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BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8(th) edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

In 2003, randomized trials demonstrated potentially improved outcomes when local instead of general anesthesia is used for inguinal hernia repair. Our study aimed to evaluate how the use of local anesthesia for this procedure changed over time following the publication of the trials' level 1 evidence.We used the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database to identify adults who underwent open, unilateral inguinal hernia repair under local or general anesthesia. Our primary outcome was the percentage of cases performed under local anesthesia. We used a time-series design to examine the trend and rate of change of the use of local anesthesia.We included 97,437 veterans, of which 22,333 (22.9%) had hernia surgery under local anesthesia. The median age of veterans receiving local anesthesia remained stable at 64-67 years over time. The use of local anesthesia decreased steadily, from 38.2% at the beginning year to 15.1% in the final year (P 0.0001). The publication of results from randomized trials (in 2003) did not appear to increase the overall use or change the rate of decline in the use of local anesthesia. Overall, we found that the use of local anesthesia decreased by about 1.5% per year.The utilization of local anesthesia for inguinal hernia repair in the VA has steadily declined over the last 20 + years, despite data showing equivalence or superiority to general anesthesia. Future studies should explore barriers to the use of local anesthesia for hernia repair.

Previous studies have reported healthcare disparities in the Texas-Mexico border population. Our aim was to evaluate treatment utilization and oncologic outcomes of colon cancer patients in this vulnerable population.Patients with localized and regional colon cancer (CC) were identified in the Texas Cancer Registry (1995-2016). Clinicopathological data, hospital factors, receipt of optimal treatment, and overall survival (OS) were compared between Texas-Mexico Border (TMB) and the Non-Texas-Mexico Border (NTMB) cohorts. Multivariable analysis was performed to identify risk factors associated with decreased survival.We identified 43,557 patients with localized/regional CC (9% TMB and 91% NTMB). TMB patients were more likely to be Hispanic (73% versus 13%), less likely to have private insurance (13% versus 21%), were more often treated at safety net hospitals (82% versus 22%) and less likely at ACS-CoC accredited hospitals (32% versus 57%). TMB patients were more likely to receive suboptimal treatment (21% versus 16%) and had a lower median OS for localized (8.58 versus 9.58 y) and regional colon cancer (5.75 versus 6.18 y, all P0.001). In multivariable analysis, TMB status was not associated with worse OS. Factors associated with worse survival included receipt of suboptimal treatment, Medicare/insured status, and treatment in safety net and non-accredited ACS-CoC hospitals (all P0.001) CONCLUSIONS: While TMB CC patients had worse OS, TMB status itself was not found to be a risk factor for decreased survival. This survival disparity is likely associated with higher rate of suboptimal treatment, Medicare/Uninsured status, and decreased access to ACS-CoC accredited hospitals.

Background The optimal anesthesia modality for umbilical hernia repair is unclear. We hypothesized that using local rather than general anesthesia would be associated with improved outcomes, especially for frail patients. Methods We utilized the 1998-2018 Veterans Affairs Surgical Quality Improvement Program to identify patients who underwent elective, open umbilical hernia repair under general or local anesthesia. We used the Risk Analysis Index to measure frailty. Outcomes included complications and operative time. Results There were 4958 Veterans (13%) whose hernias were repaired under local anesthesia. Compared to general anesthesia, local was associated with a 12%-24% faster operative time for all patients, and an 86% lower (OR 0.14, 95%CI 0.03-0.72) complication rate for frail patients. Conclusions Local anesthesia may reduce the operative time for all patients and complications for frail patients having umbilical hernia repair.

Introduction Preoperative autophagy inhibition with hydroxychloroquine (HCQ) in combination with gemcitabine in pancreatic adenocarcinoma (PDAC) has been shown to be safe and effective in inducing a serum biomarker response and increase resection rates in a previous phase I/II clinical trial. We aimed to analyze the long‐term outcomes of preoperative HCQ with gemcitabine for this cohort. Methods A review of patients enrolled between July 2010 and February 2013 in the completed phase I/II single arm (two doses of fixed‐dose gemcitabine (1500 mg/m2) in combination with oral hydroxychloroquine administered for 31 consecutive days until the day of surgery for high‐risk pancreatic cancer) was undertaken. Progression‐free survival (PFS) and overall survival analysis (OS) using Kaplan–Meier estimates were performed. Results Of 35 patients initially enrolled, 29 patients underwent surgical resection (median age at diagnosis: 62 years, 45% females). Median duration of follow‐up was 7.5 years. There was a median 15% decrease in the serum CA19‐9 levels following completion of neoadjuvant therapy and 83% of the cohort underwent a pancreaticoduodenectomy, 7 (24%) patients had a concomitant venous resection. On histopathology, 14 (48%) patients had at least a partial treatment response. The median PFS and OS were 11 months (95% Confidence interval [CI]: 7–28) and 31 months (95% CI: 13–47), respectively, while 9 (31%) patients survived beyond 5 years from diagnosis; a rate that compares very favorably with contemporaneous series. Conclusion Compared to historical data, neoadjuvant autophagy inhibition with HCQ plus gemcitabine is associated with encouraging long‐term survival for patients with PDAC., Preoperative autophagy inhibition with hydroxychloroquine enhances the therapeutic efficacy of neoadjuvant chemotherapy leading to a sustained and improved survival benefit in high‐risk pancreatic cancer.

SMAD4, a tumor suppressor gene, is lost in up to 60%–90% of pancreatic adenocarcinomas (PDAs). Loss of SMAD4 allows tumor progression by upregulating autophagy, a cell survival mechanism that counteracts apoptosis and allows intracellular recycling of macromolecules. Hydroxychloroquine (HCQ) is an autophagy inhibitor. We studied whether HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. We retrospectively analyzed the SMAD4 status of patients with PDA enrolled in two prospective clinical trials evaluating pre‐operative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ (NCT01128296). More recently, a randomized trial of gemcitabine/nab‐paclitaxel +/− HCQ evaluated Evans Grade histopathologic response (NCT01978184). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher’s exact test and log‐rank test were used to assess response and survival. Fifty‐two patients receiving HCQ with neoadjuvant chemotherapy were studied. Twenty‐five patients had SMAD4 loss (48%). 76% of HCQ‐treated patients with SMAD4 loss obtained a histopathologic response greater than or equal to 2A, compared with only 37% with SMAD4 intact (p = 0.006). Although loss of SMAD4 has been associated with worse outcomes, in the current study, loss of SMAD4 was not associated with a detriment in median overall survival in HCQ‐treated patients (34.43 months in SMAD4 loss vs. 27.27 months in SMAD4 intact, p = 0.18). The addition of HCQ to neoadjuvant chemotherapy in patients with PDA may improve treatment response in those with SMAD4 loss. Further study of the relationship among SMAD4, autophagy, and treatment outcomes in PDA is warranted.

