Pancreatic ductal adenocarcinoma (PDAC) has traditionally been thought of as an immunologically quiescent tumor type presumably because of a relatively low tumor mutational burden (TMB) and poor responses to checkpoint blockade therapy. However, many PDAC tumors exhibit T cell inflamed phenotypes. The presence of tertiary lymphoid structures (TLS) has recently been shown to be predictive of checkpoint blockade response in melanomas and sarcomas, and are prognostic for survival in PDAC. In order to more comprehensively understand tumor immunity in PDAC patients with TLS, we performed RNA-seq, single and multiplex IHC, flow cytometry and predictive genomic analysis on treatment naïve, PDAC surgical specimens. Forty-six percent of tumors contained distinct T and B cell aggregates reflective of “early-stage TLS” (ES-TLS), which correlated with longer overall and progression-free survival. These tumors had greater CD8 + T cell infiltration but were not defined by previously published TLS gene-expression signatures. ES-TLS + tumors were enriched for IgG1 class-switched memory B cells and memory CD4 + T cells, suggesting durable immunological memory persisted in these patients. We also observed the presence of active germinal centers (mature-TLS) in 31% of tumors with lymphocyte clusters, whose patients had long-term survival (median 56 months). M-TLS-positive tumors had equivalent overall T cell infiltration to ES-TLS, but were enriched for activated CD4 + memory cells, naive B cells and NK cells. Finally, using a TCGA-PDAC dataset, ES-TLS + tumors harbored a decreased TMB, but M-TLS with germinal centers expressed significantly more MHCI-restricted neoantigens as determined by an in silico neoantigen prediction method. Interestingly, M-TLS + tumors also had evidence of increased rates of B cell somatic hypermutation, suggesting that germinal centers form in the presence of high-quality tumor neoantigens leading to increased humoral immunity that confers improved survival for PDAC patients. Abbreviations TLS: tertiary lymphoid structures; GC: germinal center(s); PDAC: pancreatic ductal adenocarcinoma; RNA-seq: RNA sequencing; BCRseq: B cell receptor sequencing; HEV: high endothelial venule; PNAd: peripheral node addressin; TMB: tumor mutational burden; TCGA: the cancer genome atlas; PAAD: pancreatic adenocarcinoma; FFPE: formalin fixed paraffin embedded; TIME: tumor immune microenvironment.

Long-term survival of patients with resected colorectal cancer lung metastases in routine practice is comparable to outcomes reported in institutional case series. Lymph node positivity is strongly associated with reduced survival. Combining size and number of metastatic lesions in advance of the operation may facilitate treatment decision making.

Background: Square knots are the gold standard in hand-tie wound closure, but are difficult to reproduce in deep cavities, inadvertently resulting in slipknots. The reversing half-hitch alternating post (RHAP) knot has been suggested as an alternative owing to its nonslip nature and reproducibility in limited spaces. We explored whether the RHAP knot is noninferior to the square knot by assessing tensile strength. Methods:We conducted 10 trials for each baseline and knot configuration, using 3-0 silk and 3-0 polyglactin 910 sutures. We compared tensile strength between knot configurations at the point of knot failure between slippage and breakage.Results: Maximal failure strength (mean ± SD) in square knots was reached with 4-throw in both silk (30 ± 1.5 N) and polyglactin 910 (39 ± 12 N). For RHAP knots, maximal failure strength was reached at 5-throw for both silk (31 ± 1.5 N) and polyglactin 910 (41 ± 13 N). In both sutures, there were no strength differences between 3-throw square and 4-throw RHAP, between 4-throw square and 5-throw RHAP, or between 5-throw square and 6-throw RHAP knots. Polyglactin 910 sutures, in all knot configurations, were more prone to slippage than silk sutures (p < 0.001).

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Introduction: After nearly four years of Canadian experience with medical assistance in dying (MAiD), the clinical volume of organ transplantation following MAiD remains low. This is the first Canadian report evaluating recipient outcomes from kidney transplantation following MAiD. Methods: This was a retrospective review of the first nine cases of kidney transplants following MAiD at a Canadian transplant center. Results: Nine patients underwent MAiD followed by kidney retrieval during the study period. Their diagnoses were largely neuromuscular diseases. The mean warm ischemic time was 20 minutes (standard deviation [SD] 7). The nine recipients had a mean age of 60 (SD 19.7). The mean cold ischemic time was 525 minutes (SD 126). Delayed graft function occurred in only one patient out of nine. The mean 30-day creatinine was 124 umol/L (SD 52) . The mean three-month creatinine was 115 umol/L (SD 29). Conclusions: We report nine cases of kidney transplantation following MAiD. The process minimized warm ischemia, resulting in low delayed graft function rates, and acceptable post-transplant outcomes. Further large-scale research is necessary to optimize processes and outcomes in this novel clinical pathway.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Liver transplant tourism is travel for transplantation involving organ trafficking and/or transplant commercialism. Various medical, financial, and organizational factors play a role in transplant care including waiting lists, Model for End-Stage Liver Disease scores, and financial aid. We outline the international experiences with transplant tourism (TT) and its effect on their medical communities and patients. For clinicians providing care to patients involved in TT, we also discuss pretransplant counseling and posttransplant care. Liver Transplantation 26 276-282 2020 AASLD. liveR tRAnsplAntAtion, vol. 26, no. 2, 2020 Hindi et Al. Review ARticle | 277 TT ReformAt the Declaration of Istanbul (DoI) summit in 2008, international transplant researchers and politicians defined specific acts related to the process of illegal organ transplantation. The DoI acknowledged TT and provided ethical and social transplant guidelines for individual countries in an effort to curb TT. Moreover, the differences in definitions for travel for transplantation and TT were distinguished. Travel for transplantation is the movement of organs, donors, recipients, or transplant professionals across jurisdictional borders Zaid Hindi and Mayur Brahmania were responsible for the study concept and design and for drafting the manuscript.

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