Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome

BACKGROUND Lynch syndrome(LS)is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers.While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines,there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS,including small intestinal cancer(SIC)and urinary tract cancer(UTC).Given the limited evidence,guidelines do not consistently recommend surveillance for SIC and UTC,and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance recommendations.AIM To study factors associated with SIC and UTC surveillance uptake and outcomes in LS.METHODS This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral center.Included individuals had a pathogenic or likely pathogenic variant in MLH1,MSH2,MSH6,PMS2,or EPCAM,or were a confirmed obligate carrier,and had at least one documented visit to our center.Information regarding SIC and UTC surveillance was captured for each individual,and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center’s dedicated high-risk LS clinic between January 1,2017 and October 29,2020.During these initial management visits,all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC surveillance.Statistical analysis using Pearson’s chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance,and a P value below 0.05 was deemed statistically significant.RESULTS Of 317 individuals with LS,86(27%)underwent a total of 105 SIC surveillance examinations,with 5 leading to additional work-up and no SICs diagnosed.Additionally,99(31%)patients underwent a total of 303 UTC surveillance examinations,with 19 requiring further evaluation and 1 UTC identified.Of 155 individuals who had an initial LS management visit between January 1,2017 and October 29,2020,63(41%)chose to undergo SIC surveillance and 58(37%)chose to undergo UTC surveillance.However,only 26(41%)and 32(55%)of those who initially chose to undergo SIC or UTC surveillance,respectively,successfully completed their surveillance examinations.Individuals with a pathogenic variant in MSH2 or EPCAM were more likely to initially choose to undergo SIC surveillance(P=0.034),and older individuals were more likely to complete SIC surveillance(P=0.007).Choosing to pursue UTC surveillance was more frequent among older individuals(P=0.018),and females more frequently completed UTC surveillance(P=0.002).Personal history of cancer and family history of SIC or UTC were not significantly associated with electing nor completing surveillance.Lastly,the provider discussing SIC/UTC surveillance was significantly associated with subsequent surveillance choices.CONCLUSION Pursuing and completing SIC/UTC surveillance in LS is influenced by several factors,however broad incorporation in LS management is likely unhelpful due to low yield and frequent false positive results.

Era of Barrett’s surveillance: Does equipment matter?

Barrett’s esophagus is a consequence of long standing gastro-esophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Regular surveillance endoscopies can detect curable early neoplasia in asymptomatic patients, which in turn could improve the prognosis compared to symptomatic cancer. Early neoplastic lesions, which are amenable for local therapy, could be treated endoscopically, avoiding a major surgery. However, in the absence of obvious mucosal lesions, random four quadrant biopsies are done, which is associated with significant sampling error. Newer imaging modalities, such as autofluorescence endoscopy, are helpful in detecting subtle lesions that could be examined in detail with narrow band imaging to characterize and target biopsies. This has the potential benefit of reducing the number of random biopsies with a better yield of dysplasia. Confocal endomicroscopy provides "optical biopsies" and is a valuable tool in targeting biopsies to improve dysplasia detection; however, this is technically challenging. Fuji intelligent chromoendoscopy and I-Scan are recent additions to the imaging armamentarium that have produced notable early results. While all these additional new imaging techniques are promising, a thorough examination by high resolution white light endoscopy after clearing the mucosa with mucolytics should be the minimum standard to improve dysplasia detection during Barrett’s surveillance.