Here we present two robotic sample changers integrated into the experimental stations for the macromolecular crystallography (MX) beamlines AMX and FMX, and the biological small-angle scattering (bioSAXS) beamline LiX. They enable fully automated unattended data collection and remote access to the beamlines. The system designs incorporate high-throughput, versatility, high-capacity, resource sharing and robustness. All systems are centered around a six-axis industrial robotic arm coupled with a force torque sensor and in-house end effectors (grippers). They have the same software architecture and the facility standard EPICS-based BEAST alarm system. The MX system is compatible with SPINE bases and Unipucks. It comprises a liquid nitrogen dewar holding 384 samples (24 Unipucks) and a stay-cold gripper, and utilizes machine vision software to track the sample during operations and to calculate the final mount position on the goniometer. The bioSAXS system has an in-house engineered sample storage unit that can hold up to 360 samples (20 sample holders) which keeps samples at a user-set temperature (277 K to 300 K). The MX systems were deployed in early 2017 and the bioSAXS system in early 2019.

Pancreatic cancer is a devastating gastrointestinal cancer characterized by late diagnosis, limited treatment success and dismal prognosis. Exocrine tumours account for 95% of pancreatic cancers and the most common pathological type is pancreatic ductal adenocarcinoma (PDAC). The occurrence and progression of PDAC involve multiple factors, including internal genetic alterations and external inflammatory stimuli. The biology and therapeutic response of PDAC are further shaped by various forms of regulated cell death, such as apoptosis, necroptosis, ferroptosis, pyroptosis and alkaliptosis. Cell death induced by local or systemic treatments suppresses tumour proliferation, invasion and metastasis. However, unrestricted cell death or tissue damage might result in an inflammation-related immunosuppressive microenvironment, which is conducive to tumour progression or recurrence. The precise extent to which cell death affects PDAC is not yet well described. A growing body of preclinical and clinical studies document significant correlations between mutations (for example, in KRAS and TP53), stress responses (such as hypoxia and autophagy), metabolic reprogramming and chemotherapeutic responses. Here, we describe the molecular machinery of cell death, discuss the complexity and multifaceted nature of lethal signalling in PDAC cells, and highlight the challenges and opportunities for activating cell death pathways through precision oncology treatments.

OBJECTIVE: During the initial wave of the COVID-19 pandemic, organ transplantation was classified a CMS Tier 3b procedure which should not be postponed. The differential impact of the pandemic on access to liver transplantation was assessed. SUMMARY BACKGROUND DATA: Disparities in organ access and transplant outcomes among vulnerable populations have served as obstacles in liver transplantation. METHODS: Using UNOS STARfile data, adult waitlisted candidates were identified from March 1, 2020 to November 30, 2020 (n = 21,702 pandemic) and March 1, 2019 to November 30, 2019 (n = 22,797 pre-pandemic), and further categorized and analyzed by time periods: March to May (Period 1), June to August (Period 2), and September to November (Period 3). Comparisons between pandemic and pre-pandemic groups included: Minority status, demographics, diagnosis, MELD, insurance type, and transplant center characteristics. Liver transplant centers (n = 113) were divided into tertiles by volume (small, medium, large) for further analyses. Multivariable logistic regression was fitted to assess odds of transplant. Competing risk regression was used to predict probability of removal from the waitlist due to transplantation or death and sickness. Additional temporal analyses were performed to assess changes in outcomes over the course of the pandemic. RESULTS: During Period 1 of the pandemic, Minorities showed greater reduction in both listing (-14% vs -12% Whites), and transplant (-15% vs -7% Whites), despite a higher median MELD at transplant (23 vs 20 Whites, P < 0.001). Of candidates with public insurance, Minorities demonstrated an 18.5% decrease in transplants during Period 1 (vs -8% Whites). Although large programs increased transplants during Period 1, accounting for 61.5% of liver transplants versus 53.4% pre-pandemic (P < 0.001), Minorities constituted significantly fewer transplants at these programs during this time period (27.7% pandemic vs 31.7% pre-pandemic, P = 0.04). Although improvements in disparities in candidate listings, removals, and transplants were observed during Periods 2 and 3, the adjusted odds ratio of transplant for Minorities was 0.89 (95% CI 0.83-0.96, P = 0.001) over the entire pandemic period. CONCLUSIONS: COVID-19's effect on access to liver transplantation has been ubiquitous. However, Minorities, especially those with public insurance, have been disproportionately affected. Importantly, despite the uncertainty and challenges, our systems have remarkable resiliency, as demonstrated by the temporal improvements observed during Periods 2 and 3. As the pandemic persists, and the aftermath ensues, health care systems must consciously strive to identify and equitably serve vulnerable populations.

Minimally invasive distal pancreatectomy has become increasingly used in practice. While laparoscopic approach is the most commonly used technique, robotic distal pancreatectomy (RDP) has emerged as a safe, feasible and effective approach for distal pancreatectomy. Most studies have shown that RDP improved perioperative surgical outcomes and has equivalent oncologic outcomes to open technique. Widespread adoption is limited by a steep learning curve, higher costs and the need for institutional training protocols in place for safe integration of the platform into practice.

A positive microscopic margin (R1) following resection of pancreatic ductal adenocarcinoma (PDAC) can occur in up to 80% of patients and is associated with reduced survival and increased recurrence. Our aim was to characterize the impact of neoadjuvant therapy (NAT) on survival and recurrence in patients with PDAC following an R1 resection. A retrospective analysis of patients with PDAC who underwent pancreatectomy from 2008 to 2017 was performed. Patients were staged according to the American Joint Committee on Cancer 8th edition and stratified based on resection margin (R0 vs. R1) and treatment sequence (NAT vs. surgery first [SF]). Conditional survival analysis was performed using Cox regression and inverse probability weighted estimates. Among 580 patients, 59% received NAT and 41% underwent SF. On final pathology, the NAT cohort had smaller tumors and less lymph node (LN) positivity (p

Background Inguinal hernia repair is the most common general surgery procedure and can be performed under local or general anesthesia. We hypothesized that using local rather than general anesthesia would improve outcomes, especially for older adults. Methods This is a retrospective review of 97,437 patients in the Veterans Affairs Surgical Quality Improvement Program who had open inguinal hernia surgery under local or general anesthesia. Outcomes included 30-day postoperative complications, operative time, and recovery time. Results Our cohort included 22,333 (23%) Veterans who received local and 75,104 (77%) who received general anesthesia. Mean age was 62 years. Local anesthesia was associated with a 37% decrease in the odds of postoperative complications (95% CI 0.54–0.73), a 13% decrease in operative time (95% CI 17.5–7.5), and a 27% shorter recovery room stay (95% CI 27.5–25.5), regardless of age. Conclusions Using local rather than general anesthesia is associated with a profound decrease in complications (equivalent to “de-aging” patients by 30 years) and could significantly reduce costs for this common procedure.

