Annals of Diagnostic Paediatric Pathology

108
Introduction
In the last 15 years a steady increase in survival in pediatric
liver tumors has been noted. First observations on improvement
in survival with the use of adjuvant chemotherapy came
from Children’s Cancer Study Group (CCSG) and Pediatric
Oncology Group (POG) in the late 70’s. Later in unresectable
cases neoadjuvant chemotherapy was applied [3, 9]. In 1986
Belgian and Canadian centers introduced in hepatoblastoma
standard pre- and postoperative chemotherapy consisting of
cisplatin and adriamycin. This chemotherapy protocol, called
later PLADO, has become a golden standard of
hepatoblastoma (HB) treatment in many centers, including
Mother and Child Memorial Hospital in Warsaw. Efficacy of
further modified protocols was tested by the multinational
SIOPEL group in three subsequent trials: SIOPEL 1-3 [9-11].
It was shown that cisplatin alone is as effective as PLADO in
standard risk HB [9, 10].
Despite chemotherapy progress complete tumor resection
remains a goal of treatment and prerequisite for cure. If it
cannot be achieved it is better to abandon any surgical attempt
and resort to another treatment modality and/or consult the
case with referral center. Our remarks on principles of the
surgical treatment of liver tumors were presented during Surgical
Workshop in Szklarska Porêba, Poland in 2002 [13]. It
was reported that progress in surgical management of liver
tumors had been associated with better knowledge of its
anatomy, improved surgical technique and equipment (ultrasonic
and water-jet dissectors, argon beam coagulation,
thrombostatic materials), as well as new imaging techniques,
new method of anesthesia and improved perioperative care.
Presented results emerged from multicenter cooperation
of 13 Polish institutions within the study devoted to surgical
treatment of malignant epithelial tumors of childhood
including patients’ stratification according to risk groups in
cooperation with the International Childhood Liver Tumors
Strategy Group (SIOPEL). This study is coordinated in Poland
by the Department of Pediatric Surgery of the Medical
University of Gdansk.
Material and methods
In the period 1998-2002 all together 34 cases of primary epithelial
liver tumors were treated in 11 Polish paediatric oncology
centers. Twenty-eight were HB and 6 were HCC including
one transitional (HB/HCC) liver tumor. Patients’ characteristics
and stage are shown in Tab.1 and 2. Maximal tumor
diameter ranged from 5 to 18 cm. Among HB 23 tumors (82%)
were unifocal and 6 – multifocal. In HCC multifocal tumors
prevailed: 4 out of 5. Eight HB cases (29%) were qualified to
the high risk group according to the SIOPEL protocol definition.
Alphafetoprotein (AFP) was elevated in all but one HB
case (from 150 ng/ml to 2.480.000 ng/ml), in which AFP level
was < 100 ng/ml. In all HCC cases AFP was elevated (from
150 ng/ml to 2.500.000 ng/ml). Lung metastases were present
in one HB case (3,6%) and in 3 HCC cases (50%). In one
HCC case metastases involved also mediastinal and retroperitoneal
lymph nodes.
Treatment protocols were based on consecutive SIOPEL studies:
SIOPEL 2 and 3. Standard imaging methods included:
abdominal ultrasonography (US), chest X-ray (AP and lateral),
computed tomography (CT) of the abdomen (with and
without i.v. contrast) and chest (to detect eventual pulmonary
metastases) and/or magnetic resonance imaging (MRI). Also
complete blood count (including platelet level) and serum AFP
were obtained at diagnosis. AFP, if elevated, was used to monitor
response to treatment. The protocol required preoperative
assessment of tumor extent according to PRETEXT classification,
which is described in details elsewhere [12]. Closed
needle biopsy was performed in 2 cases, open biopsies were
done in 21 cases (18 – wedge and 3 – open needle biopsies).
In one case liver biopsy was done laparoscopically. In 5 cases
diagnosis was made on the clinical ground. In 4 patients data
on biopsy are missing. Patients with biopsy proven HB and
HCC were qualified to two risk groups on the basis of PRE-
TEXT grouping. High risk tumors were those PRETEXT 4
(involving the whole liver) or belonging to any PRETEXT
category with the following features: significant intravascular
involvement (V or P), extrahepatic extension and/or distant
metastases (M). Hence high risk tumors were primarily
unresectable. All others formed standard risk group. In tumors
occurring between 6 months and 3 years of age with
unequivocal imaging and increased AFP level diagnosis of
hepatoblastoma on clinical ground was allowed. Before definite
surgery Doppler US and helical CT were required. All
patients with hepatoblastoma received preoperative chemotherapy
which was dependent on the risk group assignment.
Standard risk tumors were treated either cisplatin monotherapy
or PLADO regimen (those registered in the SIOPEL 3 trial
were randomized), however few patients were not randomized.
High risk patients were treated with SuperPLADO regimen,
which included 2-weekly cisplatin alternating with
doxorubicin administered together with carboplatin. Four triweekly
chemotherapy courses were given. Postoperatively two
more courses of the same chemotherapy were administered.
For details of the treatment protocol check elsewhere [9, 10,
11]. Cisplatin alone was used in 10 children, PLADO in 7
cases and SuperPLADO in 9 cases. In 2 cases details on preoperative
chemotherapy are missing. Twenty-one HB cases
were operated in a delayed setting. Type and completeness of
performed surgery is shown in Table 3. Treatment of operable
hepatocellular carcinoma (HCC) patients was started with tumor
resection followed by 6 postoperative courses of
SuperPLADO regimen. Two HCC cases were primarily operated
including one orthotopic liver transplantation Treatment
of unresectable and/or metastatic HCC was identical with high
risk HB. One child with HCC was operated in a delayed setting
after partial response to preoperative chemotherapy. In
non-responders (2 cases) chemoembolization was used.