Hereditary Colorectal Cancer and Polyposis Syndromes Caused by Variants in Uncommon Genes.

A substantial number of hereditary colorectal cancer (CRC) and colonic polyposis cannot be explained by alteration in confirmed predisposition genes, such as mismatch repair (MMR) genes, APC and MUTYH. Recently, a certain number of potential predisposition genes have been suggested, involving each a small number of cases reported so far. Here, we describe the detection of rare variants in the NTLH1, AXIN2, RNF43, BUB1, and TP53 genes in nine unrelated patients who were suspected for inherited CRC and/or colonic polyposis. Seven of them were classified as pathogenic or likely pathogenic variants (PV/LPV). Clinical manifestations of carriers were largely consistent with reported cases with, nevertheless, distinct characteristics. PV/LPV in these uncommon gene can be responsible for up to 2.7% of inherited CRC or colonic polyposis syndromes. Our findings provide supporting evidence for the role of these genes in cancer predisposition, and contribute to the determination of related cancer spectrum and cancer risk for carriers, allowing for the establishment of appropriate screening strategy and genetic counseling in affected families.

Deciphering the clinical spectrum of gastric disease in patients with juvenile polyposis syndrome.

BACKGROUND AND AIMS: Juvenile polyposis syndrome (JPS) is a rare hereditary autosomal dominant cancer-predisposition syndrome caused by germline pathogenic variants (PVs) located in SMAD4 or BMPR1A genes. Accurate clinical and endoscopic data regarding the evolution of gastric lesions remain sparse. METHODS: Clinical, endoscopic, genetic, and pathologic data from patients with SMAD4 or BMPR1A PVs included between 2007 and 2020 in the French network on rare digestive polyposis (RENAPOL [French National Polyposis Register]) database were prospectively collected to address uncertainties regarding gastric involvement. RESULTS: Thirty-six patients were included: 25 (69.5%) had SMAD4 PVs, and 11 had BMPR1A PVs. For SMAD4 PV carriers, median age at inclusion was 43.0 years (range, 10-78 years). At baseline EGD, 22 (88%) of 25 patients exhibited at least 1 gastric juvenile polyp, and 5 (20%) of 25 had macroscopic signs of inflammatory gastritis. Early gastric disease was mostly located under the cardia, then progressed to the gastric antrum and body. During a mean follow-up period of 55.0 months, 12 of 25 patients had gastric disease progression (ie, new juvenile polyps [91.6%], diffuse gastric involvement [41.6%], inflammatory flat progression [25%]). Among 62 biopsies, low-grade dysplasia was observed in 5 (7.5%) samples from 2 patients. Nine carriers (36%) underwent gastrectomy (mean age, 47.2 years) due to diffuse gastric involvement or worsening clinical symptoms. Gastric adenocarcinoma (T1) was found in 1 gastrectomy specimen. Among the 11 patients with BMPR1A PVs, 2 had gastric hamartomatomas at baseline EGD, none with dysplasia or symptoms. CONCLUSIONS: Gastric involvement in JPS seems to be progressive over a lifetime, initiates in the cardia area, and mostly involves SMAD4 PV carriers.

Coordinated prospective follow-up of Lynch syndrome is able to detect the majority of incident cancers.

BACKGROUND: Lynch syndrome is one of the most common genetic predispositions to many cancers, most of which do not have a consensus recommendation for screening. AIMS: We studied in our region the value of a systematized and coordinated follow-up program for patients with Lynch syndrome on all organs at risk. METHODS: A multicenter prospective cohort evaluation was performed, from January 2016 to June 2021. RESULTS: One hundred and seventy-eight patients were prospectively included (104 women (58%), median age 44 years, range 35-56 years) with a median follow-up of 4 years (range 2.5-5 years), corresponding to a total of 652 patient-years. The overall cancer incidence rate was 13.80 per 1000 patient-years. Seven of nine cancers (78%) were detected during the follow-up program, with all cancers identified at an early stage. The detection rate of adenomas during colonoscopies was 24%. CONCLUSION: These preliminary data suggest that coordinated prospective follow-up of Lynch syndrome is capable of detecting the majority of incident cancers, particularly for locations not covered by an international follow-up recommendation. However, these results need to be confirmed by larger-scale studies.

Juvenile polyposis: Focus on less described manifestations.

Juvenile polyposis represents an heterogeneous disease as different genetic dominant backgrounds have been evidenced leading to different clinical presentations. It is associated in some patients with a different syndrome, Hereditary Hemorragic Telangiectasia, justifying a complementary and different management. Recent international recommendations help in managing this very rare disease, and this management should probably be restricted to expert centers able to take care of the multiple manifestations and risks of these patients and families. This paper will focus on the poorly known and evaluated aspects of juvenile polyposis, excluding the colonic involvement and epidemiology that are addressed in a different article of this issue.

Zenker diverticulum treatment: retrospective comparison of flexible endoscopic window technique and surgical approaches.

INTRODUCTION: Different treatments exist for Zenker diverticulum. We compared flexible endoscopic myotomy of the cricopharyngeal muscle, using a technique called the "window technique" in order to improve the field of view, to surgical approaches. MATERIALS AND METHODS: Patients were retrospectively included and divided into a gastrointestinal group, with flexible endoscopic myotomy, and an ear-nose-throat treatments group with either rigid endoscopic treatment, either cervicotomy. We evaluated effectiveness in terms of quality of life (on a scale on 0 to 10) safety and technical aspects of each procedure. RESULTS: A total 106 patients who underwent 128 interventions were included. Rigid endoscopic procedures were the shortest (p < 0.001), with no difference for adverse event. Endoscopic approaches, flexible and rigid ones, were associated with shorter time to intake resumption (1 and 3 days, respectively, vs 6 after cervicotomy) and shorter length of hospital stay (3 and 4 days, respectively, vs 7 after cervicotomy) (p = 0.001). Post-operative QoL was better after flexible endoscopy (9/10) and open cervicotomy (9/10) than after rigid endoscopy (7/10) (p = 0.004). Patients declared fewer residual symptoms after open cervicotomy (77% of low symptomatic patients) and flexible endoscopy (80%) than after rigid endoscopy (43%) (p = 0.003). Conversion to open surgery was more frequent during rigid than flexible endoscopies (18% vs 0%, p = 0.0008). CONCLUSION: Flexible endoscopic approach of Zenker diverticulum treatment seems to be safe and effective and may be an alternative to surgical approaches. Myotomy can be eventually helped by the window technique.