The influence of preoperative chemotherapy and surgical technique in the treatment of hepatoblastoma--a report from the German Cooperative Liver Tumour Studies HB 89 and HB 94.

UNLABELLED: Despite the success of chemotherapy in the treatment of hepatoblastoma (HB), the complete surgical resection of the primary liver tumour and metastases is the most important factor for survival. METHODS: From 1989 to 1998, 141 children with HB were treated in the German Cooperative Paediatric Liver Tumour Study HB 89 and HB 94. The study determines the results of surgical strategy, which adapts the procedure at the initial operation to the tumour extension in the liver and the occurrence of metastases. RESULTS: The median follow-up of the survivors was 72 months (range 24 - 132 months). 98/141 (78 %) patients were alive and 31/141 (22 %) died. 12/141 (8.5 %) children had no surgical treatment. A complete resection of the primary tumour was achieved in 107/129 (83 %) cases. Forty-eight children were primary resected and eighty-one children were operated on after initial chemotherapy. In 36 cases, an atypical tumour resection, in 90 cases an anatomical liver resection, was performed. Three children were transplanted. There was no perioperative death. 14/48 (30 %) children with primary tumour resection had microscopical or macroscopical residual tumour in the liver. Despite the larger number of advanced HB in the primary chemotherapy group, an incomplete tumour resection was performed in only 15/78 (19 %) cases after liver resection (p < 0.044). 14/36 (38 %) cases with atypical tumour resection and only 16/90 (18 %) cases with anatomical liver resection had residual tumours in the liver (p < 0.019). These results underline the necessity for preoperative chemotherapy in all HB, which was accepted in the following study HB 99. Atypical tumour resection should be avoided because of the higher rate of incomplete tumour resections and local relapse compared to the group with anatomical tumour resection.

Successful therapy of subcutaneously growing human hepatoblastoma xenografts with topotecan.

BACKGROUND: Human hepatoblastoma is an infrequent liver tumor in children. Although many hepatoblastomas can be treated adequately with well-defined treatment regimens, problems still persist with advanced and non-resectable tumors; in these cases, an effective chemotherapy is necessary to improve the patients' prognosis. This underlines the need for alternative anti-tumor agents in the treatment of human hepatoblastoma. The aim of this study was to investigate the therapeutic effects of topotecan, a water-soluble camptothecin analog (topoisomerase-I-antagonist), in an in vivo model of three human hepatoblastomas xenografted subcutaneously into nude mice. PROCEDURE: Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). Treatment with topotecan was initiated when the tumors reached a volume between 50 and 80 mm(3). A dose of 6.6 mg/kg of topotecan were given intraperitoneally every 4 days on four occasions. The tumor volume development and alpha-fetoprotein alterations were measured and statistically analyzed. After the treatment, the tumors were investigated histologically and by immunohistochemistry. RESULTS: There was a significant reduction of tumor growth in all treated tumor xenografts vs. untreated control groups (mean relative volume 3.1 vs. 47.4; P = 0,0015-0,0079). Serum alpha-fetoprotein levels were reduced in all three cell lines, in two of them significantly (mean 44,535 kU/l vs. 228,883 kU/l; P = 0.005-0.246). Histologically, the tumor necrosis rates were higher and immunohistochemistry showed lower proliferation activities in the treated tumor xenografts vs. the control groups. CONCLUSION: The data show that topotecan is an effective agent in the treatment of human hepatoblastoma xenografts. From these results, treatment with topotecan appears to be a promising alternative in the pre- and postoperative therapy of patients suffering from human hepatoblastoma

[Extended liver resection in small children under circulatory arrest and "low-flow" cardiopulmonary bypass]. / Ausgedehnte Leberresektionen bei Kleinkindern im Kreislaufstillstand und unter Low-flow-Kreislaufbedingungen an der Herz-Lungen-Maschine.

In order to perform resections of tumors at critical sites in the liver in young children, liver resections in cardiac arrest and deep hypothermia under cardiopulmonary bypass have been developed. We report our experience with liver resection under cardiopulmonary bypass in three children with hepatoblastoma. In the first child the operation was performed under cardiac arrest and, the other two children were operated on under "low flow" conditions. The periods under cardiopulmonary bypass circulation were well tolerated. Extended right liver resections with vascular reconstructions were performed. The postoperative increase of liver enzymes was moderate. The increase in GOT was between 100 and 200 U/l. In spite of the extended tumor growth, reasonable long-term results were achieved by resection in combination with chemotherapy. One child has been living 8 years and another 10 months without tumor recurrence. The third child died due to sepsis during adjuvant chemotherapy, after she had recovered well from liver resection.

