Gastroesophageal Reflux Disease, Barrett’s Esophagus, and Esophageal Adenocarcinoma

Abstract & Commentary

Synopsis: Esophageal adenocarcinoma (EAC), GERD, and Barrett’s esophagus (BE) are all on the rise, and there is no doubt that BE is a major risk factor for EAC. However, many unanswered questions surround screening GERD patients for BE and cancer.

Source: Chang JT, et al. Arch Intern Med. 2004;164: 1482-1488.

EAC has risen 300-350% since the 1970s from 0.7 to 3.2 per 100,000 population. Squamous carcinoma of the esophagus has declined from 3.4 to 2.2 per 100,000. EAC is particularly likely to occur in white males older than age 65. Regional differences in inci-idence also exist, eg, twice as many cases in the Seattle area as in Utah. Although the precise pathogenesis of EAC is uncertain, its rise seems to correlate with GERD that may be symptomatic in up to 20% of the US population. Other EAC risk factors include GERD that awakens patients from sleep and reflux symptoms that have been present for more than 5 years. BE is the single most important risk factor for EAC. BE is defined as the replacement of normal squamous mucosa in the distal esophagus with specialized columnar mucosa. This article describes 10%-15% of GERD patients as having BE although these numbers may relate to collection of data primarily in tertiary centers. To confuse issues further, a recent survey of asymptomatic individuals described 25% prevalence of BE. Although some authorities believe that cancer risk is related to the length of BE, others attribute equal cancer risk to very short BE segments. It is said that BE increases the risk of EAC by 30 to 120 times over normal, and this article gives some credence to the notion that chronic GERD may be a pre-disposition to EAC even in the absence of BE. BE seems to have some genetic characteristics in that relatives of BE patients have variably increased likelihood of having both GERD and BE.

Chang and associates suggest that screening is appropriate for white male patients with more than 5 years of GERD occurring 2 times weekly who are older than age 50. They urge that patients without dysplasia should be screened every 3 years and that those with low grade dysplasia should have endoscopic surveillance annually. For high-grade dysplasia (particularly if multifocal or nodular), esophagectomy is recommended. In poor surgical candidates, nonsurgical ablation can be considered (despite poor and inadequate efficacy data). Although there is general agreement among pathologists about the presence of high-grade dysplasia (85%), the natural history of high-grade dysplasia is uncertain with 13-16% of patients with high-grade dysplasia progressing to EAC over periods of 3-7 years.

Esophagectomy is a procedure with substantial morbidity and mortality. No data confirm the use of any medical or surgical therapy for the prevention of the development of BE or progression to EAC. Several cost-effectiveness models of screening were described. One such model supported screening only of men older than age 50 with GERD, then surveillance only for those with both BE and dysplasia (cost, $10,440 per quality-adjusted life year), and another found similar costs-benefits for screening all 55 year old men with BE every five years. Chang et al remind us that there were 7860 cases of EAC in 2002 as compared to 107,300 new colon cancers and 169,400 new lung cancers.

Comment Malcolm Robinson MD, FACP, FACG

There seems little doubt that GERD and BE predispose to esophageal adenocarcinoma (EAC). However, the arguments for expensive and widespread endoscopic surveillance seem less compelling. In addition to the almost infinitesimal risks of EAC for most patients with GERD, even BE patients will mostly have normal life expectancy with only 1-2% of deaths over 9-10 years of follow-up being due to EAC. The diagnosis of BE in any otherwise healthy patient has a number of potentially evil consequences including chronic psychological distress, and possible uninsurability (life, health, and disability). Nevertheless, the American College of Gastroenterology currently does somewhat indefinitely suggest possible screening of GERD patients for BE (nothing cited about age or duration of symptoms). Although I am a proud member of the ACG, it is hard not to think of this suggestion in the same light as asking a barber about desirability of a haircut. One hopes we will have clearer and increasingly data-based guidelines regarding GERD, BE, and EAC in the future.

Dr. Robineson, Medical Director, Oklahoma Foundation for Digestive Research; Clinical Professor of Medicine, University of Oklahoma College of Medicine Oklahoma City, OK, is Associate Editor of Internal Medicine Alert.