760例肝细胞癌根治术的临床疗效及预后因素分析

Clinical efficacy and prognostic factors analysis of radical hepatectomy of hepatocellular carcinoma in 760 patients

目的探讨肝细胞癌（HCC）根治术的临床疗效及其预后因素。方法采用回顾性病例对照研究方法。收集2003年8月至2015年6月南京医科大学第一附属医院收治的760例行HCC根治术患者的临床病理资料。根据肿瘤位置、数目和大小，以及与重要脉管解剖关系，确定手术方式。观察指标：（1）术中及术后情况：手术方式、手术时间、术中出血量、术中输血例数、术后并发症发生情况、术后住院时间、术后病理学检查情况。（2）随访情况：患者术后1、3、5年总体和无瘤生存情况。（3）行HCC根治术患者预后因素分析。采用门诊和电话方式进行随访，了解患者生存情况。随访时间截至2016年1月。正态分布的计量资料以x^-±s表示。采用Kaplan—Meier法绘制生存曲线，计算生存率。采用COX回归模型进行单因素和多因素分析。结果（1）术中及术后情况：760例患者均顺利完成手术，其中行解剖性肝切除术419例，非解剖性肝切除术341例；Rn切除742例，R、切除18例。合并门静脉切除重建2例，合并下腔静脉切除重建1例。760例患者手术时间为（226±115）min，术中出血量为（714±706）mL，术中输血例数为88例。55例患者发生术后并发症，包括腹腔积液或脓肿20例，胸腔积液16例，反复发热9例，切VI感染8例，腹腔内出血7例，肝衰竭6例，幽门梗阻或肠梗阻3例，肾衰竭2例，其中部分患者同时合并多种并发症；7例出血患者行再次手术或介入治疗，其余行保守对症治疗。55例患者中5例死亡，50例好转。760例患者术后住院时间为（14＋_6）d。肿瘤最小切缘≤1．0erfl457例，〉1．0CITI303例。（2）随访情况：760例患者均获得术后随访，随访时间为1。139个月，中位随访时间为25个月。760例患者总体中位生存时间为59个月，l、3、5年总体生存率分别为81．7％、63．4％和47．9％；无瘤中位生存时间为31个月，1、3、5年无瘤生存率分别为68．7％、44．9％和29．6％。（3）行HCC根治术患者预后因素分析：单因素分析结果显示：临床症状、AFP、巴塞罗那临床肝癌分期、手术方式、术中输血、肿瘤最小切缘、肿瘤数目、肿瘤直径、肿瘤包膜、肿瘤分化程度、脉管癌栓、大血管侵犯、美国癌症联合会（AJCC）肿瘤分期是影响行HCC根治术患者预后的相关因素，差异均有统计学意义（HR=1．39，1．50，1．92，0．65，1．45，1．68，1．96，1．66，2．26，1．50，2．68，3．37，2．0H0，95％可信区间：1．08～1．79，1．16～1．94，1．68—2．20，0．50—0．84，1．04—2．02，1．28～2．20，1．54～2．49，1．42～1．94，1．69～3．02，1．22～1．85．1．99～3．60，2．61～4．36，1．77～2．27，P〈0．05）。多因素分析结果显示：AFP、肿瘤数目、肿瘤直径、肿瘤分化程度、AJcc肿瘤分期是影响行HCC根治术患者预后的独立因素，差异均有统计学意义（HR=1．61，1．62，1．31，1．40，1．78，95％可信区间：1．14～2．26，1．22～2．14，1．06～1．63，1．10～1．79，1．27～2．51，P〈0．05）。结论选择合适的HCC患者行解剖性肝切除术与非解剖性肝切除术均安全可行，远期疗效较好。AFP、肿瘤数目、肿瘤直径、肿瘤分化程度、AJCC肿瘤分期是影响行HCC根治术患者预后的独立因素。

