title: Liver transplantation in cirrhotic patients with small hepatocellular carcinoma: an analysis of pre-operative imaging, explant histology and prognostic histologic indicators.
abstract: BACKGROUND
  In recent years, liver transplantation in patients with hepatocellular cancers and cirrhosis has been restricted to those with small cancers (<5 cm for solitary and <3 cm for multifocal HCC with <3 nodules). The selection of patients for liver transplantation is based on pre-operative imaging. The accuracy of imaging correlated with explant histology and the effect of tumour stage has not been evaluated in this selected population.
  
  
  METHODS
  In this study, prospectively collected data for 30 patients who underwent orthotopic liver transplantation for cirrhosis complicated by small hepatocellular carcinoma (HCC) at a single centre have been reviewed with the aim of correlating radiological findings, explant histology and patient outcome. Patients who underwent orthotopic liver transplantation between 1995 and 1999 had plain and contrast-enhanced dual-phase spiral CT (DCT) scans of the liver. Patients suspected of having HCC on CT scan or due to elevated serum alpha-fetoprotein underwent iodized oil CT (IOCT). Following transplantation, the explanted liver was serially sectioned at 10-mm intervals and examined by a pathologist blinded to the results of imaging. Data collected prospectively on imaging and histology were compared with outcome data. The median period of follow-up was 1,139 days (range 690-1,955 days) after transplantation. All patients were followed up by clinical assessment, assessment of serum alpha-protein levels and imaging when indicated.
  
  
  RESULTS
  All the patients transplanted fulfilled the selective criteria on the basis of imaging (solitary HCC <5 cm in diameter or multifocal HCC <3 cm in diameter with <3 nodules). Of the 30 patients transplanted, 46 HCCs were detected on explant histology with a median size of 24 mm (range 6-75 mm). Ten patients had multifocal disease (median number of lesions 2, range 2-4). No significant difference was observed between IOCT and DCT with regards to the sensitivity (67.4 vs. 68%) and specificity (78.97 vs. 88.6%) of detecting HCCs. IOCT had a positive predictive value of 78.9% as compared to 82.8% for DCT. IOCT had an overall sensitivity of 40% as compared to 30% for DCT in detecting multifocal disease (not significant). Histological assessment of the explanted livers showed that 8 patients had well-, 17 moderate and 5 poorly differentiated HCCs. Tumour size and the presence of multifocal disease did not influence survival in this study. Microvascular invasion was more common with larger tumours (from 38% with lesions less than 40 mm in diameter to 60% with lesions >40 mm in diameter; p < 0.01) and with moderately (29.4%) or poorly differentiated (60%) HCCs than well-differentiated HCC (12.5%) (p < 0.04 and 0.01 for well- vs. moderately and poorly differentiated HCC, respectively). Microvascular invasion on explant histology was associated with poor survival. Of the 17 transplant recipients without vascular invasion, 15 were alive at 1 and 2 years in comparison to 7 of 9 with microscopic vascular invasion (p < 0.01). Four patients died in the post-transplant period due to recurrent HCC. Overall survival [after excluding early post-transplant sepsis-induced deaths (n = 4)] at 1 year was 83.3%.
  
  
  CONCLUSIONS
  Selective criteria for transplantation of HCC in cirrhosis are associated with a 1-year and 3-year survival rate of 73.3% (including early post-transplant sepsis-induced deaths). IOCT and DCT are similar in their ability to detect unifocal or multifocal HCC. Tumour size and number are not predictive of recurrence with these selective criteria, but microscopic vascular invasion is a bad prognostic factor.
authors.affiliation: Department of Surgery, Royal Free Hospital, Royal Free and University College School of Medicine, London, UK.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Bhattacharjya
authors.forename: Tanushree
authors.initials: T
authors.lastname: Bhattacharjya
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.forename: Amar Pal
authors.initials: AP
authors.lastname: Dhillon
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
authors.forename: David W
authors.initials: DW
authors.lastname: Patch
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Tibballs
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Watkinson
authors.forename: Keith
authors.initials: K
authors.lastname: Rolles
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000601:surgery; D008113:Liver Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000401:mortality*; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome