Table of Contents

HK J Paediatr (New Series)
Vol 1. No. 1, 1996

HK J Paediatr (New Series) 1996;1:60-63

Original Article

Primary Paediatric Liver Tumours - Queen Mary Hospital Experience

KL Chan, H Saing, ST Fan, I Ng, CF Chan, SY Ha, YL Lau


Abstract

Ten children were admitted into Queen Mary Hospital in recent six years with primary liver tumours. The ages of 7 girls and 3 boys ranged from newborn to 14 years (mean 5 years). They presented with abdominal mass (4) abdominal pain (3), vomiting (2), abdominal distension (2), weight loss (2), gastrointestinal bleeding (1), hirsutism (1) and antenatal ultrasound diagnosis of liver tumour (1). The diagnoses were hepatoblastoma (3), hepatocellular carcinoma (HCC) (4), mesenchymal harmatoma (1), adenoma (1) and cavernous haemangioma (1). Although the mean size of the hepatoblastomas was 12 cm, after resection and postoperative chemotherapy, the patients are alive without evidence of recurrence for a mean period of 4.3 years. Only one patient (25%) with HCC was operable. Patients with inoperable HCC died within a mean period of 6 months inspite of chemotherapy. There was no mortality and minimal morbidity from the six liver resections. Primary liver tumours in children are relatively uncommon and the majority of malignant tumours presented late. For large hepatoblastoma, surgical resection and postoperative chemotherapy is recommended.

Keyword : Primary liver tumours


Abstract in Chinese

Introduction

Primary neoplasms of the liver constitute between 0.5 and 2% of all paediatric tumours in large series, but they have received unusual attention possibly because of the vast histological variety, uncertainty about pathogenesis, relationship to antecedent diseases and difficulties in treatment.1

Adult hepatocellular carcinoma (HCC) has been shown to have marked differences between Asian countries and the West including Europe and North America as far as the incidence and presence of hepatitis B cirrhosis is concerned.2 Since at least 50% of the patients present late and cannot receive any kind of treatment, screening for early diagnosis of HCC has been suggested. However, its application for paediatric liver tumours is doubtful.

Methods and Materials

The medical records of the paediatric patients admitted into Queen Mary Hospital with the final diagnosis of primary liver tumours were reviewed retrospectively with the emphasis on the types of tumours, different forms of presentations and results of treatment.

Results

From August, 1989 to November, 1995, ten patients were admitted into Queen Mary Hospital with the final diagnosis of primary liver tumours. Their ages ranged from newborn to 14 years with the mean of 5 years. The female male ratio was 7:3.

The presentation of these patients usually started with some degree of abdominal discomfort such as pain or distension, which prompted the parents to feel their children's abdomens (Table I). Liver masses were then discovered by the parents. One patient with cirrhosis of liver and bilobe, diffuse type of HCC presented to us with severe oesophageal variceal bleeding. Hirsutism was the first symptom in a girl with adenoma of the liver. Her serum ACTH and cortisol levels were found to be abnormally high. With improvement in antenatal diagnosis, one patient with cavernous haemangioma was detected by antenatal ultrasound (Fig. 1).

Table I Mode of Presentation in the Ten Patients
Presentation Percentage (%)
1. Abdominal mass 40
2. Abdominal pain 30
3. Abdominal distension 20
4. Vomiting 20
5. Weight loss 20
6. Gastrointestinal bleeding 10
7. Hirsutism 10
8. Antenatal diagnosis 10

 

Fig. 1 Antenatal ultrasound study showed a well defined hypoechoic area (arrow heads) in the caudate lobe of the foetal liver. Postnatal ultrasound study and contrast CT scan confirmed the lesion to be cavernous haemangioma.

There was a wide variety of histological types in our patients (Table II). The three patients with hepatoblastoma were between one to three years of age (mean : 2.3 years) at presentation. They were all negative for hepatitis B surface antigen (HBsAg). Their alpha-foetoprotein levels ranged from 670 to 180,000 ng/ml (mean : 6,500 ng/ ml). Although the tumours were large and their sizes ranged from ten to fifteen cm (mean : 12 cm), all of them were resectable. The histology of the tumours showed foetal type of hepatoblastoma. In view of the large size of the tumours, adriamycin (30 mg/m2/dose) and carboplatin (450 mg/m2/dose) were given to them for 4 cycles with three weeks intervals. During follow up period of 19 to 71 months (mean: 52 months), they were all well, without any evidence of recurrence of the tumour.

