Original Article
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World J Gastroenterol. Sep 14, 2013; 19(34): 5622-5632
Published online Sep 14, 2013. doi: 10.3748/wjg.v19.i34.5622
Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation
Daniele Nicolini, Gianluca Svegliati-Baroni, Roberto Candelari, Cinzia Mincarelli, Alessandra Mandolesi, Italo Bearzi, Federico Mocchegiani, Andrea Vecchi, Roberto Montalti, Antonio Benedetti, Andrea Risaliti, Marco Vivarelli
Daniele Nicolini, Federico Mocchegiani, Andrea Vecchi, Roberto Montalti, Marco Vivarelli, Division of Hepatobiliary and Transplant Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, 60129 Ancona, Italy
Gianluca Svegliati-Baroni, Antonio Benedetti, Division of Gastroenterology, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, 60129 Ancona, Italy
Roberto Candelari, Cinzia Mincarelli, Division of Interventional Radiology, Department of Radiological Sciences, Polytechnic University of Marche, 60129 Ancona, Italy
Alessandra Mandolesi, Italo Bearzi, Division of Pathology, Department of Pathology, Polytechnic University of Marche, 60129 Ancona, Italy
Andrea Risaliti, Division of Hepatobiliary and Transplant Surgery, Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy
Author contributions: Nicolini D designed the study, collected data, wrote the paper, and performed the statistical analysis; Svegliati-Baroni G performed clinical management of patients before and after radiological procedures; Candelari R and Mincarelli C performed all transcatheter arterial chemoembolization procedures; Mandolesi A and Bearzi I performed all histological examinations of explanted livers; Mocchegiani F and Vecchi A performed clinical follow-up of patients after liver transplantation; Montalti R performed the statistical analysis and edited the manuscript; Benedetti A involved in manuscript editing; Risaliti A performed transplant procedures; Vivarelli M performed transplant procedures, designed the study, and edited the manuscript.
Correspondence to: Daniele Nicolini, MD, Division of Hepatobiliary and Transplant Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, Ospedali Riuniti, via Conca n° 71, 60129 Ancona, Italy. nicolini_daniele@yahoo.it
Telephone: +39-71-5965051 Fax: +39-71-5965100
Received: April 25, 2013
Revised: July 10, 2013
Accepted: July 17, 2013
Published online: September 14, 2013
Processing time: 141 Days and 13.5 Hours
Abstract

AIM: To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization (TACE) on recurrence-free survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and to analyze the effects of TACE on tumor histology.

METHODS: We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation. Patients who received any other type of treatment such as radiofrequency tumor ablation, percutaneous ethanol ablation or who were not treated at all were excluded. All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation. Doxorubicin-eluting bead TACE (DEB-TACE) was performed in 22 patients (38 nodules), and conventional TACE (c-TACE) in 16 (25 nodules). Patients’ and tumors’ characteristics were retrospectively reviewed. We performed a per-nodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE (conventional or DEB) and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area, including 21 nodules not reached by TACE. Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent, moderate and enhanced reaction. Uni- and multivariate analysis of risk factors for HCC-recurrence were performed.

RESULTS: The number and diameter of the nodules, the time spent on the waiting list and the number of treatments were similar in the two groups. A trend towards higher appropriate response rates (necrosis ≥ 90%) was observed in the DEB-TACE group (44.7% vs 32.0%, P = 0.2834). The mean percentage of necrosis in the cumulative tumor area was 58.8% ± 36.6% in the DEB-TACE group and 50.2% ± 38.1% in the c-TACE group (P = 0.4856). Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group (P < 0.0001, for both the parameters). The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients (87.4% vs 61.5%, P = 0.0493). Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination, the percentage of necrosis on CTA ≤ 50% and a pre-transplant serum α-fetoprotein level greater than 70 ng/mL. On multivariate analysis, the lack of treatment with DEB-TACE, high levels of α-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence.

CONCLUSION: DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.

Keywords: Liver transplantation; Hepatocellular carcinoma; Transcatheter arterial chemoembolization; Doxorubicin-eluting bead; Tumor histology; Recurrence-free survival; Locoregional therapies

Core tip: The manuscript reports the experience with a newer technique of transcatheter arterial chemoembolization (TACE) that uses doxorubicin-eluting beads (DEB) for the treatment of hepatocellular carcinoma in liver transplant candidates. The results of DEB-TACE were compared to those of conventional TACE, and remarkably, a significantly higher recurrence-free survival after liver transplantation was observed in patients who were treated with DEB-TACE. The histological pattern observed in the area surrounding the tumor nodules of DEB-TACE patients was characterized by an intense inflammatory and fibrotic reaction, which could play a role in limiting tumor spread during waiting list time.