Stomach cancer primary prevention
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]
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Overview
Effective measures for the primary prevention of stomach cancer include smoking cessation, helicobacter pylori infection eradication, and having a balanced diet rich in fruits and vegetables.
Primary prevention
Enviromental changes
- Tobacco use is the single greatest avoidable risk factor for cancer mortality worldwide, causing an estimated 22% of cancer deaths per year. In 2004, 1.6 million of the 7.4 million cancer deaths were due to tobacco use. Due to the seriousness of reversing the tobacco epidemic, the WHO has implemented initiatives to monitor the extent of the problem and to help countries putting in place the effective measures to combat the tobacco epidemic. These tools are essential components of national cancer prevention programmes and will play a key role in reducing cancer incidence.
- Dietary modification is another important approach to cancer control. There is a link between physical inactivity and obesity to many types of cancer. Diets with low consumption of red meat, high in fruits and vegetables may have a protective effect against many cancers. (They are also associated with a lower of cardiovascular disease.) The World Health Assembly adopted the WHO Global Strategy on Diet, Physical Activity and Health, in May 2004 to reduce deaths and diseases.
H.pylori eradication
- Recent meta-analyses have each found that the incidence of metachronous gastric cancer following the endoscopic resection of a gastric neoplasm was reduced by the eradication of H. pylori infection ( 31–33 ).
- Most recently, a meta-analysis comprising 24 studies (22 out of which were conducted in Asia) confirmed a lower rate of metachronous EGC following treatment of H. pylori infection; the incidence rate ratio was 0.54 (95% CI 0.46–0.65) ( 34 ).
Recommended first-line therapies for H pylori infection:
| Regimen | Drug dose | Dosing frequency | Duration(days) | FDA approval |
|---|---|---|---|---|
| Clarithromycin triple | PPI(standard or double dose
Clarithromycin(500mg) Amoxicillin(1gm)or Metronidazole(500mg TID) |
BID | 14 days | YES† |
| Bismuth Quadruple | PPI(standard dose)
Bismuth subcitrate (120-300mg)or Subsalicylate (300mg) Tetracyclin(500mg) Metronidazole(250-500mg) |
BID
QID QID TID to QID (500mg) |
10-14 days | NO‡ |
| Concomitant | PPI (standard dose)
Clarithromycin (500mg) Amoxicillin(1gm) Nitroimidazole(500mg)c |
BID | 10 -14 days | NO |
| Sequential | PPI(standard dose)+Amoxicillin(1gm)
PPI,Clarithromycin(500mg)+Nitroimidazole(500mg)c |
BID
BID |
5-7 days
5-7 days |
NO |
| Hybrid | PPI(standard)+Amoxicillin(1gm)
PPI,Amoxicillin,Clarithromycin(500mg),Nitroimidazole(500mg)c |
BID
BID |
7 days
7 days |
NO |
| Levofloxacin triple | PPI(standard dose)
Levofloxacin(500mg) Amoxicillin(1gm) |
BID
QID BID |
10-14 days | NO |
| Levofloxacin sequential | PPI(standard or double dose)+Amoxicillin(1 gm)
PPI,Amoxicillin,Levofloxacin(500mg QD),Nitroimidazole(500mg)c |
BID
BID |
5-7 days | NO |
| LOAD | Levofloxacin(250mg)
PPI(double dose) Nitazoxanide(500mg)c Doxycycline(100mg) |
QD
QD BID QD |
7-10 days | NO |
| †: Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval, PPI, Clarithromycin, Metronidazole are not an FDA approved treatment regimen.
‡: PPI, Bismuth, Tetracycline, and metronidazole prescribed separately are not an FDA approved treatment regimen. However, Pylera, a combination product containing Bismuth subcitrate, Tetracycline, Metronidazole combination with PPI for 10 days is an FDA approved regimen.
c:Metronidazole or Tinidazole[1] | ||||
After the failure of first-line therapy, such patients should be considered for referral for salvage treatment.
| Salvage therapies for Helicobacter pylori infection | ||||
|---|---|---|---|---|
| Regimen | Drugs(doses) | Dosing frequency | Duration(days) | FDA approval |
| Bismuth quadruple |
|
BID
QID QID TID or QID |
14 | NO |
| Levofloxacin triple |
|
BID
QD BID |
14 | NO |
| Concomitant |
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BID
BID BID BID or TID |
10-14 | NO |
| Rifabutin triple |
|
BID
QD BID |
10 | NO |
| High-dose dual |
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TID or QID
TID or QID |
14 | NO |
- Whenever H. pylori infection is identified and treated, testing to prove eradication should be performed using:
- a urea breath test
- fecal antigen test
- biopsy-based testing at least 4 weeks after the completion of antibiotic therapy and after PPI therapy has been withheld for 1–2 weeks.
