Introduction

This chapter focuses on clinical gastroenterology issues of interest to pathologists, including endoscopic diagnosis and management of Barrett esophagus, management of intestinal metaplasia in the setting of chronic gastritis, and surveillance in patients with inflammatory bowel disease, colonic polyps, and colon cancer.

Surveillance in Patients with Barrett Esophagus

Most authorities recommend that patients with chronic reflux symptoms lasting 5 or more years undergo an upper endoscopy to screen for Barrett esophagus (Table 2.1). The benefits of screening programs for Barrett esophagus are controversial because of a lack of sufficient evidence that such programs improve survival rates or are cost-effective.¹ Furthermore, there is only indirect evidence to suggest that patients diagnosed with adenocarcinoma while undergoing surveillance have an increased chance of survival. Nevertheless, the current standard of care dictates that if Barrett esophagus is diagnosed, the patient should be entered into an endoscopic surveillance program for early detection of dysplasia and adenocarcinoma.²

Data from Spechler SJ, Sharma P, Souza RF, et al. American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology. 2011;140:1084-1091.

Surveillance in Patients with Chronic Gastritis and Intestinal Metaplasia or Dysplasia

The most common causes of chronic gastritis are Helicobacter pylori infection, environmental exposures including smoking, and autoimmune processes. Biopsies obtained during endoscopy from patients with chronic gastritis may reveal intestinal metaplasia (IM). A study from the United States demonstrated that 13% of patients at low risk for gastric cancer, and 50% of patients at high risk, had IM on biopsies from normal-appearing gastric mucosa.¹¹ Although gastric IM (incomplete type) is considered a premalignant lesion, the overall risk of gastric cancer in patients with gastric IM is very low. However, patients with IM and dysplasia have an approximately 100-fold increased risk of gastric cancer.¹¹

In the United States, where the incidence of gastric cancer is low, endoscopic surveillance of patients with gastric IM is not recommended in patients who are at low risk for gastric cancer.¹¹ Low-risk patients include those living in developed countries, whites without any family history of gastric cancer, and individuals without dysplasia on gastric biopsy. The likelihood that endoscopic surveillance of low-risk patients with IM will increase detection of curable gastric cancer is very low, and therefore it is not likely to be cost-effective. Furthermore, IM is a histologic lesion that is not visible by the endoscopist. This makes endoscopic surveillance difficult, because numerous biopsies mapping the stomach would be needed to obtain a significant yield.

Surveillance in patients with IM who are at high risk for gastric cancer is controversial. High-risk patients include those with a family history of gastric cancer, Hispanics, blacks, and immigrants from higher-risk geographic locations. No formal recommendations or data exist to support the implementation of an endoscopic surveillance program in high-risk patients with gastric IM. The American Society of Gastrointestinal Endoscopy (ASGE) concluded that patients who are at increased risk for gastric cancer on the basis of ethnic background or family history may benefit from surveillance, but there was no specific recommendation on the frequency of endoscopy. If surveillance is performed, the ASGE recommended that endoscopic surveillance with gastric biopsies should incorporate a topographic mapping of the entire stomach histologically.¹²

The location and type of dysplasia found determine the surveillance guidelines for patients with IM. The histopathologic classification divides cases into the subtypes of incomplete and complete IM, a distinction best determined after assessment for and eradication of H. pylori infection. Studies have suggested that if the patient has incomplete or extensive IM, topographic mapping of the gastric mucosa should be performed at 1 year, followed by repeated surveillance endoscopy every 3 years if extensive metaplasia persists.¹³ There is no consensus regarding surveillance in LGD, but most studies suggest that surveillance is not warranted in average-risk patients.¹² The ASGE recommends that patients with confirmed HGD on gastric biopsies be considered for gastrectomy or EMR.¹¹ We expect that further recommendations regarding appropriate intervals for surveillance endoscopy and the use of new techniques will be formalized in the near future.

Pernicious anemia, which can occur as a result of autoimmune chronic atrophic gastritis, is another potential risk factor for gastric cancer and gastric carcinoid. A twofold to threefold increased risk of gastric cancer has been seen, depending on the location and duration of disease.¹⁴ Clear guidelines for surveillance in atrophic gastritis have not yet been established. Current guidelines from the ASGE advocate performance of a screening upper endoscopy at the time of diagnosis of pernicious anemia to identify lesions such a carcinoid or gastric cancer, but there are only weak data to support subsequent surveillance endoscopy if the initial test is negative.¹²

Surveillance for Colorectal Neoplasia in Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), which comprises ulcerative colitis (UC) and Crohn’s disease, is the second most common inflammatory disorder after rheumatoid arthritis. There are approximately 1.4 million patients with IBD in the United States.^14a Each year, between 20,000 and 25,000 new cases are diagnosed. The peak incidence occurs between the ages of 15 to 35, with males and females equally affected.

The goal of colonoscopic surveillance is to minimize the morbidity and mortality from colorectal cancer (CRC) with appropriate and timely referral for colectomy. Close interaction between endoscopist and the pathologist is crucial in the management of IBD.¹⁵ Although no prospective randomized studies have been performed to evaluate the efficacy of surveillance colonoscopy to detect dysplasia or CRC in UC patients, case-control studies suggest a reduction in mortality in those undergoing surveillance.¹⁶ Surveillance colonoscopy should optimally be performed when the patient is in clinical remission, because active inflammation may hinder the histologic diagnosis of dysplasia.

Biopsies taken during surveillance colonoscopy are graded as positive for dysplasia, negative for dysplasia, or indefinite for dysplasia. Dysplasia is further classified as LGD, HGD, or carcinoma.¹⁷ The greatest interobserver variability among pathologists lies in the interpretation of the LGD and indefinite-for-dysplasia categories. Therefore, once dysplasia is detected, a second pathologist with expertise in interpretation of gastrointestinal biopsies should confirm the diagnosis. Dysplastic mucosa may be characterized as either flat or raised. Flat dysplasia is generally considered to be endoscopically undetectable, is identified by random biopsies, and can be further classified as either multifocal or unifocal. Raised or polypoid dysplasia is referred to by the acronym DALM: dysplasia-associated lesion or mass.

Current guidelines from the American College of Gastroenterology (ACG), the American Gastroenterology Association (AGA) (Table 2.3), and the British Society of Gastroenterology(BSG) (Table 2.4) recommend that colonoscopic surveillance begin 8 to 10 years after the onset of symptoms of colitis in patients with UC or with Crohn’s colitis involving at least one third of the colon.^18–20 The results of the colonoscopy determine the extent of disease, and appropriate patients are then entered into a surveillance program. Repeated surveillance colonoscopy is performed every 1 to 3 years (AGA) or 1 to 5 years (BSG).¹⁸ Patients with coexisting primary sclerosing cholangitis should begin surveillance colonoscopy at the time of diagnosis of liver disease and continue annually thereafter regardless of the extent of disease. Other risk factors associated with an increased risk of developing colorectal neoplasia include CRC in a first-degree relative, ongoing active endoscopic or histologic inflammation, and anatomic abnormalities such as a foreshortened colon, stricture, or multiple inflammatory pseudopolyps. Several studies have correlated increased severity of colonoscopic macroscopic and histologic inflammation with a higher risk of CRC.^21,22 Male gender has been identified as a risk factor for development of CRC.^23,24 Patients with proctitis or distal proctosigmoiditis are not at increased risk for the development of CRC and do not need to undergo surveillance.

CRC, Colorectal cancer; IBD, inflammatory bowel disease; PSC, primary sclerosing cholangitis.

From Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology. 2010;138:746-774.e4.

Screening and Surveillance Guidelines for Colon Polyps

The following is a review of the management of colonic polyps in patients who do not have IBD.^41,42 This summary includes screening for colon polyps, surveillance after polypectomy and resection for CRC, and the approach to the patient with a malignant polyp.

CRC is the second most common cause of cancer death in the United States. The overall mortality rate approaches 60%. Approximately 5% to 6% of U.S.-born individuals will develop colon cancer in their lifetime, and 2.5% will die of the disease. The incidence does not vary significantly between men and women. It is estimated that almost 143,000 new cases of CRC will be diagnosed and almost 51,000 deaths will occur from CRC in the United States in 2013.⁴³ CRC is a suitable disease for screening because it is a common malignancy with a long, asymptomatic preclinical phase and a high survival rate if detected in its early stage. Prevention of CRC should be achievable by application of screening programs to identify asymptomatic patients with adenomatous polyps and to remove them. In The National Polyp Study, colonoscopic polypectomy decreased the expected incidence of CRC by 53%.⁴⁴ An estimated 14.2 million colonoscopies and 2.8 million flexible sigmoidoscopies were performed in 2002 in the United States.⁴⁵

Hyperplastic Polyposis Syndromes

Serrated polyposis syndrome (SPS), formerly known as hyperplastic polyposis, is a syndrome characterized by the presence of multiple serrated lesions, either serrated adenomas or hyperplastic polyps. The World Health Organization has defined SPS as a syndrome meeting one of the following criteria: (1) at least five serrated polyps proximal to the sigmoid colon, with two or more being larger than 10 mm; (2) any serrated polyps proximal to the sigmoid colon in any patient who has a first-degree relative with SPS; (3) more than 20 serrated polyps of any size in any location throughout the colon.⁵⁶ The risk of cancer in SPS is unknown but is believed to be increased, and a retrospective study showed a 7% risk of cancer at 5 years in patients undergoing surveillance.⁵⁷ Surveillance colonoscopy is recommended at 1-year intervals to clear the proximal colon of lesions larger than 5 mm; however, surgical resection is recommended if carcinoma is discovered or the number of polyps is too great to be endoscopically managed. Surgery should involve resection of the portion of the colon that contains the cancer as well as that which has the largest polyps; usually, an extended right hemicolectomy or subtotal colectomy is performed. Patients will then need annual surveillance of the remaining colon and rectum.

