PA1 PRIMARY HEPATOCELLULAR CARCINOMA IN NON-CIRRHOTIC CHILDREN: FAVORABLE OUTCOME

Abstract

Background: Primary neoplasms of the liver are rare in children, comprising only 1.1% of malignancies in younger than 20 years of age. Hepatoblastoma comprises over two-thirds of the malignant tumors of the liver in children and hepatocellular carcinoma (HCC) accounts for most of the remaining cases. In pediatric population, HCC is a very rare tumour and is traditionally linked to liver chirrosis and to ongoing process of liver necrosis/regeneration (viral hepatitis or metabolic disease) but could also be observed in a non-chirrotic liver. In contrast to the age-incidence relationship for hepatoblastoma, the incidence of HCC increased with each successive 5-year age group. We report our single center experience with 3 patients with HCC in non-chirrotic liver and their therapeutic management. Methods: The medical records of 3 male children, with median age of 9 years (range, 8–10) who presented, with primary hepatocellular carcinoma on non –chirrotic liver, at our centre were reviewed. Ultrasonography, computed tomographic (CT) scan, and needle biopsy were the initial methods used to diagnose malignant tumors. The following data were analyzed: age at diagnosis, treatment modalities, histopathologic findings, surgical details, operative complications, and treatment results. Data related to surgery included the extent of the hepatic resection, macroscopic margins, and operative complications. When the tumor was considered unresectable by the postchemotherapy CT scan, transplantation was considered. Before that could occur, the patient underwent extensive scanning to assess for distant metastases. Treatment results were evaluated by the occurrence of local or distant recurrence and duration of survival. Results: In all patients clinical symptoms were history of fever, abdominal pain, and hepatosplenomegaly. Their serum α-fetoprotein level at presentation was markedly raised, with median value of 41142 ng/mL (range 1266070768). Hepatic biopsy was performed under sonographic guidance, and the diagnosis of HCC was made. In 1 case the extent of disease, limited to the liver, lead to tumour resection with hepatectomy, nevertheless 2 years later he underwent to repeated resection for primary liver tumor recurrence. Actually he is in well clinical condition, his serum α-fetoprotein is in the normal range and the radiological assessment show the absence of distant metastases. In 2 cases chemotherapy treatment was started according to the protocols of SIOPEL V, but the tumor did not respond to allow a resection. This fact, along with the absence of distant metastases on whole-body CT, suggested liver transplantation as a possible therapeutic option. The patients underwent surgical resection en bloc of the native liver and received a whole liver transplant. Immunosuppression with Tacrolimus was started first days after surgery. The serum α-fetoprotein level after transplantation fell down reaching normal values in 1 month for both patients (median value 9.5 ng/mL, range 9-10 ng/mL). Our 2 patients received tacrolimus as primary component of their post-OLT immunosuppression, adding SRL at least 1 month after transplantation to reduce the risk of delayed wound healing or incisional hernia due to the property of mTor inhibitor. Both transplanted patients recieved 1 year neoadiuvant therapy post OLTx. Contrast-enhanced CT of the transplanted liver was performed once a year: no lesion was seen in the liver parenchyma and the absence of liver metastasis was confirmed. In their 2 years follow-up survival and event free survival were comparable even better between this group and all patients who underwent OLTx for all the other indications. Discussion: Non-resectable forms of intrahepatic recurrence may, in the absence of extrahepatic spread, benefit from liver transplantation. This attitude may broaden the curative possibilities. Recurrence of hepatocellular carcinoma after liver transplantation is common (30% in adults), and the prognosis is not favorable. We try to avoid possible recurrence drawing a specific immunosuppression regimen. Experience with sirolimus (SRL)-based immunosuppression following OLT is rapidly accumulating. In different models, mTOR inhibitors (mTORIs) were effective in reducing cell growth and tumor vascularity. In combination with calcineurin inhibitors, SRL may reduce the incidence of acute rejection and lower overall required drug levels. Different studies indicate that sirolimus might be a promising drug for this treatment, but further clinical studies elucidating the biological effects are advocated to reach further improvement in the management of advanced disease. Repeat resection for primary liver tumor recurrence is feasible in patients with recurrence limited to the liver and good liver function. A survival at 5 years of 59% similar to that after the first hepatectomy, suggests a benefit from a hepatectomy for recurrent HCC.