PURPOSE: To implement a mastery-based robotic surgery curriculum using virtual reality (VR) and inanimate reality (IR) drills at multiple Complex General Surgical Oncology (CGSO) fellowships. METHODS: A prospective study of curriculum feasibility and efficacy was conducted at four CGSO fellowship sites. All sites had simulators, and kits were provided to perform 19 biotissue drills. Fellows from three non-UPMC sites (n=15) in 2016–2018 were compared to fellows from University of Pittsburgh (UPMC; n=15) where the curriculum was validated in 2014–2018. RESULTS: All fellows completed the pre- and post-test. There was no difference in pre-test scores between UPMC and non-UPMC sites. Only 7 of 15 non-UPMC fellows completed the VR curriculum (47% compliance) compared to all 15 UPMC fellows completing the VR curriculum (100% compliance). UPMC had higher curriculum times (217 vs 93 mins) and % mastery (86 vs. 55%). Time spent on curriculum was associated with % mastery (p=0.01). Both groups showed improvement between pre- and post-test. Post-test VR scores trended higher for UPMC (221 vs 180). Between the non-UPMC sites, there was a difference in compliance (p=0.03) and % mastery (p=0.03). Zero non-UPMC fellows performed the biotissue drills, while 5 contemporary UPMC fellows completed 253 biotissue drills. Approximately 140 UPMC faculty and 300 staff hours were spent on the pilot. CONCLUSIONS: A proficiency curriculum can result in improved robotic console skills. However multiple barriers to implementation potentially exist, including availability of simulators, availability of a training robot, on-site support staff, and universal buy-in from fellows, faculty, and leadership.

Prolonged operative duration is an independent risk factor for postoperative complications in many orthopedic procedures ranging from shoulder arthroscopy to total hip and knee arthroplasties. It has not been well studied in unicompartmental knee arthroplasty (UKA). The purpose of this study is to assess the effect of operative duration on complications after UKA.Using the American College of Surgeons National Surgical Quality Improvement Program registry, we identified all primary unilateral UKAs from 2005 to 18. Patients were divided into three cohorts based on the operative duration:90 minutes, between 90 and 120 minutes, and120 minutes. Baseline patient and operative demographics (age, gender, etc.) and thirty-day complications were compared using bivariate analysis. Multivariate analysis was used to assess the independent effect of operative duration on postoperative outcomes after adjusting for differences in baseline characteristics.We identified 11,806 patients who underwent primary UKA from 2005 to 18. There was no difference in the "any complication" rate between cohorts. However, operative duration120 minutes was associated with a significantly higher likelihood of reoperation (odds ratio [OR] 2.02, 95% confidence interval [CI]: 1.15-3.57, P = .015), non-home discharge (OR: 2.14, CI: 1.65-2.77, P.001), surgical site infection (OR: 1.76, CI: 1.03-3.01, P = .038), and blood transfusions (OR: 3.23, CI: 1.44-7.22, P = .004) when compared with operative duration90 minutes. There was no difference in mortality rates.Increased operative duration greater than 2 hours in primary UKA is associated with an increased risk of non-home discharge, surgical site infection, reoperation, and blood transfusion.

Performance of technically complex surgery at high-volume (HV) centers is associated with improved outcomes. The aim of this study was to assess whether hospital gastrectomy volume is associated with surgical outcomes, and what threshold of case volume meaningfully impacts surgical outcomes. We conducted a retrospective review of adult NCDB patients with gastric adenocarcinoma undergoing gastrectomy between 2004 and 2015. A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital gastrectomy volume and overall survival. Bootstrap simulation was used to estimate the cut-point corresponding to maximum change in log hazard ratio. Hospitals were divided into HV (≥ 17 cases/year) and low-volume (LV

Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon’s timelines were performed. 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3–5 cases per surgeon were needed to optimize operative metrics. LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.

AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors’ pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p

Accurate clinical staging (CS) of gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly imprecise. Our study evaluates factors associated with inaccurate CS, the impact of inaccurate CS on outcomes, and utilization of adjuvant therapy in patients who are understaged. We conducted a retrospective review of NCDB patients diagnosed with clinical early stage gastric adenocarcinoma (cT1-2N0M0) between 2004 and 2016. Patients not undergoing upfront gastrectomy or with missing pathologic staging were excluded. Patients were classified as accurately staged, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS−). Logistic regression was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan–Meier and Cox proportional hazard methods were used for survival analysis. Approximately 40% of patients were inaccurately staged (IS). cT2, moderately/poorly differentiated, and site-overlapping tumors were associated with increased likelihood of being IS. Treatment at an academic facility was associated with decreased likelihood of understaging. Only 54% of patients who were IS received adjuvant therapy. Accurate CS of gastric cancer remains inadequate. Understaging is associated with detrimental effects on receiving guideline-concordant care and, possibly, patient outcomes. Targeted interventions reducing the proportion of understaged patients and ensuring receipt of appropriate therapy is needed to optimize outcomes. Patients with high-risk disease that are frequently understaged may benefit from selective neoadjuvant therapy. Centralization of gastric cancer care may also be a key strategy in improving receipt of guideline-concordant therapies.

