{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:19:31Z","timestamp":1771305571291,"version":"3.50.1"},"reference-count":14,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Introduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable. Methods: We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher\u2019s exact test. Results: In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology (p = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue (p = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again. Conclusions: Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable.<\/jats:p>","DOI":"10.3390\/cancers14030728","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T01:46:08Z","timestamp":1643593568000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes"],"prefix":"10.3390","volume":"14","author":[{"given":"Joseph D.","family":"Forrester","sequence":"first","affiliation":[{"name":"Department of Surgery, Stanford University Medical Center, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8372-4722","authenticated-orcid":false,"given":"Deshka","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University Medical Center, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Ford","sequence":"additional","affiliation":[{"name":"Departments of Medical Oncology, Stanford University Medical Center, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teri A.","family":"Longacre","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uri","family":"Ladabaum","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Stanford University Medical Center, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Fry","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University Medical Center, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University Medical Center, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1016\/S1470-2045(14)71016-2","article-title":"Familial gastric cancer: Genetic susceptibility, pathology, and implications for management","volume":"16","author":"Oliveira","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_2","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":"ref_3","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/32918","article-title":"E-cadherin germ line mutations in familial gastric cancer","volume":"392","author":"Guilford","year":"1998","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.scr.2015.02.002","article-title":"CDH2 and CDH11 act as regulators of stem cell fate decisions","volume":"14","author":"Alimperti","year":"2015","journal-title":"Stem Cell Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1053\/gast.2001.29611","article-title":"Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families","volume":"121","author":"Pharoah","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_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":"ref_7","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1097\/01.sla.0000254370.29893.e4","article-title":"CDH1 truncating mutations in the E-cadherin gene: An indication for total gastrectomy to treat hereditary diffuse gastric cancer","volume":"245","author":"Norton","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/PAS.0b013e31815e7f1a","article-title":"Risk-reducing Total Gastrectomy for Germline Mutations in E-cadherin (CDH1): Pathologic Findings With Clinical Implications","volume":"32","author":"Rogers","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_9","first-page":"1","article-title":"Laparoscopic versus open gastrectomy for gastric cancer","volume":"3","author":"Best","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1001\/jamaoncol.2020.3152","article-title":"Morbidity and Mortality of Laparoscopic vs Open Total Gastrectomy for Clinical Stage I Gastric Cancer","volume":"6","author":"Liu","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1097\/SLA.0000000000002030","article-title":"Total Gastrectomy for Hereditary Diffuse Gastric Cancer at a Single Center: Postsurgical Outcomes in 41 Patients","volume":"266","author":"Strong","year":"2017","journal-title":"Ann. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1097\/SLA.0000000000000446","article-title":"The impact of prophylactic total gastrectomy on health-related quality of life: A prospective cohort study","volume":"260","author":"Worster","year":"2014","journal-title":"Ann. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1007\/s11605-016-3287-8","article-title":"Prophylactic Total Gastrectomy: A Prospective Cohort Study of Long-Term Impact on Quality of Life","volume":"20","author":"Muir","year":"2016","journal-title":"J. Gastrointest. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e386","DOI":"10.1016\/S1470-2045(20)30219-9","article-title":"Hereditary diffuse gastric cancer: Updated clinical practice guidelines","volume":"21","author":"Blair","year":"2020","journal-title":"Lancet Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/3\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:11:35Z","timestamp":1760134295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/3\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,30]]},"references-count":14,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cancers14030728"],"URL":"https:\/\/doi.org\/10.3390\/cancers14030728","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,30]]}}}