Preoperative hepatic artery chemoembolization followed by orthotopic liver transplantation for hepatocellular carcinoma

Abstract

In our experience, the primary obstacle precluding the widespread use of orthotopic liver transplantation (OLT) for definitive therapy of hepatocellular carcinoma (HCC), even for early-stage disease, is preventing tumor recurrence. Chemoembolization is an attractive strategy to minimize tumor progression before OLT because of its shown antitumor effect, ability to be repeated, and minimal systemic toxicity. Thus, this pilot study was undertaken to determine the tolerability and treatment outcomes of pretransplantation chemoembolization of HCC followed by OLT. Between 1992 and 1997, 27 patients with HCC who had cirrhosis, no extrahepatic metastasis, less than three tumor nodules of less than 5 cm each, and no evidence of vascular invasion on preoperative imaging studies were enrolled onto the protocol. Chemoembolization was performed using Ivalon particles with mitomycin, doxorubicin, and cisplatin. Twenty-four patients completed the protocol with chemoembolization and a liver transplant. The mean United Network of Organ Sharing waiting time was 167 days. Chemoembolization was well tolerated. On examination of the explanted liver, the majority of patients had a single lesion, mean tumor size was 3.66 cm (range, 1.5 to 6 cm), and the majority of patients had stage II disease. None of the transplant recipients has developed recurrent HCC (mean follow-up, 29.2 months; range, 9 to 55 months). The 1-and 2-year disease-free survival rates are 91% and 84%, respectively. In conclusion, chemoembolization followed by OLT is well tolerated and associated with excellent outcomes in selected patients with HCC. Copyright 1999 by the American Association for the Study of Liver DiseasesH epatocellular carcinoma (HCC) is one of the most common malignant tumors occurring in men worldwide, with an estimated annual incidence of 1 million cases. In the United States, HCC ranks as the 22nd most common form of cancer, with an annual incidence of approximately 2:100,000. 1 HCC is associated with chronic hepatitis B carrier state, chronic hepatitis C, cirrhosis from a wide variety of causes, iron-overload states, and exposure to aflatoxins. In one study, the natural history of 102 patients with cirrhosis with HCC who were not treated within prospective randomized trials was investigated. 2 After a median follow-up of 17 months, the 1-, 2-, and 3-year survival rates were 54%, 40%, and 28%, respectively. The adverse natural history attests to the need for establishing effective therapies for this aggressive malignancy.A variety of therapeutic modalities have been tried in the treatment of advanced HCC, including systemic chemotherapy, hepatic artery infusion of chemotherapeutic agents, hepatic artery embolization, hormonal therapy, and radiation therapy, all without long-term success. [3][4][5][6][7][8] Although surgical resection of HCC is considered the treatment of choice whenever technically feasible, long-term results after resection of even small tumors in patients with cirrhosis are disappointing; the 5-year recurrence rate is 52% a...

Resultados do transplante hepático em portadores de hepatocarcinoma

“…Para superar esses obstáculos, diferentes estratégias têm sido utilizadas tais como o emprego de fígados retirados de portadores de doenças metabólicas, tais como a polineuropatia amiloidótica familial (transplante dominó), fígados marginais e, mais recentemente, a possibilidade de realização de transplante inter vivo, utilizando-se o lobo direito do doador (17) . Como essas alternativas são acessíveis a poucos candidatos a TH, muitos programas de transplante preconizam tratamento antineoplásico adjuvante durante o período pré-TH através da quimioembolização arterial do HCC (3,7,17) . Na presente série, quatro pacientes com diagnóstico tumoral pré-transplante realizaram quimioembolização arterial do HCC em intervalo variável antes da cirurgia do transplante (4 a 18 meses).…”

“…Recentemente HARNOIS et al (7) publicaram a experiência da Clinica Mayo na realização periódica de quimioembolização arterial do HCC em pacientes cirróticos aguardando o TH. Vinte e quatro pacientes cirróticos com menos de três lesões tumorais com diâmetro inferior a 5 cm cada e sem evidência de invasão vascular ou de metástases extra-hepáticas completaram o protocolo de quimioembolizações a cada 2 meses com mitomicina, doxorrubicina e cisplatina.…”

“…Devido a atual tendência de aumento do tempo de espera em lista para TH, hoje oscilando entre 10 a 12 meses, tem-se adotado a prática de realizar, a cada 2 meses, arteriografia hepática com quimioembolização do HCC, enquanto o paciente aguarda a cirurgia do transplante, baseado nos bons resultados obtidos com essa prática no Programa de Transplante Hepático da Clínica Mayo (7) . De acordo com a experiência de HARNOIS et al (7) , tem-se restringido a realização de quimioembolização em pacientes com reserva hepática funcional razoável (Child A e B), pelo risco elevado de grave descompensação de doença hepática em pacientes Child C.…”

Reply: Selection criteria for liver transplantation in patients with hepatocellular carcinoma: Beyond tumor size and number?

“…It has been performed by several transplantation centers. [3][4][5][6] The new aspect in our approach is that patients exceeding the Milan criteria 7 were downstaged, 8 and, in contrast to any other study, the patients listed for LT were continuously treated by TACE during the waiting period according to a strict protocol. Risk of tumor recurrence was low in the patients without measurable tumor progress compared with patients with minimal tumor progress during the waiting time, even if this "progress" remained within the official definition of stable disease.…”

When should a liver mass suspected of being a hepatocellular carcinoma be biopsied?

“…We realize our approach may appear aggressive, but in our transplant experience, we have never had a misdiagnosis. 12 What will become the gold standard for the diagnosis of HCC in clinical studies if biopsies are to be avoided? This is a question for academic pursuits rather than one for improving patient care.…”