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Calinescu et al. Hepatoma Res 2021;7:54 https://dx.doi.org/10.20517/2394-5079.2021.25 Page 5 of 9

8% after IRS III regimens 38 and 35, respectively, where two thirds of the complications were reported to be
[20]
secondary to sepsis developed after neutropenia ; cardiac toxicity, metabolic complications, respiratory
distress syndrome and central nervous system toxicity were less frequently described. Of note, within the
EpSSG protocol the number of chemotherapy cycles remains the same even if upfront surgery is performed,
which supports the safer attitude of preoperative chemotherapy . Yet, there is not enough solid evidence to
[9]
support the benefit of systematic neoadjuvant chemotherapy versus upfront surgery and larger prospective,
multicentric studies are required to draw a conclusion.

SURGICAL STRATEGIES
The surgical challenges in the treatment of UESL are mainly related to the large size at the moment of
[10]
diagnosis . Fortunately, initial aggressive surgeries are less required nowadays, since, as stated above,
neoadjuvant chemotherapy decreases tumor size and makes it more amenable to a more standard complete
resection [20,21] . The most frequently performed surgical resections are hemihepatectomy (37%), followed by
sectionectomy (28%) and trisectionectomy (10%) . But to allow for proper patient management (i.e.,
[12]
surgery planning), a preoperative staging system is needed.

UESL staging system
Regrettably, preoperative staging such as COG-staging or PRETEXT is not always mentioned in the
[12]
literature , making interpretations and comparison of publications more difficult. One of the first series
[22]
reporting on UESL used Intergroup Rhabdomyosarcoma Study clinical grouping [Table 2] . In a series of 5
patients, the American COG stage was reported as stage I in 4 patients and stage II in 1 patient
(preoperative rupture); no correlations could be found with this tumor staging given the small sample
size . PRETEXT staging was used for the UESL in only two series, a review of pediatric liver malignancies
[23]
in Finland with 7 PRETEXT II-III tumors and a monocentric retrospective review of 6 PRETEXT II-III
tumors. Again, given the small sample size, conclusions for tumor size correlation with survival were
difficult to draw [10,24] . Finally, European prognosis groups are stratified according to the
[9]
International Rhabdomyosarcoma Study group . Given the heterogeneity of staging for UESL, no clear
correlations between extent of disease and survival can be made. A uniform reporting with the PRETEXT
grouping system might be helpful for the standardization of patient grouping, and subsequent patient
management, and thus survival analysis. Additional data including age and size of the tumor, together with
the PRETEXT grouping system, could be included in a new risk stratification protocol for UESL.

Positive resection margins
The significance of microscopic residuum is still debated. In a cohort of 103 patients of which 20 had
positive microscopic margins, R1 resection did not seem to affect outcome, (P = 0.11), but the best survival
rates are still reported for patients with negative margins 95% 5-year survival vs. 83% 5-year survival for
patients with positive margins (i.e., R0 resection) [11,12,23] . Nevertheless, the burden of treatment could not be
evaluated in the 103 patient cohort of the American National Cancer Database , but consisted in 52%
[12]
neoadjuvant chemotherapy in a smaller CWS cohort of 25 patients in which resection type impacted
[11]
survival . Again, larger, standardized studies focusing on the matter are needed to obtain a definite answer
on the effect of microscopic margins on outcome.

Metastatic UESL
Although UESL metastases are seen in only 15% of cases , overall survival falls from 91% in patients
[12]
[12]
without metastatic disease to 70% in patients with metastatic UESL . The most common sites for
metastasis are the lungs, adrenal gland, peritoneum, and pleura [12,25-28] . Cardiac metastases are found in 10%-
25% of the patients dying from UESL. Surgical approach in this situation is tailored to the tumor type and
extension; staged approaches are reported: either removal of cardiac extension under cardiopulmonary