Role of chest computed tomography at diagnosis in the management of Wilms' tumor: a study by the United Kingdom Children's Cancer Study Group.

PURPOSE: This study sought to determine whether the identification of minimal pulmonary metastatic disease by chest computed tomography (CT) performed at diagnosis in patients with Wilms' tumor and normal chest x-rays (CXR) could predict a subgroup of children at increased risk of pulmonary relapse. PATIENTS AND METHODS: A retrospective analysis was carried out of the records of 449 children entered onto the United Kingdom Childrens' Cancer Study Group Second Wilms' Tumor Study between July 1986 and September 1991. The imaging protocol did not stipulate chest CT at diagnosis, but 141 children who had normal frontal and lateral CXRs and a chest CT scan performed at diagnosis were eligible for analysis. After surgery, children with stage I Wilms' tumor received single-agent chemotherapy (vincristine), whereas children with stages II, III, and bilateral Wilms' tumor received combination chemotherapy. Most children with stage III tumors were also treated with abdominal radiotherapy (20 Gy). RESULTS: In 31 patients (22%), pulmonary nodules were visible on chest CT; eight experienced relapse, four (15%) in the lungs. When only stage I patients were analyzed, there was a significant difference between the pulmonary relapse rate of 43% (three of seven) in the CT-positive group and 10% (five of 48) in the CT-negative group (P =.02). Four of eight patients with stage I disease with pulmonary relapse died. CONCLUSION: CT seemed to identify a subgroup of stage I patients who were at increased risk of pulmonary relapse. These children had received only single-agent chemotherapy. A prospective randomized trial is needed to clarify whether these children would benefit from combination chemotherapy.

Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach--results of the first prospective study of the International Society of Pediatric Oncology.

PURPOSE: Hepatoblastoma (HB) is a rare malignant liver tumor which occurs almost exclusively in childhood. In the 1970s, survival was approximately 20% to 30%. Since the introduction of cisplatin (PLA) and doxorubicin (DO) into the chemotherapy regimens used to treat these patients, the survival rate has improved dramatically. In most recent studies, primary surgery preceded chemotherapy. In this study by the liver group of the International Society of Pediatric Oncology the aim was to improve survival and reduce operative morbidity and mortality by using preoperative chemotherapy. PATIENTS AND METHODS: After biopsy and assessment of pretreatment extent of disease all patients were treated with continuous 24-hour intravenous infusion of PLA 80 mg/m(2) followed by DO 60 mg/m(2) over 48 hours (PLADO). After four courses of this chemotherapy, patients were reassessed. Where possible, the primary tumor was resected and treatment completed with two more courses of chemotherapy. RESULTS: One hundred fifty-four patients were registered in the study, and 138 received preoperative chemotherapy. One hundred thirteen (82%) showed a partial response with tumor shrinkage and serial decrease of serum alpha-fetoprotein levels. One hundred fifteen patients had delayed surgery, and 106 (including six with liver transplants) had complete resection of primary tumor. Five-year event-free survival was 66%, and overall survival was 75%. CONCLUSION: This study demonstrates that international collaboration on a large scale is feasible. The toxicity of chemotherapy and morbidity of surgery were acceptable and the overall survival gratifyingly high. We now regard PLADO chemotherapy and delayed surgery to be the best available treatment for children with HB. Other treatment programs should be measured against this standard.

Pretreatment prognostic factors for children with hepatoblastoma-- results from the International Society of Paediatric Oncology (SIOP) study SIOPEL 1.

The aim of this study was to investigate the prognostic significance of pretreatment patient and tumour characteristics for overall (OS) and event-free (EFS) survival in 154 children affected by hepatoblastoma (HB) in the first prospective liver tumour study run by the International Society of Paediatric Oncology. The pretreatment characteristics studied were age, alpha-fetoprotein, platelet count, histology; from radiology: intrahepatic tumour extension (PRETEXT), lung metastases, enlarged hilar lymph nodes, vena cava or extrahepatic vena porta tumour extension and tumour focality. Five-year OS was 75% (95% confidence interval (CI) 68-82%) and EFS 66% (95% CI 59-74%). Both were univariately associated with PRETEXT and the presence of metastases. Additionally tumour focality and enlargement of hilar lymph nodes at diagnosis were univariately associated with EFS. In multivariate analysis, PRETEXT was the only predictor of OS; PRETEXT and metastases were predictors of EFS. There is a need to investigate further these factors to confirm their validity.

