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.