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

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. BID, twice daily; FDA, Food and Drug Administration; PPI, proton pump inhibitor; TID, three times daily; QD, once daily; QID, four times daily. c:Metronidazole or Tinidazole

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	PPI(standard dose) Bismuth subciitrate 120-300mg or sub salicylate 300mg Tetracycline 500mg Metronidazole 500mg	BID QID QID TID or QID	14	NO
Levofloxacin triple	PPI(standard dose) Levofloxacin 500mg Amoxicillin 1gm	BID QD BID	14	NO
Concomitant	PPI(standard dose) Clarithromycin 500mg Amoxicillin 1gm Nitroimidazole 500mg	BID BID BID BID or TID	10-14	NO
Rifabutin triple	PPI(standard dose) Rifabutin 300mg Amoxicillin 1gm	BID QD BID	10	NO
High-dose dual	PPI(standard to double dose) Amoxicillin 1gm TID or 750mg QID	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.

Hereditary cancer 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