Objectives: Our aim was to analyze our experience with orthotopic liver transplant for hepatoblastoma patients.
Materials and Methods: We performed a single-center retrospective analysis of 6 orthotopic liver transplant cases in children with hepatoblastoma from 2001 to March 2015. We evaluated patient demographic features, pretreatment extent of disease stage, type of transplant, change in serum alpha-fetoprotein levels, complications, and follow-up results.
Results: Orthotopic liver transplant was performed for pretreatment extent of disease stage III with a central location (n = 3) and pretreatment extent of disease stage IV (n = 3). All children underwent living-donor orthotopic liver transplant. Postoperative serum alpha-fetoprotein levels remained below 10 ng/mL during the follow-up period in 3 patients who were free of recurrences or metastases. Five patients were free of tumor recurrences at a median follow-up of 29.9 months.
Conclusions: The limited number of cases we present without long-term follow-up of orthotopic liver transplant for unresectable hepatoblastoma seemed to show good clinical results.
Key words : Alpha-fetoprotein, Chemotherapy, Liver masses
Hepatoblastoma (HB), the most common malignant liver tumor in children (67%), accounts for more than 50% of liver masses. With the advent of effective chemotherapy, primary tumor resection rates and survival outcomes have improved over the past several decades. However, approximately 20% of HB cases remain unresectable after chemotherapy. Because complete tumor removal is the most important prognostic factor in children with HB, orthotopic liver transplant (OLT) has been used for patients without extrahepatic metastasis. Recent reports have shown a more than 80% survival rate at 5 years after OLT for these HB patients.1-3
Several factors have been reported as having a significant impact on treatment results, including tumor stage (pretreatment extent of disease), histopathologic subtype, alpha-fetoprotein (AFP) concentration at diagnosis and after chemotherapy, and presence of extrahepatic disease.1-3 Because liver transplant is now considered an option for patients with HB, it is also crucial to properly assess tumor resectability to determine the type of primary surgery to be performed. This decision is important because patients who develop tumor recurrence in the remnant of the liver after resection have a poor prognosis.4 The aim of the study was to analyze the changing treatment of children with HB in our center over the past 14 years.
Materials and Methods
We performed a single-center retrospective analysis of 6 cases of OLT in children with HB from 2001 to March 2015. We evaluated patient demographic features, pretreatment extent of disease stage, type of transplant, change in serum AFP levels, complications, and follow-up results. Three patients had pretreatment extent of disease stage III HB in a central location, and the remaining 3 patients had initial pretreatment extent of disease stage IV HB. There were 4 girls and 2 boys. The median age at surgery was 57 months (range, 12 mo to 9 y). The median weight was 15.5 kg (range, 9-26 kg). The follow-ups ranged from 12 to 98.3 months.
In all 6 cases, preoperative chemotherapy treatment that included cisplatin and doxorubicin and ranged from 5 cycles to a maximum of 16 cycles was administered. Postoperative chemotherapy was prescribed in 1 patient who showed pulmonary metastasis after transplant. All patients received living-donor OLT. Four children underwent left lateral transplant; 2 children received a left hemiliver graft. One patient required hepatic vein stent insertion owing to stenosis and another experienced biliary leakage that was treated with percutaneous drainage and conservative management. Serum AFP levels showed a median value of 153 000 ng/mL (range, 6020-486 000 ng/mL) at the time of diagnosis and a median value of 68.9 ng/mL (range, 17.8-52 000 ng/mL) at the time of transplant. Postoperative serum AFP levels remained below 10 ng/mL during follow-up in 5 patients who were free of recurrences or metastases (Tables 1 and 2). A pulmonary metastasis was observed at postoperative month 2 in 1 female patient who underwent a pulmonary resection. The other patients were free of tumor recurrence at a median follow-up of 29.9 months.
In this limited number of patients without long-term follow-up, OLT for unresectable HB seemed to show good clinical results.
Improved outcomes in children with HB are largely the result of effective chemotherapy and advances in surgical treatment strategies, including OLT. The current overall survival rate of patients with HB is 70% to 80%.4-6 The outcomes of OLT patients with a tumor that remains unresectable after chemotherapy compares favorably with outcomes after partial hepatectomy in patients with a resectable tumor. Our experience also has shown good clinical results in advanced-stage HB patients. Although the benefit of chemotherapy for HB patients before OLT is obvious, the optimal amount and timing of treatment before OLT remain largely unknown. Normally, we make a decision about resectability after 3 or 4 courses of chemotherapy. Previous studies of OLT in HB patients clearly showed that salvage OLT (liver transplant after postresection recurrence) was associated with poorer outcomes. Therefore, if the tumor remains unresectable and a potential living donor is available, the donor work-up and OLT preparation should be initiated by the fourth or fifth cycle of chemotherapy. In our series, all living-donor OLT were performed after 6 to 8 courses of chemotherapy, except for the first case. The timing of transplant surgery needs to comply with the chemotherapy schedule. Living-donor OLT has this unique advantage over deceased-donor OLT in HB patients.1,2,7
The necessity and value of chemotherapy after OLT is another consideration. Otte and associates reviewed the world experience of OLT for HB, comparing 65 patients who received chemotherapy after OLT with 82 patients who did not; there were no significant differences in 5-year survival rates (77% vs 70%) between the 2 groups.8-10 Considering the additive morbidity of chemotherapy on immunosuppression, some centers (including ours) avoid routine chemotherapy after OLT. However, this issue needs further study with a sufficient number of patients.3,8
In determining appropriate patients for chemotherapy after OLT, our data showed that serum AFP levels may be a good indicator of recurrence or metastasis. Although AFP has been reported to be associated with outcomes in HB patients, no reports have focused on changes in AFP levels after OLT. In our study, serum AFP levels after OLT in the 5 patients free of tumor recurrence dropped rapidly and were below 10 ng/mL throughout the 29.9-month median follow-up. In 1 patient who displayed a pulmonary metastasis at postoperative month 2, serum AFP levels after transplant were never below 10 ng/mL and increased gradually.1,9
Although we have presented a limited number of cases without long-term follow-up, OLT for unresectable HB seemed to show good clinical results. The roles of chemotherapy and serum AFP levels after liver transplant need further investigation.
Volume : 15
Issue : 1
Pages : 50 - 52
DOI : 10.6002/ect.mesot2016.O29
From the Departments of 1Transplant Surgery, 2Pediatric Gastroenterology, and
3Pathology, Baskent University, Ankara, Turkey
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Mehmet Haberal, Baskent University, Taskent Caddesi No:77, Bahcelievler, Ankara 06490, Turkey
Phone: +90 312 212 7393
Table 1. Patients Demographics, PRETEX Stage, and Liver Transplant Related Data
Table 2. Change in Serum Alpha-feroprotein Levels
Figure 1. Photographic and Radiologic Image of Hepatoblastoma