Intestinal Metaplasia

of the StomachA Review

Kent Humble MDAssistant Professor of Family Medicine

LSU School of Medicine

Objectives

Discuss relationship between gastric IM and gastric cancer

Review pathophysiology and epidemiology of gastric IM

Review guidelines concerning endoscopic surveillance

Gastric Cancer

Gastric Cancer in US

US Incidence byEthnic Background

2008

Int J Cancer 2010;127(12):2893

Highest incidence in East Asia, Eastern Europe, and Western South America

Worldwide Incidence Rates

Intestinal Type

Diffuse Type

Gastric CancerIntestinal Type

70-80% of cases

Predominantly in high risk areas

Develops from precursors

Male to Female 2:1

Diffuse Type

20-30% of cases

Uniform across countries

Younger age (mean 38)

No identified precursors

Male to Female 1:1

Older age (mean 69)

Environmental factors

Genetic factors

What is Gastric IM?

GastritisAtrophic Gastritis

IntestinalMetaplasi

a

Dysplasia

Cancer

Correa Progression

Gastric IM is likely the 'breaking point' between chronic gastritis and dysplasia

Am J Physiol Gastrointest Liver Physiol 291: G999 –G1004, 2006

What is Gastric IM?• Foci appear at junction of Antrum & Body, often

at Angularis

• Enlarge, coalesce, extending to Antrum & Body

• Small foci of dysplasia may appear in areas of IM, subject to sampling error

• Severity & tempo of progression may be influenced by virulence of H Pylori (?cagA), environmental, host genetic factors

Epidemiology of Gastric IM

EPIDEMIOLOGY OF IM

H. pylori infection significantly raises IM prevalence

Increases with patient age

Higher in first degree relatives with gastric cancer

Cancer Epidemiol Biomarkers Prev 1992;1:293–296.

Found in up to 25% US Adults13% of Caucasians

50% of Blacks/Hispanics

• Systematic review:

Gastroenterology 2008; 134: 945-952Gastroenterology 2008; 134: 945-952

Am J Surg Pathol 2000; 24: 167-176Am J Surg Pathol 2000; 24: 167-176

EPIDEMIOLOGY OF IM

• Dutch study:Histology based

• 61,707 pts with IM

• 874 developed gastric CA over 10 years

• 0.18%yearly

Patients with IM Gastric cancer incidence varied 0-10%

ARE ALL PATIENTS WITH IM AT EQUAL RISK OF

GASTRIC CANCER?

ARE ALL PATIENTS WITH IM AT EQUAL RISK OF GASTRIC

CANCER?

Int J Cancer 2010; 127: 2654-2660Int J Cancer 2010; 127: 2654-2660

The presence of incomplete-type IM is associated with a higher gastric cancer risk compared to complete-type IM.

Spain study:Mean follow-up 12.8

years

• Complete IM: 1 of 104 pts (0.96%) developed gastric CA

• Incomplete IM: 16 of 88 pts (18.2%) developed gastric CA

ARE ALL PATIENTS WITH IM AT EQUAL RISK OF GASTRIC

CANCER?

Gastric cancer risk is associated with IM topography.

Am J Gastroenterol 2000; 95: 1431-1438Am J Gastroenterol 2000; 95: 1431-1438

Columbia study:

Compared to antral predominate (focal)

• Extension through angularis- risk 5.7 fold

• Antrum plus body (diffuse)- risk 12.2 fold

Incomplete IM presents as diffuse more commonly than focal

ARE ALL PATIENTS WITH IM AT EQUAL RISK OF GASTRIC

CANCER?

Extensive IM increases the risk of progression to dysplasia.

Hum Pathol 2006; 37 1489-1497Hum Pathol 2006; 37 1489-1497

IM may be considered extensive when it involves at least two locations or when it is moderate or marked in more than one biopsy specimen

Italian Study

• The rate of gastric cancer appeared to increase with increasing IM extension

IS IM REVERSIBLE?

IS IM REVERSIBLE?H. pylori eradication may slow IM progression.