Background Cholangitis due to anastomotic stricture of the hepaticojejunostomy (HJ) following pancreaticoduodenectomy (PD), while uncommon, adversely affects postoperative quality-of-life. While prior studies have identified patient-related risk factors for these biliary complications, technical risk factors have not been systematically examined. Video review of surgical procedures has helped define technical details predictive of postoperative complications in bariatric and hepato-pancreato-biliary (HPB) surgery. Similarly, the present study utilized video review to identify technical factors associated with cholangitis and anastomotic biliary stricture following robotic PD. Methods This was an observational study. A blinded experienced HPB surgeon reviewed videos of post-learning-curve HJs performed during robotic PD and extracted 20 technical variables. Other demographic and clinical variables were collected from a prospectively maintained database. Results 241 robotic PD videos were reviewed. 29 (12.0%) developed cholangitis and/or biliary stricture, with a median time-to-event of 189 (IQR 78–365) days. Several clinical and technical factors were independently predictive of cholangitis and/or biliary stricture: preoperative radiotherapy, small duct size ( 10 mm) from the hilar plate, and continuous suturing technique. Conclusion Post-hoc video review of HJ is a powerful method to predict biliary complications. Moreover, altering specific technical factors might enable surgeons to improve postoperative outcomes.

OBJECTIVEThe objective of this study was to measure the concentration of nimodipine in CSF and plasma after intraventricular injection of a sustained-release formulation of nimodipine (EG-1962) in patients with aneurysmal subarachnoid hemorrhage (SAH).METHODSPatients with SAH repaired by clip placement or coil embolization were randomized to EG-1962 or oral nimodipine. Patients were classified as grade 2–4 on the World Federation of Neurosurgical Societies grading scale for SAH and had an external ventricular drain inserted as part of their standard of care. Cohorts of 12 patients received 100–1200 mg of EG-1962 as a single intraventricular injection (9 per cohort) or they remained on oral nimodipine (3 per cohort). Plasma and CSF were collected from each patient for measurement of nimodipine concentrations and calculation of maximum plasma and CSF concentration, area under the concentration-time curve from day 0 to 14, and steady-state concentration.RESULTSFifty-four patients in North America were randomized to EG-1962 and 18 to oral nimodipine. Plasma concentrations increased with escalating doses of EG-1962, remained stable for 14 to 21 days, and were detectable at day 30. Plasma concentrations in the oral nimodipine group were more variable than for EG-1962 and were approximately equal to those occurring at the EG-1962 800-mg dose. CSF concentrations of nimodipine in the EG-1962 groups were 2–3 orders of magnitude higher than in the oral nimodipine group, in which nimodipine was only detected at low concentrations in 10% (21/213) of samples. In the EG-1962 groups, CSF nimodipine concentrations were 1000 times higher than plasma concentrations.CONCLUSIONSPlasma concentrations of nimodipine similar to those achieved with oral nimodipine and lasting for 21 days could be achieved after a single intraventricular injection of EG-1962. The CSF concentrations from EG-1962, however, were at least 2 orders of magnitude higher than those with oral nimodipine. These results supported a phase 3 study that demonstrated a favorable safety profile for EG-1962 but yielded inconclusive efficacy results due to notable differences in clinical outcome based on baseline disease severity.Clinical trial registration no.: NCT01893190 (ClinicalTrials.gov).

BACKGROUND. Neoadjuvant therapy is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC). It is unknown whether neoadjuvant chemoradiotherapy is more effective than chemotherapy (NCRT vs. NAC). We aim to compare pathological and survival outcomes of NCRT and NAC in patients with PDAC. PATIENTS AND METHODS. Single-center analysis of PDAC patients treated with NCRT or NAC followed by resection between December 2008 and December 2018 was performed. Average treatment effect (ATE) was estimated after case–control matching using Mahalanobis distance nearest-neighbor matching. Inverse probability weighted estimates (IPWE)-based ATE was estimated for disease-free survival (DFS) and overall survival (OS). RESULTS. Among the 418 patients (mean age 66.8 years, 51% female) included in the study, 327 received NAC and 91 received NCRT. NCRT patients had higher rates of locally advanced disease, number of neoadjuvant chemotherapy cycles, more chemotherapy regimen crossover (gemcitabine and 5-FU based), and were more likely to undergo open surgical procedures and/or vascular resection (all p < 0.05). After matched analysis, NCRT was associated with a significant reduction in lymph node positive disease [ATE = (−)0.24, p = 0.007] and lymphovascular invasion [ATE = (−)0.20, p = 0.02]. While NCRT was associated with significantly improved DFS by 9.5 months (p = 0.006), it did not affect OS by IPWE-based ATE after adjusting for adjuvant therapy (ATE = 5.5 months; p = 0.32). CONCLUSION. Compared with NAC alone, NCRT is associated with improved pathologic surrogates and disease-free survival, but not overall survival in patients with PDAC.

OBJECTIVE To evaluate the significance of UDD in IPMNs. BACKGROUND The uncinate process of the pancreas has an independent ductal drainage system. International consensus guidelines of IPMNs still consider it as a branch-duct, even though it is the main drainage system for the uncinate process. METHODS A retrospective review of all surgically treated IPMNs at our institution after 2008 was performed. Preoperative radiological studies were reviewed by an abdominal radiologist who was blinded to the pathological results. In addition to the Fukuoka criteria, presence of UDD was recorded. Using multivariate analysis, the pathological significance of UDD in predicting advanced neoplasia [high grade dysplasia or invasive carcinoma (HGD/IC)] was determined. RESULTS Two hundred sixty patients were identified (mean age at diagnosis was 68 years and 49% were females): 122 (47%) had HGD/IC. UDD was noted in 59 (23%), of which 36 (61%) had HGD/IC (P < 0.003). On multivariate analysis, UDD was an independent predictor of HGD/IC (odds ratio = 2.99, P < 0.04). Subgroup analysis on patients with IPMNs confined to the dorsal portion of the gland (n = 161), also demonstrated UDD to be a significant predictor of HGD/IC in those remote lesions (odds ratio: 4.41, P = 0.039). CONCLUSIONS This is the largest study to evaluate the significance of UDD in IPMNs and shows it to be a high-risk feature. This association persisted for remote IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive phenotype even in remote IPMN lesions.

Introduction The learning curve associated with robotic pancreatoduodenectomy (RPD) is a hurdle for new programs to achieve optimal results. Since early analysis, robotic training has recently expanded, and the RPD approach has been refined. The purpose of this study is to examine RPD outcomes for surgeons who implemented a new program after receiving formal RPD training to determine if such training reduces the learning curve. Methods Outcomes for consecutive patients undergoing RPD at a single tertiary institution were compared to optimal RPD benchmarks from a previously reported learning curve analysis. Two surgical oncologists with formal RPD training performed all operations with one surgeon as bedside assistant and the other at the console. Results Forty consecutive RPD operations were evaluated. Mean operative time was 354 ± 54 min, and blood loss was 300 ml. Length of stay was 7 days. Three patients (7.5%) underwent conversion to open. Pancreatic fistula affected five patients (12.5%). Operative time was stable over the study and lower than the reported benchmark. These RPD operative outcomes were similar to reported surgeon outcomes after the learning curve. Conclusion This study suggests formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing or eliminating the learning curve.

