 0.001). Textbook outcome was associated with improved overall survival independent of volume., Conclusions: Regionalization of care for pancreaticoduodenectomy to high volume centers is ongoing and is associated with improved quality of care., (© 2021 Wiley Periodicals LLC.)

Background: Intensive care unit (ICU) use has increased among patients with cancer. We sought to define factors associated with ICU admissions among patients with pancreatic cancer and characterize trends in mortality among hospital survivors., Methods: The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database was used to identify patients with pancreatic cancer who underwent resection. Multivariable analyses were conducted to identify factors associated with ICU admission and mortality among hospital survivors., Results: Among 6422 Medicare beneficiaries who underwent resection of pancreatic cancer, 2386 (37.1%) had an ICU admission. Patients with ICU admissions were more likely to be younger (10-year increase odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.77-0.89), male (OR: 1.17, 95% CI 1.05-1.30) and undergo resection at a teaching hospital (OR: 1.19, 95% CI: 1.05-1.36). While the majority of patients survived to hospital discharge (n = 2106; 88.3%), a majority of patients (n = 1296; 54.3%) died within 6 months. Among patients who had subsequent ICU admissions, 1- and 5-year survival was only 31.8% and 11.0%, respectively., Conclusions: Over one-third of patients with pancreatic cancer had an ICU admission. While most patients survived hospitalization, more than one-half of patients died within 6 months of discharge and two-thirds died within 1 year. These data should serve to guide patient-provider discussions around prognosis relative to ICU utilization., (© 2021 Wiley Periodicals LLC.)

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 < 0.001)., Conclusions: Pancreatic adenocarcinoma patients differed with regards to health care utilization, hospice use and expenditures following diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Increasing hospital or surgeon volume is associated with improved outcomes among patients with pancreatic cancer. Promotion of regionalized care is based on this volume-outcome association. However, other research has exposed nuances and complexities inherent to this association that should be considered when promoting regionalized care models. We herein provide a critical review of the literature on the volume-outcome association and a discussion of areas of ongoing controversy., Methods: A PubMed literature search was conducted for the years 1995-2020. Peer reviewed original research studies were selected for critical review based on study design, potential to draw meaningful conclusions from the data, and discussion of current knowledge gaps., Results: Based on the cumulative published literature, hospital/surgeon volume and patient mortality are inversely related. However, it remains unclear whether volume is a proxy for other more causative variables inherent in high-volume centers. Interpretation of the volume-outcome association is made more difficult to interpret due to the large variation in the definition of high volume, difficulty in isolating the individual impact of surgeon versus hospital volume, challenges in quantifying health system processes related to volume, and the fact that some low-volume centers consistently achieve excellent clinical results. Implementation of true regionalized care models has been rare, likely reflecting both health system and patient level challenges., Conclusion: The volume-outcome association has been consistently demonstrated to be important to the care of patients with pancreas cancer. The underlying mechanism of this association to explain the overall benefit is likely multifactorial. Better understanding of what drives the volume-outcome association may increase access to optimized care for a broader range of hospital systems and patients., (© 2021. Society of Surgical Oncology.)

Introduction: Neoadjuvant therapy (NT) is increasingly used for localized pancreatic ductal adenocarcinoma (PDAC). The impact of care fragmentation during NT on the outcomes of patients with PDAC is unknown., Methods: Adult patients with Stage I-III PDAC who received NT and patients who underwent surgery first followed by adjuvant therapy (AT) between 2004 and 2016 were queried from the National Cancer Database. Short- and long-term outcomes were compared between patients who received fragmented care (FC; care provided at >1 hospital) versus integrated care (IC; care at a single institution)., Results: Among 6522 patients who underwent NT before pancreatectomy, 3755 (57.6%) received FC and 2767 (42.4%) received IC. While patients who received FC had a longer time to initiation of treatment (33.2 vs. 29.7 days, p < 0.001), there was no difference in median overall survival (OS) (26.7 vs. 26.5 months, p = 0.6). Among patients who underwent upfront surgery followed by AT (n = 15 291), patients who received FC had a longer time from diagnosis to undergoing surgery but less time from surgery to AT and no difference in OS (24.0 vs. 24.0 months, p = 0.910)., Conclusion: Although care fragmentation was associated with slightly longer times to initiate and complete treatment among patients with localized PDAC, long-term survival outcomes were similar., (© 2021 Wiley Periodicals LLC.)

