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Diagnosing gastric cancer in its early stages provides the best chance for survival but is a difficult task. Symptoms due to gastric cancer often do not appear until the disease is more advanced and are generally non-specific. When the diagnosis of gastric cancer is established, it is most often advanced. A total gastrectomy (surgery to remove the entire stomach) is indicated in an individual with HDGC and any evidence of stomach cancer, as typically even a small number of cancer cells on a biopsy means there are multiple areas of hidden tumor throughout the entire stomach.
Genetic testing for CDH1 gene mutations
For those individuals carrying known CDH1 mutations, but without evidence for gastric cancer, recommendations include intensive and regular screening with endoscopy (a flexible scope passed down the throat to examine the surface of the stomach and take small samples or biopsies) every 6-12 months with multiple biopsies of any suspicious site as well as random biopsies throughout the stomach.
Screening for gastric cancer
Endoscopy is generally considered to be the best method to screen for gastric cancer, but diagnosing diffuse gastric carcinoma is most difficult, as these cancer cells do not form a visible mass, but rather spread under the surface of the stomach as single cells or clustered islands of cells. New techniques for diagnosing diffuse gastric cancer cells are under investigation but none have been proven effective in early detection at this time.
Treatment for gastric cancer with HDGC
Therefore, individuals from HDGC families should also discuss the option of prophylactic (preventative) total gastrectomy. The lifetime risk of stomach cancer is very high in CDH1 carriers and without a proven effective screening test, surgery is a realistic and reasonable option. Gastrectomy in CDH1 gene carriers has to date been performed in only a very few patients. However, our experience at Stanford suggests that this may be the best approach to prevention at the current time. Meet our team of experts at the Stanford Cancer Genetics Program.
Our experience and expertise
We have studied individuals from several families with HDGC (including one large family with 10 CDH1 mutation carriers) to evaluate the usefulness of several screening tests including:
Upper GI endoscopy with random gastric biopsies
High-magnification endoscopy with methylene blue chromoscopy
CT scan and PET scans
Circulating tumor markers
All these patients elected to proceed with a prophylactic gastrectomy following these studies. In every patient to date, all screening tests have been normal, and yet on microscopic analysis after surgery, every patient had multiple clusters of invasive signet ring gastric cancer throughout the stomach. As all these clusters were very early, Stage 1, the likelihood that surgery provided a complete cure is very high. Nevertheless, this experience makes it difficult to have confidence in our current ability to adequately screen for gastric cancer in HDGC families.
We and other groups are exploring new technologies and approaches for screening, but consideration of a prophylactic gastrectomy should be seriously discussed as part of genetic counseling for HDGC. Learn more about genetic counseling at Stanford. The decision to carry out a prophylactic gastrectomy must consider the 1-2% risk of death associated with the procedure and nearly 100% risk of long term complications such as chronic diarrhea, dumping syndrome and weight loss, 10% rate of post-surgical complications including infection, and leakage at the surgery site as well as the fact that not every CDH1 carrier will develop gastric cancer.
HDGC patients seriously considering prophylactic gastrectomy should make sure their surgeon is well experienced in this procedure and is knowledgeable about HDGC cancer risks to ensure that the best technique is chosen while minimizing the risk of surgical complications.
There remain many open questions that will require long-term follow up of HDGC families, including whether the presence of hidden cancer cells found after surgery absolutely predicts for eventual progression to invasive gastric cancer and at what age is surgical prevention most appropriate.
Clearly, any such procedures should be discussed with genetic and surgical professionals at an established high-risk cancer program. Future studies will need to evaluate the effect on quality of life after preventative gastrectomy, long-term survival, and the risk for development of other cancers.
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