DOI: 10.1097/SLA.0b013e31816a5092

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Issn Print: 0003-4932

Publication Date: 2008/04/01


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Identifying and Preventing High-risk Gastric Cancer Individuals With CDH1 Mutations

Jeffrey A. Norton; James M. Ford

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Author Information: janorton@stanford.edu

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We thank Ziogas et al for their letter concerning our article.1 We agree with their comments about the value of prophylactic gastrectomy in these patients. As the letter points out and our report demonstrates, even though the literature predicts that the probability of gastric cancer is approximately 70% and each preoperative diagnostic study suggests that no patient had gastric cancer, each patient (n = 6) had a multifocal T1, N0 signet ring cell adenocarcinoma of the stomach. Thus, as they point out the gastric surgery was really therapeutic, and not merely prophylactic. Furthermore, we have performed the same surgery on 2 subsequent patients from 2 additional families. Each was found to have multifocal signet ring cell adenocarcinoma of the stomach without lymph node metastases.2 When we did stomach surgery on CDH1 mutation family patients with symptoms, 3 of 4 patients had T3 or T4 signet ring cell adenocarcinoma with nodal metastases.2 The pathology of the 8 patients without symptoms diagnosed only by CDH1 mutation demonstrated that the signet ring cell cancer was multifocal with an average of 8 different sites throughout the stomach. The proximal third of the stomach was the most common site, as 70% of the foci occurred in this location. These data suggest that total gastrectomy is clearly indicated, and surgeons should not leave a proximal cuff of stomach.
A total of 154 lymph nodes were removed from these 8 patients, and none had any metastases. The fact that the nodes of patients diagnosed by CDH1 mutation are negative for cancer has very important prognostic significance. None of these patients was treated with chemotherapy or radiation therapy, and all are alive and disease-free. We argue that the predicted long-term survival rate for these patients with negative nodes is greater than 80%, so no additional treatment is indicated. Whereas if there is similar T stage and positive nodes, long-term survival decreases to 58%.3 We recommend continuing to perform lymph node dissection because positive lymph nodes are a deciding factor for chemotherapy. Furthermore, our recommended technique of a D2 lymph node dissection means that we remove the greater omentum and lymph nodes in the distribution of the left gastric artery. In our series, this has resulted in no complications, no extra blood loss, or prolongation of operating time. In fact, the mean hospitalization time of the last 6 patients was only 5 days. Because we believe that these patients have cancer, a cancer operation is indicated.
A bigger issue is when to perform gastrectomy on a patient from a family who is asymptomatic and known to be a CDH1 mutation carrier. A major problem in the management is confirmed by our study.1 State-of-the-art screening procedures have not been diagnostic even with the use of multiple blind biopsies. Our careful pathologic study of the distribution of these signet ring cell cancers within the stomach may help with screening.2 It now appears that endoscopy should focus primarily on the proximal third of the stomach. Because of the weight loss and chronic morbidity of total gastrectomy, we do not believe that it should be done at a young age as the accompanying letter suggests. Rather, we think that careful history and analysis of the family pedigree is indicated to help determine the youngest age that a member developed gastric cancer. We recommend surgery (total gastrectomy and D2 lymph node dissection) 5 years earlier than the youngest family member with a diagnosis of gastric cancer.

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