Risk Factors for Esophageal Carcinoma: Gastroesophageal Reflux Disease and Barrett’s Esophagus

Barrett’s esophagus (BE), considered the greatest risk factor for distal esophageal cancer, develops in some patients with gastroesophageal reflux (GER) disease (GERD), the prevalence of which is high in the general population. The acid in gastroesophageal reflux that causes GERD damages the defense mechanisms of the esophageal mucosa, either microscopically or macroscopically, by activating both the direct and inflammatory mechanisms in the distal esophagus, with the most damage resulting from the immunological activation stimulated by inflammation. Macroscopic mucosal damage is not seen in 70% of patients with GERD, and around 30% develop mild, intermediate, or severe esophagitis. The immunological activation caused by chronic inflammation in some patients with GERD triggers the conversion of squamous cells into columnar cells in the distal esophagus. In cases of BE—a recently identified clinical picture related to the distal esophagus—microscopic changes bring about a color change in the mucosa that can be seen endoscopically. BE is divided into two groups: short-segment (SS) and long-segment (LS) BE, depending on the length of the area undergoing macroscopic change. The risk of cancer development is particularly high in long-segment BE. Definitive diagnosis is based on the determination of columnar cell change in biopsies of the areas undergoing color change. To increase the diagnostic rate, biopsies should also be taken from the point closest to the gastroesophageal junction. Acid suppression by proton pump inhibitors (PPIs) can reverse the cellular change after patients have been diagnosed at the BE phase. The development of BE is relatively rapid in GERD, and a vast majority of patients remain in this phase, although low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinoma may develop in a small percentage of patients that develop BE. Since dysplasia is a subjective histological finding, patient biopsies should be reevaluated by a specialist pathologist trained specifically in this area. The presence of at least one factor among the prevalent risk factors is an indication of gastroscopy in patients with chronic GERD, although routine gastroscopy is not recommended in all patients with GERD. The early diagnosis of dysplastic changes and adenocarcinoma has been made easier as a result of technological advances and the close follow-up of patients. An early diagnosis can lead to favorable outcomes in cancers and can increase the chance of a cure, whereas undiagnosed adenocarcinomas have a poor prognosis.