Fouad A. Fouad saleep MD., Ihab samy Fayek MD. Department of Surgical Oncology – National Cancer Institute – Cairo University - Egypt. Kasr el-aini medical journal Volume 18, No.4, October 2012.

1. 1
Treatment and outcome of 11 children
with hepatoblastoma
Fouad A. Fouad saleep MD., Ihab samy Fayek MD.
Department of Surgical Oncology – National Cancer Institute – Cairo University - Egypt
Abstract:
Aim : This study was designed to retrospectively review our experience National Cancer
Institute,Cairo University with the multimodality management of hepatoblastomas (HB) and to
assess the outcome of childhood hepatoblastoma after a combination therapy of resection and
chemotherapy. Materials and Methods: eleven patients were treated for HB between 2006 and
2010. The clinical presentations, chemotherapy tolerance and response and surgical procedure
undertaken were analysed. Results: Median age of the population was 15 months (6-37
months), mean age was 16.7 months; with a male-to-female ratio of 4.5:1. Nine patients were
treated with neoadjuvant chemotherapy incorporating cisplatin and adriamycin. Primary surgery
was done in two patients. Extent of hepatic resection in the operated patients varied. Mixed
type was the predominant histopathological diagnosis. Adjuvant chemotherapy was well
tolerated with no morbidity or mortality. All the nine patients who could complete
multimodality treatment are alive with no evidence of disease or complications with median
follow-up of 13 months (7-19 months), mean follow up was 12.2 months. Overall Survival of all
11 patients is 91%. Conclusion: Treatment of HB with multidisciplinary approach was well
tolerated. Overall Survival of patients were comparable with published studies.
Keywords: hepatic resections, Chemotherapy , hepatoblastoma, multimodality treatment,
neoadjuvant treatment.
Introduction:
Hepatoblastomas (HB) are rare pediatric
neoplasms, with incidence of 1.5 per
million, and comprising 1% of pediatric
malignancies (1). Till 1970s, surgery was
the primary modality of treatment of HB.
Unfortunately, up to 60% of the patients
present in an unresectable stage(1,2).
Later, the chemo-responsiveness of the
tumor was demonstrated which led to the
incorporation of adjuvant chemotherapy
with cisplatinum and doxorubicin in the
treatment of HB (3,4,5). International
Society of Pediatric Oncology (SIOP)
pioneered the concept of neoadjuvant
chemotherapy in the management of HB
(6,7). Surgical resection of the tumors were
made easier by reducing the size and
vascularity of the tumor, and the chances
for obtaining negative margins of resection
were more (7,8). A partial response (PR)
status could be achieved in 82% of the
cases in SIOPEL-1 study. Surgical resection

2. 2
after neoadjuvant chemotherapy could be
done in 87% of the cases whereas
historically only 30% of the cases were
operable upfront. Surgical morbidity was
also less if resection was performed after
neoadjuvant chemotherapy. Extended
surgical resections of HB have been safely
performed in the pediatric age group (8).
Orthotopic Liver transplant (OLT) is an
effective treatment for unresectable HB
with survival rates of 82% if done as a
primary treatment (1). Combined modality
treatment is now the standard of care in
HB. Management of HB over 4 years is
reviewed in this article.
Materials and Methods:
This study included patients diagnosed to
have HB and treated between January 2006
and December 2010 at National Cancer
Institute,Cairo University. Patient
demographics, mode of presentation,
method of diagnosis, extent of tumor at
diagnosis, surgical procedures performed,
complications of treatment and outcome
were recorded. Based on imaging using a
computerized tomography (CT) scan (fig. 1)
and/or magnetic resonance imaging (MRI),
all patients were assigned a PRETEXT (Pre-
treatment extent of disease) stage and four
groups of patients were identified as
PRETEXT I-IV.
Nine patients received neoadjuvant
chemotherapy followed by surgical
resection. The standard of care,
cisplatinum and adriamycin as in the PLADO
(PLA, Platinum; DO, Doxorubicin) regimen
was administered to the nine patients every
21 days. PLADO chemotherapy consisted of
PLA on day 1 at a dose of 80 mg/m2,
administered in a continuous 24-h infusion
and DO at a dose of 30 mg/m2 per day,
administered as a continuous 24-h
intravenous (IV) infusion on days 2 and 3.
Both drugs were administered via a central
venous catheter.
Patients were routinely reassessed after
three cycles for surgical resection. If the
tumor was found to be inoperable, patient
was given one more cycle of chemotherapy.
The decision regarding timing of surgery
was taken by the surgical oncology team.
Postoperatively, two to three cycles of
chemotherapy were given to a total of six
cycles. The patients were followed up after
treatment with serial AFP levels and
imaging. Follow-up was complete for all
treated patients. Resection is typically
performed through a bilateral subcostal
incision . Intraoperative ultrasonography
has been applied to determine the exact
location of the tumor relative to the vessels.
Unresectability is usually determined by
involvement of hilar structures or all
hepatic veins, invasion of inferior vena cava
(IVC) or portal vein. Centrally located
tumors are, by definition, more likely
unresectable. Once deemed resectable, the
resection is marked out and various tools
may then be used to perform the resection;
electrocautery, bipolar devices such as
LigaSure for hemostasis have been used
(fig. 2,3,4,5).

