title: Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?
abstract: BACKGROUND
  Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences.
  
  
  OBJECTIVE
  To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT).
  
  
  METHODS
  We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011.
  
  
  RESULTS
  Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704).
  
  
  CONCLUSIONS
  Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.
authors: Liver Transplantation Unit, University Hospital of Santiago, Santiago de Compostela, Spain. javier.fernandez.castroagudin@sergas.es
authors: J F
authors: JF
authors: Castroagudín
authors: E
authors: E
authors: Molina-Pérez
authors: R
authors: R
authors: Ferreiro-Iglesias
authors: I
authors: I
authors: Abdulkader
authors: E
authors: E
authors: Otero-Antón
authors: S
authors: S
authors: Tomé
authors: E
authors: E
authors: Varo-Pérez
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D016461:Chemoembolization, Therapeutic; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012086:Reoperation; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents