Selecting patients with hepatocellular carcinoma for transplantation

Abstract

The article by Otto et al.,1 published in Liver Transplantion in the August 2006 issue, provides intriguing results concerning the possibility to select patients with hepatocellular carcinoma for transplantation according to an indirect assessment of tumor biology, namely the response to transarterial chemoembolization, regardless of the initial radiologic staging. The widely accepted Milan criteria,2 based on imaging findings of size and number of tumor nodules, were also selected because considered indirect markers of the tumor biology and thus predictors of the risk of posttransplantation hepatocellular carcinoma recurrence. Indeed, on a general basis, the larger the tumor (and, similarly, the higher the number of tumors) the poorer the differentiation and the higher the rate of microvascular invasion, both parameters being features related to the risk of recurrence. The approach of Otto et al.1 consisted in judging the biology of the tumor following the response to repeat transarterial chemoembolization treatments. Although this is a reasonable approach, it should be acknowledged that technical problems might prevent adequate treatment of tumors in various instances, in otherwise biologically suitable candidates for transplantation. For instance, hepatic artery stenosis after initial transarterial chemoembolization sessions, progression of liver failure, and anatomical variants of liver arterial vascularization, may all limit the possibility to perform or repeat transarterial chemoembolization treatments. Interestingly, an information on the grading of the tumors, obtained by means of liver biopsy, was available in the vast majority of the patients studied by Otto et al.1 Despite the possible intrinsic limitation of percutaneous biopsy in comparison to whole nodule pathologic analysis, in establishing the exact tumor grading, due to the risk of undergrading in bioptic specimens, we believe that a reanalysis of data of Otto et al.,1 could provide additional interesting results. In particular, we would suggest a further analysis, with patients grouped according to tumor grading, assessing: 1) the outcome of patients in terms of transplantations on an intention-to-treat basis; 2) the outcome of transplanted patients in terms of recurrence rate; and 3) the rate of dropout due to tumor progression during the waiting time. Possible findings to be tested should also be whether patients with well differentiated tumors have lower dropout rates for tumor progression or have lower recurrence rates, regardless of the initial tumor size. This would make them potentially transplantable also in those instances in which technical feasibility of repeated transarterial chemoembolization is lacking. On the other hand, it may also be tested whether patients with poorly differentiated tumors are poor transplant candidates, even when they respond adequately to transarterial chemoembolization treatments. Since an answer on these points might be of particular relevance for the liver transplant community, a further analysis by Otto et al.1 is warranted. Fabio Piscaglia*, Alice Gianstefani*, Roberto Righini*, Luigi Bolondi*, * Unit of Internal Medicine, Department of Internal Medicine and Gastroenterology University of Bologna Bologna, Italy.