Development of a nurse-led sedation service for paediatric magnetic resonance imaging.

BACKGROUND: Children generally lie still enough for magnetic resonance imaging (MRI) only if they are asleep, either under sedation, which is deeper than conscious sedation, or under anaesthesia. Anaesthesia resources, however, are limited, and non-anaesthetists must use sedation frequently. Demand for MRI has increased and the failure of our sedation regimen led to an impractical demand for anaesthesia and unacceptable waiting times for scanning. We have therefore developed a nurse-led sedation service in a designated unit next to the scanner. This study assessed the safety and efficacy of this approach. METHODS: Children who required MRI were sedated in the unit by designated sedationist nurses, who used an oral drug regimen (according to weight and age from conception: weight <5 kg, 50 mg/kg chloral hydrate; 5-10 kg, 100 mg/kg chloral hydrate; 10-20 kg, 1 mg/kg temazepam plus 0.25 mg/kg droperidol; >20 kg temazepam and droperidol as directed by radiologist, maximum doses 20 mg and 5 mg respectively). Nurses checked patients for their suitability, charted and administered the drugs according to a protocol, and monitored the children throughout the sedation. We prospectively audited failure and complications of sedation. FINDINGS: During the 30 month study, there were 1155 sedations. 61 (5%) were unsuccessful, and there were no adverse events relating to the airway or breathing. After scanning had finished all children, in response to gently pinching the nose, could open their mouths to maintain their airway. INTERPRETATION: This study suggests that it is possible to have a nurse-led sedation service for MRI of children that is both successful and safe.

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted.

Total body irradiation-induced osteochondromata.

Nine patients developed osteochondromata, a mean of 6 years after total body irradiation (TBI) given before bone marrow transplantation for childhood leukaemia. This represents 23% of patients receiving TBI during the period from 1981 to 1989 surviving > or =5 years after bone marrow transplantation. The patients were followed up for a mean of 12.5 years from diagnosis of leukaemia and a mean of 2.5 years from diagnosis of osteochondromata. No osteochondroma, including three lesions removed surgically, showed evidence of malignant change. Six patients received growth hormone for irradiation-induced growth hormone deficiency, but this did not appear to influence the natural history of the osteochondromata. Radiation-induced osteochondromata (RIO) are often multiple and are indistinguishable from the more common idiopathic type. The incidence of RIO after TBI was higher than that reported after local irradiation.

Suprarenal cystic masses: unusual causes.

Two cases of large suprarenal cystic masses with extremely rare histological diagnoses of adrenal neurogenous choristoma and multicystic intrarenal neuroblastoma are presented. Ultrasonographic, CT scanning and histological features are described and differential diagnosis discussed.

The significance of hepatic lesions associated with small adrenocortical tumours in childhood.

Small adrenocortical tumours in children are rarely associated with hepatic pathology. We present two case reports of children with hepatic pathology associated with small adrenal tumours on computed tomography. One child had multiple granulomatous lesions due to toxocariasis and the other had focal nodular hyperplasia. Hepatic lesions seen in association with small adrenal tumours in childhood may represent coincidental rather than metastatic pathology.

Redefining the genital abnormality in the Robinow syndrome. -004.

PURPOSE: We defined the anatomical structure of the male genital abnormality in the Robinow syndrome. Features of this syndrome include mesomelic brachymelia of the arms, bifid terminal phalanges of the hands and feet, characteristic facies, skeletal anomalies and hypoplastic external genitalia. MATERIALS AND METHODS: Penile anatomy of 3 patients with the Robinow syndrome was assessed using computerized tomography and magnetic resonance imaging. Results were compared to those of 4 controls who underwent imaging for pelvic malignancies. RESULTS: Cross-sectional imaging showed that normal penile crura were inserted onto the anteromedial aspect of the pubic bone. In contrast, in the Robinow syndrome they were inserted inferiorly and posteriorly onto the medial aspect of the ischial tuberosity. In addition, the crura in the Robinow syndrome extended posterior to a line intersecting both femoral shafts. Compared to controls, there was a significant gap between the symphysis pubis and dorsal aspect of the penis. CONCLUSIONS: The penile anomaly in the Robinow syndrome is due to abnormal insertion of the penile crura, resulting in a penis that appears shorter and more inferiorly placed between the legs.