Management of Large Pedunculated Polyps

Endoscopic resection of large polyps can be challenging because of the risks of hemorrhage, perforation, and incomplete resection. Most endoscopists resect large pedunculated polyps using a hot snare. However, EMR has been shown to be successful for large pedunculated polyps with flat broad stalks.⁵⁸

Large pedunculated polyps (≥1 cm in diameter) resected in one piece should be examined by the pathologist for adequacy of resection. The guidelines for polyp specimen processing were discussed in Chapter 1. Piecemeal resection of large pedunculated polyps impedes, but does not preclude, pathologic assessment of adequacy of resection. However, in this instance, the pathologist depends on the endoscopist to deliver a readily available stalk.

Management of Large Sessile Polyps

The prevalence of large sessile polyps is approximately 0.8% to 5.2% in patients undergoing colonoscopy. Malignancy is found in 5% to 22% of these polyps. These polyps tend to recur locally after resection, and one study quoted a rate as high as 46%.⁵⁹ This same study found that the recurrence rate could be reduced to 3.8% with repeated endoscopic procedures and the use of argon plasma coagulation. Another investigation found that the use of EMR for resection of large sessile polyps was successful in 90% of cases, with size larger than 40 mm and use of argon plasma coagulation leading to lower success rates.^59a

Assessment of the adequacy of excision of a large sessile polyp (≥2 cm) is problematic and depends on both the endoscopist’s assessment of whether a residual lesion is present and the pathologist’s ability to identify resection margins with confidence. This includes the issue of whether a large sessile polyp is resected intact or piecemeal. The endoscopist may tattoo the polypectomy site with India ink after endoscopic resection to facilitate visualization during a subsequent endoscopic procedure. General practice has suggested that a patient who has undergone colonoscopic excision of a large sessile polyp in piecemeal fashion should have follow-up colonoscopy in 2 to 6 months to verify complete removal. If residual polyp tissue is present, it should be resected, and the completeness of this resection should be documented within another 2- to 6-month interval. Once complete removal has been established, subsequent surveillance is recommended in 1 year. If complete resection is not possible after two or three procedures, surgical resection should be considered.⁴¹

Postpolypectomy Surveillance

Because a large number of patients with adenomas are being identified by colonoscopy, the burden placed on medical resources (i.e., the timely availability of colonoscopy) is increasing dramatically.⁶⁰ The U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society recently revised the recommendations for surveillance colonoscopy after polypectomy. Updated guidelines emphasize stratification of patients into high- and low-risk groups (Table 2.6) and are based on the assumption that the initial screening colonoscopy was of optimal quality. However, certain studies have shown that approximately 17% of polyps larger than 10 mm are missed during optical colonoscopy and that these missed polyps account for the majority of interval cancers.⁴¹

From Lieberman DA. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012;143(3):844-857.

Management of Malignant Polyps

A malignant polyp is defined as an adenomatous polyp with cancer invading the submucosa; favorable and unfavorable histologic features are reviewed in Table 2.8. Guidelines for the management of malignant polyps are reviewed in Table 2.9.⁶¹

From Winawer SJ, O’Brien MJ. Management of malignant polyps. In: Waye JD, Rex DK, Williams CB, eds. Colonoscopy: Principles and Practice. 2nd ed. Oxford: Wiley-Blackwell; 2009.

1. The polyp is considered by the endoscopist to have been completely excised and is submitted in toto for pathologic examination.

2. In the pathology laboratory, the polyp is fixed and sectioned so that it is possible for the pathologist to accurately determine the depth of invasion, grade of differentiation, and completeness of excision of the carcinoma.

3. The cancer is not poorly differentiated (i.e., not grade III).

4. There is no evidence of vascular or lymphatic involvement.

5. The margin of excision is not involved. Invasion of the stalk of a pedunculated polyp in itself is not an unfavorable prognostic finding as long as the cancer does not extend within 2 mm of the deep margin of stalk resection.

Colonoscopic Surveillance after Colon Cancer Resection

Patients who have undergone resection for colon cancer should be entered into a surveillance program to detect early recurrence of the initial primary cancer and to detect metachronous colorectal neoplasms. Numerous studies have found that 2% to 7% of patients with CRC have one or more synchronous cancers in the colon and rectum at the time of initial diagnosis.³⁵ It has also been shown that the annual incidence for metachronous cancers in surveillance groups after cancer resection is 0.35% per year.⁶³

On the basis of the available data, patients should undergo a high-quality perioperative clearing by colonoscopy in nonobstructive tumors, and by computed tomographic colonography or double-contrast barium enema in obstructing tumors. A subsequent colonoscopy should be performed within 3 to 6 months or intraoperatively in patients with obstructing tumors. Surveillance endoscopy should be performed in all patients 1 year after resection because of the high yield of detecting early metachronous cancers. If the first surveillance colonoscopy is negative, the next examination needs to be done after a 3-year interval. Recommendations for surveillance in patients after CRC resection are reviewed in Table 2.10.

Interaction of Gastrointestinal Endoscopists and Pathologists

An ACG review on quality improvement in colonoscopy emphasizes the great importance of the interaction between the pathologist and the gastrointestinal endoscopist in the management of these patients.⁶⁴ The quality improvement targets identified to improve care provided to patients undergoing colonoscopy and polypectomy are indicated in Table 2.11.