3. 3
Results: (Tables 1 & 2)
Eleven patients were diagnosed and treated
for HB. All the patients had elevated AFP
levels and pathological confirmation was
done in all feasible cases. There were nine
males and two were females in the group
(M:F, 4.5:1). The median age was 15
months (range, 6-37 months). None of the
patients had any cardiac anomalies. The
commonest presenting feature was that of
an abdominal mass (in 10 out of 11
patients). One patient was diagnosed while
being evaluated for fever. None of the
patients had jaundice or was seropositive
for Hepatitis B or C. All the patients had
palpable hepatomegaly. AFP was elevated
in all the cases with a median level of
20,000 ng/ml (range, 620-1,42,000 ng/ml).
CT scan was done for 6 patients and MRI for
5. PRETEXT staging distribution was as
follows; PRETEXT Stage 9.1% (n = 1), Stage II
54.5% (n = 6), Stage III 36.4% (n = 4), and
Stage IV 0% (n = 0). Patients who
underwent straight surgery did not have
preoperative biopsy. Eight of the remaining
nine patients had pretreatment fine needle
aspiration (FNA) or Trucut biopsy.
Surgical procedures performed included
right hepatectomy in five patients,
extended right hepatectomy in three
patients, and left hepatectomy in
three.Neoadjuvant chemotherapy was
given to 9 of 11 patients. The remaining two
had initial surgery (Table 1). An 18-month-
child with PRETEXT 2 disease who
underwent upfront surgery died 8 months
later from extensive lung metastases which
led to pulmonary insufficiency and failure.
Of the neoadjuvant group, three patients
completed four cycles and another six
completed three cycles of chemotherapy
before surgery. All nine patients received
adjuvant chemotherapy also for a total of
six cycles. The two patients who had
primary surgery received adjuvant
chemotherapy also.
The median duration of surgery was 180
min (range, 120-260 min). The median
blood loss was 250 ml (100-400 ml). The
median length of postoperative hospital
stay was 10 days (range, 6-17 days). The
only postoperative complication was
intestinal obstruction in one patient which
was managed conservatively. There was no
postoperative mortality.
Histopathology and margins
The histological types encountered were as
follows: embryonal and mixed
embryonal/foetal subtype in four patients
and mixed epithelial and mesenchymal in
seven. Pathological complete remission was
noted in one patient after neoadjuvant
chemotherapy, others having residual
tumor. Among the eleven patients eight
had tumor-free margin of at least 5 mm,
three had close margins (<5 mm).

