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.