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During a four-year period, 57 children with malignant disease had a central intravenous catheter inserted to facilitate administration of cytotoxic drugs and parenteral nutrition. Despite the fact that all children were immunosuppressed and frequently profoundly neu-tropenic, only three episodes of septicaemia occurred as a direct result of catheter infection. Local damage to the silastic catheter tubing was the most common problem encountered. Education of the parents and child in the techniques of catheter care is probably the main factor in avoiding complications. The availability of a central intravenous catheter reduces psychological and physical trauma to the child and results in a considerable improvement in the child's general care. We now recommend insertion of a central catheter in all children with malignant disease who require intensive therapy.

Testicular function was studied in 40 males treated in childhood for Hodgkin's disease at St Bartholomew's Hospital, and the Hospital for Sick Children, London, between 1971-1985. All patients were 16 years or over at evaluation, and off treatment more than 6 years. Basal FSH, LH and testosterone levels were measured. Testicular size was measured using a Prader orchidometer, and all patients were offered a seminal analysis. Twenty-eight patients were treated with chemotherapy, usually ChlVPP. Twenty-one also had radiotherapy, five below the diaphragm. Twelve patients were treated with radiotherapy alone (five below the diaphragm). Twenty-six of 28 patients treated with chemotherapy and three of five patients treated with radiotherapy alone below the diaphragm have elevated basal FSH levels, and 18 of these also have elevated basal LH levels. Median testicular volume is 11 ml (range 5-25 ml). Eleven of 13 patients investigated are azoospermic. All patients have normal testosterone levels, and normal secondary sexual characteristics. There is no biochemical evidence of healing of the damaged germinal epithelium with elevated FSH levels persisting up to 17 years from the end of therapy. These results indicate a high incidence of damage to the germinal epithelium in patients treated with ChlVPP chemotherapy and/or radiotherapy below the diaphragm. Appropriate counselling of these patients with regard to their reproductive capabilities is essential.

During the period 1974-89, 169 children with Hodgkin's disease were treated in the Paediatric Oncology Units of the Royal Marsden and St Bartholomew's Hospitals. The overall actuarial survival for the whole group was 81% at 10 years. Thirty-five of the 169 children either did not achieve a complete remission or subsequently relapsed. The estimated actuarial survival from initial relapse or failure of primary treatment was 60% at 5 years and 45% at 10 years. Over half of the patients requiring salvage therapy had declared themselves within 2 years and only 3 relapses occurred more than 3 years from diagnosis. Very few patients remain disease free long term after failure of primary and initial salvage therapy. Patients relapsing within a year of diagnosis or not achieving a complete response to primary therapy and those with disseminated relapse had a poor response to salvage therapy. A significant subgroup of patients had prolonged survival despite multiple relapses. Neither initial histology nor stage affected survival from relapse although numbers in each subgroup were small.

One hundred and sixty one children who have developed more than one primary neoplasm have been identified. Children with tumours of the central nervous system, retinoblastoma and leukaemia were those most frequently observed to develop a second malignancy whilst osteosarcoma was the most common second tumour. The patterns of second neoplasms appear to be changing and a recent increase in the number of children with leukaemia and lymphoma who develop second primary tumours has been observed. In this series, the two most frequent associations of tumours were retinoblastoma followed by osteosarcoma and the combination of acute leukaemia with a tumour of the central nervous system. Genetic factors which may have contributed to the development of the second primary tumour were identified in 53 patients (33%), 33 of whom had the genetic form of retinoblastoma. In an analysis of the treatment of 151 patients, for whom the interval between the two neoplasms was greater than 12 months, the second malignancy was considered to be 'radiation associated' in 93 (61%). Fifty children (33%) had been treated with either single or multiple agent chemotherapy which included an alkylating agent in 38. Forty five children had received a combination of chemotherapy and radiotherapy and of these, 10 developed leukaemia as their second tumour. Of the 19 secondary leukaemias, 16 have occurred in patients treated since 1970.

Among a cohort of 10,106 three-year survivors of childhood cancer, 90 second primary tumours (SPTs) were observed. Within 25 years of 3-year survival about 4% developed a SPT, about 6-fold expected, the relative risk not varying much with increasing follow-up. Following genetic retinoblastoma we observed 30-fold the expected number of SPTs, and over 400-fold the expected number of osteosarcomas. The risk of SPT in the absence of radiotherapy and chemotherapy (inherent risk) following genetic retinoblastoma was 13-fold expected and over 200-fold the expected number of osteosarcomas were observed. There was evidence that both radiotherapy and cyclophosphamide were associated with an increased risk of SPT. After all first primary tumours (FPTs) excluding retinoblastoma we observed almost 5-fold the expected number of SPTs. The inherent risk was 4-fold expected, the relative risks associated with radiotherapy but no chemotherapy, and both radiotherapy and chemotherapy were 6- and 9-fold expected respectively. There were about 20-fold the number of malignant bone tumours expected, most were osteosarcoma; also 7-fold the number of central nervous system tumours expected. There were 8 basal cell carcinomas and it seems likely that radiotherapy was involved in the development of some of these. Radiotherapy appears to have been involved in the development of many of the SPTs observed following all FPTs excluding retinoblastoma, particularly after CNS tumours, Wilms' tumour and Hodgkin's disease. Currently there is insufficient follow-up to examine the risk following chemotherapy. After acute leukaemia there was 20-fold the expected number of central nervous system tumours, though this is based on only 3 cases; whether therapy is directly involved in their development is uncertain. The risks we report are rarely greater than those reported in previous large-scale studies; in most instances they are substantially less. It is very unlikely that many SPTs were missed with our follow-up system so alternative explanations require further investigation; in particular it is possible the lower risks in our data compared to series treated in the United States may be explained, in part, by less combination therapy and lower doses of radiotherapy.

The RB1 gene mutation was investigated in a child with ectopic intracranial retinoblastoma using DNA obtained from both the pineal and retinal tumours of the patient. A nonsense mutation in exon 17 (codon 556) of the RB1 gene was found to be present homozygously in both the retinal and the pineal tumours. The same mutation was present heterozygously in the DNA from the constitutional cells of the patient, proving it to be of germline origin. The initial mutation was shown to have occurred in the paternally derived RB1 allele. The mutation is in an area of the gene that encodes the protein-binding region known as the 'pocket' region and has been detected in other cases of retinoblastoma.