Gastric cancer is an aggressive solid-tumor malignancy with poor prognosis. The epidemiologic face of gastric cancer is changing and further insight into its heterogenous immunohistopathologic nature is needed to develop personalized therapies for specific patient populations. In this review, we highlight changes in gastric cancer epidemiology with a special emphasis on racial and ethnic variations and discuss the implications of current clinical and preclinical treatment advances.

BACKGROUND When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC. METHODS Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression. RESULTS Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P

A paucity of data exists regarding adenosquamous carcinoma of the gallbladder, a histology comprising under 10% of gallbladder cancer diagnoses. The aim of this study is to characterize the clinicopathological features of these tumors utilizing a population-based dataset compared with gallbladder adenocarcinoma. We identified patients with gallbladder adenosquamous and adenocarcinoma from the National Cancer Database from 2004 to 2015. Patient demographics, tumor characteristics, treatment regimens, and overall survival were analyzed between the groups. We identified 13,158 patients: 12,455 (95%) with a diagnosis of gallbladder adenocarcinoma and 703 (5%) with adenosquamous carcinoma. Adenosquamous tumors were larger, poorly differentiated, and presented with Stage III/IV disease (75% vs 69%, p

OBJECTIVE Normothermic machine perfusion (NMP) enables optimized ex-vivo preservation of a donor liver in a normal physiologic state. The impact of this emerging technology on donor liver utilization has yet to be assessed. SUMMARY BACKGROUND DATA NMP of the donor liver and ex-vivo enhancement of its function has been envisioned for decades, however only with recent technological advances have devices been suitable for transition to clinical practice. The present study examines the effect NMP on liver utilization in the United States. METHODS The United Network for Organ Sharing database was queried to identify deceased donor livers procured from 2016 to 2019 (n = 30596). Donor livers were divided by preservation method: standard cold-static preservation (COLD, n = 30,368) versus NMP (n = 228). Donor and recipient risk factors, liver disposition, and discard reasons were analyzed. The primary outcome was liver discard rate between 2 groups. RESULTS A total of 4037 livers were discarded. The NMP group had a 3.5% discard rate versus 13.3% in the COLD group (P < 0.001), and this was despite NMP donors being older (47.7 vs 39.5 years, P < 0.0001), more frequently donation after cardiac death (DCD) (18% vs 7%, P < 0.001), and having a greater donor risk index (1.6 vs 1.5, P < 0.05). The most common reasons for liver discard in the COLD group were biopsy findings (38%), DCD warm ischemic time (11%), and prolonged preservation time (10%). Survival analysis, following propensity score matching, found no significant difference in 1-year overall survival between recipients of NMP versus COLD livers. CONCLUSIONS NMP reduces the discard rate of procured livers despite its use in donors traditionally considered of more marginal quality. NMP maintains excellent graft and patient survival. Broader application of NMP technology holds the potential to generate a significant number of additional liver grafts for transplantation every year, thus greatly reducing the nationwide disparity between supply and demand.

Pancreatoduodenectomy (PD) is often performed in frail patients and is associated with significant morbidity. The five-factor modified frailty index (mFI-5) has been utilized to predict adverse postoperative outcomes, but has not been tested in PD. We aimed to develop risk tools to generate and predict 30-day outcomes after PD and compare their performance with the mFI-5. Risk tools were then used to generate a PD-specific calculator. Elective PDs from the 2014–2016 ACS NSQIP® Procedure Targeted Pancreatectomy PUFs were identified. Multivariable logistic regression models were constructed to predict postoperative mortality, any complication, serious complication, clinically relevant postoperative pancreatic fistula (CR-POPF), and discharge not-to-home. Predictive accuracy was evaluated through repeated stratified tenfold cross-validation and compared to the mFI-5. Nine thousand eight hundred sixty-seven PDs were captured. Nine risk factors were retained: sex, age, BMI, DM, HTN, ASA classification, pancreatic duct size, gland texture, and adenocarcinoma. Cross-validated C-indices ranged from 0.49 to 0.61 for the mFI-5 and 0.63 to 0.75 for our risk models. The best-performing model was for discharge not-to-home (C = 0.75), and the model delivering the largest increase in predictive accuracy was for CR-POPF (CmFI-5/Model = 0.49/0.70). A user-friendly risk calculator was created predicting the five outcomes of interest. We have created a PD-specific risk calculator that outperforms the mFI-5. This calculator may serve as a useful adjunct in shared decision-making for patients and surgeons.

Background and Purpose— EG-1962 is a sustained release formulation of nimodipine administered via external ventricular drain in patients with aneurysmal subarachnoid hemorrhage. A randomized, open-label, phase 1/2a, dose-escalation study provided impetus for this study to evaluate efficacy and safety of a single intraventricular 600 mg dose of EG-1962 to patients with aneurysmal subarachnoid hemorrhage, compared with standard of care oral nimodipine. Methods— Subjects were World Federation of Neurological Surgeons grades 2–4, modified Fisher grades 2–4 and had an external ventricular drain inserted as part of standard of care. The primary end point was the proportion of subjects with favorable outcome at day 90 after aneurysmal subarachnoid hemorrhage (extended Glasgow outcome scale 6–8). The proportion of subjects with favorable outcome at day 90 on the Montreal cognitive assessment, as well as the incidence of delayed cerebral ischemia and infarction, use of rescue therapy and safety were evaluated. Results— The study was halted by the independent data monitoring board after planned interim analysis of 210 subjects (289 randomized) with day 90 outcome found the study was unlikely to achieve its primary end point. After day 90 follow-up of all subjects, the proportion with favorable outcome on the extended Glasgow outcome scale was 45% (65/144) in the EG-1962 and 42% (62/145) in the placebo group (risk ratio, 1.01 [95% CI, 0.83–1.22], P =0.95). Consistent with its mechanism of action, EG-1962 significantly reduced vasospasm (50% [69/138] EG-1962 versus 63% [91/144], P =0.025) and hypotension (7% [9/138] versus 10% [14/144]). Analysis of prespecified subject strata suggested potential efficacy in World Federation of Neurological Surgeons 3–4 subjects (46% [32/69] EG-1962 versus 32% [24/75] placebo, odds ratio, 1.22 [95% CI, 0.94–1.58], P =0.13). No safety concerns were identified that halted the study or that preclude further development. Conclusions— There was no significant increase in favorable outcome for EG-1962 compared with standard of care in the overall study population. The safety profile was acceptable. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02790632.

