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BackgroundThe robotic platform in pancreatic disease has gained popularity in the hepatobiliary community due to significant advantages it technically offers over conventional open and laparoscopic techniques. Despite promising initial studies, there remains scant literature on operative and oncologic outcomes of robotic pancreaticoduodenectomy (RPD) for pancreatic adenocarcinoma.MethodsA retrospective review evaluated all RPD performed for pancreatic adenocarcinoma from 2008 to 2019 in a single tertiary institution. RPD cases were matched to open cases (OPD) by demographic and oncologic characteristics and outcomes compared using Mann–Whitney U test, log rank tests, and Kaplan–Meier methods.ResultsThirty-eight RPD cases were matched to 38 OPD. RPD had significantly higher lymph node (LN) yield (21.5 vs 13.5; p = 0.0036) and no difference in operative time or estimated blood loss (EBL). RPD had significantly lower rate of delayed gastric emptying (DGE) (3% vs 32%; p = 0.0009) but no difference in leaks, infections, hemorrhage, urinary retention ,or ileus. RPD had significantly shorter length of stay (LOS) (7.5 vs. 9; p = 0.0209). There were no differences in 30- or 90-day readmissions or 90-day mortality. There was an equivalent R0 resection rate and LN positivity ratio. There was a trend towards improved median overall survival in RPD (30.4 vs. 23.0 months; p = 0.1105) and longer time to recurrence (402 vs. 284 days; p = 0.7471). OPD had two times the local recurrent rate (16% vs. 8%) but no difference in distant recurrence.ConclusionsWhile the feasibility and safety of RPD has been demonstrated, the impact on oncologic outcomes had yet to be investigated. We demonstrate that RPD not only offers similar if not superior immediate post-operative benefit by decreasing DGE but more importantly may offer improved oncologic outcomes. The significantly higher LN yield and decreased inflammatory response demonstrated in robotic surgery may improve overall survival.

TLRs are recognized as promoters of tissue damage, even in the absence of pathogens. TLR binding to damage-associated molecular patterns (DAMPs) released by injured host cells unleashes an inflammatory cascade that amplifies tissue destruction. However, whether TLRs possess the reciprocal ability to curtail the extent of sterile inflammation is uncertain. Here, we investigated this possibility in mice by studying the role of conventional DCs (cDCs) in liver ischemia/reperfusion (I/R) injury, a model of sterile inflammation. Targeted depletion of mouse cDCs increased liver injury after I/R, as assessed by serum alanine aminotransferase and histologic analysis. In vitro, we identified hepatocyte DNA as an endogenous ligand to TLR9 that promoted cDCs to secrete IL-10. In vivo, cDC production of IL-10 required TLR9 and reduced liver injury. In addition, we found that inflammatory monocytes recruited to the liver via chemokine receptor 2 were downstream targets of cDC IL-10. IL-10 from cDCs reduced production of TNF, IL-6, and ROS by inflammatory monocytes. Our results implicate inflammatory monocytes as mediators of liver I/R injury and reveal that cDCs respond to DAMPS during sterile inflammation, providing the host with protection from progressive tissue damage.

