We appreciate the insightful replies from the Children's Oncology Group (COG; Meyers et al) and International Childhood Liver Tumors Strategy Group (SIOPEL; Czauderna et al) regarding our article, “Successful nontransplant resection of POST-TEXT III and IV hepatoblastoma.”1 We strongly agree with COG and SIOPEL on: 1) the importance of the PRETreatment EXTent of Disease (PRETEXT) staging system as an initial triage tool, 2) the need to avoid hazardous attempts at resection at centers that lack experience in advanced pediatric hepatobiliary surgery, and 3) the clear benefit of transplantation for tumors that remain truly unresectable after neoadjuvant chemotherapy.2 These points are made emphatically in our article. Our intended goal was not to undermine the importance of transplantation in the treatment of very large hepatoblastoma, but to point out that in a substantial proportion of children who might now be steered toward transplantation, successful nontransplant resection can be achieved and a decision to perform transplantation should not always be based on PRETEXT or POST-TEXT staging alone. The SIOPEL group itself has demonstrated that 37% of children with hepatoblastoma are overstaged by the PRETEXT system when compared to pathology findings.3
To comment on the specific issues raised in both letters regarding the accuracy of the preoperative staging, all our patients underwent imaging at Children's Memorial Hospital immediately prior to resection, even though initial imaging from the referral center was lacking in some patients. Therefore, accurate POST-TEXT staging was available in all cases.
Both letters state that separate wedge resections of widely separate nodules or the shaving of margins off portal structures are not standard practices and should not be recommended when liver transplantation is available. These comments speak to the very point of the article and are best addressed by our results. We would argue that because these methods result in a high cure rate without the need for transplantation, they should be considered for use more frequently under the right circumstances.
Our determination about which tumors might have been otherwise considered for transplantation was based on published SIOPEL guidelines stating that “If the tumor remained localized to the liver but still remained unresectable (PRETEXT group IV or III tumors in contact with hepatic vein or portal vein(s) precluding radical excision, or centrally located hepatoblastoma), liver transplantation was recommended as primary surgery.”4 We agree that most PRETEXT III tumors truly invading or encasing both portal venous branches (P2) require the patient to undergo transplantation. In our experience, the distinction between PRETEXT III tumors that invade the portal bifurcation versus those that abut and compress it may be impossible to make by imaging alone and requires surgical dissection of the portal structures to determine resectability.
Excellent results were achieved with careful separation of these tumors off the portal or hepatic veins, often with little or no margin of normal tissue at the resection margin. We agree with the comments by Meyers et al regarding the uncertain significance of less-than-ideal resection margins. We know of no good evidence that microscopically positive margins along the portal vessels are associated with adverse oncologic outcome in hepatoblastoma. We agree that this is an important area for future research, but in the meantime, we feel that the current evidence supports the aggressive position described in our article, in which resection for cure is possible even without an ideal margin of normal tissue.
Both letters comment on the lack of detail regarding the technique for surgical exploration. This was beyond the scope of the article, but we feel that this is an extension of the method proposed in the letter by Meyers and colleagues of combining preoperative imaging with intraoperative ultrasound. However, rather than basing the decision solely on intraoperative ultrasound, we also advocate mobilization of the liver.
We have long advocated for transplantation for patients who have liver tumors that are truly unresectable. Eight of the 23 patients in this series underwent transplantation, and several more not included here underwent transplantation based on the POST-TEXT imaging alone. Moreover, all families of patients undergoing exploration for extended resection are prepared for the possibility of transplantation. However, transplantation is not without its drawbacks. Until the shortage of organs can be resolved, and the long-term consequences of lifelong immune suppression mitigated by tolerance strategies, it is essential to avoid transplantation when an equivalent alternative is possible. On the other hand, because survival after primary transplant for hepatoblastoma is excellent, and poor after rescue transplant,5 it is incumbent upon advocates for advanced liver resection to achieve equivalent results. Our single-institution case series demonstrates that excellent results are achievable with resection of very large tumors in experienced hands. We look forward to future studies on this topic from multi-institutional study groups.