Martin G. Mott

An unusual intraosseous lesion with fibroblastic, osteoclastic, osteoblastic, aneurysmal and fibromyxoid elements. “Solid” variant of aneurysmal bone cyst

Four examples are reported of an unusual noncystic intraosseous lesion which does not conform to any hitherto recognized entity and which can be mistaken, not only by the general histopathologist but by the osteoarticular pathologist, for a variety of other conditions, including sarcoma and giant‐cell tumor. They were in patients aged 5 to 13 years; three in the spine, one in the ethmoid. Local excision, supplemented by low‐dose radiotherapy in cases with cord compression, produced a satisfactory outcome in all cases. At presentation the radiologic findings were nonspecific but, following treatment, an eggshell rim of bone developed in those lesions which had been incompletely excised. Histologically, they are characterised by florid fibroblastic or fibrohistiocytic proliferation, osteoblastic differentiation with osteoid production, areas rich in osteoclast‐type giant cells, aneurysmal sinusoids, and occasional foci of degenerate calcifying fibromyxoid tissue. Because this combination of histologic features can be found in the solid parts of aneurysmal bone cyst and in no other condition, at this centre we have regarded this lesion as a variant of aneurysmal bone cyst devoid of any cystic component.

Bacteraemia related to indwelling central venous catheters: Prevention, diagnosis and treatment

Infective episodes in immunocompromised children with indwelling central venous catheters were studied prospectively for one year. Culture of catheter hubs and skin at catheter entry sites during the first six months suggested that hub contamination was important in the pathogenesis of catheter colonization. The incidence of catheter-related bacteraemia, and possible catheter-related bacteraemia, fell by 56.5 % following alterations in the protocol for manipulative care of catheters, from 5.82 per 1000 catheter days in the first six months to 2.53 per 1000 catheter days in the subsequent six months. A firm diagnosis of catheter-related bacteraemia was made simply and economically by a pour-plate quantitative blood culture technique. Attempts at eradication of catheter-related bacteraemia without removal of the catheter were successful in all cases.

Left Ventricular Diastolic Filling Patterns Associated with Progressive Anthracycline-Induced Myocardial Damage: A Prospective Study

Abstract. The objective of this study was to examine changes in diastolic function associated with progressive myocardial damage and their implications. We used prospective sequential Doppler echocardiographic studies of left ventricular (LV) function. The study included 125 consecutive children (median age 6.3 years) receiving anthracyclines to cumulative doses between 45 and 1150 mg/m2 (median 270 mg/m2). We measured peak early (E) and atrial (A) phase filling velocities, EA ratio, deceleration and isovolumic relaxation times (EDecT and IVRT), heart rate, and fractional shortening (SF). Results were compared serially and with individually paired control data matched for body surface area. Progressive myocardial damage was evidenced by a mean SF decrease of 1 absolute %/100 mg/m2 of anthracycline. Six patients developed cardiac failure. After 1–100 mg/m2 of anthracyclines, the EA ratio decreased (mean 1.54–1.40, p= 0.02) and IVRT became prolonged (54 vs 52 msec in controls, p= 0.03). EA ratio increased again with the next dose, usually normalizing thereafter. Twelve patients ended treatment with an EA ratio <1 (1 cardiac death) and 17 with EA ratio >2 (2 cardiac deaths). Diastolic abnormalities were not strongly predictive of reduced SF. Modest changes in left ventricular diastolic filling patterns occur during anthracycline treatment of childhood malignancies. Although 20% of patients have significant abnormalities of diastolic filling by the end of treatment, considerable individual variability renders the pathophysiological and clinical implications of the early changes uncertain.