Background: Pancreatectomy is the main curative therapeutic option for pancreatic neuroendocrine tumors (pNETs). Given the indolent behavior of pNETs and the relatively limited lifetime of elderly patients, the impact of primary site surgery (PSS) of pNETs on long-term outcomes among older patients has been a topic of debate., Methods: Patients aged 70 or older with pNETs were identified in the Surveillance, Epidemiology and the End Results (SEER) database from 1998 to 2016. Propensity score matching was used to compare overall (OS) and cancer-specific survival (CSS) of patients who did versus did not undergo PSS., Results: Among 2,319 elderly patients with pNETs, 942 patients (40.6%) underwent PSS, while 1,377 (59.4%) did not undergo PSS (non-PSS: NPSS). After propensity score matching (n = 433 in each group), PSS group had improved survival compared with the NPSS group (5-year OS: 53.4% vs. 37.3%; 5-year CSS: 77.2% vs. 58.1%, both p < 0.001). In contrast, subgroup analysis of individuals aged ≥ 80 revealed no difference in 5-year CSS (PSS: 69.2% vs. NPSS: 67.4%, p = 0.27). A subgroup analysis among patients who had small (≤ 2 cm) non-functional (NF) pNETs noted comparable long-term outcomes among patients who underwent PSS versus NPSS patients (5-year OS: 73.1% vs. 66.5%, p = 0.19; 5-year CSS: 98.5% vs. 95.2%, p = 0.14)., Conclusions: Approximately 2 in 5 elderly patients with pNETs underwent PSS. While PSS was generally associated with prolonged OS and CSS among older patients, PSS was not associated with improved CSS among a subset of patients aged 80 or older, as well as among patients age ≥ 70 years with NF-pNET less than 2 cm., (© 2021. Société Internationale de Chirurgie.)