Gut 2004; 53: 1244-1249Gut 2004; 53: 1244-1249

Hong Kong Study

• 537 pts with IM and H. Pylori randomized to treatment or placebo

• H Pylori eradication prevented IM progression

• Odds ratio 0.48 (95% CI: 0.32-0.74)

IS IM REVERSIBLE?IM does not appear to regress following H. pylori

eradication.

Helicobacter 2007; 12 Suppl 2: 32-38Helicobacter 2007; 12 Suppl 2: 32-38

Digestion 2011; 83: 253-260Digestion 2011; 83: 253-260

Meta-analysis of 7 studies

• Unlike atrophy, no significant IM regression occurred following H. Pylori eradication

Meta-analysis of 12 studies

• Atrophy improved in the body but not antrum• IM did not improve after

eradication

IS IM REVERSIBLE?

Aliment Pharma- col Ther 2000; 14: 1303-1309Aliment Pharma- col Ther 2000; 14: 1303-1309

J Gastroenterology Hepatol 2010; 25: 48-53J Gastroenterology Hepatol 2010; 25: 48-53

Taiwan Study• IM regressed in 24% of 33 pts following 8 wks of treatment

with celecoxib 200 mg/d after H. Pylori eradication

• 6 months of ascorbic acid qOD following H. Pylori eradication helped reduce IM

Italian Study

What About Surveillance?

What About Surveillance?

Dutch study: Can extension be predicted?

88 patients with previous IM on gastric biopsyRepeat EGD & blood tests done

Most important predictors of extensive IM:

Family history of gastric cancerAlcohol use 10ml per dayMarked IM of index biopsyPepsinogen I/II ratio < 3.0

Gastrointestinal Endoscopy Vol 70, No.1:2009

PG I & II

PG II

PG II

What do Guidelines say?

2006 ASGE Guideline

• Endoscopic surveillance for gastric intestinal metaplasia has not been extensively studied in the U.S. and therefore cannot be uniformly recommended

• Patients at increased risk for gastric cancer due to ethnic background or family history may benefit from surveillance

• Endoscopic surveillance should incorporate topo- graphic mapping of the entire stomachGastrointestinal Endoscopy Volume 63, No.

4 : 2006

2012 European Guideline

• Conventional white light endoscopy cannot accurately differentiate between benign and precancerous gastric conditions/lesions

• Magnification chromoendoscopy (MCE) or narrow-band imaging (NBI) endoscopy with or without magnification may be offered in these cases as it improves diagnosis of such lesions

• At least four non-targeted biopsies of the proximal and distal stomach, on the lesser and greater curvatures, are needed for adequate assessment of premalignant gastric conditionsVirchows Arch. 2012 Jan;460(1):19-46. Epub 2011

Dec 22.

2012 European Guideline

• Patients with extensive atrophy and/or extensive IM should be offered endoscopic surveillance every 3 years

• Further studies are needed however, to accurately estimate the cost–effectiveness of such an approach

• Patients with mild to moderate atrophy/IM only in Antrum do not need follow-up

• Sub-typing of IM is not recommended for clinical practice

Virchows Arch. 2012 Jan;460(1):19-46. Epub 2011 Dec 22.

• COX-2 inhibitors, or the use of dietary supplementation with antioxidants (ascorbic acid and beta-carotene) are not endorsed as approaches to decrease the risk of progression of gastric precancerous lesions

2012 European Guideline

• Neither age, gender, H. pylori virulence factors, or host genetic variations change these clinical recommendations

Virchows Arch. 2012 Jan;460(1):19-46. Epub 2011 Dec 22.

2012 European Guideline

Virchows Arch. 2012 Jan;460(1):19-46. Epub 2011 Dec 22.

IM may be considered extensive when it involves at least two locations or when it is moderate or marked in more than one biopsy specimen

What's new?OLGA

Operative Link for Gastritis Assessment

OLGIMOperative link on Gastric Intestinal Metaplasia

Assessment.

Gastritis staging systems that arrange histological phenotypes of gastritis along a scale of progressively increasing gastric cancer risk, from the lowest (stage 0) to the highest (stage IV).

khumbl@lsuhsc.edu

Thank You