Neonatal thymic haemorrhage.

Thymic haemorrhage in a neonate is an exceedingly rare condition. A case is presented of a neonate presenting at birth with cyanosis, respiratory distress and an anterior mediastinal mass. The radiological findings are demonstrated. After surgical excision and histopathological examination the lesion was found to be spontaneous haemorrhage into normal thymic tissue. Spontaneous thymic haemorrhage should be considered in any neonate developing acute respiratory distress with widening of the mediastinum and pleural effusion on chest radiography. Ultrasound may be used to support the diagnosis.

Phase II study of 21 day schedule oral etoposide in children. New Agents Group of the United Kingdom Children's Cancer Study Group (UKCCSG).

We report a multicentre phase II study of orally administered prolonged schedule etoposide in children with refractory or relapsed malignancy. 83 children were entered into the study. The largest diagnostic groups were neuroblastoma (n = 20), rhabdomyosarcoma/soft tissue sarcoma (n = 16) and brain tumours (n = 16). Etoposide was administered twice daily at a dose of 50 mg/m2/day for 21 days using the intravenous preparation given orally. Disease reassessment was performed after the second course. Etoposide plasma concentrations were measured by HPLC, 2 and 6 h after administration of therapy on days 7 and 14 in 15 patients. 61 patients completed two courses and were evaluable for response. There was 1 complete response (CR), 5 partial responses (PR) 22 stable disease (SD) and 33 progressive disease (PD). Of the 6 with responses, 3 had a diagnosis of medulloblastoma/cerebral primitive neuroectodermal tumour. 24 of 26 patients with SD/PR/CR received further courses with excellent palliative effect. The main toxicity observed was myelosuppression, with 8% and 7% of evaluable courses complicated by grade III-IV neutropenia and thrombocytopenia, respectively. Severe infection (grade III-IV) was rare, complicating only 2/94 evaluable courses. Plasma etoposide median concentrations at 2 h after administration on day 7 of course 1 were 1.5 (range 0.6-2.4) micrograms/ml. Total course 1 area under the etoposide plasma concentration versus time curve (AUC) values were estimated using a limited sampling model. Grade > or = 2 leucopenia was only observed in patients with a day 72 h etoposide concentration of > 2 micrograms/ml or a course 1 AUC of > 35 mg/ml.min. It is concluded that given at a dose of 50 mg/m2/day in two doses for 21 day courses, oral etoposide is well tolerated in children. A correlation between drug concentrations and toxicity was observed. Overall, a low response rate was seen (approximately 10%), but disease stabilisation appears to occur, and useful palliative effect was frequently noted. The response in brain tumours was more encouraging (3/14 PR) and this group requires further evaluation.

Gastric malignant schwannoma in a child.

Malignant schwannoma (malignant peripheral nerve sheath tumour, MPNST) is a high grade sarcoma with a potential for local recurrence and distant metastasis that may occur at any site in the body where there is neural tissue. MPNST is rare in children and is unreported in the stomach in the paediatric age group. MPNST presents either as an expanding mass, with or without pain, or in the gastrointestinal tract with haemorrhage or obstruction. Many cases occur without evidence of neurofibromatosis but thers is a reported association between MPNST and neurofibromatosis of up to 50%. MPNST has a higher incidence at sites of previous irradiation. Treatment is by complete surgical excision. Radiology is of value in initial diagnosis and staging prior to surgery. The definitive diagnosis is made on the histopathological appearance and immunohistochemical profile. The findings on barium meal, abdominal ultrasound and CT are presented.

Posterior urethral valves in male infants and newborns: detection with US of the urethra before and during voiding.

