The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.

Mature tertiary lymphoid structures are key niches of tumour-specific immune responses in pancreatic ductal adenocarcinomas.

OBJECTIVE: To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures (TLSs) for the generation of local antitumour immunity. DESIGN: We characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial. RESULTS: We found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-ß may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expanded CXCL13 + tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens. CONCLUSION: We provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.

[Predictors of choledocholithiasis in patients sustaining gallstones]. / Fatores preditivos de coledocolitíase em doentes com litíase vesicular.

BACKGROUND: The aim of this study was to identify clinical, biochemical and ultrasonographic predictors of choledocholithiasis in patients sustaining gallstones assessed by cholangiography. METHODS: In a prospective study, 148 patients were analyzed regarding clinical, biochemical and ultrasonographic data. All patients underwent cholangiography, either preoperative endoscopic or during cholecystectomy. Each variable was compared between the ones who sustained lithiasis in the biliary tree and the others, in order to find out the predictors of choledocholithiasis. Sensibility, specificity, positive predictive value, negative predictive value (NPV) and accuracy were calculated. Spearman correlation, Odds ratio and logistic regression were employed for the statistical analysis, considering p<0.05 as significant. RESULTS: The variables that showed statistical significance were: presence of jaundice, elevated blood serum levels of alkaline phosphatase, g glutamyltransferase (gamma GT), aspartate aminotransferase, alanine aminotransferase, total bilirrubin, and biliary tract dilatation or choledocholithiasis in the ultrasound. The logistic regression presented an equation capable of predicting the probability of choledocholithiasis based in the variables: jaundice, presence of choledocholithiasis in the ultrasound, and blood levels of gamma GT. The best option to exclude the presence of choledocholithiasis was gamma GT, as it held the higher NPV. Every patient with choledocholithiasis in this sample sustained at least one of the preoperative criteria analyzed. CONCLUSIONS: Jaundice and choledocholithiasis at the ultrasound were the best predictors of choledocholithiasis; as well as gamma GT was the most reliable factor to exclude this diagnosis.

[Cholecystectomy in the elderly: early results of open versus laparoscopic approach]. / Tratamento cirúrgico da litíase vesicular no idoso: análise dos resultados imediatos da colecistectomia por via aberta e videolaparoscópica.

UNLABELLED: The rise of elderly population is due to the improvement of life expectancy. The biliary lithiasis is the most common condition requiring intra-abdominal surgery. Half of these patients sustain associated diseases and frequently develops acute and complicated forms of cholelithiasis. Therefore, cholecystectomy is indicated for patients with chronic symptomatic disease. During a long period open cholecystectomy has been practiced, with low complications and mortality rates. Videolaparoscopy has been recently proposed as an option in these cases, however, few studies compared its advantages over open cholecystectomy for elderly patients. OBJECTIVE: To access the early results of the surgical treatment for cholelithiasis in the elderly submitted to an open or laparoscopic cholecystectomy. METHODS: retrospective study with 246 patients > 65 years old, who underwent elective cholecystectomy through a subcostal incision (group I) or laparoscopic approach (group II). We employed Student's t test and Spearman's correlation for statistical analysis, considering p < 0,05 as significant. RESULTS: A hundred and twenty patients were arranged in group I and 126 in group II. Associated diseases were present in 155 cases (63). There were no differences between the groups regarding both the distribution of comorbid conditions. Conversion was evaluated in 10 patients (8.3%). The mean operative time was 133 minutes in group I and 112 minutes in group II (p=0.001). The mean hospital stay in group I was 3,3 days and in group II was 3.2 days p=0.698. Thirteen patients in each group developed complications: group I (10.8%) and group II (10.3%) p=0,896. There was no statistis significance in complication rate related to gender, age, associated diseases and ASA when the both groups were compared. There were two deaths, both in group II, although the mortality rate was not statiscally significant between the groups (p=0.158). CONCLUSION: Both open and laparoscopic cholecystectomy can be practiced in the elderly with low and similar rate of complications.