Nephron-sparing surgery in synchronous bilateral Wilms' tumors.

BACKGROUND: Synchronous bilateral Wilms' tumor is rare and experience with renal salvage procedures and their limitations accumulates slowly at single institutions. The authors analyzed whether their growing experience with atypical renal resections and awareness of nephroblastomatosis had influenced the outcome of surgical procedures. METHODS: Retrospective analysis of patients treated from 1977 to 1995 was performed. Surgical reports, clinical sheets, and follow-up data were evaluated. All pathology slides were reviewed for histological classification and presence of nephroblastomatosis. Renal function was evaluated pre- and postoperatively and at final follow-up. RESULTS: Fourteen patients were treated. Two to 20 years after surgery, 13 patients are alive, and none has had renal failure. Five patients had unilateral nephrectomies, and a renal salvage procedure was performed on 22 kidneys. One patient with an anaplastic bilateral Wilms' tumor died of tumor progress 1 year after surgery. Several kidneys, which would have been sacrificed by application of traditional criteria, could be salvaged by atypical and unconventional tumor resections and by superficial dissection and enucleation of supposed nephroblastomatosis. Nephrectomy appeared unavoidable with hilar invasion by tumor. CONCLUSION: Atypical resections of localized lesions and superficial dissections of suspected nephroblastomatosis appeared as valid surgical treatment options for patients who would otherwise have been candidates for nephrectomy. In the case of hilar tumor invasion, however, nephrectomy seems unavoidable.

Analysis of treatment efficiency of carboplatin and etoposide in combination with radical surgery in advanced and recurrent childhood hepatoblastoma: a report of the German Cooperative Pediatric Liver Tumor Study HB 89 and HB 94.

BACKGROUND: Hepatoblastoma (HB) is the most common liver tumor of childhood, and comprises approximately 1% of all pediatric malignancies. Although recent data from multicenter trials of GPOH, SIOP, CCG and POG indicate a remarkable improvement of therapy results, the prognosis of advanced or recurrent HB is still not satisfying. PATIENTS AND METHODS: During 1989 and 1997, the German Cooperative Pediatric Liver Tumor Studies HB 89 and HB 94 registered 141 patients with HB, who were treated according to the study protocols. These patients received standard chemotherapy with ifosfamide, cisplatin and doxorubicin (IPA) pre-operatively and/or post-operatively. Fourteen children with recurrent or advanced HB were additionally treated with carboplatin and etoposide (CARBO/VP 16), the reason being observations of drug resistance in children with HB after four or more courses of IPA-therapy in the HB 89 study. The clinical data and course of these patients were evaluated to investigate the efficiency of CARBO/VP 16 chemotherapy and for analyzing the role of surgery. RESULTS: Mean follow-up for survivors was 4.3 years (range 13 months-8 years). Tumor resection was attempted in 13 children but, in only 3 cases, was a complete tumor resection achieved in one operation. There was no perioperative death, and 7 of the patients (50%) are in remission. Two patients underwent adjuvant chemotherapy with CARBO/VP 16 for advanced HB at first operation: all are alive and well. Five patients with local relapse and/or distant metastases responded partially to CARBO/VP 16 therapy, and a complete remission was achieved in one patient. In five patients, progressive disease was observed during therapy with CARBO/VP 16. One patient, stable while on chemotherapy, had a successful resection. Acute toxicity of chemotherapy was observed in 7 patients (50%). CONCLUSION: An aggressive approach using IPA and CARBO/VP 16 chemotherapy and highly developed surgical techniques may improve the prognosis of advanced or recurrent HBs.

Feminizing genital reconstruction, sigmoid vaginal replacement and anorectoplasty as a one-stage procedure for anorectal atresia associated with ambiguous genitalia.

Anorectal atresia associated with male pseudohermaphroditism presents both diagnostic and surgical challenges. In the past, multiple operations were necessary for feminizing genitoplasty in gender-reassigned children with ambiguous genitalia. We combined the repair of an imperforate anus with a feminizing genitoplasty, including sigmoid vaginal replacement using the posterior sagittal approach in a 3-months-old infant. We conclude that a primary complete reconstruction is advantageous and should be performed in this condition.

Progress in developing animal models for biliary atresia.

