Retrospective Study
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World J Gastroenterol. Oct 7, 2014; 20(37): 13538-13545
Published online Oct 7, 2014. doi: 10.3748/wjg.v20.i37.13538
Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation
Francesco Vasuri, Deborah Malvi, Francesca Rosini, Pamela Baldin, Michelangelo Fiorentino, Alexandro Paccapelo, Giorgio Ercolani, Antonio Daniele Pinna, Rita Golfieri, Antonio Maria Morselli-Labate, Walter Franco Grigioni, Antonia D’Errico-Grigioni
Francesco Vasuri, Deborah Malvi, Francesca Rosini, Pamela Baldin, Michelangelo Fiorentino, Walter Franco Grigioni, Antonia D’Errico-Grigioni, “F. Addarii” Institute of Oncology and Transplantation Pathology, S.Orsola-Malpighi Hospital, Bologna University, 40138 Bologna, Italy
Alexandro Paccapelo, Antonio Maria Morselli-Labate, Department of Medical and Surgical Sciences, Bologna University, 40138 Bologna, Italy
Giorgio Ercolani, Antonio Daniele Pinna, Department of Surgery and Transplantation, S.Orsola-Malpighi Hospital, Bologna University, 40138 Bologna, Italy
Rita Golfieri, Radiology Unit, S. Orsola-Malpighi Hospital, Bologna University, 40138 Bologna, Italy
Author contributions: Vasuri F designed and performed the research, revised the histology, collected and analyzed data, wrote the manuscript; Malvi D performed the research, revised the histology, wrote the manuscript; Rosini F, Baldin P and Fiorentino M revised the histology and collected pathological data; Paccapelo A and Morselli-Labate AM performed the statistical analysis and calculate the histological score; Ercolani G and Pinna AD collected clinical data and critically reviewed the manuscript; Golfieri R and Grigioni WF analyzed data and critically reviewed the manuscript; D’Errico-Grigioni A designed the research and critically reviewed the manuscript.
Correspondence to: Antonia D’Errico-Grigioni, MD, “F. Addarii” Institute of Oncology and Transplantation Pathology, S.Orsola-Malpighi Hospital, Bologna University, V.le Ercolani 4/2, 40138 Bologna, Italy. derrico@aosp.bo.it
Telephone: +39-51-6364546 Fax: +39-51-6364403
Received: February 16, 2014
Revised: April 18, 2014
Accepted: May 25, 2014
Published online: October 7, 2014
Abstract

AIM: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification.

METHODS: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondson's grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score.

RESULTS: The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up.

CONCLUSION: The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT).

Keywords: Chemoembolization, Hepatocellular carcinoma, Histopathology, Orthotopic liver transplantation, Cancer recurrence, Transarterial chemoembolization

Core tip: Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is used for down-staging before orthotopic liver transplantation (OLT), and as “bridging therapy” to reduce the drop-out rates in the waiting list. A discrepancy exists between the pre-transplant (radiological) and post-transplant (pathological) staging. Few study analyzing the histology of TACE-treated HCC exist. Here we analyzed 11 histological variables in 275 nodules from 101 consecutive OLT recipients and we computed a histological score to stratify recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates. The histological score allows a better stratification of those recipients beyond the Milan criteria after OLT.