Objective To investigate the clinical efficacy and prognostic factors of radical hepatectomy of hepatocellular carcinoma （HCC）. Methods The retrospective case-control study was conducted. The clinicopathological data of 760 HCC patients who were admitted to the First Affiliated Hospital of Nanjing Medical University from August 2003 to June 2015 were collected. Surgical procedures were determined according to the location, number and size of tumors and anatomical relations among vessels. Observation indicators included： （ 1 ） intra- and post-operative situations ： surgical procedures, operation time, volume of intraoperative blood loss, cases of intraoperative blood transfusion, postoperative complications, duration of postoperative hospital stay and pathological examination; （2） follow-up： 1-, 3-, 5-year overall and tumor-free survival situations; （3） prognostic factors analysis of HCC patients. Follow-up using outpatient examination and telephone interview was performed to detect patients＇ survival up to January 2016. Measurement data with normal distribution were represented as x^-±s. The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method. The univariate analysis and multivariate analysis were done using the COX regression model. Results （ 1 ） Intra- and post-operative situations： all the 760 patients underwent successful operations, including 419 undergoing anatomical hepatectomy and 341 undergoing non-anatomical hepatectomy. R0 and R1 resections were respectively applied to 742 and 18 patients. Two patients were combined with portal vein resection and reconstruction and 1 was combined with resection and reconstruction of inferior vena cava. Operation time, volume of intraoperative blood loss and cases of intraoperative blood transfusion were （226± 115）minutes, （714±706）mL and 88, respectively. Fifty-five patients had postoperative complications, including 20 with abdominal effusion or abscess, 16 with pleural effusion, 9 with recurrent fever, 8 with incisional infection, 7 with intra-abdominal hemorrhage, 6 with liver failure, 3 with pyloric or intestinal obstruction and 2 with renal failure （some patients with multiple complications）. Of the 55 patients with postoperative complications, 7 with hemorrhage underwent reoperation or interventional therapy and other patients underwent conventional symptomatic treatment. Of 55 patients, 5 patients died and other 50 patients were improved. Duration of postoperative hospital stay was （14±6） days. There were 457 patients with minimum margin of tumors ≤ 1.0 cm and 303 with minimum margin of tumors 〉 h0 cm. （2） Follow- up： all the 760 patients were followed up for 1-139 months, with a median time of 25 months. The overall and tumor-free median survival times were 59 months and 31 months, respectively. The 1-, 3-, 5-year overall and tumor-free survival rates were 81.7%, 63.4%, 47.9% and 68.7%, 44.9%, 29.6%, respectively. （3） Prognostic factors analysis of HCC patients： results of univariate analysis showed that clinical symptoms, alpha-fetoprotein （AFP）, Barcelona clinic liver cancer staging, surgical procedures, intraoperative blood transfusion, minimum margin of tumors, number and diameter of tumors, tumor capsule, tumor differentiation, vascular cancer embolus, macrovascular invasion and tumor staging of American Joint Committee on Cancer （AJCC） were related factors affecting prognosis of HCC patients after radical hepatectomy [ HR = 1.39, 1.50, 1.92, 0. 65, 1.45, 1.68, 1.96, 1.66, 2.26, 1.50, 2.68, 3.37, 2.00, 95% confidence interval （CI）：1.08-1.79, 1.16-1.94, 1.68- 2.20, 0.50-0.84, 1.04-2.02, 1.28-2.20, 1,54-2.49, 1.42-1.94, 1.69-3.02, 1.22-1.85,1.99-3.60, 2. 61-4. 36, 1.77-2. 27, P〈0. 051. Results of multivariate analysis showed that AFP, number and diameter of tumors, tumor differentiation and tumor staging of AJCC were independent factors affecting prognosis of HCC patients after radical hepatectomy （HR = 1.61, 1.62, 1.31, 1.40, 1.78, 95%CI： 1.14-2. 26, 1.22-2. 14, 1.06 - 1.63, 1.10 - 1.79, 1.27 - 2. 51, P 〈 0. 05 ）. Conclusions The anatomical and non-anatomical hepatectomies are safe and feasible for optional HCC patients, with a good long-term outcome. AFP, number and diameter of tumors, tumor differentiation and tumor staging of AJCC are independent factors affecting prognosis of HCC patients after radical hepatectomy.