It should be noted that the Milan criteria for liver transplantation is directed toward adults with cirrhosis and hepatocellular carcinoma. It should not be applied to children and adolescents with hepatocellular carcinoma, especially those without cirrhosis.
Special considerations for surgical resection
Tumor rupture at presentation, resulting in major hemorrhage that can be controlled by transcatheter arterial embolization or partial resection to stabilize the patient, does not preclude a favorable outcome when followed by chemotherapy and definitive surgery.
Microscopic residual disease after resection
Second resection of positive margins and/or radiation therapy may not be necessary in patients with incompletely resected hepatoblastoma whose residual tumor is microscopic and who receive subsequent chemotherapy.[16,25] In a European study conducted between 1990 and 1994, 11 patients had tumor found at the surgical margins following hepatic resection and only two patients died, neither of whom had a local recurrence. None of the 11 patients underwent a second resection and only one patient received radiation therapy postoperatively. All of the patients were treated with four courses of cisplatin and doxorubicin prior to surgery and received two courses of postoperative chemotherapy. In another European study of high-risk hepatoblastoma, 11 patients had microscopic residual tumor remaining after initial surgery and received two to four postoperative cycles of chemotherapy with no additional surgery. Of these 11 patients, 9 survived.
Surgical resection for metastatic disease
Surgical resection of distant disease has also contributed to the cure of children with hepatoblastoma. Resection of pulmonary metastases is recommended when the number of metastases is limited [26,27] and is often performed at the same time as resection of the primary tumor. When possible, resection of areas of locally invasive disease, such as in the diaphragm, and of isolated brain metastasis is recommended.
In recent years, virtually all children with hepatoblastoma have been treated with chemotherapy, and in some centers, even children with resectable hepatoblastoma are treated with preoperative chemotherapy, which may reduce the incidence of surgical complications at the time of resection.[25,29,30]
In an international study, pre-resection neoadjuvant chemotherapy (doxorubicin and cisplatin) was given to all children with hepatoblastoma with or without metastases. The chemotherapy was well tolerated. Following chemotherapy, and excluding those who received liver transplant (less than 5% of patients), complete resection was obtained in 87% of children. This strategy resulted in an overall survival (OS) of 75% at 5 years after diagnosis for all children entered in the study. Identical overall results were seen in a follow-up international study. The International Society of Pediatric Oncology Epithelial Liver Tumor Group (SIOPEL) compared cisplatin alone with cisplatin and doxorubicin in patients with preoperative standard-risk hepatoblastoma. Standard-risk was defined as tumor confined to the liver and not involving more than three sectors. The rates of resection were similar for the cisplatin (95%) and cisplatin/doxorubicin (93%) groups, as were OS (95% and 93%), respectively.[Level of evidence:1iiA] Another SIOPEL study of high-risk hepatoblastoma patients treated with cisplatin alternating with carboplatin/doxorubicin in a dose intensive fashion. In 74 patients with PRETEXT stage 4 tumors, 22 of whom also had metastases, 31 became resectable and 26 underwent transplant. The 3-year OS of this group was 69% ± 11%. The 3-year OS of all patients with metastases was 62% ± 12%.