Animal models for extrahepatic biliary atresia (EHBA) have failed to simulate the course of the disease. Until now only a few aspects of the entity could be investigated and no model was helpful in discovering the etiology of EHBA. Following the suspicion of a viral and hepatotropic infection, investigations in an infectious mouse model were continued. The results of previous and topical studies are summarized here. Infection of newborn Balb/c-mice with rhesus rotavirus (RRV) leads to cholestasis in 85% of the animals followed by a lethality of 90%. Preparation and histomorphological investigation of liver and ligamentum duodenale reveal EHBA of varying extent. Clinical course and morphological findings in mice are very similar to EHBA in newborn children and the results are presented in a chronological table. Hepatobiliary morbidity and lethality after RRV infection is higher in Balb/c-mice than in other mouse strains. This observation supports the suspicion that immunocompetence might be a determining factor in the etiology of EHBA. Initial therapeutic trials were made using this model by treating infected newborn mice with interferon-alpha (IFN). The prophylactic application of IFN protects the infected mice from cholestatic symptoms and appears to induce partial immunity. Their descendants are protected against the hepatotropic effect of RRV infection. Infected animals presenting with clinical signs of cholestasis can be treated successfully by IFN-therapy for one week. In the presented animal model. EHBA can be better induced and simulated than by any other method. As a first trial, a non-surgical and more etiologically orientated therapeutic method is tested in this model.

Diagnosis and current management of penile agenesis.

Penile agenesis is a rare congenital anomaly in which early gender reassignment is recommended. In the past, multiple operations were carried out to form feminized external genitalia. The authors performed a definite genital reconstruction in a neonate using the posterior sagittal approach. Preoperatively, a magnetic resonance imaging (MRI) scan demonstrated erectile tissue, which was preserved and incorporated into the genital plasty. The operation included bilateral orchiectomy, urethral reconstruction, sigmoid vaginal replacement, and formation of the labia. The authors discuss the controversy around gender assessment. They emphasize the urethral hypotrophy to be a main challenge in this anomaly and conclude that immediate complete reconstruction is possible and should be performed in patients with this delicate condition.

Etiologic classification of severe hypospadias: implications for prognosis and management.

OBJECTIVE: Classification of severe hypospadias employing a broad array of diagnostic tools. Standardization of a diagnostic approach to children with hypospadias. Indentification of patients at risk of having malignancies and endocrine problems. DESIGN: Retrospective analysis of patients in a single-center study. SUBJECTS: Thirty-three patients with severe (scrotal or penoscrotal) hypospadias, aged 1 to 18 years. METHODS: Clinical assessment, ultrasonography, karyotyping, endocrine evaluation including adrenal steroid concentrations, sex hormone-binding globulin test for androgen sensitivity, human chorionic gonadotropin stimulation with determination of testosterone and dihydrotestosterone concentrations to exclude 5 alpha-reductase deficiency, and molecular genetic analysis of the androgen receptor gene and the 5 alpha-reductase gene. RESULTS: In 12 patients the cause was clarified. Diagnoses included Drash syndrome with Wilms tumor in infancy (3 patients), partial androgen insensitivity resulting from androgen receptor mutations (2), true hermaphroditism (2), chromosomal aberration (1), deficiency of antimüllerian hormone (1), gonadal dysgenesis (1), partial 5 alpha-reductase deficiency caused by a novel point mutation (1), and XX-male syndrome (1). Twelve patients had associated findings such as cardiac malformations (3 patients), rectal atresia (1), dilation of urinary tract (2), cystinuria (1), and others. CONCLUSIONS: Patients with severe hypospadias should be submitted to a standardized set of diagnostic procedures in infancy. A stepwise diagnostic study avoids unnecessary, invasive, and expensive testing. A high proportion of classified causes can be expected. Patients at risk of having malignancies or hormonal disorders must remain under close surveillance.

New aspects in a murine model for extrahepatic biliary atresia.

The cause of extrahepatic biliary atresia (EHBA) remains unknown, and even an animal model is still lacking. Observations in a murine infectious model (newborn Balb/c mice infected with rhesus rotavirus group A [RRV]) reported extrahepatic biliary obstruction similar to findings in children who have EHBA. In the present study, this animal experiment was repeated, and the clinical and histomorphologic changes were observed over 3 weeks. Eighty-nine newborn mice were infected with RRV, and 67% showed signs of cholestasis and delayed growth. Eight of these animals recovered spontaneously whereas the others remained icteric. Fourty-six pups were prepared for microscopic examination following a 2-day interval. From the fifth day, the whole biliary tract showed edematous swelling with cellular infiltration. Ten days later, in the extrahepatic bile duct, a transformation took place in which concentric infiltration led to complete obstruction, sometimes with prestenotic dilatation. The intrahepatic changes showed reactive necrosis and proliferation of the small bile ducts. In one 19-day-old mouse, a ballooning dilatation was observed, similar to a developing choledochal cyst. Infection with RRV induces in newborn Balb/c mice a cholestatic clinical picture with different courses of the disease leading mostly to complete biliary obstruction and secondary hepatic changes similar to EHBA in children. This is the first animal model for EHBA with complete obstruction of the extrahepatic bile duct induced by infection. These findings present a new basis for further studies.

