PRECANCEROUS LESIONS OF THE DIGESTIVE TRACT

An Evidence-Based Review
Zvi Bernstein M.D. LISSOD, Ukraine - Israel

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Grading recommendations

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Guyatt G , Gutterman D , Baumann MH et al. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians Task Force. Chest 2006 ; 129 : 174 81 .
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Fecal Occult Blood Testing

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BARRETTS ESOPHAGUS

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Incidence of Esophageal Adenocarcinoma & Other Malignancies 1975-2001

Esophageal AdenoCa

Melanoma Prostate Breast

Lung Colorectal

Pohl H & Welch G. JNCI 2005;97:142-6

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Key questions
Do current medical and surgical GERD treatments prevent esophageal adenocarcinomas? Are current screening and surveillance recommendations evidence-based? Have current screening and surveillance practices made a positive difference in preventing cancers and saving lives? Are current screening and surveillance practices justified based on the evidence?

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Estimated prevalence of Barretts esophagus

6-12% of patients who undergo EGD for GERD. Short-segment BE: 6-12% Long-segment BE: 1-5% 1-2% of unselected patients who undergo EGD Most cases go undetected in the general population [Autopsy data]. Perhaps 5% of patients with BE are currently being diagnosed.
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Is Helicobacter pylori infection a risk factor of Barretts esophagus?

No. Individuals with H. pylori infection/gastritis tend to have less problems with GERD. Thus, H. pylori infection may even have a protective effect against GERD and BE.

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Potential ways of reducing the cancer risk associated with Barretts esophagus Aggressive anti-reflux medical therapy or surgical fundoplication. Screen individuals with chronic GERD for BE. In patients known to have BE, perform surveillance to take biopsies to look for dysplasia.

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Does aggressive medical therapy for GERD reduce the cancer risk in patients with BE?
Proton pump inhibitors are the cornerstone of medical therapy for BE. They consistently result in symptomatic GERD relief and heal esophagitis. PPI therapy rarely results in significant regression of BE. While it makes theoretical sense that PPIs might reduce cancer risk in BE, there is little proof to date.

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Does anti-reflux surgery reduce cancer risk in patients with BE?

Anti-reflux surgery effectively alleviates GERD symptoms in BE patients. Effectiveness depends on the skill of the particular surgeon. Incomplete regression of BE is occasionally seen after surgery, but complete regression is rare. No credible evidence to date that anti-reflux surgery decreases cancer risk.
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Chemoprevention in BE?
Chemoprevention strategies in BE are just starting to be examined (e.g. COX-2 inhibitors). However, there is no current proof that chemopreventive agents effectively reduce cancer risk.

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Rationale for surveillance (EGD with Bx)

Endoscopic surveillance can detect dysplasia in BE, which is a further marker of cancer risk:
No dysplasia-- cancer risk 2% Low-grade dysplasia-- cancer risk 7% High-grade dysplasia-- cancer risk 22%

Asymptomatic cancers detected during surveillance are less advanced than those which present with symptoms. [If wait for symptoms, 5-year survival only 14%.]
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ACG Practice Guideline: Surveillance in Barretts esophagus

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Critical issues relating to screening and surveillance in Barretts esophagus

No data proving effectiveness of current strategies. Currently <5% of patients with esoph adenoCA diagnosed during BE screening & surveillance. Perhaps 40% of esoph adenoCA patients dont have GERD symptoms. Economic models of surveillance in pts with no dysplasia do not demonstrate cost effectiveness.

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So, where do we stand as regards our Key Questions?

Do current medical and surgical GERD treatments prevent esophageal adenocarcinomas? Sounds appealing, but no data to show that they do. Are current screening and surveillance recommendations evidence-based? No. Have current screening and surveillance practices made a positive difference in preventing cancers and saving lives? Their overall impact has been quite small. Are current screening and surveillance practices justified based on the evidence? Modification of current practice guidelines is needed.

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GASTRIC LESIONS

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Endoscopy. 2012 Jan;44(1):74-94.

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The basic principle

From: Potet F, Barge J. Ann Pathol. 1991. Review [Dysplasia in the digestive tract].

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Gastric carcinogenesis
Gastric cancer is believed to arise via a multistage process that includes chronic gastritis, gastric atrophy, usually with intestinal metaplasia, and finally dysplasia.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial processfirst American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res 1992;52:673540. Sobala GM, OConnor HJ, Dewar EP, et al. Bile reflux and intestinal metaplasia in gastric mucosa. J Clin Pathol 1993; 46:23540. Correa P, Duque E, Duque E, et al. Gastric cancer in Colombia. III. Natural history of precursor lesions. J Natl Cancer Inst 1976; 57:102735.
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Intestinal metaplasia
Morson & Belcher 1952 Intestinal metaplasia (IM) and gastric dysplasia are the main precancerous lesions of the stomach and usually found in patients infected with H. pylori. Helicobacter pylori (H. pylori) eradication is recommended as it is able to reduce gastric cancer incidence up to 35%
Parsonnet J, Friedman GD, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991;325:112731. Fuccio L, Eusebi LH, et al. Gastric cancer, Helicobacter pylori infection and other risk factors. World J Gastrointest Oncol 2010; 2: 342-347 de Vries AC, Kuipers EJ. Epidemiology of premalignant gastric lesions: implications for the development of screening and surveillance strategies. Helicobacter 2007; 12 Suppl 2: 22-31