Background: The utilization of cancer-directed treatment for patients with all stages of pancreatic cancer in the USA is unknown. This study sought to examine national practice patterns and identify patient, hospital, regional, and other factors associated with disparities in the use of guideline-concordant cancer-directed therapy., Methods: Patients diagnosed with PDAC between 2004 and 2015 were queried from the National Cancer Data Base. Standard of care cancer-directed treatment was defined as surgical resection plus chemotherapy or chemoradiation for patients with stage 1 and 2 disease, chemotherapy for patients with metastatic disease (stage 4), and chemotherapy with or without surgery or chemoradiation for patients with locally advanced stage 3 disease., Results: A total of 336,629 patients with stage 1 (n = 38,443, 11.4%), stage 2 (n = 93,923, 27.9%), stage 3 (n = 37,492, 11.1%), or stage 4 metastatic (n = 166,771, 49.5%) disease were identified. Adherence with stage-specific standard of care treatment occurred in only 45.3% (n = 152,560) of patients among the entire cohort and varied by stage of disease (stage 1: 14.6% vs. stage 2: 39.9% vs. stage 3: 67.6%, vs. stage 4: 50.9%). Older age (OR 0.95, 95%CI 0.94-0.95; p < 0.001), female sex (OR 0.94, 95%CI 0.943-0.97; p < 0.001), African Americans (OR 0.89, 95%CI 0.87-0.91; P < 0.001), and increasing comorbidity burden (Charlson-Deyo score ≥3: OR 0.52, 95%CI 0.50-0.55; P < 0.001) were associated with a lower likelihood of receiving stage-specific standard of care treatment. Conversely, treatment at a high-volume center (quartile 4: OR: 1.13, 95%CI 1.10-1.16; P < 0.001) and higher education level (OR 1.32, 95%CI 1.28-1.36; p < 0.001) was associated with higher likelihood of receiving stage-specific standard of care treatment. Patients who received standard of care treatment had a 47% lower risk of death compared with patients who did not receive standard of care treatment (HR 0.53, 95%CI 0.52-0.53; P < 0.001)., Conclusion: Pancreatic adenocarcinoma is a complex disease requiring a multi-disciplinary approach for optimal outcomes. Receipt of stage-specific standard of care treatment for PDAC is associated with improved long-term oncological outcomes, but is only achieved in less than half of patients. Further studies are needed to evaluate interventions to address these treatment disparities for patients with PDAC., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: Patients can experience barriers and disparities to access high-quality cancer care. This study sought to characterize receipt of surgery and chemotherapy among Medicare beneficiaries with a diagnosis of early-stage pancreatic adenocarcinoma cancer (PDAC) relative to race/ethnicity and social vulnerability., Methods: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify patients with a diagnosis of early-stage (stage 1 or 2) PDAC between 2004 and 2016. Data were merged with the CDC's Social Vulnerability Index (SVI) at the beneficiary's county of residence. Multivariable, mixed-effects logistic regression was used to assess the association of SVI with resection., Results: Among 15,931 older Medicare beneficiaries with early-stage PDAC (median age, 77 years; interquartile range [IQR], 71-82 years), the majority was White (n = 12,737, 80.0 %), whereas a smaller subset was Black or Latino (n = 3194, 20.0 %) A minority of patients was more likely to live in highly vulnerable communities (low SVI: white [90.5 %] vs minority [9.5 %] vs high SVI: white [71.9 %] vs minority [28.1 %]; p < 0.001). Use of resection for early-stage PDAC was lowest among the patients who resided in high-SVI areas (low [38.0 %] vs average [34.3 %] vs high [31.9 %]; p < 0.001). The minority patients were less likely to undergo resection than the White patients (no resection: white [64.1 %] vs minority [70.7 %]; p < 0.001). The median SVI was higher among the patients who underwent resection (57.6; IQR, 36.0-81.0) than among those who did not (60.4; IQR, 41.9-84.3), and increased SVI resulted in a decline in the likelihood of resection (SVI trend: OR, 0.98; 95 % confidence interval [CI], 0.97-1.00), especially among the minority patients. Minority patients from high-SVI counties had markedly lower odds of preoperative chemotherapy than minority patients from a low-SVI neighborhood (OR, 0.62; 95 % CI, 0.52-0.73)., Conclusions: Older Medicare beneficiaries with early-stage PDAC residing in counties with higher social vulnerability had lower odds of undergoing pancreatic resection, which was more pronounced among minority versus older White Medicare beneficiaries., (© 2021. Society of Surgical Oncology.)

Background: The relationship between hospital Magnet status recognition and postoperative outcomes following complex cancer surgery remains ill-defined. We sought to characterize Textbook Outcome (TO) rates among patients undergoing (HP) surgery for cancer in Magnet versus non-Magnet centers., Methods: Medicare beneficiaries undergoing HP surgery between 2015 and 2017 were identified. The association of postoperative TO (no complications/extended length-of-stay/90-day mortality/90-day readmission) with Magnet designation was examined after adjusting for competing risk factors., Results: Among 10,997 patients, 21.3% (n = 2337) patients underwent surgery at Magnet hospitals (non-Magnet centers: 78.7%, n = 8660). On multivariable analysis, patients undergoing HP surgery had comparable odds of achieving a TO at Magnet versus non-Magnet hospitals (hepatectomy: odds ratio [OR]: 1.05, 95% confidence interval [CI]: 0.94-1.17; pancreatectomy-OR: 0.88, 95% CI: 0.74-1.06). Patients treated at hospitals with a high nurse-to-bed ratio had higher odds of achieving a TO irrespective of whether they received surgery at Magnet (high vs. low nurse-to-bed ratio; OR: 1.38; 95% CI: 1.01-1.89) or non-Magnet centers (OR: 1.26; 95% CI: 1.10-1.45). Similarly, hospital HP volume was strongly associated with higher odds of TO following HP surgery in both Magnet (Leapfrog compliant vs. noncompliant; OR: 1.24, 95% CI: 1.06-1.44) and non-Magnet centers (OR: 1.18; 95% CI: 1.11-1.26)., Conclusion: Hospital Magnet designation was not an independent factor of superior outcomes after HP surgery. Rather, hospital-level factors such as nurse-to-bed ratio and HP procedural volume drove outcomes., (© 2021 Wiley Periodicals LLC.)