Outcomes of Endoscopic Surveillance in Individuals With Genetic Predisposition to Hereditary Diffuse Gastric Cancer.

BACKGROUND & AIMS: Pathogenic germline variants in CDH1 are associated with risk for diffuse gastric cancer (DGC) and lobular breast cancer. The reported high incidence of DGC and limited sensitivity of endoscopy in detection have prompted recommendation for total prophylactic gastrectomy for carriers of pathogenic or likely pathogenic (PLP) germline variants of CDH1. Multigene panel tests have identified increasing numbers of carriers of PLP variants in CDH1 who lack a family history of DGC. We evaluated outcomes of endoscopic surveillance for carriers of PLP variants of CDH1 with and without family history of DGC. METHODS: Individuals from 13 families with germline PLP variants of CDH1 were evaluated at the Michigan Medicine Cancer Genetics Clinic from January 1998 through May 2018. Outcomes of esophagogastroduodenoscopy examinations, histopathology analyses, and surgery were compared between individuals with and without a family history of DGC. RESULTS: We identified 20 carriers of germline CDH1 PLP variants; they underwent endoscopic examinations and/or gastrectomy. None had abnormal findings visible during endoscopy. Signet ring cell carcinoma (SRCC) was detected in 12 of 20 subjects. All but 1 of the carcinomas were tiny and confined to the lamina propria, and 1 was transmural. Seven of 12 subjects who had SRCC reported no diagnoses of DGC in first-degree relatives and did not meet established criteria for CDH1 analysis based on a 3-generation family pedigree. CONCLUSIONS: More than half of individuals with germlines variants of CDH1 that are PLP had histopathologic evidence for DGC on endoscopy and/or gastrectomy. Family history of DGC and endoscopic findings therefore do not appear to be reliable determinants of risk of SRCC in individuals with genetic predisposition to DGC.

Impact of De Novo and Preexisting Inflammatory Bowel Disease on the Outcome of Orthotopic Liver Transplantation.

BACKGROUND: Diarrhea is a common problem in the setting of solid-organ transplantation, especially orthotopic liver transplant (OLT). De novo or preexisting inflammatory bowel disease (IBD) is one of the differential diagnoses. The aims of our study were to evaluate the frequency of de novo IBD in patients with OLT and to assess the impact of de novo IBD and preexisting IBD on the outcome of OLT. METHODS: This case-control study included all eligible patients who had OLT from January 2001 to December 2009. The study group included all patients who had a biopsy-proven diagnosis of IBD after their OLT (the de novo IBD group). The control groups included patients with existing IBD before OLT and those without IBD before and after OLT. The groups were matched based on their underlying diagnoses of end-stage liver disease. Univariate and multivariate analyses were performed. RESULTS: A total of 66 subjects were included in the study. The mean age was 45.4 ± 13.4 years, with 44 (66.7%) being male. Fifteen patients (23%) had de novo IBD, 21 (32%) had existing IBD before OLT, and 30 (45%) had no underlying IBD before or after OLT. There were no significant differences between the 2 IBD groups in any of the IBD characteristics, including IBD medications. Subjects without IBD were more likely to receive mycophenolate mofetil within 1 week of OLT than those in the de novo or preexisting IBD (70% versus 23% P = 0.018). Episodes of graft rejection were more commonly observed in subjects with preexisting IBD (52%) than de novo IBD (27%) or no IBD (20%) (P = 0.045). The rate of retransplantation was highest in the de novo IBD group followed by the preexisting IBD group and non-IBD group (20% versus 14% versus 0%; P = 0.029). Combined together, patients with IBD in the setting of OLT were more likely to be retransplanted than those without IBD (16.7% versus 0%, P = 0.045). In multivariate analysis, we found that patients with IBD were 6.7 (95% confidence interval, 1.9-23.9) times more likely to have an adverse outcome after liver transplant (P = 0.004), after adjusting for primary sclerosing cholangitis. CONCLUSIONS: De novo IBD can occur in patients after OLT. De novo IBD and preexisting IBD were found to be associated with a higher risk for graft failure, suggesting that early diagnosis and closer monitoring of the patients at risk are critical.