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-t...

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

“…Several groups have reported that increasing tumor size, number of nodules, and degree of differentiation predicts the presence of microvascular invasion. [31][32][33][34][35][36][37][38] Tumor size greater than 2-5 cm has been correlated with increased risk of microvascular invasion, as has the existence of multiple tumor nodules and lower histologic grade. Conversely, the degree of tumor cell differentiation is inversely associated with recurrent disease in that well-differentiated HCC is associated with decreased risk for recurrence.…”

Diagnostic Accuracy of Multi-/Single-Detector Row CT and Contrast-Enhanced MRI in the Detection of Hepatocellular Carcinomas Meeting the Milan Criteria before Liver Transplantation

“…Even though there have been very few reports regarding the accuracy of pre-operative radiologic studies in selecting patients eligible for transplantation according to the Milan or UCSF criteria [21,22] , multiple studies have been published evaluating the sensitivity and positive predictive value of radiologic modalities in detecting HCCs. Table 1 summarizes the diagnostic performances of SDCT, MDCT, dynamic gadolinium (Gd)-enhanced MRI, superparamagnetic iron oxide (SPIO)-enhanced MRI and double-contrast MRI using both gadolinium and SPIO.…”

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis

“…96 In the most recent published UK cohort of patients undergoing OLT for HCC (1995)(1996)(1997)(1998)(1999), median time on the waiting list was 36 days (range 1-370 days). 214 However, it appears that waiting times may be getting longer: at present, adults in the UK wait a median of 73 days for a suitable liver. 225 In March 2005, there were 271 patients on the transplantation list.…”