Table II Pattern of Tumours in the Ten Patients
Tumour type Percentage
A) Malignant
  a. Hepatoblastoma (3) 30
  b. Hepatocellular carcinoma (4) 40
B) Benign
  a. Mesenchymal harmatoma (1) 10
  b. Adenoma (1) 10
  c. Cavernous haemangioma (1) 10

The ages of the patients with HCC were three to fourteen years (mean eight years). Only two of them (50%) were positive for HBsAg. Their alpha-foetoprotein levels were over 100,000 ng/ml. Even in the one patient (25%) in whom the tumour was resectable, the operation was palliative and the left lateral segmentectomy was performed with partial gastrectomy and transverse colectomy because the tumour had infiltrated these organs. In spite of the postoperative chemotherapy with carboplatin, mitomycin and 5-fluorouracil, multiple pulmonary secondaries were detected, and he survived for five months. All the remaining three inoperable patients with HCC died and their survival time ranged from one to fourteen months (mean 6 months). One of these patients presented to us with oesophageal variceal bleeding and ultrasound liver showed diffuse hyperechoic liver parenchyma with tumour thrombus in the portal vein (Fig. 2a). Trucut biopsy showed diffuse infiltrating HCC (Fig. 2b). The patient died within 1 month after the presentation. Another patient presented with a huge liver tumour on the right lobe. It was inoperable because the middle hepatic vein was encased by tumour (Fig. 3a). Transarterial oily chemoembolization (TOCE) using cisplatin as chemotherapeutic agent was given to the child via the hepatic artery (Fig. 3b), but the tumour showed only slight shrinkage. Systemic chemotherapy was added, but again the response was poor. The patient died fourteen months after the diagnosis. No therapy was attempted for the third child who had pulmonary secondaries at presentation after a detailed discussion with the parents. The child died four months after the presentation.

Fig. 2a Ultrasound study showed diffusely hyperechoic appearance throughout the liver parenchyma and tumour thrombus in the portal vein (arrow head).

Fig. 2b Trucut biopsy showed a diffuse form of hepatocellular carcinoma. (Haematoxylin and eosin stain, magnification x 100).

 

Fig. 3a Ultrasound study showed a large hepatocellular carcinoma at the right lobe of the liver and middle hepatic vein encased by tumour which made the tumour unresectable.

Fig. 3b Hepatic arteriogram done before the TOCE and showed a large tumour at the right lobe of the liver with tumour satellites.

Fig. 4a Contrast CT scan of the liver showed a hypodense tumour mass in segment IV.

Fig. 4b The right hepatic artery was stretched and displaced by the adenoma.

Two patients with benign tumours underwent surgery; right trisegmentectomy for adenoma and right lobectomy for mesenchymal harmatoma. The patient with adenoma presented with hirsutism and hepatomegaly. Her serum ACTH level was 20.5 pmol/l (normal 2.0-11.5 pmol/l) and cortisol level was 1354 nmol/l (normal 150-720 nmol/l). CT scan showed a well circumscribed hypodense tumour in segment IV (Fig. 4a). Hepatic arteriogram showed a very much displaced and stretched right hepatic artery (Fig. 4b). After the operation, the hirsutism disappeared and the ACTH and cortisol levels returned to normal. The mesenchymal harmatoma enlarged rapidly in a one month old girl. The liver reached below her umbilicus at operation (Fig. 5a). Right lobectomy was performed uneventfully for the infant (Fig. 5b). The newborn with prenatal diagnosis of cavernous haemangioma was asymptomatic and was managed conservatively.

Fig. 5a The liver was grossly enlarged to below the umbilicus of the infant.

Fig. 5b Right lobectomy specimen of the mesenchymal harmatoma.

There was no mortality and minimal morbidity such as pain in all six liver resections. The operation time ranged from 4.2 to 6.5 hours (mean : 5.2 hours) and the blood loss during operation ranged from 20 to 40 ml/kg (mean: 36 ml/kg).

Discussion

Based on replies of questionnaires sent to members of the surgical section of the Academy of Pediatrics in 1974, Exelby, et al analysed in detail 375 hepatic tumours in children within ten years in the United States.3 Thirty-three percent of the tumours were benign. In our own small series, 30% tumours were also benign.

