BACKGROUND & AIMS: Lynch syndrome is a form of hereditary colorectal cancer (CRC) caused by pathogenic germline variants (PV) in DNA mismatch repair (MMR) genes. Currently, many Western... Show moreBACKGROUND & AIMS: Lynch syndrome is a form of hereditary colorectal cancer (CRC) caused by pathogenic germline variants (PV) in DNA mismatch repair (MMR) genes. Currently, many Western countries perform universal immunohistochemistry testing on CRC to increase the identification of Lynch syndrome patients and their relatives. For a clear understanding of health benefits and costs, data on its outcomes are required: proportions of Lynch syndrome, sporadic MMR-deficient (MMRd) cases, and unexplained MMRd cases.METHODS: Ovid Medline, Embase, and Cochrane CENTRAL were searched for studies reporting on universal MMR immunohistochemistry, followed by MMR germline analysis, until March 20, 2020. Proportions were calculated, subgroup analyses were performed based on age and diagnostics used, and random effects meta-analyses were conducted. Quality was assessed using the Joanna Briggs Critical Appraisal Tool for Prevalence Studies.RESULTS: Of 2723 identified articles, 56 studies covering 58,580 CRCs were included. In 6.22% (95% CI, 5.08%-7.61%; I-2 = 96%) MMRd was identified. MMR germline PV was present in 2.00% (95% CI, 1.59%-2.50%; I-2 = 92%), ranging from 1.80% to 7.27% based on completeness of diagnostics and age restriction. Immunohistochemistry outcomes were missing in 11.81%, and germline testing was performed in 76.30% of eligible patients. In 7 studies, including 6848 CRCs completing all diagnostic stages, germline PV and biallelic somatic MMR inactivation were found in 3.01% and 1.75%, respectively; 0.61% remained unexplained MMRd.CONCLUSIONS: Age, completeness, and type of diagnostics affect the percentage of MMR PV and unexplained MMRd percentages. Complete diagnostics explain almost all MMRd CRCs, reducing the amount of subsequent multigene panel testing. This contributes to optimizing testing and surveillance in MMRd CRC patients and relatives. Show less
The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to... Show moreThe scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when >= 80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated. Show less
Main Recommendations ESGE recommends that individuals with Lynch syndrome should be followed in dedicated units that practice monitoring of compliance and endoscopic performance measures. Strong... Show moreMain Recommendations ESGE recommends that individuals with Lynch syndrome should be followed in dedicated units that practice monitoring of compliance and endoscopic performance measures. Strong recommendation, low quality evidence, level of agreement 100 %. ESGE recommends starting colonoscopy surveillance at the age of 25 years for MLH1 and MSH2 mutation carriers and at the age of 35 years for MSH6 and PMS2 mutation carriers. Strong recommendation, moderate quality evidence, level of agreement 100 %. ESGE recommends the routine use of high-definition endoscopy systems in individuals with Lynch syndrome. Strong recommendation, high quality evidence, level of agreement 100 %. ESGE suggests the use of chromoendoscopy may be of benefit in individuals with Lynch syndrome undergoing colonoscopy; however routine use must be balanced against costs, training, and practical considerations. Weak recommendation, moderate quality evidence, level of agreement 89 %. ESGE recommends definition of familial risk of colorectal cancer as the presence of at least two first-degree relatives with colorectal cancer or at least one first-degree relative with colorectal cancer before the age of 50 years. Strong recommendation, moderate quality evidence, level of agreement 92 %. ESGE recommends colonoscopy surveillance in first-degree relatives of colorectal cancer patients in families that fulfill the definition of familial risk of colorectal cancer. Strong recommendation, moderate quality evidence, level of agreement 100 %. Show less
