There are no effective screening regimens or surveillance modalities. Upper endoscopy with biopsy, endoscopic ultrasound, and/or chemoendoscopy appears to have no value in the detection of early and potentially curable multifocal submucosal gastric cancer. Surveillance endoscopy was unable to detect early cancer found in prophylactic total gastrectomy specimens. Surveillance modalities that can identify carriers who would benefit from early prophylactic gastrectomy are being evaluated. These include endoscopic surveillance with optical coherent tomography and molecular marker analysis of gastric lavage fluid.

There are no known nonsurgical prevention strategies for CDH1 carriers at this time. However, prophylactic treatment with demethylating agents, such as 5-azadeoxycystidine, has been suggested based on the observation that some tumors demonstrated methylation of the CDH1 promoter as the ''second hit.''[16,17] A recent report also suggests that E-cadherin methylation is an early event in gastric carcinogenesis and is initiated by H. pylori infection.[18] Another potential strategy is early and annual screening and complete eradication of H. pylori infection in CDH1 carriers, similar to the recommendation of the Maastricht 2-2000 Consensus

Table 3 Molecular techniques for genetic testing


Features and limitations

DNA sequencing Exon scanning

Protein truncation testing (PTT) Southern blot

Allele-specific oligonucleotide (ASO) Recombination-specific polymerase chain reaction (PCR)

Highest overall level of sensitivity

May detect variants of unknown clinical significance

Intronic mutations, genomic rearrangements may be missed

Higher cost, longer turnaround time than most other techniques

Rapid, low-cost initial screening technique

Requires sequencing to confirm the exact nature of the mutation

Useful for detecting loss-of-function mutations

Change-of-function mutations may be missed

Requires sequencing to confirm the exact nature of the mutation

Can screen for large genomic rearrangements

Will not detect point mutations or small deletions and insertions

High level of sensitivity for mutation-specific testing

Rapid, low-cost technique

Only screens for specific known mutations

Can detect specific genomic rearrangements

Only screens for specific known rearrangements

Table 4 Long-term complications after total gastrectomy

• Esophagojejunostomy anastomotic stricture (10-15%)

Lactose intolerance: occurs in approximately 50% of patients

• Malabsorption and steatorrhea: occur in 66-100% of patients due to relative pancreatic insufficiency, bacterial overgrowth, and rapid intestinal transient time

• Postprandial fullness and dumping syndrome: occur in 20-30% of patients due to rapid emptying of hyperosmotic carbohydrates into the small bowel and the release of enteric hormones

• Iron and vitamin B12 deficiency

• Weight loss: approximately 10% (average of 4-7 kg) of the preoperative weight (mainly body fat) during the first year

Report, stating that patients with a family history of gastric cancer should undergo H. pylori eradication therapy.[19] Several analyses showed an association between H. pylori seropositivity (especially CagA-positive strains) and gastric cancer, particularly in younger patients and non-cardia adenocarcinoma.1-20,21-1 The increased prevalence of H. pylori infection and H. pylori-associated precan-cerous changes has also been observed in first-degree relatives of sporadic gastric cancer patients.[21] In a cluster of familial gastric cancer, genetic abnormalities were found in first-degree relatives only in the presence of H. pylori infection.[22] Successful eradication of H. pylori improves the secretion of vitamin C into gastric juice, which may increase protection against gastric cancer. A randomized, placebo-controlled trial in people at high risk for developing gastric cancer showed that effective anti-H. pylori treatment and dietary supplementation with antioxidants were statistically significant in promoting the regression of precancerous lesions.[23]

The optimal clinical management of E-cadherin germline mutation carriers is unclear and controversial, especially in regard to the role of prophylactic gastrectomy. Prophylactic total gastrectomies in five patients (ages 37, 39, 40, 41, and 47 years) with a known E-cadherin germline mutation were first reported in 2001.[24] All five patients had negative endoscopic evaluation, yet all postgastrectomy specimens demonstrated occult microscopic foci of intramucosal signet ring cell adenocarcino-ma in various regions of the stomach. Huntsman et al.[25] reported similar findings in another five subjects (ages between 22 and 40 years). At present, the International Gastric Cancer Consortium (IGCC) recommends testing for E-cadherin alterations in patients with diffuse gastric cancer and suggests prophylactic total gastrectomy in carriers of E-cadherin germline mutations.[14] Complete removal of gastric mucosa should be confirmed intra-operatively on frozen section by a demonstration of esophageal and duodenal mucosa at the proximal and distal margins, respectively. Prophylactic gastrectomy also has the potential benefit of anxiety reduction and perhaps improvement of the overall quality of life in these mutation carriers. However, there are several concerns for adopting a universal policy of prophylactic gastrectomy in CDH1 mutation carriers. Prophylactic gastrectomy would result in a nontherapeutic surgery in 30% of these carriers. The biological behavior of these early submucosal multifocal lesions is not known. The age at which prophylactic surgery should be recommended is not clear. Although prophylactic gastrectomy at a young-enough age reduces the risk of gastric cancer development, its effect on the overall life expectancy is unknown and unproven. Carriers of the CDH1 gene are at increased risk for developing other malignancies and require regular screening. Gastrectomies, in general, are associated with operative mortality of 5% or less and a morbidity rate of 35-40%. Significant long-term sequels (Table 4) can have a significant negative impact on quality of life. Clinical studies have shown that patients with jejunal pouch reconstruction have better food intake, fewer postprandial symptoms, less weight loss, and a chance for a better quality of life. However, it is expected that prophylactic total gastrectomy in these otherwise healthy young individuals would have lower morbidity and less negative impact on quality of life.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment