The genetic landscape of Lynch syndrome in the Israeli population.

Deciphering the spectrum and founder disease-causing variants (DCVs) in specific populations can shape and facilitate the diagnostic process of Lynch Syndrome (LS). The aim of this report was to comprehensively update on the genetic landscape of LS in the ethnically diverse Israeli-Jewish population. The cohort included 1080 carriers from 588 families; some from underrepresented, understudied Israeli ethnic groups recruited from 8 genetic institutes and high-risk clinics throughout the country.

Serum matrix metalloproteinase-7, Syndecan-1, and CA 19-9 as a biomarker panel for diagnosis of pancreatic ductal adenocarcinoma.

Aims And Background: Matrix metalloproteinase-7 (MMP-7) and Syndecan-1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts.

Methods: In this case-control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups.

Unsedated colonoscopy utilizing virtual reality distraction: a pilot-controlled study.

Background: Sedation increases colonoscopy risks and prolongs recovery time. We examined whether virtual reality (VR) can substitute for sedation. The primary outcome was the overall satisfaction of patients who underwent colonoscopy with VR headset compared with patients who underwent standard sedation.

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes.

Background: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas.

The benefit of pancreatic cancer surveillance in carriers of germline BRCA1/2 pathogenic variants.

Background: Surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes of PDAC and its precursor lesions in BRCA1/2 pathogenic variants (PVs) carriers undergoing pancreatic surveillance.

Methods: A retrospective multicenter cohort study of pancreatic surveillance outcomes in Israeli BRCA1/2 carriers preferably with a family history of PDAC.

Serum matrix metalloproteinase-7: a potential biomarker in patients with Lynch Syndrome.

Background And Aims: The expression of tissue and serum matrix metalloproteinase-7 (MMP-7) was shown to be elevated both in colon cancer and dysplastic lesions. We aimed to evaluate, for the first time, its role as a diagnostic marker in Lynch syndrome (LS) carriers, a hereditary syndrome with predisposition to colon cancer.

Methods: This was a case control study.

High prevalence of MUTYH associated polyposis among minority populations in Israel, due to rare founder pathogenic variants.

Background: Autosomal recessive conditions are common in consanguineous populations. Since consanguinity is common in the Israeli Arab population, we evaluated the rate of MUTYH polyposis (MAP) among polyposis patients in this population and studied Pathogenic Variants (PVs) spectrum.

Methods: We reviewed health records of all Arab and Druze polyposis patients referred for counseling during 2013-2020 who fulfilled the Israeli Genetic Society criteria for MUTYH/APC testing, in a tertiary center in Northern Israel and four additional gastro-genetic clinics in Israel.

Risk of colorectal advanced neoplasia in patients with acute diverticulitis with and without previous colonoscopy.

Background And Aim: Guidelines recommend a colonoscopy after an episode of complicated diverticulitis and after a first episode of uncomplicated diverticulitis. The influence of a previous colonoscopy on postdiverticulitis colonoscopic findings has not been studied. The aim of this work was to examine the incidence of adenoma detection rate (ADR), advanced adenoma (AA) and colorectal cancer (CRC) in patients with diverticulitis with and without previous colonoscopy.

Risk factors and prediction algorithm for advanced neoplasia on screening colonoscopy for average-risk individuals.

Background: Screening with colonoscopy for all average-risk population is probably not cost-effective due to the limited sources and over-generalization of the risk, and risk stratification can be used to optimize colorectal cancer screening.

Objectives: We aimed to assess risk factors for advanced neoplasia (AN) and a classification tree algorithm to predict the risk.

Design: This is a retrospective cross-sectional study.

Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: an ECCO CONFER Multicentre Case Series.

Background: Hereditary colorectal cancer syndromes [HCCS] are rare polyposis or nonpolyposis syndromes with a higher risk of developing colorectal cancer [CRC]. Coexisting inflammatory bowel disease [IBD], including ulcerative colitis [UC] and Crohn's disease [CD], with HCCS is exceedingly rare and presumably increases the risk of early-onset CRC.

Methods: This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project.

Serum Syndecan-1: A Novel Biomarker for Pancreatic Ductal Adenocarcinoma.

Introduction: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled alongside healthy individuals in a derivation-validation cohort design.

Genetic testing for assessment of lynch syndrome in young patients with polyps.

Background: Routine screening for establishing Lynch syndrome (LS) in young individuals diagnosed with adenomas is not recommended due to its low yield, and limited sensitivity of the employment of immunohistochemistry for DNA mismatch-repair proteins on polyps. Hence we aimed to evaluate the yield of germline mutational analysis in diagnosis of LS in a young Israeli cohort with colorectal adenomatous polyps.

Methods: Data were retrospectively collected on consecutive patients, age ≤ 45 years, who underwent colonoscopy with removal of at least one adenoma during 2015-2020, and subsequently genetic testing by multigene panel or LS-Jewish founder mutation panel.

Double heterozygotes of BRCA1/BRCA2 and mismatch repair gene pathogenic variants: case series and clinical implications.

Background: Hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS), the most common inherited cancer syndromes, are attributed to a single heterozygous pathogenic variant (PV) in BRCA1/2 or in a DNA MMR gene, respectively. Little is known about the phenotype in double heterozygotes who carry PVs in both genes.

Methods: Carriers of double-PVs in any DNA MMR gene and BRCA1/2 attending one of three tertiary oncogenetic clinics between 1/2005 and 1/2020 were identified by database search, and their relevant data were retrieved and analyzed.

Post-polypectomy surveillance colonoscopy: Comparison of the updated guidelines.

Background: Recently, three updated guidelines for post-polypectomy colonoscopy surveillance (PPCS) have been published. These guidelines are based on a comprehensive summary of the literature, while some recommendations are similar, different surveillance intervals are recommended after detection of specific types of polyps.

Aim: In this review, we aimed to compare and contrast these recommendations.

Distinct Prognostic Factors in Sporadic and Multiple Endocrine Neoplasia Type 1-Related Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (PNET) may develop sporadically or in the context of hereditary syndromes. In patients with multiple endocrine neoplasia type 1 (MEN1), PNET is the leading cause of death. Our aim was to compare the mortality risk in sporadic and MEN1-related PNETs and identify high-risk populations.

Heat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer.

In the colon, long-term exposure to chronic inflammation drives colitis-associated colon cancer (CAC) in patients with inflammatory bowel disease. While the causal and clinical links are well established, molecular understanding of how chronic inflammation leads to the development of colon cancer is lacking. Here we deconstruct the evolving microenvironment of CAC by measuring proteomic changes and extracellular matrix (ECM) organization over time in a mouse model of CAC.

Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants.

Background: Carriers of pathogenic variants (PVs) in moderate-high-penetrance cancer susceptibility genes are offered tailored surveillance schemes for early cancer diagnosis. The clinical implications of low-penetrance variant carriers are less clear.

Methods: Clinical and demographic data were retrieved for a cohort of Israeli individuals who underwent oncogenetic testing by the 30-gene cancer panel at Color Genomics laboratory, between 04/2013 and 12/2018.

Serum MMP-9: a novel biomarker for prediction of clinical relapse in patients with quiescent Crohn's disease, a analysis.

Background: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn's disease (CD).

Methods: This study was a analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period.