Last week, we discussed the dramatic increase in the incidence of esophageal adenocarcinoma in the United States and the European Union over the past 50 years or more. This malignancy occurs primarily in the part of the esophagus that is adjacent to the stomach. It is predominantly in males and in those of upper socioeconomic status. While its precise etiologic factors are not all known, it does appear to be closely tied to obesity and to gastroesophageal reflux disease (GERD). The latter, as we described last week, is the chronic occurrence of heartburn in an individual as a result of the backflow of gastric acid into an individual’s esophagus, leading to inflammation and irritation. The occurrence of this condition may be exacerbated by obesity, with the extra abdominal adiposity pressing down on the abdomen and thereby increasing intra-abdominal pressure which enhances the reflux. Another factor that may increase the occurrence of GERD is weakening of the lower esophageal sphincter, allowing more acid to reflux into the lower esophagus.
Barrett’s esophagus is a pathologic condition in which the squamous epithelium of the lower esophagus becomes metaplastic in response to GERD. Metaplasia occurs when normal epithelial cells change their makeup and appearance in response to an external stressor and transform into a different cell type which is usually abnormal and has an increased risk of progression to cancer.
Barrett’s esophagus can be diagnosed in the esophagus by biopsies after endoscopic examination of the esophagus. As with esophageal adenocarcinoma (EAC, a common subtype of esophageal cancer), it is found much more commonly in Whites than in Blacks and is several times more prevalent in males than in females.
It is difficult to state the exact prevalence of Barrett’s in the general population inasmuch as an upper GI endoscopy or EGD (esophagogastroduodenoscopy) is not performed routinely on large asymptomatic populations but only on people with symptoms, but it appears to be present in that setting in 5% or more of those over age 50.
Again, the etiologic factors associated with Barrett’s esophagus parallel those found with EAC. Those with symptomatic GERD have five times or greater the risk of having Barrett’s esophagus. Those with a body mass index of 30 or more (a BMI over 30 is generally defined as obese) had a 40% increased risk of Barrett’s esophagus. Interestingly, cigarette smoking also increased the risk of Barrett’s.
Of itself, Barrett’s esophagus is clinically unimportant. The same can be said for the precursor lesions of other epithelial tumors in other organs. But as we have discussed on other occasions, it represents the precursor lesion for most cases of EAC and thus gives us the opportunity to interrupt the carcinogenesis pathway. Barrett’s progresses to dysplasia and through various stages of increasing abnormality, including carcinoma in-situ, until it eventuates in full-blown adenocarcinoma; we include malignancies of the gastroesophageal junction (GEJ) in this sequence and process—it does appear that Barrett’s is also the precursor lesion for most GEJ adenocarcinomas.
The strongest evidence for the link between esophageal adenocarcinoma (EAC) and Barrett’s esophagus comes from a study conducted in Northern Ireland, published in the Journal of the National Cancer Institute in 2011. This study followed 8522 patients with Barrett’s esophagus for 7 years and the incidence rate of cancer was 0.8% per year versus 0.07% for the general population for a hazard ratio of 3.54.
It should not surprise the astute reader of this column that the above has led to efforts to screen appropriate individuals for Barrett’s in order to try to prevent progression to cancer, as we do for other precursor lesions in colorectal and cervical neoplasia. The reader should appreciate, however, that there are no randomized trials that establish the efficacy or utility of this type of screening in terms of EAC incidence prevention or EAC mortality prevention. Nonetheless, various gastroenterology societies have issued guidelines for such screening, and I provide them with these warnings—caveat emptor.
As a sample, I provide those of the American College of Gastroenterology. They recommend a single screening EGD should be performed for those with chronic GERD symptoms and with three or more of the following—male sex, age greater than 50 years, White race, cigarette smoking, family history of esophageal adenocarcinoma, and/or obesity (BMI greater than 30). Nonetheless, an interesting study found that over 50% of EAC patients would not have fulfilled these criteria for screening for Barrett’s.
Another problem is that the appropriate or recommended interventions to pursue for those who are diagnosed with Barrett’s esophagus is controversial. Most gastroenterologists would probably recommend long-term proton pump inhibitor use (for example, omeprazole) for those diagnosed with Barrett’s esophagus. If the Barrett’s were accompanied by high-grade dysplasia or carcinoma in-situ, one would need to intervene more aggressively for sure, as the apparent risk of progression to full-blown cancer would be extremely high. The exact method is controversial and a matter of judgment; I would leave that to the individual to work out with his/her gastroenterologist or surgeon. For low-grade dysplasia, there is even more controversy as to whether any intervention is necessary or whether observation would suffice.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