PURPOSE: To document the appearance and width of the posterior urethra with transperineal ultrasound (US) before and during voiding in male infants and newborns with posterior urethral valves. MATERIALS AND METHODS: Thirty-three patients with bilateral hydronephrosis underwent prospective transabdominal and transperineal US. RESULTS: Fifteen patients had proved posterior urethral valves (obstructed group); 18 patients had no obstruction (unobstructed group). In the obstructed group, the median posterior urethral width was 4.5 mm before and 10.0 mm during voiding. In the unobstructed group, the median posterior urethral width was 1.0 mm (P = .046) before and 4.0 mm (P < .001) during voiding. Bladder wall thickness was 3.0-7.6 mm (obstructed group) and 2.0-5.0 mm (unobstructed group; P < .001). With a posterior urethral diameter of at least 6 mm during voiding as a criterion for transperineal US diagnosis of obstruction, sensitivity was 100%; specificity, 89%; and positive predictive value, 88%. CONCLUSION: Transperineal voiding US is noninvasive and useful in diagnosing posterior urethral valves.

Improved outcome for children with hepatoblastoma.

Between 1981 and 1993, 41 children were treated for hepatoblastoma. Clinical, radiological and pathological data were reviewed retrospectively, focusing on surgical aspects of treatment and outcome. Fourteen children underwent primary resection of the hepatic tumour. One infant with severe congenital anomalies received only palliative treatment. Of 26 with irresectable disease, pulsed cytotoxic chemotherapy (cisplatin and doxorubicin) enabled subsequent surgical excision in 22 and one child with persistent extensive intrahepatic disease was successfully treated by liver transplantation. Thus, with a policy of selective preoperative chemotherapy, 90 per cent of hepatoblastomas were resectable. There were no perioperative deaths from haemorrhage but one child died from an intraoperative tumour embolus. A total of 28 survivors, 27 of whom are disease-free, were followed for a median of 5 years. The cumulative probability of survival in patients treated with intent to cure was 67 per cent. Analysis of survival data suggested a favourable outcome for those with a pure fetal histological tumour subtype. These results demonstrate significant progress in the treatment of hepatoblastoma.

Hepatic ultrasound findings in the glycogen storage diseases.

Hepatic ultrasonography was performed on 70 patients with the hepatic glycogen storage diseases (GSDs) to assess parenchymal echogenicity. 27 patients had GSD-I, 24 had GSD-III and 19 had GSDs-VI/IX; ages varied from 0.6 to 35.7 years (median 11.7). 31 (44%) had normal or mild parenchymal changes, and 41% (11/27) of those with GSD-I, 25% (6/24) with GSD-III and 11% (2/19) with GSDs-VI/IX had marked changes. No relationships were found between the ultrasonographic appearances and other indices of metabolic control, including plasma triglycerides, total cholesterol or height standard deviation score. Seven adult patients (21-29 years) were found to have hepatic tumours: six with GSD-I and one with GSD-III. Those with GSD-I and tumours tended to have the more severe hepatic parenchymal changes. We conclude that ultrasonography may be useful in identifying patients with GSD-I at risk of hepatic tumour formation.

Conservative surgery in multimodal therapy for pelvic rhabdomyosarcoma in children.

Twenty-six previously untreated children, median age 3.4 years, with pelvic rhabdomyosarcoma (RMS) were seen between 1983 and 1988. Fourteen were girls. The planned strategy was to conserve pelvic organs, especially the bladder, by using primary chemotherapy, conservative surgery and, in most cases, radiotherapy. With a median follow-up of 71 months (range 34-103 months) overall survival was 73%, with no treatment-related death. The bladder salvage rate of 88% in survivors with bladder base/prostate primaries was much higher than that reported by the United States Intergroup Rhabdomyosarcoma Studies (IRS), though many of the preserved bladders did not function normally. We identified problems with both radiological and histological off-treatment monitoring. The overall accuracy of computerised tomographic (CT) scanning for prediction of tumour recurrence was only 81%, and endoscopic biopsies proved misleading in four of the ten bladder base/prostate patients monitored by serial cystoscopy. We conclude that a higher cure rate can be achieved by using intensive chemotherapy/radiotherapy and conservative surgery to treat children with pelvic RMS. Factors that might contribute to our favourable bladder salvage results, compared with those of the IRS, include (a) the fact that one of two specialist surgeons monitored and operated on all these patients and (b) our increasing awareness, during the study, that post-chemotherapy/radiotherapy histopathology and pelvic CT scan appearances may be misleading. Referral to paediatric centres with special experience of pelvic RMS may help raise the rate of bladder salvage in these children.