Screening
In countries with a high incidence of gastric cancer such as east asia countaries, universal screening is recommended. [17-19]
In Japan, population-based screening for gastric cancer is recommended for individuals older than 50 years with conventional double-contrast barium radiograph with photofluorography every year or upper endoscopy every two to three years [20,33,34].
Screening interval is recommended to be every two years but may be widened to a three-year rather than a two-year interval without significant effect [38-40].
Hereditary cancer prevention
Screening
In areas of low gastric cancer incidence, screening for gastric cancer with upper endoscopy should be reserved for specific high-risk subgroups [41-52].
Individuals at increased risk for gastric cancer include those with the following:
- Gastric adenomas
- Pernicious anemia
- Gastric intestinal metaplasia
- Familial adenomatous polyposis
- Lynch syndrome
- Peutz-Jeghers syndrome
- Juvenile polyposis syndrome
Prevention
- Asymptomatic patients with a family history of HDGC and CDH1 mutations have a high probability of developing signet ring cell adenocarcinoma of the stomach. Prophylactic total gastrectomy is recommended for patients with family history of HDGC and CDH1mutations [11].
- For patients with a CDH1 mutation but who are not from an HDGC family, we recommend individualized evaluation at an experienced center before prophylactic total gastrectomy is offered. [12].
- Prophylactic gastrectomy is often advised between age 20 and 30 [12]. Some suggest timing total gastrectomy in CDH1 mutation carriers at an age that is five years younger than the youngest family member who developed gastric cancer [20,21]. Older patients are less likely to benefit from a prophylactic gastrectomy than younger patients because of a shorter life-expectancy and a higher perioperative risk.
- patients who are older than 75 years should not undergo such a procedure, as their mortality from the procedure outweighs their mortality from gastric cancer. Decisions should be individualized based upon their comorbidities and the age of gastric cancer onset in their respective kindred.
Gatric polyps
Polypectomy should be performed for all known neoplastic polyps and for all polyps ≥1 cm in diameter, as biopsies alone cannot exclude foci of high-grade dysplasia or early gastric cancer.
In patients with multiple polyps, the largest polyp should be excised and representative biopsies obtained from the remaining polyps.
- Fundic gland polyps are associated with a low risk of progression to cancer.
- Small proximal gastric polyps should be biopsied in patients with FAP to confirm their histology.
- Large or irregular appearing polyps should be biopsied or resected completely to assess for dysplasia.
- Low-grade dysplasia is common in fundic gland polyps, but surgery should be reserved for high-grade dysplasia or cancer [1].
- Antral polyps are usually adenomas and should be completely resected endoscopically if possible.
Hyperplastic polyps occur in association with H. pylori-related atrophic gastritis. They have some malignant potential. Hyperplastic polyps >0.5 cm should be resected completely. Surveillance with upper endoscopy should be performed based on the cancer risk due to concurrent chronic atrophic gastritis and other risk factors for gastric cancer.
We perform an upper endoscopy for surveillance one year after initial resection of adenomatous gastric polyps. In individuals at high risk for gastric cancer, surveillance is continued indefinitely.
For type 1 and 2 gastric neuroendocrine tumors smaller than 1 to 2 cm, endoscopic resection is the treatment of choice.
Type 3 tumors are treated by partial or total gastrectomy with local lymph node resection.
Juvenile polyposis syndrome
- Screening the upper gastrointestinal tract with upper endoscopy starting at the age of 12 years.
- If polyps are detected, upper endoscopy should be repeated annually.
- In the absence of upper gastrointestinal tract polyps, upper endoscopy can be performed every two to three years [9].
Lynch syndrome
- Individuals with a pathogenic germline mutation in the DNA mismatch repair (MMR) or EPCAM genes have a definitive diagnosis of Lynch syndrome and should undergo screening for Lynch syndrome associated cancers. Screening recommendations for these individuals are discussed in detail below.
- Screening for Lynch syndrome related cancers should also be considered in individuals at risk for Lynch syndrome who have either not undergone genetic evaluation or have indeterminate genetic test results.
- extent of screening in these individuals can be individualized based on their personal and family cancer history and evidence of microsatellite instability on tumor testing. Individuals at risk for Lynch syndrome include:
Individuals in families meeting Amsterdam I or II criteria or revised Bethesda guidelines:
- Endometrial cancer prior to age 50 years
- First-degree relative of those with known MMR/EPCAM gene mutation
- Individuals with >5 percent chance of a MMR gene mutation by prediction models
References
- ↑ "www.nature.com" (PDF).