Elsevier

Surgery

Volume 149, Issue 3, March 2011, Pages 347-355
Surgery

Original Communication
Prophylactic total gastrectomy for individuals with germline CDH1 mutation

Presented at the 63rd Annual Meeting of the Society of Surgical Oncology, St. Louis, Missouri, March 3–7, 2010
https://doi.org/10.1016/j.surg.2010.07.005Get rights and content

Background

Germline mutation of the CDH1 gene, which encodes for the E-cadherin adhesion protein, is rare but confers an estimated lifetime risk of hereditary diffuse gastric cancer of 87%. Fewer than 100 prophylactic total gastrectomies have been reported for this condition.

Methods

Patients with germline CDH1 mutation who underwent multidisciplinary counseling followed by prophylactic total gastrectomy were reviewed.

Results

Ten patients (6 male, 4 female) with a median age of 42 years (range, 26–51) underwent prophylactic total gastrectomy between 2006 and 2009. Of the 6 families represented, there were 4 missense, 1 frameshift, and 1 splice site mutation. Median time from genetic testing to surgery was 3 months (range, 1–7). All patients had an upper endoscopy before surgery, identifying only 1 patient with a focus of diffuse gastric cancer. After prophylactic total gastrectomy, extensive pathologic analysis demonstrated that 9 patients had up to 77 foci of noninvasive cancer, and 2 of these patients had 4–12 foci of T1 invasive cancer. Median operative time was 213 minutes; there were no anastomotic leaks, and the length of stay was 7–8 days. One patient had a complication within 30 days (pulmonary embolism), and 3 patients had late complications (2 small bowel obstructions and 1 anastomotic stricture). Median weight loss at 6 months was 19%.

Conclusion

The majority of patients with germline CDH1 mutation have foci of noninvasive or invasive gastric cancer by middle age. Serial upper endoscopies provide inadequate screening. Prophylactic total gastrectomy is the procedure of choice for definitive treatment.

Section snippets

Patients

All patients with germline CDH1 mutations who were referred to our institution for prophylactic total gastrectomy between April 2006 and March 2009 are included in this report. Patients were evaluated preoperatively by a multidisciplinary team that included a genetic counselor, gastroenterologist, surgical oncologist, and nutritionist. A complete history and physical examination were performed, CDH1 mutation testing records were obtained, and prior endoscopy reports and other relevant

Results

Ten patients (6 male, 4 female) from 6 different families with known CDH1 mutation were referred to our institution for surgical evaluation from April 2006 to March 2009. There were 6 males and 4 females. The median age was 42 years (range, 27–51).

All 6 families had a strong family history of GC and 5 of 6 families met IGCLC criteria.8 The first patient to undergo prophylactic total gastrectomy for germline CDH1 mutation at our institution has been previously described.21 Figure 1 demonstrates

Discussion

There are few series on prophylactic total gastrectomy for germline CDH1 mutation given the rarity of this mutation and the magnitude of the surgery. In this article, we have described our results in 10 patients with germline CDH1 mutation who underwent prophylactic total gastrectomy. All 10 patients had a strong family history of gastric cancer.8 Preoperative endoscopy identified a focus of diffuse gastric cancer in only 1 patient. Similar to prior series, pathologic analysis of gastrectomy

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      All surveillance programmes should be audited and ideally included in a prospective clinical trial. Recent studies from expert centres in HDGC surveillance endoscopy report that signet ring cell carcinoma lesions are detected in gastric biopsies in 40–61% of these carriers of CDH1 variants, most often at the baseline endoscopy (van Dieren J, Netherlands Cancer Institute, personal communication),38,39 although older studies report a lower detection rate of 9–16%.53–56 High-definition endoscopes, image-enhancing techniques (eg, narrow band imaging), and the experience of the endoscopist and pathologist are all factors likely to be related to the increase in signet ring cell carcinoma detection rates in more recent studies.

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