Surgical therapy and follow-up of pancreatitis in children.

BACKGROUND: Acute and chronic pancreatitis in children differ from that in adults both from the etiology and the therapeutic approach. Within the frame of a blunt abdominal trauma-the most frequent cause in children-acute pancreatitis is often detected by emergency laparotomy and external drainage is recommended. Chronic relapsing pancreatitis, and particularly its hereditary form, is very rare in children and requires a different therapeutic concept. The results of surgical therapy for both forms of pancreatitis in childhood were evaluated in the present study. METHODS: Sixteen patients with acute and chronic relapsing pancreatitis were operated on in our facility between 1976 and 1988. Their history and postoperative course were analyzed in a retrospective study, including a final examination at the end of the follow-up period. RESULTS: Eight children with acute pancreatitis were operated on at an average age of 6 years and were followed up for an average of 7.5 years, with good results. The remaining children, aged between 3 and 14 years (average age of 9 years), were operated on for chronic relapsing pancreatitis. Our experience with early operative treatment, on average 2.7 years after onset of symptoms, is presented. Only three patients experienced a mild relapse during the follow-up period of 2-13 years (average of 5.4 years). CONCLUSIONS: For acute pancreatitis in childhood, operative treatment by inner drainage is necessary and effective only in case of complications, should conservative treatment fail. In children with chronic relapsing pancreatitis, the good exocrine and the normal endocrine function of the pancreas in these patients justified the early operation. Timely treatment is recommended in cases with typical changes of the pancreatic duct so as to shorten the relapsing clinical problems of the children and to maintain the function of the pancreas.

Efficiency and toxicity of ifosfamide, cisplatin and doxorubicin in the treatment of childhood hepatoblastoma. Study Committee of the Cooperative Paediatric Liver Tumour Study HB89 of the German Society for Paediatric Oncology and Haematology.

The Cooperative German Paediatric Liver Tumour Study HB89 was conceived to evaluate the efficiency and toxicity of ifosfamide, cisplatin and doxorubicin (IPA) in children with resectable and non-resectable hepatoblastoma (HB) and to determine late sequelae including tubular nephropathy of tumour treatment. The study also assessed the results of a surgical strategy, which adapts the procedure at the initial operation to the tumour's extension in the liver. The relationship of the tumours' histological differentiation to response to chemotherapy was also examined. Patients with a HB restricted to one liver lobe underwent primary resection. Larger tumours were initially treated with IPA chemotherapy and resected at second-look surgery. All patients received IPA adjuvantly after tumour resection. The IPA regimen consisted of ifosfamide 3.5 g/m2 (over 72 h days 1-3), cisplatin 100 mg/m2 (over 5 days 4-8) and doxorubicin 60 mg/m2 (over 48 h, days 9-10). Median follow-up of survivors was 64 months (range 28-82). Long-term disease-free survival (DFS) was for stage I: 21/21; stage II: 3/6; stage III: 28/38; and stage IV: 2/7 (overall 75%). Severe surgical complications occurred in 15% (4/27) of primary and 21% (8/38) of secondary resections with no lethality. 44/45 stage III/IV HB displayed PR after two IPA courses. Drug resistance developed in 8/12 tumours after four or five chemotherapy courses. Acute toxicity was observed in 34/242 (14%) IPA courses. Late sequelae were found in 7/54 (13%) of survivors, and subclinical renal tubulopathy occurred in 7/41 investigated patients (17%). Despite a more favourable prognosis in pure fetal and predominantly fetal histology, statistical analysis revealed no relationship between tumour differentiation and response to chemotherapy. In conclusion, IPA chemotherapy in combination with delayed surgery was highly effective in the treatment of HB.

Retroperitoneal lymphangiomyoma in an infant.

