Adam René, Azoulay Daniel, Castaing Denis, Eshkenazy Rony, Pascal Gérard, Hashizume Kentaro, Samuel Didier, Bismuth Henri
Centre Hépato-Biliare, Hospital Paul Brousse, Assistance Publique, Hospitaux de Paris Université Paris-Sud Villejuif, France.
Ann Surg. 2003 Oct;238(4):508-18; discussion 518-9. doi: 10.1097/01.sla.0000090449.87109.44.
To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis.
LT is the optimal treatment of HCC with cirrhosis. Owing to organ shortage, liver resection is considered as a reasonable first-line treatment of patients with small HCC and good liver function, with secondary LT as a perspective in case of recurrence. The viability of such strategy, positively explored in theoretical models, is not documented in clinical practice.
Among 358 consecutive patients with HCC on cirrhosis treated by liver resection (n = 163; 98 of whom were transplantable) or transplantation (n = 195), the feasibility and outcome of secondary transplantation was evaluated in a 2-step fashion. First, secondary LT for tumor recurrence after resection (n = 17) was compared with primary LT (n = 195), to assess the risk and the outcome of secondary LT in patients who effectively succeeded to be treated by this approach. Second, primary resection in transplantable patients (n = 98) was compared with that of primary LT (n = 195) on an intention-to-treat basis, to assess the outcome of each treatment strategy and to determine the proportion of resected patients likely to be switched for secondary LT. Transplantability of resected patients was retrospectively determined according to selection criteria of LT for HCC.
Operative mortality (< or =2 months) of secondary LT was significantly higher than that of primary LT (28.6% versus 2.1%; P = 0.0008) as was intraoperative bleeding (mean transfused blood units, 20.7 versus 10.5; P = 0.0001). Tumor recurrence occurred more frequently after secondary than after primary LT (54% versus 18%; P = 0.001). Posttransplant 5-year overall survival was 41% versus 61% (P = 0.03), and disease-free survival was 29% versus 58% (P = 0.003) for secondary and primary LT, respectively. Of 98 patients treated by resection while initially eligible for transplantation, only 20 (20%) were secondarily transplanted, 17 of whom (17%) for tumor recurrence and 3 (3%) for hepatic decompensation. Transplantability of tumoral recurrence was 25% (17 of 69 recurrences). Compared with primarily transplanted patients, transplantable resected patients had a decreased 5-year overall survival (50% versus 61%; P = 0.05) and disease-free survival (18% versus 58%; P < 0.0001), despite the use of secondary LT. On a multivariate analysis including 271 patients eligible for transplantation and treated by either liver resection or primary LT, liver resection alone (P < 0.0001; risk ratio [RR] = 3.27) or liver resection with secondary LT (P < 0.05; RR= 1.87) emerged as negative independent factors of disease-free survival as compared with primary LT. A number of nodules > 3 (P = 0.002; RR= 2.02) and a maximum tumor size exceeding 30 mm (P < 0.0001; RR=1.93) were also predictive of lower disease-free survival.
LT after liver resection is associated with a higher operative mortality, an increased risk of recurrence, and a poorer outcome than primary LT. In addition, liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable.
评估原发性肝癌伴肝硬化患者行一期肝切除联合二期肝移植(LT)策略的可行性。
LT是治疗肝癌伴肝硬化的最佳方法。由于器官短缺,肝切除被认为是肝功能良好的小肝癌患者合理的一线治疗方法,二期LT作为复发时的一种选择。这种策略在理论模型中得到了积极探索,但在临床实践中尚无文献记载。
在358例连续接受肝切除(n = 163;其中98例适合移植)或移植(n = 195)治疗的肝癌伴肝硬化患者中,分两步评估二期移植的可行性和结果。首先,将肝切除术后肿瘤复发患者的二期LT(n = 17)与一期LT(n = 195)进行比较,以评估有效接受该方法治疗的患者二期LT的风险和结果。其次,在意向性治疗基础上,将适合移植患者的一期肝切除(n = 98)与一期LT(n = 195)进行比较,以评估每种治疗策略的结果,并确定可能转为二期LT的肝切除患者比例。根据肝癌LT的选择标准,回顾性确定肝切除患者的可移植性。
二期LT的手术死亡率(≤2个月)显著高于一期LT(28.6%对2.1%;P = 0.0008),术中出血量也更高(平均输血量,20.7对10.5;P = 0.0001)。二期LT后肿瘤复发比一期LT更频繁(54%对18%;P = 0.001)。二期和一期LT的移植后5年总生存率分别为41%对61%(P = 0.03),无病生存率分别为29%对58%(P = 0.003)。在98例最初适合移植但接受肝切除治疗的患者中,只有20例(20%)接受了二期移植,其中17例(17%)因肿瘤复发,3例(3%)因肝失代偿。肿瘤复发的可移植性为25%(69例复发中的17例)。与一期移植患者相比,可移植的肝切除患者5年总生存率(50%对61%;P = 0.05)和无病生存率(18%对58%;P < 0.0001)降低,尽管采用了二期LT。在一项包括271例适合移植并接受肝切除或一期LT治疗的患者的多变量分析中,与一期LT相比,单纯肝切除(P < 0.0001;风险比[RR] = 3.27)或肝切除联合二期LT(P < 0.05;RR = 1.87)是无病生存的负面独立因素。结节数>3个(P = 0.002;RR = 2.02)和最大肿瘤大小超过30 mm(P < 0.0001;RR = 1.93)也预示着无病生存率较低。
肝切除术后LT与更高的手术死亡率、更高的复发风险以及比一期LT更差的结果相关。此外,作为LT桥梁的肝切除会损害患者的可移植性和肝癌伴肝硬化患者的长期生存机会。因此,即使肿瘤可切除,一期LT仍应是肝癌伴肝硬化患者的理想治疗选择。