They also found that in 15% of the 223 operations performed for these tumours, there was severe bleeding. Out of the 15%, a quarter had cardiac arrest during the operations. The operative mortality was high especially when these patients did not have cirrhosis.4 The use of ultrasound dissector, anterior approach for large tumours and argon beam coagulator to stop bleeding has greatly reduced the amount of bleeding and mortality in our patients.5,6

The main reason for mortality in malignant HCC is the late presentation. Seventy-five percent of our HCC patients were inoperable. These tumours were also not chemosensitive. All HCC patients in Exelby's series on therapeutic chemotherapy were dead during the time of questionnaire.3 Although it had been reported that 55% inoperable HCC responded to the use of transcatheter arterial chemoembolization (TOCE) using an emulsion of cisplatin in iodized oil and gelfoam, the mean survival of these patients was merely 13 months.7

Orthotopic liver transplantation has been considered in some locally extensive tumours. The paediatric liver transplant programme in our institution has been successful with patient survival of 100%.8 However, the patient with large tumour encasing the middle hepatic vein and positive for HBsAg must be considered not suitable for liver transplantation.9

The cost-effectiveness in screening for favourable HCC for resection has been doubted in adult series.2 For paediatric patients, the positivity of HBsAg is much lower. In this present series, only 50% patients with HCC were positive and no patient with hepatoblastoma was positive for HBsAg. In addition, the incidence of primary malignant liver tumour in paediatric patients is much less. Also, HCC in paediatric patients may result from a variety of chronic liver diseases such as biliary atresia, chronic active non-A non-B non-C hepatitis, tyrosinaemia, idiopathic neonatal hepatitis and neonatal iron storage disease.10 Thus, the cost-effectiveness of the screening is much in doubt. However, routine neonatal hepatitis B vaccination in Hong Kong may decrease the overall incidence of HCC in the future. Children in a family with high incidence of HCC should also be included in regular ultrasound study to detect early small HCC because this tumour can also occur in paediatric age as shown in this series.

All of our patients with hepatoblastomas survived, though the tumours were more than 10 cm in diameter at diagnosis. The main contributing factor is because histologically they were all of the favourable foetal variant of hepatoblastoma. Postoperative chemotherapy is still advisable because the long term survival of patients with resectable hepatoblastoma who were not given chemotherapy was 61 %.11 The chosen chemotherapeutic agents namely, carboplatin and adriamycin have acceptable toxicity if given with care.12 Sometimes, unresectable hepatoblastomas or extremely huge tumours expected to have severe bleeding at operation can be converted to safely resectable ones by chemotherapy, thus improving the outcome of these patients.13,14

Paediatric surgeons have been frequently consulted for many antenatally diagnosed surgical conditions. The management depends on gestational age, the nature of the foetal surgical conditions, severity of hydrops and associated anamolies.15 Our patient with cavernous haemangioma was delivered uneventfully without any prenatal intervension. Victor, et al16 reviewed 49 patients with hepatic cavernous haemangioma and found 36 patients without any symptoms or ill-effects after 15 years of follow-up. They emphasized the benign course of this tumour. In large haemangiomas with consumptive coagulopathy, interferon alpha-2a has been used successfully to control the platelet count.17 Surgery is only considered if conservative treatment fails to alleviate life threatening condition such as intractable heart failure or shock resulting from severe bleeding.18 On follow up of our patient, the haemangioma actually showed development of sclerosis.

The prevalent theory for mesenchymal harmatoma is aberrant development of primitive mesenchyme in the portal tracts, most likely from bile ducts.19 The fast increase in size has been attributed to enlarging cystic components of the mass due to accumulation of fluid with electrolytes similar to plasma.20 Heart failure, dehydration, respiratory distress and obstruction of a major duct leading to progressive proximal ducts dilatation have been reported.1 Prognosis after resection is very good as illustrated by our patient who survived 6 years without symptoms.

The ACTH secreting adenoma of liver in children is rare.21 In view of danger of rupture and haemorrhage,22 the tumour was resected. The hirsutism of the child disappeared after the operation and the serum ACTH also became normal.

In conclusion, primary paediatric liver tumour is rare. Majority of the malignant hepatic tumours present late. For large hepatoblastoma, resection with postoperative chemotherapy is recommended.


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