Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes

Area of Science:

• Oncology
• Gastroenterology
• Genetics

Background:

• Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant condition linked to CDH1 gene mutations.
• An estimated 70% of individuals with CDH1 mutations develop gastric cancer.
• This study investigated the high rate of signet ring cell cancer in asymptomatic CDH1 mutation carriers.

Purpose of the Study:

• To evaluate the role of total gastrectomy in patients with CDH1 mutations.
• To assess the incidence of signet ring cell cancer in asymptomatic carriers.
• To determine the short-term and long-term outcomes and quality of life after prophylactic gastrectomy.

Main Methods:

• Prospective study of 43 patients with CDH1 mutations (8 symptomatic, 35 asymptomatic).
• Total gastrectomy was recommended to all patients.
• Quality of life was assessed post-prophylactic gastrectomy; statistical comparisons used Fisher's exact test.

Main Results:

• 21/22 (95%) asymptomatic patients had signet ring cell cancer on final pathology, versus 3/13 (14%) preoperatively.
• Symptomatic patients had more advanced tumors (T3-T4) and lymph node involvement compared to asymptomatic patients (T1, N0).
• Prophylactic gastrectomy had no operative complications or deaths; survival was significantly better than in symptomatic patients (95% vs. 37%).

Conclusions:

• Total gastrectomy is indicated for individuals with inherited CDH1 mutations.
• Endoscopic screening is unreliable for detecting signet ring cell cancer.
• Delaying surgery until symptom onset leads to advanced disease and reduced survival; prophylactic surgery offers minimal complications and acceptable quality of life.