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      Call for Papers: Current Management of Duodenal Neoplasia

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      Increased Number of Colorectal Interval Cancers in Lynch Syndrome after the SARS-CoV-2 Pandemic: A Survey-Based Study

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          Abstract

          Background: Hereditary colorectal cancer syndromes require timely endoscopic surveillance. Methods: This study evaluated the approach of Italian gastroenterologists to the management of such patients. It then assessed the impact of SARS-CoV-2. All members affiliated with the leading Italian gastroenterology societies (AIGO, SIED, and SIGE) received an online questionnaire. Results: One hundred and twenty-one clinicians from 96 centers answered, not necessarily experts in the field (mean age 50.26 ± 11.22 years). Many collected family history for genetic risk assessment (74.4%), but only 14.0% used an online predictive software. 65.6% discussed cases in multidisciplinary units. Genetic analysis was available to most centers, but only a few hospitals offered dedicated endoscopy (19.0%), outpatient clinics (33.9%), or surgeries (23.1%). Since the start of the SARS-CoV-2 pandemic, the number of clinicians with a high volume of patients decreased (from 38.8% to 28.1%). Almost half of the responders (45.5%) reported a delay in the surveillance (median: 4–12 months). Ultimately, 30.6% detected one interval colorectal cancer in at least one of their patients. Conclusion: The SARS-CoV-2 pandemic directly affected the surveillance of hereditary colorectal cancer syndromes in Italy. Endoscopic surveillance should resume in all centers to avoid the possible long-term consequences of its interruption, especially for inherited colorectal cancer syndromes.

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          Most cited references29

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          ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.

          This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.
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            Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

            Purpose Hereditary factors play an important role in colorectal cancer (CRC) risk, yet the prevalence of germline cancer susceptibility gene mutations in patients with CRC unselected for high-risk features (eg, early age at diagnosis, personal/family history of cancer or polyps, tumor microsatellite instability [MSI], mismatch repair [MMR] deficiency) is unknown. Patients and Methods We recruited 1,058 participants who received CRC care in a clinic-based setting without preselection for age at diagnosis, personal/family history, or MSI/MMR results. All participants underwent germline testing for mutations in 25 genes associated with inherited cancer risk. Each gene was categorized as high penetrance or moderate penetrance on the basis of published estimates of the lifetime cancer risks conferred by pathogenic germline mutations in that gene. Results One hundred five (9.9%; 95% CI, 8.2% to 11.9%) of 1,058 participants carried one or more pathogenic mutations, including 33 (3.1%) with Lynch syndrome (LS). Twenty-eight (96.6%) of 29 available LS CRCs demonstrated abnormal MSI/MMR results. Seventy-four (7.0%) of 1,058 participants carried non-LS gene mutations, including 23 (2.2%) with mutations in high-penetrance genes (five APC, three biallelic MUTYH, 11 BRCA1/2, two PALB2, one CDKN2A, and one TP53), 15 of whom lacked clinical histories suggestive of their underlying mutation. Thirty-eight (3.6%) participants had moderate-penetrance CRC risk gene mutations (19 monoallelic MUTYH, 17 APC*I1307K, two CHEK2). Neither proband age at CRC diagnosis, family history of CRC, nor personal history of other cancers significantly predicted the presence of pathogenic mutations in non-LS genes. Conclusion Germline cancer susceptibility gene mutations are carried by 9.9% of patients with CRC. MSI/MMR testing reliably identifies LS probands, although 7.0% of patients with CRC carry non-LS mutations, including 1.0% with BRCA1/2 mutations.
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              Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine

              This chapter reviews genes and syndromes associated with predisposition to colorectal cancer (CRC), with an overview of gene variant classification. We include updates on the application of preventive and therapeutic measures, focusing on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and immunotherapy. Germline pathogenic variants in genes conferring high or moderate risk to cancer are detected in 6–10% of all CRCs and 20% of those diagnosed before age 50. CRC syndromes can be subdivided into nonpolyposis and polyposis entities, the most common of which are Lynch syndrome and familial adenomatous polyposis. In addition to known and novel genes associated with highly penetrant CRC risk, identification of pathogenic germline variants in genes associated with moderate-penetrance cancer risk and/or hereditary cancer syndromes not traditionally linked to CRC may have an impact on genetic testing, counseling and surveillance. The use of multigene panels in genetic testing has exposed challenges in the classification of variants of uncertain significance. We provide an overview of the main classification systems and strategies for improving these. Finally, we highlight approaches for integrating chemoprevention in the care of individuals with genetic predisposition to CRC and use of targeted agents and immunotherapy for treatment of mismatch repair deficient and hypermutant tumors.
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                Author and article information

                Journal
                DDI
                Dig Dis
                10.1159/issn.0257-2753
                Digestive Diseases
                Dig Dis
                S. Karger AG
                0257-2753
                1421-9875
                2023
                March 2023
                25 April 2022
                : 41
                : 2
                : 227-232
                Affiliations
                [_a] aGastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [_b] bMedical Biotechnologies Department, University of Siena, Siena, Italy
                [_c] cGastroenterology Unit 1, Gastroenterological Hospital “S. De Bellis” IRCCS, Castellana Grotte, Italy
                [_d] dOncological Gastroenterology Unit, CRO, Aviano, Italy
                [_e] eGastroenterology and Digestive Endoscopy, Ospedale di Cattinara, Trieste, Italy
                [_f] fGastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria, S. Orsola Hospital, Bologna, Italy
                [_g] gDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
                [_h] hGastroenterology Unit, S.O. Frangipane Hospital, Ariano Irpino, Italy
                [_i] iMedical Department II, University Hospital, Ludwig Maximilians-University, Munich, Germany
                [_j] jDigestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milan, Italy
                [_k] kDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
                [_l] lIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
                Author information
                https://orcid.org/0000-0002-1655-6762
                https://orcid.org/0000-0001-9959-9604
                https://orcid.org/0000-0002-2020-222X
                https://orcid.org/0000-0002-3094-9968
                Article
                524393 PMC9393779 Dig Dis 2023;41:227–232
                10.1159/000524393
                PMC9393779
                35468603
                e8df2311-4881-48fd-ae0d-e19079d0256a
                © 2022 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

                History
                : 28 September 2021
                : 28 February 2022
                Page count
                Figures: 2, Pages: 6
                Funding
                This research received no external funding.
                Categories
                Small and Large Bowel: Research Article

                Medicine
                Colorectal cancer,Hereditary,COVID-19,Surveillance
                Medicine
                Colorectal cancer, Hereditary, COVID-19, Surveillance

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