Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Surgery. 2011 Mar;149(3):347-55. doi: 10.1016/j.surg.2010.07.005. Epub 2010 Aug 17.
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.
Patients with germline CDH1 mutation who underwent multidisciplinary counseling followed by prophylactic total gastrectomy were reviewed.
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%.
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.
CDH1 基因的胚系突变，该基因编码 E-钙黏蛋白黏附蛋白，较为罕见，但估计遗传性弥漫性胃癌的终身风险为 87%。据报道，这种情况下只有不到 100 例预防性全胃切除术。
对接受多学科咨询后行预防性全胃切除术的 CDH1 胚系突变患者进行回顾性分析。
10 例（6 男 4 女）患者的中位年龄为 42 岁（范围 26-51），于 2006 年至 2009 年间行预防性全胃切除术。所代表的 6 个家族中，有 4 个错义突变、1 个移码突变和 1 个剪接位点突变。基因检测到手术的中位时间为 3 个月（范围 1-7）。所有患者术前均行上消化道内镜检查，仅发现 1 例弥漫性胃癌病灶。行预防性全胃切除术后，广泛的病理分析显示 9 例患者有多达 77 个非浸润性癌灶，其中 2 例患者有 4-12 个 T1 浸润性癌灶。中位手术时间为 213 分钟；无吻合口漏，住院时间为 7-8 天。1 例患者术后 30 天内发生并发症（肺栓塞），3 例患者发生晚期并发症（2 例小肠梗阻和 1 例吻合口狭窄）。6 个月时的中位体重减轻为 19%。
大多数 CDH1 基因胚系突变患者中年时会出现非浸润性或浸润性胃癌病灶。连续上消化道内镜检查提供的筛查不足。预防性全胃切除术是明确治疗的首选方法。
