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]

Stomach cancer Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Stomach Cancer from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic study of choice
Staging
History and Symptoms
Physical Examination
Laboratory Findings
Endoscopy and Biopsy
Chest X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Stomach cancer primary prevention On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Stomach cancer primary prevention All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Stomach cancer primary prevention
CDC on Stomach cancer primary prevention
Stomach cancer primary prevention in the news
Blogs on Stomach cancer primary prevention
Directions to Hospitals Treating Stomach cancer
Risk calculators and risk factors for Stomach cancer primary prevention

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

• Dietary modification is important approach to control gastric cancer. 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.
• 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

• The incidence of metachronous gastric cancer following the endoscopic resection of a gastric neoplasm was reduced by the eradication of H. pylori infection.

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)	BID BID	5-7 days 5-7 days	NO
Hybrid	PPI (standard) + Amoxicillin (1gm) PPI, Amoxicillin, Clarithromycin (500mg), Nitroimidazole (500mg)	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)	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. 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 120-300mg or 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.

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

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 CDH1 mutations.

• 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.

• Prophylactic gastrectomy is often advised between age 20 and 30.
• 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.
• 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