4. 4
Patient
No.
Age AFP Preop Liver segments involved PRETEXT Staging Initial ttt.
1 11 2,000 5,6,7 2 CHEMO
2 7 35,618 2,3,4 2 CHEMO
3 16 5,692 5,6,7 2 CHEMO
4 6 620 2,3 1 Surgery
5 8 131,861 5,6,7,8,4 3 CHEMO
6 12 960 4,8 3 CHEMO
7 32 142,000 4,5,6,7,8 3 CHEMO
8 18 121,150 5,6,8 2 Surgery
9 22 20,000 4,7,8 3 CHEMO
10 37 130,605 5,6,7 2 CHEMO
11 15 730 5,6,8 2 CHEMO
Table 1: Preoperative Evaluation and treatment
Patient
No.
Extent of liver
resection
Operative
time (min.)
Blood
loss (ml.)
PO hosp.
stay (days)
FU Current
Status
1 Rt. hepatectomy 210 190 10 14 CR
2 Left hepatectomy 160 150 7 9 CR
3 Rt. hepatectomy 170 250 10 7 CR
4 Left hepatectomy 120 100 6 11 CR
5 Extended RT
trisegmentectomy
230 300 17 13 CR
6 Left hepatectomy 130 150 8 18 CR
7 Extended RT
trisegmentectomy
260 400 14 13 CR
8 Rt. hepatectomy 210 250 7 8 dead
9 Extended RT.
trisegmentectomy
260 350 11 19 CR
10 Rt. hepatectomy 160 250 10 8 CR
11 Rt. hepatectomy 180 190 11 14 CR
Table 2: Operative and Postoperative details
Discussion
Hepatoblastomas are the most common
pediatric primary liver malignancy
accounting for more than 90% of the liver
tumors in less than 5 years of age (1). Most
of the cases are asymptomatic and present
in an advanced stage. The exact etiology is
unknown. The association with preterm
births and genetic conditions like Beckwith-
Wiedemann syndrome is well documented
in the literature (9,10). Surgical resection is
the cornerstone for successful management
of HB. Management of HB has evolved from
extensive surgical resections through the
incorporation of adjuvant chemotherapy to
the current standard of care of neoadjuvant
chemotherapy followed by surgery. The

5. 5
survival in 1970s with surgical resection
alone was a meagre 10-20% (11). However
with the arrival of chemotherapeutic
regimens such as PLADO, the surgical
outcomes improved tremendously.
Neoadjuvant chemotherapy pioneered by
SIOP has reduced the surgical
complications, facilitated more complete
resections and improved the cure rates (7).
Presently, survival is between 75% and 90%
(12,13,14). Multi-institutional trials have
confirmed the feasibility of this approach in
limited resource settings also (15,16). An
initial surgical approach may be acceptable
for resectable disease, but a neoadjuvant
approach may be preferable in advanced
stages (13).
The patients in our study had a lower
median age of presentation (15 months)
and male predominance compared to some
of the previous reports. PRETEXT stage II
predominated in our series (54.5%). All
patients in our series had a mixed type of
HB comprising foetal, embryonal, and
epithelial elements. Chemotherapy-related
long-term toxicities were absent in our
study. Most importantly all the nine
patients who completed multimodality
treatment are long-term survivors (up to 19
months). Relapse of the disease was not
observed in any of the survivors. Only one
patient died from extensive lung
metastases which led to pulmonary
insufficiency and failure.
Excellent results have been reported from
tertiary care centers in HB, thus reaffirming
the role of expertise in the management of
this rare neoplasm. Bajpai et al. reported
excellent outcome in 10 patients with HB.
Three patients recurred in their study. Fetal
subtype was the most common histology
(16). Ang et al. analysed outcome of 30
patients with HB treated at Royal Children's
Hospital Australia, from 1984 to 2004. The
5-year EFS was 75.7% (14).
From a malignancy with dismal outcome,
HB has come a long way through mainly
because of the combined modality
treatment with improved
chemotherapeutic regimes and surgical
techniques. HB is one cancer where the
coordinated effort of multiple specialities
has given a leap in the cure rates.
Conclusion:
Treatment of HB with multidisciplinary approach was well tolerated, safe with promising long
term survivors.

6. Figure 1: CT post chemotherapy
Figure 3: Exploration of the vena cava and the hilum
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Figure 5: Cut surface of the liver
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