Universal germline testing among patients with colorectal cancer: clinical actionability and optimised panel.

PURPOSE: Universal germline testing in patients with colorectal cancer (CRC) with a multigene panel can detect various hereditary cancer syndromes. This study was performed to understand how to choose a testing panel and whether the result would affect clinical management. METHODS: We prospectively enrolled 486 eligible patients with CRC, including all patients with CRC diagnosed under age 70 years and patients with CRC diagnosed over 70 years with hereditary risk features between November 2017 and January 2018. All participants received germline testing for various hereditary cancer syndromes. RESULTS: The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes was 7.8% (38/486), including 25 PVs in genes with high-risk CRC susceptibility (the minimal testing set) and 13 PVs in genes with moderate-risk CRC susceptibility or increased cancer risk other than CRC (the additional testing set). All the clinically relevant PVs were found in patients diagnosed under age 70 years. Among them, 11 patients would not have been diagnosed if testing reserved to present guidelines. Most (36/38) of the patients with PVs benefited from enhanced surveillance and tailored treatment. PVs in genes from the minimal testing set were found in all age groups, while patients carried PVs in genes from the additional testing set were older than 40 years. CONCLUSION: Universal germline testing for cancer susceptibility genes should be recommended among all patients with CRC diagnosed under age 70 years. A broad panel including genes from the additional testing set might be considered for patients with CRC older than 40 years to clarify inheritance risks. TRIAL REGISTRATION NUMBER: NCT03365986.

Effects of biliary drainage on the intestinal barrier function in obstructive jaundice.

BACKGROUND/AIMS: Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates. In obstructive jaundice, intestinal barrier dysfunction has been postulated to be a key factor contributing to high postoperative morbidity and mortality rates. Since surgery in patients with jaundice is thought to increase the risk of postoperative complications, preoperative biliary drainage (PBD) was introduced to improve the postoperative outcome. To date, whether biliary drainage should be routinely performed in patients with jaundice undergoing a pancreatoduodenectomy remains controversial, and the effect of biliary drainage on the intestinal barrier function in obstructive jaundice remains unknown. RESULTS: Biliary drainage is almost exclusively associated with beneficial results, such as improved intestinal barrier function in experimental models. However, clinical data in this field are limited, indirect and remain controversial. Most importantly, routine PBD will result in a highly procedure-related complication rate and an increase in operative infectious complications. CONCLUSIONS: PBD should not be performed routinely, unless further improved PBD techniques would become available in clinical studies. Future studies should focus on PBD techniques, and then on the effects of biliary drainage on intestinal mucosa in obstructive jaundice in clinical.