Lymphangiomyomatosis (LAM) is a benign tumor-like lesion of lymphatic vessels with unknown etiology. 80 cases of LAM are presently described. So far, it appears that only women in their reproductive years seem to be affected. Here, we describe the first LAM in an 11-months-old infant with a presumably local form of LAM. This leads us to consider the possibility that this tumor-like lesion may originate from a hamartomateous malformation. The diagnosis is based on pre-operative sonography and CT, as well as on histological and immunohistochemical examination of the tumor.

One-stage reconstruction of bladder exstrophy.

From 1984 to 1990 a primary one-stage reconstruction of bladder exstrophy was performed at our hospital on 15 consecutive infants. Reconstruction included Cohen's ureteral reimplantation, bladder neck reconstruction according to Young-Dees, bladder closure, symphyseal bone approximation, abdominal wall closure, and repair of epispadias in females. Postoperatively, all patients were immobilized by overhead extension. Iliac osteotomy was done in 9 children, but was abandoned in recent years for infants less than one month old Follow-up examinations included an interview with the parents, clinical examinations, blood and urine analyses, uroflowmetry, and ultrasound scan of the abdomen. Nuclear renal scan, i.v. pyelography, and cystography were carried out as indicated. At the time of last evaluation the children were between 3 and 9 years of age. The cosmetic results were satisfactory in all cases. Eight of 15 children were dry day and night with micturition intervals more than 3 hours during day time (complete continence). Five children were dry during day time with micturition intervals up to 3 hours, but occasionally wet their beds (partial continence). Two children were incontinent. Eleven of 15 children had a bladder capacity of more than 100 ml. Renal function was normal in all patients. Two children showed a mild VUR, and no other abnormalities of the upper urinary tracts were found. Iliac osteotomy did not influence the functional or cosmetic results, but in two patients asymmetry of pelvic bones with consecutive lumbar scoliosis was found. Comparing these results with reports on staged reconstructive procedures, we conclude that by primary complete one-stage reconstruction a well acceptable success rate is achieved, and that by this method possibly some advantages are offered to patients with bladder exstrophy.

[Surgical strategy in pediatric liver malignancies]. / Die chirurgische Strategie bei kindlichen Lebermalignomen.

The therapeutic results of two groups of children with liver tumours were compared: group 1 [29 hepatoblastomas (HB) and five liver carcinomas (HCC)] were operated before 1987, and group 2 (88 HB and 16 HCC) were treated according to the studies HB 89 and HB 94 of the GPOH from 1988 onwards. Resection rates for HB were 81% (group 1) and 93% (group 2), with tumour-free survival rates of 38% and 77%, respectively: anatomic liver resections were more often radical than atypical tumour resections. Resections of lung metastases and liver transplantations increased tumour-free survival. In HCC therapeutic results were equally poor (25% cure). Thus in HB combined chemotherapy and surgery is highly effective, but HCCs are cured only by radical resections.

[Oncologic surgery of malignancies in childhood. Effect of adjuvant/neoadjuvant methods]. / Onkologische Chirurgie bei Malignomen im Kindesalter. Einfluss adjuvanter/neoadjuvanter Methoden.

Pre- and/or postoperative chemotherapy is highly effective in the treatment of pediatric malignancies and has modified surgical strategies significantly. (1) In childhood abdominal Non-Hodgkin-Lymphomas early chemotherapy has a definite priority over extended excisions. (2) In hepatoblastomas, radical excision is essential for effecting a cure. However, in the case of an advanced tumor, it is wise to start treatment with chemotherapy and then to perform surgery. (3) Pre-operative chemotherapy in Wilms' tumors effects a "down staging", which allows therapy reduction and omission of postoperative radiotherapy in the majority of cases.

Experience with repair of 120 hypospadias using Mathieu's procedure.

Between 1985 and 1993 120 boys with distal hypospadias (from distal penile shaft to glandular position) were treated using Mathieu's procedure at the department of pediatric surgery, Hannover Medical School, Germany. The outcome of these cases has been analysed. Fistula-rate was 12.5%. Results are compared with published reports, recent developments and changes in treatment are discussed.

Complete resection before development of drug resistance is essential for survival from advanced hepatoblastoma--a report from the German Cooperative Pediatric Liver Tumor Study HB-89.