Neoadjuvant therapy (NT) is a growing strategy in localized head pancreatic adenocarcinoma (PDC). However, a significant portion of NT patients do not reach resection due to disease progression or performance status decline. We sought to identify predictors of disease progression or performance status decline during NT. Retrospective cohort analysis of consecutive patients with localized head-PDC who received NT at a tertiary referral center between 2005 and 2017. Univariate and multivariate (MVA) analysis were performed to identify factors associated with disease progression or performance status decline during NT preventing surgical resection. A total of 479 patients with PDC underwent NT; 71.2% proceeded to surgery, 20.5% had disease progression, and 8.3% experienced performance status decline. Median OS was 28 [95% confidence interval (CI) 23.8–32.3], 12.8 (CI 11.2–14.3), and 6.9 (CI 5.2–9.4) months, respectively (p

Over the last two decades, there have been significant changes in the management of patients with localized pancreatic cancer. The rationale for an evolution toward a neoadjuvant approach and summary of relevant clinical trials is reviewed. Controversies in identifying optimal neoadjuvant therapeutic approaches are discussed.

INTRODUCTION: Optimal cut-offs for CA19-9 response after neoadjuvant therapy (NT) for pancreatic adenocarcinoma (PDAC) are not well characterized. This study aims to analyze the relationship of serum CA19-9 with other markers of response and identify thresholds correlating to outcomes. METHODS: Retrospective review of resected PDAC patients from 2010 to 2017 at an academic tertiary referral center. RESULTS: Two hundred and fifty subjects entered the analysis. Normalization and multiple cut-off points for CA19-9 response were assessed. Normalization was not associated with improved survival (35.17 vs 29.43 months; p=0.173). While a response ≥45% was associated with longer survival (35 vs 20 months; p=0.018), a response ≥85% was optimal (55.7 vs 25.97 months; p

This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.

OBJECTIVES: This study aims to present the outcomes of our decade-long experience of robotic pancreatoduodenectomy and provide insights into successful program implementation. BACKGROUND: Despite significant improvement inmortality over the past 30 years, morbidity following open pancreatoduodenectomy remains high. Weimplemented a minimally invasive pancreatic surgery program based on the robotic platform as one potential method of improving outcomes for this operation. METHODS: A retrospective review of a prospectively maintained institutional database was performed to identify patients who underwent robotic pancreatoduodenectomy (RPD) between 2008 and 2017 at the University of Pittsburgh. RESULTS: In total, 500 consecutive RPDs were included. Operative time, conversion to open, blood loss, and clinically relevant postoperative pancreatic fistula improved early in the experience and have remained low despite increasing complexity of case selection as reflected by increasing number of patients with pancreatic cancer, vascular resections, and higher Charlson Comorbidity scores (all P2) occurred in less than 24%, clinically relevant postoperative pancreatic fistula in 7.8%, 30- and 90-day mortality were 1.4% and 3.1% respectively, and median length of stay was 8 days. Outcomes were not impacted by integration of trainees or expansion of selection criteria. CONCLUSIONS: Structure dimple mentation of robotic pancreatoduodenectomy can be associated with excellent outcomes. In the largest series of RPD, we establish benchmarks for the surgical community to consider when adopting this approach.

Background: Adjuvant therapy for resected pancreatic adenocarcinoma was given a category 1 NCCN recommendation in 2000, yet many patients do not receive chemotherapy after definitive surgery. Whether sociodemographic disparities exist for receipt of adjuvant chemotherapy is poorly understood. Methods: The National Cancer Database was used to identify patients diagnosed with nonmetastatic pancreatic adenocarcinoma who underwent definitive surgery from 2004 through 2015. Multivariable logistic regression defined the adjusted odds ratio (aOR) and associated 95% CI of receipt of adjuvant chemotherapy. Among patients receiving chemotherapy, multivariable logistic regression assessed the odds of treatment with multiagent chemotherapy. Results: Among 18,463 patients, 11,288 (61.1%) received any adjuvant chemotherapy. Sociodemographic factors inversely associated with receipt of any adjuvant chemotherapy included uninsured status (aOR, 0.61; 95% CI, 0.50–0.74), Medicaid insurance (aOR, 0.66; 95% CI, 0.57–0.77), and lower income (PP=.03), such that 26.4% of black versus 35.8% of nonblack young (aged ≤65 years) and healthy (Charlson-Deyo comorbidity score 0) patients received multiagent adjuvant chemotherapy (P=.006), whereas multiagent adjuvant chemotherapy rates were similar among patients who were not young and healthy (P=.15). Conclusions: In this nationally representative study, receipt of adjuvant chemotherapy appeared to be associated with sociodemographic characteristics, independent of clinical factors. Sociodemographic differences in receipt of adjuvant chemotherapy may represent a missed opportunity for improving outcomes and a driver of oncologic disparities.

Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in the pancreatic cancer microenvironment. Here, we show that neoplastic pancreatic epithelium, as well as a subset of tissue-resident macrophages, expresses the prolactin-receptor (PRLR). High mobility group box 1–induced prolactin expression in the pancreas maintained FAK1 and STAT3 phosphorylation within the epithelium and stroma. Gain-of-function and loss-of-function experiments demonstrated the essential role of prolactin in promoting collagen deposition and fibrosis. Finally, the signaling cascade downstream of prolactin/PRLR activated STAT3 rather than STAT5 in PDAC. These findings suggest that targeting prolactin together with IL6, a known major activator of STAT3, could represent a novel therapeutic strategy for treating pancreatic cancer. Significance: Prolactin is a key factor in the cross-talk between the stroma and neoplastic epithelium, functioning to promote fibrosis and PDAC progression.

Conjugated linolenic acids (CLnAs) are natural phytochemicals with known and potential bioactivities in mammals. Established CLnA sources are limited to a few common fruit seeds, notably pomegranate seeds and cherry pits, and the search for alternatives is impeded in part by cumbersome methods for reliable measurement. We investigated CLnA contents in lower value fruit seeds with a recently available facile mass spectrometry method, solvent-mediated chemical ionization, enabling and quantitative analysis. We report for the first time the detection of CLnAs in cantaloupe and honeydew seeds at levels of 2 mg CLnA/g seed kernel. Based on the combined waste stream for these muskmelons of about 1.4 billion pounds in the USA annually, we estimate that the available CLnAs amount to 37.5 tons, similar to cherry pits. Our results suggest the potentially enhanced economic value of a specific class of bioactives that may be extracted from discarded food processing waste.

Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD) is a major complication that adversely affects recovery. The robotic approach may decrease the incidence of this complication. This propensity-matched analysis evaluates the impact of robotic PD (RPD) on CR-POPF. Patients undergoing PD after the learning curve at a high-volume academic medical center were reviewed. CR-POPF outcomes after open PD (OPD) and RPD were compared. Logistic regression and propensity score matching (PSM) were used to define the independent effect of RPD on CR-POPF. Of 865 PDs performed over the study period, 405 (46.8%) were OPD and 460 (53.2%) were RPD. RPD was associated with a similar overall POPF rate, but a lower incidence of CR-POPF (6.7% vs. 15.8%, p

Pringle maneuver (PM) is used for inflow vascular control during hepatectomy, but its use remains controversial. We aimed to report its pattern of use and association with postoperative outcomes.We identified hepatectomy patients using the liver-targeted National Surgical Quality Improvement Program database (2014-2016). Associations between PM and posthepatectomy liver failure (PHLF), receipt of blood transfusion, and total hospital length of stay (LOS) were evaluated.We identified 7870 patients (74.9%) with no Pringle maneuver and 2632 (25.1%) with PM. PM patients were older (median age 61 versus 60 y, P = 0.002) and had higher ASA scores (76.1% versus 71.4% were ASA 3-4, P 0.001). PM had more malignancy (83.0% versus 73.0%, P 0.001), neoadjuvant therapy (37.7% versus 28.8%, P 0.001), total lobectomy (30.6% versus 23.2%, P 0.001), open resection (90.8% versus 74.9%, P 0.001), and longer operations (246 min versus 212 min, P 0.001). PM was associated with longer LOS (0.36 d, 95% confidence interval [CI] 0.11-0.60) and increased risk of PHLF (odds ratio [OR] 1.36, 95% CI 1.11-1.66), although not clinically significant grade B/C PHLF (OR 0.82, 95% CI 0.57-1.19), but was not associated with receipt of perioperative blood transfusions (OR 1.00, 95% CI 0.69-1.64).PM is associated with similar clinically significant PHLF and transfusion requirements but longer LOS compared with no Pringle maneuver.

We sought to investigate whether robotic pancreatoduodenectomy (RPD) mitigates adverse outcomes in patients with high-risk morphometric features compared to the open approach (OPD).Morphometric parameters for RPD and OPDs were measured by two blinded radiologists. The morphometric parameter best correlating with adverse outcomes was identified and used in multivariable models to evaluate the impact of surgical approach (open vs. robotic) on outcomes of patients with high-risk morphometric features.Of 282 PDs available for morphometric analysis, 134 (47.5%) underwent RPD. Average Psoas Density demonstrated the most frequent association with adverse outcomes, with correlations to prolonged LOS (ρ= -0.154, p=0.01), severe complications (ρ= -0.159, p=0.007), readmission (ρ= -0.16, p=0.007), and discharge to home (ρ= 0.2, p0.001). On multivariable analysis of patients with high-risk morphometric features (defined as APD ≤ 50This study confirms the association between morphometrics and outcomes following PD, and suggests that the robotic approach may be associated with improved outcomes in PD patients with high-risk morphometric features.

Platelets are activated in solid cancers, including pancreatic ductal adenocarcinoma (PDA), a highly aggressive malignancy with a devastating prognosis and limited therapeutic options. The mechanisms by which activated platelets regulate tumor progression are poorly understood. The nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) inflammasome is a key inflammatory mechanism recently identified in platelets, which controls platelet activation and aggregation. In an orthotopic PDA mouse model involving surgical implantation of Panc02 murine cancer cells into the tail of the pancreas, we show that the NLRP3 inflammasome in circulating platelets is upregulated in pancreatic cancer. Pharmacological inhibition or genetic ablation of NLRP3 in platelets resulted in decreased platelet activation, platelet aggregation, and tumor progression. Moreover, interfering with platelet NLRP3 signaling significantly improved survival of tumor-bearing mice. Hence, the platelet NLRP3 inflammasome plays a critical role in PDA and might represent a novel therapeutic target.

ObjectiveDespite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens.DesignWe prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens.ResultsThe sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients withERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response.ConclusionsThe combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.

BACKGROUND AND OBJECTIVES The clinical presentation of gastric cancer varies between racial and ethnic groups. While historically studied as a monolithic population, the Hispanic ethnicity is comprised of heterogenous groups with considerable biologic, socioeconomic, and cultural variability; therefore, intragroup differences among Hispanic gastric cancer patients may have been overlooked in past research. METHODS We conducted a retrospective review of the National Cancer Database (NCDB) to compare Hispanic patients with gastric adenocarcinoma diagnosed between 2004 and 2015, by NCDB-reported location of patient ancestry. RESULTS We identified a cohort of 3811 patients. There were higher proportions of females, patients with early disease onset, and stage 4 disease among patients of Mexican and South/Central American ancestry. Additionally, a significantly larger proportion of Mexican (15%) and South/Central American patients (11%) were diagnosed before age 40, in contrast to Cubans (2%), Dominicans (6%), and Puerto Ricans (3%; p

Background Antibiotic treatment decisions in severely ill patients must often be made in the absence of microbiologic results. The recently Food and Drug Administration–cleared BioFire FilmArray Pneumonia Panel (PN) detects 15 bacteria semiquantitatively, 3 atypical pneumonia bacteria, 8 viruses, and 7 antimicrobial resistance markers by multiplex PCR in ~1 hour in the laboratory. Previous reports have shown that the PN Panel bacterial detections are highly accurate, even when routine culture had no growth. Methods Consecutive bronchoalveolar lavage and endotracheal specimens submitted for culture between June and September 2018 from 270 patients with sufficient clinical and laboratory data were tested with the PN Panel. Patients were divided into 3 groups: (1) both culture and PN Panel positive, (2) PN Panel positive but culture uninformative (no growth or normal flora), and (3) patients with no PN Panel detections. Results Groups 1 and 2 had significantly higher maximum temperatures on the day of culture (P = .00036, analysis of variance [ANOVA] with Bonferroni correction), higher levels of an inflammatory response as measured by percent polymorphonuclear leukocytes in bronchoalveolar lavage (P = .00025, ANOVA with Bonferroni correction), and gram stain report of white blood cells, as previously reported [1]. Conclusions Both group 1 (culture and PN Panel positive), and group 2 (PN Panel positive but culture uninformative) had higher levels of host response inflammatory responses compared with group 3, which had no targets detected, suggesting that PN Panel detections need to be interpreted in the clinical context, even if cultures are discordant. Depending on laboratory turnaround time, there could be opportunities for improved diagnosis and antibiotic stewardship.

