{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:07:47Z","timestamp":1790014067419,"version":"4.0.1"},"reference-count":40,"publisher":"BMJ","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Prophylactic total gastrectomy (PTG) is a risk-reducing strategy considered in individuals at high risk for diffuse gastric cancer (DGC) associated with germline\n                      <jats:italic>CDH1<\/jats:italic>\n                      pathogenic variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic literature search (PubMed, Scopus) was conducted to identify studies that performed PTGs in\n                      <jats:italic>CDH1<\/jats:italic>\n                      carriers. Data were analysed using a random-effects generalised linear mixed model. Cochran\u2019s Q test was used to assess the heterogeneity between studies. Forest plots were used to display study-specific estimates, and the pooled estimates were calculated within three subsequent cohort periods (2001\u20132010; 2011\u20132020; 2021\u20132025). Statistical analyses were performed using R software.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 21 studies were considered out of 302 originally identified, including a total of 967\n                      <jats:italic>CDH1<\/jats:italic>\n                      carriers. PTG was performed in 62.9% of\n                      <jats:italic>CDH1<\/jats:italic>\n                      pathogenic variant carriers. Advanced DGC (&gt;pT1a) was detected in 1.1% and \u2264pT1a in 79% in postoperative PTG specimens. The majority of PTGs were reported from North America (58.9%). The pooled proportion of PTG decreased from 83.2% (95% CI 61.0% to 94.0%) in 2001\u20132010 to 71.0% (95% CI 59.0% to 80.7%) in 2011\u20132020 and to 67.5% (95% CI 48.9% to 81.8%) in 2021\u20132025 (p for trend=0.12).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      About 60% of PTGs were reported from North America. The majority of the lesions were classified as pT1a. PTG indication has been progressively and constantly decreasing during the last years considered. This can be related to the recent genetic analyses reporting a lower DGC risk in\n                      <jats:italic>CDH1<\/jats:italic>\n                      carriers and with the improvement in detection of early lesions during endoscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420261368873.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2026-111804","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:20:33Z","timestamp":1790011233000},"page":"jmg-2026-111804","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Prophylactic total gastrectomy in germline\n                    <i>CDH1<\/i>\n                    carriers: results across 25 years from a systematic review and meta-analysis"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9269-0146","authenticated-orcid":false,"given":"Giovanni","family":"Corso","sequence":"first","affiliation":[{"name":"Department of Oncology and Hematology, University of Milan, Milan, Italy"},{"name":"Division of Breast Surgery, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Quadrini","sequence":"additional","affiliation":[{"name":"Department of Statistics and Quantitative Methods, University of Milan\u2013Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Bagnardi","sequence":"additional","affiliation":[{"name":"Department of Statistics and Quantitative Methods, University of Milan\u2013Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"La Vecchia","sequence":"additional","affiliation":[{"name":"University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026092110202123000_jmg-2026-111804v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30219-9"},{"key":"2026092110202123000_jmg-2026-111804v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/32918"},{"key":"2026092110202123000_jmg-2026-111804v1.3","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1136\/jmg.36.12.873","article-title":"Familial gastric cancer: overview and guidelines for management","volume":"36","author":"Caldas","year":"1999","journal-title":"J Med Genet"},{"key":"2026092110202123000_jmg-2026-111804v1.4","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.018275"},{"key":"2026092110202123000_jmg-2026-111804v1.5","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105337"},{"key":"2026092110202123000_jmg-2026-111804v1.6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1001\/jamaoncol.2014.168","article-title":"Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond","volume":"1","author":"Hansford","year":"2015","journal-title":"JAMA Oncol"},{"key":"2026092110202123000_jmg-2026-111804v1.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106213442504"},{"key":"2026092110202123000_jmg-2026-111804v1.8","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.10852"},{"key":"2026092110202123000_jmg-2026-111804v1.9","doi-asserted-by":"crossref","DOI":"10.1200\/PO-24-00434","article-title":"A Decreased Appetite for Prophylactic Total Gastrectomy","volume":"8","author":"Davis","year":"2024","journal-title":"JCO Precis Oncol"},{"key":"2026092110202123000_jmg-2026-111804v1.10","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2025-111222"},{"key":"2026092110202123000_jmg-2026-111804v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00057-8"},{"key":"2026092110202123000_jmg-2026-111804v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00700-8"},{"key":"2026092110202123000_jmg-2026-111804v1.13","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13061269","article-title":"Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review","volume":"13","author":"Corso","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026092110202123000_jmg-2026-111804v1.14","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0061"},{"key":"2026092110202123000_jmg-2026-111804v1.15","doi-asserted-by":"publisher","DOI":"10.1111\/his.13715"},{"key":"2026092110202123000_jmg-2026-111804v1.16","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1093\/bjs\/znad192","article-title":"Shifting