Elsevier

Transplantation Proceedings

Volume 43, Issue 10, December 2011, Pages 3813-3818
Transplantation Proceedings

Liver transplantation
Complication
Rate of Tumor Growth Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation in Patients Beyond Milan or UCSF Criteria

https://doi.org/10.1016/j.transproceed.2011.09.043Get rights and content

Abstract

Background

It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC).

Methods

We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed.

Results

Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7–30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P = .001), poorly differentiated tumors (HR 13; P = .039), the presence of microvascular invasion (HR 7.9; P = .001), higher TTV (HR 1.03; P < .001), and faster tumor growth (HR 1.09; P < .001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm3/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth <1.61 cm3/mo experienced less recurrence (11% vs 58%; P = .023) than those beyond the Milan criteria with tumor growth >1.61 cm3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria.

Conclusions

Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.

Section snippets

Patients and Methods

After receiving Institutional Review Board approval, we reviewed the electronic medical records of all adult patients (age ≥18 years) who underwent LT at the Cleveland Clinic between 2002 and 2008 (n = 673). Patients who had definite diagnosis of HCC and underwent LT (n = 121) were identified. According to the American Association for the Study of Liver Diseases (AASLD) practice guidelines,14 all cirrhotic patients at our institution undergo surveillance for HCC using ultrasonography at 6-month

Patients' Characteristics

The baseline characteristics of the 92 patients included in the study who underwent LT for HCC between 2002 and 2008 are summarized in Table 1. The median age of the recipient at the time of the transplant was 56.0 years (IQR 52.2–60.9); 81 (88%) were male, and 79 (86%) were white. Hepatitis C virus (HCV) was the most common etiology of HCC, accounting for 60 of 92 cases (65%). The median calculated MELD score at the time of LT was 12.5 (IQR 9.0–15.0).

Serum AFP levels obtained at the time of

Discussion

HCC is unique among all solid tumors in that transplantation is the best therapeutic and curable option available today. Over many years, several groups from different countries have struggled to come up with criteria to limit LT for patients with good-prognostic HCC tumors and to balance the increasing demand for LT with limited organ supply. A major shortcoming of all currently proposed criteria is that they determine the risk of HCC recurrence after LT based on tumor morphology rather than

References (17)

There are more references available in the full text version of this article.

Cited by (16)

  • Surgical management of hepatocellular carcinoma within and beyond BCLC indications in a middle volume center

    2018, Journal of Visceral Surgery
    Citation Excerpt :

    BCLC classification contemplates only morphological criteria as number and dimension of the lesions to establish the belonging of a patients to stage 0, A and B, meanwhile takes into account aspects more related to tumor biology (macrovascular invasion, extrahepatic spread) for the identification of patients in stage C. Anyway, tumor morphological features do not correlate constantly to aspects related to tumor biology as tumor grading or vascular invasion those are the most relevant recognized parameters predicting tumor recurrence and tumor-related survival; microvascular invasion and high histologic grade are respectively present in 55% and 54% of HCC > 5 cm and in respectively 25–40% and 36% of HCC < 5 cm [25]. Similarly, in the field of liver transplantation, some patients with HCC beyond Milan criteria (those are morphologic criteria too) [26] but in presence of favorable tumor's characteristics as slow growth or good response to neoadjuvant treatments (as resection, ablation or TACE) demonstrated prolonged survival after transplantation [27,28]. In our series, the number of patients with histological tumor grading G3/4 and with histological microvascular invasion are similar between BCLC stage 0/A and stage B (respectively P = 0.22 and P = 0.73).

  • Incidence and risk factors of hepatocellular carcinoma after orthotopic liver transplantation

    2017, Surgery (United States)
    Citation Excerpt :

    Additionally, a study by Hanouneh et al9 demonstrated that patients excluded from liver transplant because they did not meet the current Milan or the more liberal University of California San Francisco (UCSF) criteria can still have acceptable post-transplant outcomes due to favorable biology of the HCC. The authors concluded that tumor growth rate may be a useful tool in selecting patients with HCC outside of Milan criteria for liver transplantation.9 Likewise, another study concluded that the current Milan and UCSF criteria were insufficient in predicting patients at high and low risk for recurrence of HCC after OLT.10

  • Percutaneous microwave ablation of hepatocellular carcinoma with a gas-cooled system: Initial clinical results with 107 tumors

    2015, Journal of Vascular and Interventional Radiology
    Citation Excerpt :

    This is in contradistinction to RF ablation, with which a diameter of 3.0 cm is considered the practical upper limit for obtaining local control (2,3). The limited effectiveness of RF for larger tumors is likely a result of the increased biologic aggressiveness of larger tumors, an increase in peritumoral satellitosis, and the need to create much larger zones of ablation to encompass the tumor, satellites, and a margin (Fig 2) (30–32). For example, when tumor diameter increases from 3 cm to 4 cm, the increase in ablation zone volume necessary to cover a tumor and a 5-mm margin grows from 65.6 cm3 to 113.4 cm3 (a 73% volume increase).

View all citing articles on Scopus

Supported in part by Mikati Foundation Endowed Chair in liver Disease, Beirut, Lebanon.

View full text