Unraveling the identity of gastric cardiac cancer.

The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.