Keywords
undifferentiated embryonal liver sarcoma - transarterial chemoembolization - child
Introduction
Undifferentiated embryonal liver sarcoma (UELS) accounts for only 9 to 15% of all
malignant liver tumors in children. Typically, UELS occurs in older children and presents
as an abdominal mass. Most UELS are unresectable because of the later diagnosis. The
outcome of UELS is very poor, with a 5-year overall survival of < 37.5%.[1] Recently, transarterial chemoembolization (TACE) has been used in an attempt to
reduce the toxicity of chemotherapy and this method is accepted as effective and safe
for the treatment of unresectable adult hepatocellular carcinoma (HCC).[2] We used this procedure for two children with UELS and observed a favorable response.
Herein, we report the cases of two children with UELS who underwent TACE and surgical
resection in our center within the past 10 years.
Case Report
Case 1
A 7-year-old girl had been presented with an abdominal pain and abdominal mass for
the last 7 days. She did not have any other associated symptoms. Family history was
insignificant. The weight of the patient was 26 kg. On examination, the child was
found to have a large abdominal mass in the right lobe of the liver. The laboratory
investigations revealed abnormal liver tests (alanine aminotransferase [ALT] 56 U/L),
serum α-fetoprotein (AFP), and inflammatory tests were normal. An ultrasound examination
identified it was a hepatic mass like hepatoblastoma. The patient was presumptively
diagnosed with UELS by an ultrasound-guided needle biopsy. The tumor was evaluated
with computed tomography (CT) scan and magnetic resonance imaging (MRI) to examine
the size and extent of the primary tumor and the involvement of major vessels ([Fig. 1A, B]). The tumor was considered unresectable if it involved a large part of both lobes
of the liver or had invaded the main hepatic vessels or inferior vena cava. Pulmonary
metastasis was excluded via lung CT scan.
Fig. 1 (A and B) CT and MRI scans of case 1 show an unresectable mass in the liver. (C)
Digital subtraction angiography displays the tumor's blood supply of “holding ball.”
(D) The feeding artery of the tumor was embolized. CT, computed tomography; MRI, magnetic
resonance imaging.
Under basal plus caudal anesthesia and aseptic conditions, the right femoral artery
was catheterized with a radiography catheter (5F) using the Seldinger technique. Using
digital subtraction angiography fluoroscopy, the celiac axis and proper hepatic artery
were identified. Using an intra-arterial catheter, the right hepatic artery was identified,
and diatrizoate meglumine was used to identify the location of blood vessels and the
range of the blood supply range. The tumor's vessel around the mass showed a “holding
ball” appearance ([Fig. 1C, D]). At the time of angiography, 80 mg/m2 cisplatin (PLA), 30 mg/m2 doxorubicin (DO), and 1.5 mg/m2 vincristine were mixed with saline; one portion was infused slowly (90 minutes),
and one portion was dispersed in lipiodol and injected into the feeding artery of
the tumor. After embolization, celiac angiography confirmed the patency of major vessels
and the occlusion of the feeding arteries.
TACE was successfully performed in this patient. In the first day after TACE, she
presented with vomiting, fever, and transient liver dysfunction including the rise
of ALT (63 U/L) for 1 week, without cardiac, leukocytopenia, or renal dysfunction,
and these symptoms showed dramatic improvement after symptomatic treatment. Four weeks
after TACE, abdominal ultrasonography and CT scan showed that the tumor volume decreased
by 31% and the blood flow of the tumor was clearly lower than before treatment ([Fig. 2]).
Fig. 2 The tumor shank 4 weeks after TACE of case 1. TACE, transarterial chemoembolization.
Surgical resection with right hepatectomy was performed 8 weeks after TACE when the
tumor volume appeared to be sufficiently reduced to allow safe resection using extended
lobectomy. The gross findings showed well-demarcated nodular masses covered by an
incomplete capsule well defined from the surrounding normal parenchyma. The cut surface
was soft and variegated, with white gelatinous areas and foci of tumor necrosis and
hemorrhage ([Fig. 3A]). The cellular component was composed of medium to large spindle or stellate cells
with marked nuclear pleomorphism or multinucleate forms.[3] ([Fig. 3B]). The cell borders were poorly defined. Pleomorphic multinucleated giant cells were
relatively frequent. PAS (Periodic acid-Schiff)-positive, diastase-resistant hyaline
globules, which are believed to be lysosomes or apoptotic bodies, were frequently
observed within tumor cells and in the extracellular stromata.[1]
[4] Tumor necrosis was evident.
Fig. 3 The pathology of case 1. (A) The gross findings show a well-demarcated nodular mass.