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Reports on the effect of H. pylori eradication on intestinal metaplasia

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Summary of results

Consistent reports of either stable disease or disease-progression in H. pylori-positive controls No disease progression after H. pylori eradication

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Endoscopic surveillance of gastric premalignant lesions improves cancer survival

Whiting et al. Gut 2002; 50: 278-81

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A pragmatic endoscopic surveillance for IM patients

Angelo Zullo, Cesare Hassan, et al. Follow-up of intestinal metaplasia in the stomach: When, how and why. World J Gastrointest Oncol 2012 March 15; 4(3): 30-36

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Types of gastric polyps

Fundic gland polyps Hyperplastic Adenomatous Hamartomatous polyps (Juvenile polyp, PeutzJeghers syndrome and Cowdens syndrome) Polyposis syndromes (non Hamartomatous polyps as in Juvenile polyposis, Familial adenomatous polyposis) Subepithelial masses presenting as polyp
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Fundic gland polyps (FGP)

Located in the body and fundus Uncertain cause. FGP may regress or even disappear in time Unlikely to be related to PPI use (however conflicting reports) Dysplasia occur in < 1% of sporadic FGPs

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Management of FGP
Polypectomy is not required for sporadic FGPs. Biopsy is recommended to exclude dysplasia or adenocarcinoma (and possible FAP) In patients with numerous FGP who are under 40 years of age, or with dysplasia, colonic investigation should be performed to exclude FAP

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Hyperplastic polyps
Majority of gastric polyps are hyperplastic in nature (30-93%) Multiple hyperplastic polyps occur in Menetriers disease Up to 80% of hyperplastic polyps regree after eradication of H pylori before endoscopic removal

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Management of hyperplastic polyps

Hyperplastic polyps should be biopsied The risk of adenocarcinoma in the surrounding mucosa is probably higher than in the polyp itself. Test for H Pylori and eradicate when present Symptomatic polyp or polyp with dysplastic foci should be removed

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Adenomatous polyps
These are true neoplasms and are precursors of gastric cancer Frequently arise on a background of atrophic gastritis and intestinal metaplasia, but there is no proven association with H. Pylori infection.

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Management of adenomatous polyps

Complete removal of the adenoma should be performed when safe to do so. Endoscopic follow-up is required Endoscopy should be repeated at 6 months for incompletely resected polyps or those with high grade dysplasia and after 1 year for all other polyps

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Surveillance in adenomatous polyps

There is no evidence as to whether gastric polyps need long term surveillance Only a single gastroscopy 1 year after the removal of polyps with dysplasia is recommended (in the absence of polyp syndromes) Single repeat gastroscopy should also be performed at 1 year for all polyps with dysplasia that have not been removed
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Gastric polyps associated with polyposis syndromes

BSG recommendations: A. Goddard, R.Badreldin et al. The management of gastric polyps.Guidelines. Gut 2010;59:1270 - 1276. 30.07.2012 LISSOD Endoscopists Conference 38

Endoscopy. 2012 Jan;44(1):74-94. Epub 2011 Dec 23.

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BSG algorithm for the management of gastric polyps

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COLON POLYPS

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EVIDENCE THAT COLONOSCOPIC POLYPECTOMY PREVENTS CANCER

The USA National Polyp Study observed a 70%90% lower than expected incidence of CRC in patients undergoing colonoscopic surveillance compared with three reference populations.

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Non-neoplastic polyps
90% of all epithelial polyps in large intestine are found in more than 50% of all people over 60 years of age Hyperplastic (metaplastic) polyps Hamartomatous polyps -Juvenilie polyps
-Peutz-Jeghers polyps

Reactive polyps -Inflammatory polyps

-Lymphoid polyps
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Neoplastic polyps
Adenomas:
Tubular Villous Tubulovillous Serrated Dysplasia (intraepithelial neoplasia) is necessary to diagnose adenomas Adenomas are precusor lesions for adenocarcinomas
20-30% before the age of 40, 40-50% after the age of 60

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Adenomas/carcinomas
The malignant risk is depended on: polyp size, histologic type and severity of epithelilal dysplasia Cancer is rare in tubular adenoma <1cm High risk of cancer in sessile villous adenomas >4cm Severe dysplasia is connected with high risk of malignant transformation and often is found in villous adenomas
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ACG Screening Recommendations

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ACG Postpolipectomy recommendations

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UK Surveillance guidelines risk groups

Low risk
Patients with only 12, small (<1 cm) adenomas.

Intermediate risk
Patients with 34 small adenomas or at least one >1 cm

High risk
If either of the following are detected at any single examination (at baseline or follow up): >5 adenomas or >3 adenomas at least one of which is >1cm.
W S Atkin, B P Saunders. Surveillance guidelines after removal of colorectal adenomatous polyps. Gut 2002;51(Suppl V):v6v9
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(Recommendation Grade B)

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! THANK YOU!
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