Are cancers of the esophagus, gastroesophageal junction, and cardia one disease, two, or several?

Recent epidemiological shifts have led to controversy about the etiology and treatment of gastroesophageal (GE) junction adenocarcinomas. The Siewert classification conveniently describes the anatomical location of these tumors relative to the GE junction. However, available data suggest that there may be epidemiological, clinical, and molecular differences among GE junction adenocarcinomas, depending on whether they are predominantly esophageal or gastric in location. Much more investigation is required to confirm or refute these apparent differences, which can affect clinical treatment.