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The authors V. Devezas and M. Baptista contributed equally to the first authorship.
The authors F. Carneiro and J. Barbosa contributed equally to the last authorship.
All of the authors contributed to this article. All authors approved the final manuscript.
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Hereditary diffuse gastric cancer is an autosomal dominant cancer susceptibility syndrome characterized by increased risk for gastric cancer and lobular breast cancer and mainly caused by germline alterations in the CDH1 gene.
This was an observational, retrospective, and unicentric study. Clinical data from patients with hereditary diffuse gastric cancer who had risk-reducing total gastrectomy between June 2005 and January 2018 were collected. A thorough histopathological analysis of gastrectomy specimens was performed, according to the current recommendations of the International Gastric Cancer Linkage Consortium.
In 59 families fulfilling the clinical criteria for CDH1 testing, we identified the same CDH1 missense pathogenic variant in five families. Thirty-nine CDH1 carriers were identified. Four CDH1 carriers died with advanced diffuse gastric cancer, 19 chose risk-reducing total gastrectomy, and 16 opted for endoscopic surveillance, despite being duly informed of the limited utility of periodic gastric endoscopy in this context. The 19 asymptomatic CDH1 carriers undergoing surgery had an age range of 14–63 years (median, 39 years) and the median hospital stay was 6 days. Laparoscopic total gastrectomy was performed on four of 19 CDH1 carriers. There were no cases of mortality or major morbidity in this procedure. The range of weight loss in our series was 13%. Histopathological examination of the entirety of gastric mucosa revealed intramucosal gastric carcinoma foci (pT1a) in 17 of 19 (89.5%) total gastrectomy specimens. No lymph node metastases were detected (pN0).
Risk-reducing total gastrectomy remains the best clinical management for patients with hereditary diffuse gastric cancer harboring a germline, pathogenic CDH1 variant. In our series, intramucosal carcinoma foci were found in the great majority (89.5%) of CDH1 carriers.