Clinicopathological characteristics and prognostic outcomes of resectable hepatoid adenocarcinoma of the stomach: insights from a multicenter case-control study.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC). This multicenter case-control study aimed to elucidate the clinicopathological features and prognosis of patients with resectable HAS. This retrospective study included 1387 GC patients treated at Ningbo No. 2 Hospital between January 2016 and December 2023, among whom 23 were HAS cases and incorporated 61 HAS patients from three external centers. Prognostic factors were analyzed using the Cox proportional hazards model. Propensity score matching (PSM) at a ratio of 4:1 and Kaplan-Meier survival curves were employed for analysis. The prevalence of HAS in this cohort was 1.1%. Among the 84 HAS patients with a median follow-up of 28 months, 47.6% had serum alpha-fetoprotein (AFP) levels exceeding 20 ng/mL. During the follow-up period, 44.0% of patients experienced relapses, predominantly through hepatic metastasis (62.2%). Univariate and multivariate analyses identified preoperative serum AFP levels between 200-500 ng/mL and TNM stages III/IV as independent prognostic factors for overall survival (OS). Elevated preoperative levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and TNM stages III/IV were independently associated with poorer disease-free survival (DFS). Conversely, open surgery and a Ki-67 proliferation index exceeding 50% were found to act as protective factors for both OS and DFS, with postoperative chemotherapy improving OS outcomes. After PSM adjustment, the analysis included 248 non-HAS patients and 62 HAS patients, revealing significantly better OS (P=0.043) and DFS (P=0.009) among non-HAS patients. Open radical surgery followed by adjuvant chemotherapy is recommended for the treatment of resectable HAS. Overall, patients with HAS exhibit a less favorable prognosis compared to those with non-HAS.