title: Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy?
abstract: OBJECTIVE
  To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre Hépato-Biliare, Hospital Paul Brousse, Assistance Publique, Hospitaux de Paris Université Paris-Sud Villejuif, France. rene.adam@pbr.ap-hop-paris.fr
authors.forename: René
authors.initials: R
authors.lastname: Adam
authors.forename: Daniel
authors.initials: D
authors.lastname: Azoulay
authors.forename: Denis
authors.initials: D
authors.lastname: Castaing
authors.forename: Rony
authors.initials: R
authors.lastname: Eshkenazy
authors.forename: Gérard
authors.initials: G
authors.lastname: Pascal
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hashizume
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Henri
authors.initials: H
authors.lastname: Bismuth
mesh_terms: D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000601:surgery* / Q000821:virology; D016009:Chi-Square Distribution; D005240:Feasibility Studies; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000401:mortality / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome