Multiple primary neoplasms complicated with hepatocellular carcinoma in 270 patients of mainland China: an individual patient data Meta-analysis

Objective To investigate the characteristics and prognostic factors of patients with multiple primary neoplasms complicated with hepatocellular carcinoma in mainland China. Methods Literature about multiple primary neoplasms complicated with hepatocellular carcinoma in Chinese and English published by domestic scholars was searched in the databases of SinoMed, CNKI, PubMed and EMBASE between January 1980 and May 2015. And the main keywords were hepatocellular carcinoma and multiple primary neoplasms both in Chinese and English. General conditions, clinicopathological characteristics of hepatocellular carcinoma, diagnosis, treatment and prognosis of the patients were collected. The survival analysis was performed using Kaplan-Meier method and Log-rank test. The prognostic influence factors were analyzed using Cox's proportional hazards regression model. Results A total of 92 published literatures were searched out, including 270 patients. Among the patients, 222 were males and 48 were females with a male-to-female ratio of 4.6∶1. The age of primary cancer patients ranged from 3 to 88 years old with a median age of 55 years old. And the age of secondary cancer ranged from 13 to 88 years old with a median age of 57 years old. For the diagnosis of primary cancer, 77.2% of the patients were identified by positive symptoms, and 22.8% by physical examination. For the diagnosis of secondary cancer, 41.8% of patients were identified by preoperative examination, 37.7% by positive symptoms, 11.5% by intraoperative exploration, 4.9% by physical examination and 4.1% by follow-up. The median interval time between the diagnosis of primary and secondary cancers was 2.2 (0-22.0) years. Among the patients with hepatocellular carcinoma, 76.2% of them had a medical history of hepatitis and 23.8% had no medical history of hepatitis. Among patients with extra-hepatic carcinoma, 94.4% of them developed double carcinomas and 5.6% suffered from triple carcinomas. There were significant differences in the overall survival rate and hepatocellular carcinoma-specific survival rate between the patients with synchronous carcinoma and metachronous carcinoma (χ2=4.494, 25.434; P<0.05). Synchronous diagnosis of hepatocellular carcinoma, non-radical treatment for hepatocellular carcinoma and extra-hepatic carcinoma were the independent risk factors for the overall survival rate (HR=0.243, 1.532, 1.951; P<0.05). Non-radical treatment for hepatocellular carcinoma was the independent risk factor for hepatocellular carcinoma-specific survival rate (HR=2.186, P<0.05). Conclusions Radical treatment is an independent factor for the survival rate in patients with multiple primary neoplasms complicated with hepatocellular carcinoma. Radical resection is recommended for patients with hepatocellular carcinoma and extra-hepatic carcinoma. Key words: Carcinoma, hepatocellular; Neoplasms, multiple primary; Prognosis; Meta-analysis