BACKGROUND: Many studies have identified racial disparities in healthcare, but few have described disparities in the use of anesthesia modalities. We examined racial disparities in the use of local versus general anesthesia for inguinal hernia repair. We hypothesized that African American and Hispanic patients would be less likely than Caucasians to receive local anesthesia for inguinal hernia repair. MATERIALS AND METHODS: We included 78,766 patients aged ≥18 years in the Veterans Affairs Surgical Quality Improvement Program database who underwent elective, unilateral, open inguinal hernia repair under general or local anesthesia from 1998–2018. We used multiple logistic regression to compare use of local versus general anesthesia and 30-day postoperative complications by race/ethnicity. RESULTS: In total, 17,892 (23%) patients received local anesthesia. Caucasian patients more frequently received local anesthesia (15,009; 24%), compared to African Americans (2353; 17%) and Hispanics (530; 19%), p < 0.05. After adjusting for covariates, we found that African Americans (OR 0.82, 95% CI 0.77–0.86) and Hispanics (OR 0.77, 95% CI 0.69–0.87) were significantly less likely to have hernia surgery under local anesthesia compared to Caucasians. Additionally, local anesthesia was associated with fewer postoperative complications for African American patients (OR 0.46, 95% CI 0.27–0.77). CONCLUSIONS: Although local anesthesia was associated with enhanced recovery for African American patients, they were less likely to have inguinal hernias repaired under local than Caucasians. Addressing this disparity requires a better understanding of how surgeons, anesthesiologists, and patient-related factors may affect the choice of anesthesia modality for hernia repair.

BACKGROUND: Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. OBJECTIVE: To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. METHODS: In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. RESULTS: After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. CONCLUSIONS: Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.

Background Cancer treatments can cause a variety of symptoms that impair quality of life and functioning but are frequently missed by clinicians. Smartphone and wearable sensors may capture behavioral and physiological changes indicative of symptom burden, enabling passive and remote real-time monitoring of fluctuating symptoms Objective The aim of this study was to examine whether smartphone and Fitbit data could be used to estimate daily symptom burden before and after pancreatic surgery. Methods A total of 44 patients scheduled for pancreatic surgery participated in this prospective longitudinal study and provided sufficient sensor and self-reported symptom data for analyses. Participants collected smartphone sensor and Fitbit data and completed daily symptom ratings starting at least two weeks before surgery, throughout their inpatient recovery, and for up to 60 days after postoperative discharge. Day-level behavioral features reflecting mobility and activity patterns, sleep, screen time, heart rate, and communication were extracted from raw smartphone and Fitbit data and used to classify the next day as high or low symptom burden, adjusted for each individual’s typical level of reported symptoms. In addition to the overall symptom burden, we examined pain, fatigue, and diarrhea specifically. Results Models using light gradient boosting machine (LightGBM) were able to correctly predict whether the next day would be a high symptom day with 73.5% accuracy, surpassing baseline models. The most important sensor features for discriminating high symptom days were related to physical activity bouts, sleep, heart rate, and location. LightGBM models predicting next-day diarrhea (79.0% accuracy), fatigue (75.8% accuracy), and pain (79.6% accuracy) performed similarly. Conclusions Results suggest that digital biomarkers may be useful in predicting patient-reported symptom burden before and after cancer surgery. Although model performance in this small sample may not be adequate for clinical implementation, findings support the feasibility of collecting mobile sensor data from older patients who are acutely ill as well as the potential clinical value of mobile sensing for passive monitoring of patients with cancer and suggest that data from devices that many patients already own and use may be useful in detecting worsening perioperative symptoms and triggering just-in-time symptom management interventions.

A virtual reality (VR) curriculum performed on the da Vinci Simulation System (DVSS) was previously shown to be effective in training fellows. The dV-Trainer is a separate platform with similar features to the da Vinci console, but its efficacy and utility versus the DVSS simulator are not well known.A mastery-based VR curriculum was completed by surgical fellows on the DVSS (2014-2016) and on the dV-Trainer (2016-2018) at a large academic center. Pre-test/post-test scores were used to evaluate performance between the two groups. Data was collected prospectively.Forty-six fellows enrolled in the curriculum: surgical oncology (n=31), hepatobiliary (n=5), head/neck (n=4), endocrine (n=2), cardiothoracic (n=2), gynecology (n=1) and transplant surgery (n=1). Twenty-four used the DVSS and twenty-two used the dV-Trainer. Compared to the DVSS, the dV-Trainer was associated with lower scores on 2 of 3 VR modules in the pre-test (P=0.027, P0.001, respectively) and post-test (P=0.021, P0.001, respectively). Fellows in the dV-Trainer era scored lower on inanimate drills as well. Average VR curriculum score was lower on the dV-Trainer (71.3% vs 83.34%, P0.001). dV-Trainer users spent more time completing the pre-test and post-test; however, overall simulator time to complete the curriculum was not significantly different (297 vs 231 minutes, P=0.142). Both groups showed improvement in scores after completion of the VR curriculum.The dV-Trainer simulator allows for more usability outside the operating room to complete VR modules; however, the DVSS simulator group outperformed the dV-Trainer group on the post-test.

Background Frailty predisposes patients to poor postoperative outcomes. We evaluated whether using local rather than general anesthesia for hernia repair could mitigate effects of frailty. Methods We used the Risk Analysis Index (RAI) to identify 8,038 frail patients in the 1998–2018 Veterans Affairs Surgical Quality Improvement Program database who underwent elective, open unilateral inguinal hernia repair under local or general anesthesia. Our outcome of interest was the incidence of postoperative complications. Results In total, 5,188 (65%) patients received general anesthesia and 2,850 (35%) received local. Local anesthesia was associated with a 48% reduction in complications (OR 0.52, 95%CI 0.38–0.72). Among the frailest patients (RAI≥70), predicted probability of a postoperative complication ranged from 22 to 33% with general anesthesia, compared to 13–21% with local. Conclusions Local anesthesia was associated with a ∼50% reduction in postoperative complications in frail Veterans. Given the paucity of interventions for frail patients, there is an urgent need for a randomized trial comparing effects of anesthesia modality on postoperative complications in this vulnerable population.