The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co‐segregation, family cancer history profile, co‐occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case‐control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene‐specific calibration of evidence types used for variant classification.

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Complete mesocolic excision and central vascular ligation for locally invasive right-sided colon cancer by an open approach-a video vignette.

Highlights Pancreatic acinar cell carcinoma (ACC) may present with pancreatic panniculitis. Complete surgical resection of ACC can successfully treat pancreatic panniculitis. Aggressive surgery for ACC can lead to prolonged disease-free survival.

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before establishing the TaTME plane posteriorly first, before proceeding laterally then anteriorly. The dissection was continued superiorly towards the peritoneal reflection, positively identifying important landmarks anteriorly, including periprostatic tissue and the endopelvic fascia, maintaining a complete mesorectal envelope. Once the peritoneal cavity was breached circumferentially, the dissection was continued through the transabdominal approach. Conventional robotic anterior resection and transabdominal TME is performed with mobilization of the splenic flexure to provide a tension-free anastomosis. Our preference is to extract the specimen through a Pfannenstiel incision, especially for a bulky mesorectum and tight anal sphincter, in order to prevent tractional injury [7]. A conventional TaTME end-to-end colorectal anastomosis was performed with a Covidien haemorrhoidal stapler (DST Series TM Technology, Covidien, Dublin, Ireland), with a covering loop ileostomy through a right iliac fossa port site. The total operative time was 210-250 min for the transanal phase and 160 min for the transabdominal phase. We have presented a novel modification of the Da Vinci Xi robotic platform, to perform a single-surgeon total robotic transabdominal TME and TaTME. We have demonstrated the feasibility of this novel approach and an expansion of the use of the Da Vinci Xi platform.