Background Although rare in the United States, gallbladder cancer (GBCA) is a common cause of cancer death in some parts of the world. To investigate regional differences in pathogenesis and outcomes for GBCA, tumor mutations were analyzed from a sampling of specimens. Methods Primary tumors from patients with GBCA who were treated in Chile, Japan, and the United States between 1999 and 2016 underwent targeted sequencing of known cancer‐associated genes. Fisher exact and Kruskal‐Wallis tests assessed differences in clinicopathologic and genetic factors. Kaplan‐Meier methods evaluated differences in overall survival from the time of surgery between mutations. Results A total of 81 patients were included. Japanese patients (11 patients) were older (median age, 72 years [range, 54‐81 years]) compared with patients from Chile (21 patients; median age, 59 years [range, 32‐73 years]) and the United States (49 patients; median age, 66 years [range, 46‐87 years]) (P = .002) and had more well‐differentiated tumors (46% vs 0% for Chile/United States; P < .001) and fewer gallstone‐associated cancers (36% vs 67% for Chile and 69% for the United States; P = .13). Japanese patients had a median mutation burden of 6 (range, 1‐23) compared with Chile (median mutation burden, 7 [range, 3‐20]) and the United States (median mutation burden, 4 [range, 0‐27]) (P = .006). Tumors from Japanese patients lacked AT‐rich interaction domain 1A (ARID1A) and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) mutations, whereas Chilean tumors lacked Erb‐B2 receptor tyrosine kinase 3 (ERBB3) and AT‐rich interaction domain 2 (ARID2) mutations. SMAD family member 4 (SMAD4) was found to be mutated similarly across centers (38% in Chile, 36% in Japan, and 27% in the United States; P = .68) and was univariately associated with worse overall survival (median, 10 months vs 25 months; P = .039). At least one potentially actionable gene was found to be altered in 80% of tumors. Conclusions Differences in clinicopathologic variables suggest the possibility of distinct GBCA pathogenesis in Japanese patients, which may be supported by differences in mutation pattern. Among all centers, SMAD4 mutations were detected in approximately one‐third of patients and may represent a converging factor associated with worse survival. The majority of patients carried mutations in actionable gene targets, which may inform the design of future trials.

Background:Non-thermal irreversible electroporation (NTIRE) has recently been conceived as a new minimally invasive ablation method, using microsecond electric fields to produce nanoscale defects in the cell membrane bilayer and induce cell death while keeping all other molecules, including the extracellular matrix, intact. Here, we present the first in vivo study that examines the effects of NTIRE on the small intestine, an organ whose collateral damage is of particular concern in the anticipated use of NTIRE for treatment of abdominal cancers.Methods:A typical NTIRE electrical protocol was applied directly to the rat small intestine and histological analysis was used to examine the effect of NTIRE over time.Results:The application of NTIRE led to complete cell ablation in the targeted tissue, but the animal did not show any physiological effects of the procedure and the intestine showed signs of recovery, developing an epithelial layer 3 days post treatment and regenerating its distinct layers within a week.Conclusion:Our results indicate that this novel procedure can be used for abdominal cancer treatment while minimising collateral damage to adjacent tissues because of the unique ability of the NTIRE ablation method to target the cell membrane.

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Segmenting cell nuclei within microscopy images is a ubiquitous task in biological research and clinical applications. Unfortunately, segmenting low-contrast overlapping objects that may be tightly packed is a major bottleneck in standard deep learning-based models. We report a Nuclear Segmentation Tool (NuSeT) based on deep learning that accurately segments nuclei across multiple types of fluorescence imaging data. Using a hybrid network consisting of U-Net and Region Proposal Networks (RPN), followed by a watershed step, we have achieved superior performance in detecting and delineating nuclear boundaries in 2D and 3D images of varying complexities. By using foreground normalization and additional training on synthetic images containing non-cellular artifacts, NuSeT improves nuclear detection and reduces false positives. NuSeT addresses common challenges in nuclear segmentation such as variability in nuclear signal and shape, limited training sample size, and sample preparation artifacts. Compared to other segmentation models, NuSeT consistently fares better in generating accurate segmentation masks and assigning boundaries for touching nuclei.

The formation of carbon-nitrogen (C-N) bonds is a fundamental bond construction in organic synthesis and is indispensable for the synthesis of alkaloid natural products. In the context of the synthesis of the architecturally complex Lycopodium alkaloid lyconadin A, we have discovered a highly efficient oxidative C-N bond forming reaction that relies on the union of a nitrogen anion and a carbon anion. Empirical evidence amassed during our synthetic studies suggests that the mechanism of the C-N bond forming process encompasses polar as well as radical processes. Herein, we present our study of this novel C-N bond forming reaction and its application to the enantioselective total synthesis of lyconadin A and related derivatives.

An aggressive approach for stage II pancreatic cancers with venous or arterial invasion can be performed with comparable results when it is executed by an experienced institution with skilled oncologic and vascular surgeons.

Background-Liver resection can be curative for well-selected metastatic colorectal cancer (CRC) patients. Circulating tumor DNA (ctDNA) has shown promise as a biomarker for tumor dynamics and recurrence following CRC resection. This prospective pilot study investigated the use of ctDNA to predict disease outcome in resected CRC patients. Methods-Between November 2014 and November 2015, 60 patients with CRC were identified and prospectively enrolled. During liver resection, blood was drawn from peripheral (PERIPH), portal (PV), and hepatic (HV) veins, and 3-4 weeks postoperatively from a peripheral vein (POSTOP). Kappa statistics were used to compare mutated (mt) genes in tissue and ctDNA. Disease-specific and disease-free survival (DSS and DFS) were assessed from surgery with Kaplan-Meier and Cox methods.

There has been a shift toward a reduced crystalloid volume and the recreation of whole blood from component products in resuscitation. These changes are associated with markedly improved outcomes and a new paradigm in the resuscitation of severely injured patients.