(B) The cut surface was soft and variegated, with white gelatinous areas and foci
of tumor necrosis and hemorrhage. (C) The cellular component is composed of medium
to large spindle or stellate cells with marked nuclear pleomorphism or multinucleate
forms.
Another six courses of regular venous chemotherapy (PLA + DO) were administered beginning
2 weeks after the surgery. The patient was followed up for 1 year without any complications
with CT scan.
Case 2
A 10-year-old girl presented with an abdominal mass on physical examination for the
last 24 hours. There was no history of bellyache, jaundice, fever, anorexia, or weight
loss. On examination, the child was found to have a large abdominal mass in the right
lobe of the liver, with a weight of 34 kg. Serum AFP, liver enzymes, and inflammatory
markers were normal. Likewise, abdominal ultrasonography and MRI were used to examine
the size and extent of the primary tumor and the involvement of major vessels. TACE
was performed after presumptively diagnosing with UELS by ultrasound guided needle
biopsy. One week after TACE, the patient had vomiting, fever, and bone marrow depression
with a low neutrophil count of 0.68 × 109/L. After treatment with a leukocyte increasing agent (recombinant human granulocyte
colony-stimulating factor), the neutrophil count rapidly increased to normal. Three
weeks after TACE, abdominal ultrasonography and MRI scan were used to evaluate the
tumor response. The tumor volume decreased by 23% but was still large; one course
of venous chemotherapy (PLA 80 mg/m2 + DO 30 mg/m2 × 2) was administered. Two weeks later, right hemihepatectomy was performed. Two
weeks after the surgery, six courses of regular venous chemotherapy (PLA + DO) were
administered.
The girl was followed up for 9 years without any events. Abdominal ultrasonography
or CT scan was performed every 2 months during year 1, every 4 months during year
2, and every 6 months during year 3 of follow-up. The patient was considered successfully
treated after 5 years of tumor-free follow-up from the end of treatment. No evidence
of recurrence or metastases was found.
Discussion
The prognosis of UELS has been known to rely on whether surgical resection can be
achieved, but total resection of the tumor at the time of initial diagnosis is often
difficult. However, despite apparent complete resectability in some cases, local recurrence
and distant metastases have been major impediments to achieving long-term disease-free
survival.[5] Although chemotherapy is the mainstay of treatment for UELS, its toxicity if given
systemically is high may result in early death.[6]
[7] In the late 1970s, TACE was first introduced for the treatment of adult primary
liver tumors, and its results was reported to be more effective than those obtained
by other nonsurgical treatment modalities such as systemic or regional chemotherapy.[8]
[9]
TACE was introduced for the treatment of HCC and hepatoblastoma in adults and children
and recently, several large reports of patients have shown favorable results.[10]
[11]
[12] TACE has proven to be a valuable treatment modality for the following reasons: first,
embolization increases the dwell time of the chemotherapeutic agent and second, by
occlusion of the blood supply to the tumor, ischemia ensues, followed by hypoxic tissue
damage to the tumor. Furthermore, lipiodol is effective as an emulsion agent in chemoembolization
when mixed with chemotherapeutic agents because it is selectively absorbed and retained
by emulsification and pinocytosis in hepatic tumor cells.[13] Li et al demonstrated that adult UELS who underwent interventional therapy and surgical
resection exhibited a prolonged survival compared with patients who underwent surgical
resection only.[7] However, the use of TACE in children with UELS is somewhat limited. There are no
other serious adverse effects, such as liver dysfunction, renal function failure,
cardiac damage, and myelosuppression. Thus, TACE may be considered as a safe preoperative
treatment asset to systemic chemotherapy, particularly for patients without distant
metastasis.
Conclusions
Although this is only a report of two cases, we were impressed by the dramatic reductions
in tumor size achieved with TACE. The treatment of UELS with preoperative TACE may
not only increase the frequency of complete resection but may decrease the operative
morbidity. As in both cases, one case of CT scan was given shortly after the TACE
and before re-evaluation of tumor size. Therefore, we cannot be sure whether this
effect was due to TACE or the chemotherapy or a combination of both. In conclusion,
preoperative TACE might be considered to be an effective, feasible, and safe treatment
in lieu of systemic chemotherapy for inducing tumor shrinkage in pediatric patients
with or without surgically resectable tumors or metastases. Usually, 5-year-event-free
survival is something the oncologic surgeon refers to. In patient No. 1, the follow-up
of 1 year is rather short to conclude on efficacy of this method. Further experience
and pediatric studies on TACE are necessary before any recommendations for its application
as a first-line therapy can be made.
