DISCUSSION
Sarcopenia is a clinical condition with a high prevalence in patients diagnosed with hepatoblastoma, with up to 1/3 of this population affected according our study. This data has an important clinical significance as, in this series, its presence at diagnosis has been proved to contribute, on the one hand, to increase post-surgical complications (up to 13 times), and on the other hand, to provide prognostic information, associated with a clinically relevant decrease in both EFS and OS.
These results support those from Ritz A. et al in patients with high-risk group hepatoblastoma 11 or neuroblastoma9, in which the deleterious effect of sarcopenia on EFS had already been shown. Although these studies showed no evidence of sarcopenia as a risk factor for the appearance of post-surgical complications, or for a negative effect on OS, our study and others carried out in adult oncology patients6,7have confirmed this influence.
Anthropometric and analytical parameters have been analyzed by different authors to estimate sarcopenia status, as a way to avoid others specific tests. However, these studies, as well as ours, have shown a bad correlation between these parameters and sarcopenia11. According to our study, weight is the only anthropometric parameter that could be useful in predicting sarcopenia status, so that the higher the weight, the lower the probability of presenting sarcopenia. Nevertheless, this estimation is not very reliable, and its application in clinical practice is useless. tPMA based on cross-sectional imaging at diagnosis has been proven to be a useful, replicable and widely used method to estimate the sarcopenia status17.
The relationship between sarcopenia status and poor oncologic outcomes has been proven not only in solid tumors but also in other hematological malignancies such as acute lymphoblastic leukemia10. These findings highlight the importance of considering sarcopenia as a prognostic factor for pediatric tumors in general. Although it is not entirely clear, different mechanisms that feedback on each other and could be involved in this relationship have been proposed. On the one hand, oncological diseases are associated with a proinflammatory and hypercatabolic state that leads to nutritional imbalance and, consequently, to the development of sarcopenia. For example, Hu WHet a l18 showed a significant increase in the proinflammatory cytokines levels, such as IL-23, in oncological patients diagnosed with sarcopenia. Thus, tumors with aggressive biological behavior, and therefore more prone to relapse, would favor the development of sarcopenia, a hypothesis that has been corroborated by our study. Likewise, the nutritional imbalance present in oncological patients with sarcopenia could alter the healing process, hindering post-surgical recovery and favoring the appearance of complications associated with surgery19, like it has been showed in this study.
On the other hand, sarcopenia itself is a condition that could favor tumor progression and the appearance of relapses, directly affecting survival. This theory is supported by different studies that have shown a significant reduction in the expression of the anti-inflammatory cytokine IL-15 in patients with sarcopenia. IL-15 plays an important role in the stimulation of myogenesis, as well as in the proliferation and activation of NK cells. Therefore, a decrease in this cytokine’s levels associated with sarcopenia would produce a situation of immune dysfunction that would favor tumor progression20,21.
Stopping this vicious circle by treating sarcopenia could be key to improving oncologic outcomes and to avoid post-surgical complications in sarcopenic patients with hepatoblastoma. This treatment should include the early establishment of an optimized nutritional regimen, nutritional supplementation, if necessary, as well as appropriate specific physical exercise programs. Further prospective studies evaluating the effect on complications and survival after the implementation of such programs are needed in order to establish an adequate management of these patients. We propose that the determination of sarcopenia at diagnosis should be considered part of the initial oncologic study and contemplated as a prognostic factor to be considered in clinical practice.
One of the main limitations of this study is the small sample size. The disparity of findings obtained between the different works published on this same subject may be due to different reasons. On one hand, to the small sample size of the pediatric series, and, on the other, to the lack of negative outcomes, which makes it more difficult to get statistical significancy. Collaborative works between the different institutions involved in the treatment of childhood cancer seems crucial to obtain firm results that will allow to establish a proper management and prevention of sarcopenia, in order to improve the oncological outcomes of these patients.