Clinical data and tumor histology of 37 patients with advanced and/or metastatic hepatoblastoma (32 stage III and 5 stage IV) treated according to the protocol of the German Cooperative Pediatric Liver Tumor Study HB-89 from 1988 to 1992 were studied for prognostic factors. Twenty-three patients (73%) were free of tumor 9 months to 5 years (median, 36 months) after treatment, whereas 4 experienced progressive disease, 7 had local relapse, and 3 had recurrent metastases. None of 2 patients with primary lymph node involvement or 5 with primary metastases remained disease-free. Chemotherapy with ifosfamide, cisplatin, and adriamycin was effective in reduction of tumor to resectability in 33 (89%) patients. Drug resistance developed in 6 of 11 patients treated with four or more courses of chemotherapy as could be shown by monitoring of serum-alpha-fetoprotein (AFP) and serial investigations of tumor expansion with sonography and computed tomographic (CT) scan. Only 1 of these patients survived after a liver transplantation. Completeness of tumor resection at second- or third-look laparotomy was significantly related to disease-free survival (P < .0001). Patients with initial serum-AFP values < 100 ng/mL or > 1,000,000 ng/mL had a worse outcome than those with immediate levels (P = .044). The rate of decrease of serum-AFP during chemotherapy was significantly related to prognosis (P = .003). Growth pattern of tumor within the liver (ie, defined nodes versus diffusely disseminated) (P = .011) and vascular tumor invasion (P = .026) were valuable prognostic factors, whereas tumor volume, local infiltration of surrounding tissue, histological subtypes, and epithelial differentiation were not significantly related to the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver tumors in neonates and very young infants: diagnostic pitfalls and therapeutic problems.

We report on 26 infants under 3 months of age with various liver tumors, who were treated in our hospital since 1977 and/or registered in the German Cooperative Pediatric Liver Tumor Study HB-89. 17 of these had an infantile hemangioendothelioma (inf HE), 7 a hepatoblastoma (HB), one a mesenchymal hamartoma (mes H) and one a neuroblastoma stage IV-S (Nbl). Polyhydramnios occurred in 5 cases of inf HE, in one associated with hydrops fetalis. This led to a preterm delivery of 4 infants. 7 infants with a large inf HE suffered from high output congestive heart insufficiency, 2 additionally from a Kasabach-Merritt-syndrome. Serum alpha-fetoprotein was within normal range of age in all infants except in one HB patient. Neuron-specific enolase was clearly elevated in the Nbl patient and slightly above normal range in one inf HE and 3 HB patients. Other tumor markers and platelet counts were not indicative of diagnosis. Also imaging techniques as ultrasonography, CT and angiography were not always reliable in differentiating the tumors. In 2 cases the initial histological diagnosis of an HB had to be corrected for an inf HE. In 6 children the tumors were initially treated under a wrong assumption: 4 tumors as an HB instead of an inf HE, one as an inf HE instead of a Nbl IV-S and one as a focal nodular hyperplasia of the liver instead of an HB. 7 not resected inf HEs (Dehner type I) showed spontaneous regression after 6 months to 3 years. One inf HE type II relapsed twice after resection.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical therapy of hepatoblastoma in childhood]. / Chirurgische Therapie von Hepatoblastomen im Kindesalter.

Hepatoblastoma is a rare but highly malignant liver tumour, predominantly occurring during early childhood. Clinical data of 71 children treated from 1988 to 1993 according to the protocol of the multicentre liver tumour study (HB89) of the German Society for Paediatric Oncology and Haematology were evaluated to assess the effects of surgical therapy in these patients. The protocol prescribed an initial laparotomy for all children with a liver tumour, except for infants with distant metastases and a high serum-alpha-fetoprotein; for small hepatoblastomas confined to one liver lobe primary resection by a lobectomy; and for those extending into both lobes and metastasizing tumours tumour reductive chemotherapy including ifosfamide, cisplatin and adriamycin (IPA), preparatory to resection at second-look surgery. All patients received adjuvant IPA chemotherapy after tumour resection. In 20 of the 71 cases, the hepatoblastomas were completely resected at initial laparotomy (stage I), while in 6 cases microscopic residues were left (stage II). In 38 of 45 children with extended hepatoblastomas (stage III, 38 patients) or distant metastases (stage IV, 7 patients) the tumour was resected during later surgery, and 1 patient received a liver transplant. Thus, the overall resection rate was 92% (65 of 71 hepatoblastomas). After a median follow-up of 3.8 years (range 1.0-5.9 years), 53 (75%) of the patients were tumor-free and 18 (25%) had died. Recurrence-free survival was 100% for stage I, 50% for stage II, 71% for stage III and 29% for stage IV patients (P = 0.0009).(ABSTRACT TRUNCATED AT 250 WORDS)