Discussion
Complete resection of hepatoblastoma is one of the most important factors that affect the prognosis of hepatoblastoma. Although COG and SIOP Epithelial Liver Tumor Study Group (SIOPEL)are controversial about whether early hepatoblastoma need neoadjuvant chemotherapy or primary resection, the treatment strategy of neoadjuvant chemotherapy followed by surgery has become a consensus for unresectable cases[14, 15]. At present, neoadjuvant chemotherapy based on platinum can reduce the tumor volume, avoid the risk of tumor rupture and allow many initially unresectable tumors to be safely removed [14]. The SIOPEL trials have revealed that more than half of PRETEXT IV tumors can be completely resected after intensified neoadjuvant chemotherapy[16]. Therefore, neoadjuvant chemotherapy was used in all the advanced cases in this study. And tumor size was regressed in 85.7% patients, with an average reduction of 67.45%. Despite tumor volumes regressed significantly with increasing neoadjuvant chemotherapy cycles, SIOPEL evaluated tumor resectability after four cycles of neoadjuvant chemotherapy[17], while COG evaluated every two cycles, with a maximum of six cycles[18]. In our study, the COG treatment strategy was adopted, and 81.1% of tumor can be resected within four cycles of neoadjuvant chemotherapy. Therefore, the majority of advanced hepatoblastoma became resectable through neoadjuvant chemotherapy.
Primary liver transplantation was recommended as surgical treatment option for advanced hepatoblastoma presenting as POST-TEXT IV or central POST-TEXT III stages after neoadjuvant chemotherapy. The long-term survival rates could reach up to 80% to 90% for these patients undergoing primary transplant[19-21]. In recent years, with the optimization of neoadjuvant chemotherapy, the progress of image evaluation and the improvement of surgical techniques, more and more studies reveal that non-transplant resection techniques in selected POST-TEXT III and IV hepatoblastoma achieved a similar survival rate to primary liver transplantation[10, 11, 13, 22]. What type of hepatic resection is used for POST-TEXT III and IV hepatoblastoma depends on the relationship between the tumor edge and the major liver vessels; on the other hand, it also depends on whether the tumor can be completely removed to ensure a negative margin. In this study, in addition to trilobectomy, expanded hemihepatectomy, mesohepatectomy or irregular hepatectomy were selected according to the number of hepatic segments involved and the relationship with the liver vessels. By choosing different types of hepatic resection, we can ensure that the residual liver can be preserved as much as possible on the basis of complete resection of tumor. In cases where liver tumor resection cannot be performed due to insufficient residual liver, ALPPS procedure will be of great usefulness for rapidly increasing the volume of residual liver in a short period[23, 24]. In this study, 4 patients underwent ALPPS due to insufficient residual liver. All patients had a rapid increase in residual liver volume within 2 weeks, and all tumors were successfully removed without liver dysfunction. Therefore, we believe that ALPPS could be reserved for those patients who would not have sufficient future liver remnant.
The tumors of POST-TEXT III and IV are very large or critically positioned and impinge on essential vascular structures, or tumors that are multicentric and present in three or four sectors, often requiring non-anatomical liver resection. Glissonean approach can be used to selectively block secondary Glisson pedicle according to the sectors involved, make a decrease in the amount of intraoperative bleeding, reduce the incidence of bile duct injury, and avoid intraoperative pringle maneuver[25, 26]. In this study, pringle maneuver was used only in 4 cases, while Glissonean approach was used in majority of cases (22/35). And the average blood loss of patients with Glissonean approach was significantly less than that of patients without the approach. Although the incidence of bile leak using the Glissonean approach is similar to that without the technique, and the incidence rate of ALPPS is the highest in all procedures, the incidence of biliary tract injury is significantly reduced, which reflects the advantages of this approach.
In recent years, reports of non-transplanted hepatic resection for POST-TEXT III and IV hepatoblastoma have increasingly been reported. The 5-year overall survival rate and 5-year tumor-free survival rate of these patients is 80.7% -88% and 62.2%~75%, respectively, which is similar to that of liver transplantation[10, 11, 13]. Our results are similar to those reported in the literature, indicating that it is feasible to perform hepatic resection for POST-TEXT III and IV hepatoblastoma. When hepatic resection for POST-TEXT III and IV hepatoblastoma is performed, it is sometimes difficult to guarantee a margin of resection greater than 1 cm. Although macroscopic residual tumor is an important factor affecting the prognosis of hepatoblastoma, there is still a debate about the prognostic impact of this microscopically positive resection margin[27, 28]. Recently, SIOPEL analyzed 431 cases of hepatoblastoma in its 2 and 3 trials and found that the tumor recurrence rate (6%) and 5-year survival rate (91%) of the microscopically residual cases were similar to those of the negative cases (recurrence rate: 5%, 5-year survival rate: 92%). Therefore, it is concluded that the presence of a microscopically positive resection margin did not influence the outcome even without additional local treatment[29]. In this study, we found that the recurrence rate of the patients whose tumor were resected close to the edge was higher than that of the patients who had resection margin, but the 5-year survival rate of was lower than that of the patients who had resection margin. In addition, we also observed that there was no significant correlation between the different distance of resection margin and the recurrence rate and survival rate. Therefore, our results indicate that when hepatic resection is performed on POST-TEXT III and IV hepatoblastoma, as long as a certain margin distance is ensured, tumor recurrence rate could be reduced and long-term survival rate could be improved.
In summary, non-transplant extended hepatic resection is a feasible approach for POST-TEXT III and IV hepatoblastomas. Different hepatectomy can be selected according to the different sectors of liver involved. On the basis of mastering the Glisson approach and ensuring a certain resection margin, it is possible to achieve a similar oncological outcome to liver transplantation.
Acknowledgments: We thank Professor Kai Li for her assistance with language editing and proofreading.