perceptions on endoscopic surveillance and timing of prophylactic gastrectomy for hereditary diffuse gastric cancer","volume":"110","author":"van Dieren","year":"2023","journal-title":"Br J Surg"},{"key":"2026092110202123000_jmg-2026-111804v1.17","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1001\/jamaoncol.2019.1208","article-title":"Comparison of CDH1 Penetrance Estimates in Clinically Ascertained Families vs Families Ascertained for Multiple Gastric Cancers","volume":"5","author":"Roberts","year":"2019","journal-title":"JAMA Oncol"},{"key":"2026092110202123000_jmg-2026-111804v1.18","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-105991"},{"key":"2026092110202123000_jmg-2026-111804v1.19","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.2217\/fon-2018-0834","article-title":"E-cadherin germline mutations in M\u0101ori population","volume":"15","author":"De Scalzi","year":"2019","journal-title":"Future Oncol"},{"key":"2026092110202123000_jmg-2026-111804v1.20","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz229"},{"key":"2026092110202123000_jmg-2026-111804v1.21","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010701)92:1<181::AID-CNCR1307>3.0.CO;2-J"},{"key":"2026092110202123000_jmg-2026-111804v1.22","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2001.117099"},{"key":"2026092110202123000_jmg-2026-111804v1.23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2008.01982_17.x"},{"key":"2026092110202123000_jmg-2026-111804v1.24","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23501"},{"key":"2026092110202123000_jmg-2026-111804v1.25","doi-asserted-by":"publisher","DOI":"10.4293\/108680810X12924466007449"},{"key":"2026092110202123000_jmg-2026-111804v1.26","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e32832bab9a"},{"key":"2026092110202123000_jmg-2026-111804v1.27","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1245\/s10434-011-1648-9","article-title":"A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer","volume":"18","author":"Chen","year":"2011","journal-title":"Ann Surg Oncol"},{"key":"2026092110202123000_jmg-2026-111804v1.28","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26398"},{"key":"2026092110202123000_jmg-2026-111804v1.29","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-013-9698-8"},{"key":"2026092110202123000_jmg-2026-111804v1.30","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000000446"},{"key":"2026092110202123000_jmg-2026-111804v1.31","doi-asserted-by":"crossref","first-page":"E1305","DOI":"10.1055\/s-0042-112582","article-title":"Chromoendoscopy in combination with random biopsies does not improve detection of gastric cancer foci in CDH1 mutation positive patients","volume":"4","author":"H\u00fcneburg","year":"2016","journal-title":"Endosc Int Open"},{"key":"2026092110202123000_jmg-2026-111804v1.32","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.gie.2018.02.008","article-title":"Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease","volume":"87","author":"Gullo","year":"2018","journal-title":"Gastrointest Endosc"},{"key":"2026092110202123000_jmg-2026-111804v1.33","doi-asserted-by":"crossref","first-page":"367","DOI":"10.17235\/reed.2020.6720\/2019","article-title":"Random biopsies in patients harboring a CDH1 mutation: time to change the approach?","volume":"112","author":"Castro","year":"2020","journal-title":"Rev Esp Enferm Dig"},{"key":"2026092110202123000_jmg-2026-111804v1.34","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1055\/a-1157-8678","article-title":"Gastroscopic surveillance with targeted biopsies compared with random biopsies in CDH1 mutation carriers","volume":"52","author":"van Dieren","year":"2020","journal-title":"Endoscopy"},{"key":"2026092110202123000_jmg-2026-111804v1.35","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1001\/jamasurg.2020.3356","article-title":"Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies","volume":"155","author":"Vos","year":"2020","journal-title":"JAMA Surg"},{"key":"2026092110202123000_jmg-2026-111804v1.36","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13112622","article-title":"CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance, and Secondary Cancer Risk Postulation","volume":"13","author":"Benesch","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026092110202123000_jmg-2026-111804v1.37","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-020-00197-y"},{"key":"2026092110202123000_jmg-2026-111804v1.38","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1097\/SLA.0000000000005626","article-title":"Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study","volume":"276","author":"Bres","year":"2022","journal-title":"Ann Surg"},{"key":"2026092110202123000_jmg-2026-111804v1.39","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1001\/jamasurg.2021.5118","article-title":"Association Between Hereditary Lobular Breast Cancer Due to CDH1 Variants and Gastric Cancer Risk","volume":"157","author":"Gamble","year":"2022","journal-title":"JAMA Surg"},{"key":"2026092110202123000_jmg-2026-111804v1.40","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1002\/ijc.70044","article-title":"Performance of upper gastrointestinal endoscopy in CDH1 germline pathogenic variant carriers: A multicenter study","volume":"157","author":"Castillo-Iturra","year":"2025","journal-title":"Int J Cancer"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2026-111804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:20:35Z","timestamp":1790011235000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2026-111804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":40,"alternative-id":["10.1136\/jmg-2026-111804"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2026-111804","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}