胃肝样腺癌临床病理特征、预后及复发模式研究

Clinicopathological features, prognosis and recurrence patterns of patients with hepatoid adenocarcinoma of the stomach

目的探讨胃肝样腺癌(HAS)的临床病理特征、预后因素及复发模式。方法回顾性分析中国4个中心2004年4月至2020年3月间确诊的155例(福建医科大学附属协和医院75例,华中科技大学医学院附属协和医院34例,上海交通大学医学院附属仁济医院31例,南京医科大学第一附属医院15例)原发性HAS的临床病理资料。依据病理组织学肝样分化区所占的比例不同,将其分为仅含肝样分化区的HAS,称SHAS,以及混有普通腺癌的HAS,称MHAS。采用Kaplan-Meier法绘制生存曲线并计算生存率,Cox比例风险回归模型进行预后危险因素分析,并对比两组复发模式的差异。结果与MHAS相比,SHAS术前血清甲胎蛋白(AFP)水平更高,更易出现术前肝转移,且合并肝切除比例更高(均P<0.05)。149例病人中位随访时间为34个月,SHAS与MHAS的3年总体生存率分别为56.4%与55.6%,差异无统计学意义(P=0.772)。根治术后SHAS与MHAS的3年无复发生存率分别为46.8%与52.5%,差异亦无统计学意义(P=0.636)。预后危险因素分析显示,对于SHAS,脉管侵犯是不良预后的独立危险因素(HR=2.167,95%CI 1.011~4.642,P=0.047);对于MHAS,病理T(pT)分期是总体生存的独立预后因素(P=0.007)。144例根治术后HAS病人的3年累计复发率为38.8%(SHAS比MHAS:43.9%比33.8%,P=0.424)。117例HAS病人复发模式分析表明,根治术后HAS复发以远处转移(23.9%)为主,其次是多模式复发(8.5%),单纯局部复发(0.9%)或腹膜转移(0)少见。SHAS与MHAS在总体复发率、局部复发率、腹膜转移发生率、远处转移发生率及多模式复发率上差异无统计学意义(均P>0.05),但SHAS肝转移发生率显著高于MHAS(22.6%比9.4%,P=0.048)。结论与MHAS相比,SHAS术前AFP值更高,更易合并肝转移,且术后复发肝转移多见,随访应针对性进行监测复查。

Objective To investigate the clinicopathological features, prognosis and recurrence patterns of patients with hepatoid adenocarcinoma of the stomach(HAS). Methods The clinicopathological data of 155 cases of primary HAS diagnosed between April 2004 and March2020 in 4 centers in China were retrospectively analyzed(75 cases from Fujian Medical University Union Hospital, 34 cases from Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, 31 cases from Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and 15 cases from the First Affiliated Hospital of Nanjing Medical University).According to the different proportions of the HAS components histologically,HAS was divided into two different subtypes:simple HAS(SHAS)and mixed HAS(MHAS).Survival curve was estimated using the Kaplan-Meier method.Cox proportional hazard regression model was used to analyze the prognostic risk factors.Recurrence patterns between the SHAS and MHAS were compared. Results SHAS had a higher level of preoperative serum alpha-fetoprotein(AFP),higher rate of preoperative liver metastasis,and higher rate of hepatectomy than MHAS(all P<0.05).The median follow-up time of 149 patients were 34 months and the 3-year overall survival(OS)rates of SHAS and MHAS were 56.4% and 55.6% respectively,without statistical significance(P=0.772).The 3-year recurrence-free survival rates of SHAS and MHAS after radical surgery were 46.8% and 52.5% respectively,also without statistical significance(P=0.636). Multivariate analysis showed that lymphovascular invasion was an independent risk factor for poor OS for SHAS(hazard ratio [HR]:2.167,95% confidence interval [CI]:1.011-4.642,P=0.047);while pathological(p)T category was an independent prognostic factor for OS for MHAS(P=0.007).The 3-year cumulative recurrence rate of 144 HAS patients after radical surgery was 38.8%(SHAS vs.MHAS:43.9% vs.33.8%,P=0.424).Analysis of the recurrence patterns of 117 HAS patients showed that the recurrence of HAS after radical surgery was mainly distant metastasis(23.9%),followed by multimodal recurrence(8.5%),while local recurrence(0.9%)or peritoneal metastasis(0%)were rare.There were no significant difference in overall recurrence,local recurrence,peritoneal metastasis,distant metastasis,and multimodal recurrence rates between SHAS and MHAS(all P>0.05).However,the liver metastasis rate of SHAS was significantly higher than that of MHAS(22.6% vs.9.4%,P=0.048).Conclusion Compared with MHAS,SHAS has a higher preoperative AFP level and is more likely to present with preoperative liver metastases.The recurrence of liver metastases is more common in SHAS,thus monitoring and review should be targeted.