Background Centralization of hepatopancreatobiliary procedures to more experienced centers has been recommended but remains controversial. Hospital volume and risk-stratified mortality rates (RSMR) are metrics for interhospital comparison. We compared facility operative volume with facility RSMR as a proxy for hospital quality. Patients and Methods Patients who underwent surgery for liver (LC), biliary tract (BTC), and pancreatic (PDAC) cancer were identified in the National Cancer Database (2004–2018). Hierarchical logistic regression was used to create facility-specific models for RSMR. Volume (high versus low) was determined by quintile. Performance (high versus low) was determined by RSMR tercile. Primary outcomes included median facility RSMR and RSMR distributions. Volume- and RSMR-based redistribution was simulated and compared for reductions in 90-day mortality. Results A total of 106,217 patients treated at 1282 facilities were included; 17,695 had LC, 23,075 had BTC, and 65,447 had PDAC. High-volume centers (HVC) had lower RSMR compared with medium-volume centers and low-volume centers for LC, BTC, and PDAC (all p  < 0.001). High-performance centers (HPC) had lower RSMR compared with medium-performance centers and low-performance centers for LC, BTC, and PDAC (all p  < 0.001). Volume-based redistribution required 16.0 patients for LC, 11.2 for BTC, and 14.9 for PDAC reassigned to 15, 22, and 20 centers, respectively, per life saved within each US census region. RSMR-based redistribution required 4.7 patients for LC, 4.2 for BTC, and 4.9 for PDAC reassigned to 316, 403, and 418 centers, respectively, per life saved within each US census region. Conclusions HVC and HPC have the lowest overall and risk-standardized 90-day mortality after oncologic hepatopancreatobiliary procedures, but RSMR may outperform volume as a measure of hospital quality.

ObjectivesWe used a novel combined analysis to evaluate various factors associated with failure to surgical resection in non-metastatic gastric cancer.MethodsWe identified factors associated with the receipt of surgery in publicly available clinical trial data for gastric cancer and in the National Cancer Database (NCDB) for patients with stages I–III gastric adenocarcinoma. Next, we evaluated variable importance in predicting the receipt of surgery in the NCDB.ResultsIn published clinical trial data, 10% of patients in surgery-first arms did not undergo surgery, mostly due to disease progression and 15% of patients in neoadjuvant therapy arms failed to reach surgery. Effects related to neoadjuvant administration explained the increased attrition (5%). In the NCDB, 61.7% of patients underwent definitive surgery. In a subset of NCDB patients resembling those enrolled in clinical trials (younger, healthier, and privately insured patients treated at high-volume and academic centers) the rate of surgery was 79.2%. Decreased likelihood of surgery was associated with advanced age (OR 0.97, p < 0.01), Charlson–Deyo score of 2+ (OR 0.90, p < 0.01), T4 tumors (OR 0.39, p < 0.01), N+ disease (OR 0.84, p < 0.01), low socioeconomic status (OR 0.86, p = 0.01), uninsured or on Medicaid (OR 0.58 and 0.69, respectively, p < 0.01), low facility volume (OR 0.64, p < 0.01), and non-academic cancer programs (OR 0.79, p < 0.01).ConclusionReview of clinical trials shows attrition due to unavoidable tumor and treatment factors (~ 15%). The NCDB indicates non-medical patient and provider characteristics (i.e., age, insurance status, facility volume) associated with attrition. This combined analysis highlights specific opportunities for improving potentially curative surgery rates.

Imatinib has been proposed as a therapy for gastrointestinal stromal tumors, owing to its side effects on KIT, a kinase often mutated in this type of tumor. This report shows that a key aspect of imatinib's effect is its modulation of antitumor immune responses by a mechanism regulating Ido expression. Combining imatinib with CTLA-4 blockade emerges as a potential efficacious therapeutic approach for gastrointestinal stromal tumors. Imatinib mesylate targets mutated KIT oncoproteins in gastrointestinal stromal tumor (GIST) and produces a clinical response in 80% of patients. The mechanism is believed to depend predominantly on the inhibition of KIT-driven signals for tumor-cell survival and proliferation. Using a mouse model of spontaneous GIST, we found that the immune system contributes substantially to the antitumor effects of imatinib. Imatinib therapy activated CD8 + T cells and induced regulatory T cell (T reg cell) apoptosis within the tumor by reducing tumor-cell expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido). Concurrent immunotherapy augmented the efficacy of imatinib in mouse GIST. In freshly obtained human GIST specimens, the T cell profile correlated with imatinib sensitivity and IDO expression. Thus, T cells are crucial to the antitumor effects of imatinib in GIST, and concomitant immunotherapy may further improve outcomes in human cancers treated with targeted agents.