Prolonged survival following multiple thoracotomies for metastatic hepatoblastoma

A 14-month-old boy presented with hepatoblastoma, which was completely excised. He had pulmonary metastases, diagnosed 1 year later, treated with chemotherapy followed by resection at age 2 1/2 years. At the age of 3 1/2 years a further metastasis was shown on CT scan and this was resected. Two further metastses were resected at ages 4 1/2 and 5 1/2 years. At age 9 1/2 he had a further isolated pulmonary metastasis resected and is again disease-free more than 30 months from the last thoracotomy. Prolonged survival following metastatic hepatoblastoma can be achieved with repeated thoracotomies, especially if the first recurrence is more than 6 months from diagnosis and the number of metastases is small. Follow-up examinations should be both radiological and with serum alpha fetaprotein (S alpha FP).

Unpredictable serum levels after oral methotrexate in children with acute lymphoblastic leukaemia.

SummarySerum methotrexate levels were measured for 5 h after oral intake in 11 children with acute lymphoblastic leukaemia. The curves obtained with the childs regular dose of methotrexate varied widely, and were independent of the doses used. Peak levels were found in samples taken up to 3 h after ingestion, and ranged from 300 to 1250 ng/ml. In the doses used, methotrexate toxicity was present in one of the eleven children, and was associated with a delayed peak and a high 5-h methotrexate level. Individual drug metabolism could be an important factor in the response to treatment, and needs to be evaluated in the assessment of protocols.

Decline in incidence of medulloblastoma in children

Background. Medulloblastoma is one of the most common intracranial tumors in children. The perception that the incidence of this tumor has declined is reinforced by a decline in enrollment to international trials for the disease.

Radon in Devon and Cornwall and paediatric malignancies

Exposure to radon in dwellings may cause cancer including paediatric malignancies. Devon and Cornwall have the highest exposure to radon of the counties of England. However, within these counties there is considerable variation in exposure. Exposure to radon in the 283 postcode sectors of the two counties has been published. The incidence of childhood malignancies between 1976 and 1985 was studied to compare postcode sectors of radon exposures > or = 100 Bq/m3 with sectors < 100 Bq/m3. No significant difference in the incidence rate of 106.7 per million child years in the high radon postcode sectors and 121.7 in the low (P = 0.29) was found. When the incidences of individual tumours were examined, a significantly increased rate of neuroblastoma (P = 0.02) and a non-significant increased rate of acute myeloid leukaemia were found in the high exposure postcode sectors. No association between radon exposure and overall rate of childhood malignancy was found.

Do mutations at the glycophorin A locus i patients treated for childhood Hodgkin's disease predict secondary leukaemia?

Childhood Hodgkins disease has a high cure rate but second cancers are common, related to treatment and perhaps genetic predisposition. The glycophorin A (GPA) mutation assay measures the frequency of NO and NN mutant erythrocytes of MN blood-group heterozygous individuals. Mutant frequencies in Hodgkins disease patients were compared with controls. No significant difference from controls was found pretreatment or in patients treated with radiotherapy only. Patients who received chemotherapy had a significantly increased frequency (total mutation frequency per 10(6) cells: 31 vs 11, p < 0.001), which may be relevant to their known increased risk of secondary leukaemia.

Glycophorin A mutations and risk of secondary leukaemia in patients treated for childhood acute lymphoblastic leukaemia.

Survivors of childhood acute lymphoblastic leukaemia (ALL) have a higher than expected risk of developing secondary acute myeloid leukaemia (AML). The glycophorin A (GPA) mutation assay measures the frequency of variant NO and NN erythrocytes in MN heterozygotes. A raised variant frequency (Vf) has been shown in patients treated with chemotherapy known to be at risk of secondary leukaemia. ALL patients were investigated for increased Vf using the GPA assay. Vfs at diagnosis were not significantly different from controls (NO Vf P = 0.193; NN Vf P = 0.790). During treatment Vfs increased significantly (NO Vf P = 0.001; NN Vf P = 0.001). NO Vf returned to control values (P = 0.169) within 5 years from diagnosis but NN Vf remained significantly raised (P = 0.014). Three study patients developed secondary AML. At diagnosis of AML all three had significantly increased Vf. The first had a significantly raised Vf at routine follow‐up 19 years following diagnosis of ALL then developed AML 3.5 years later. The second had a significantly raised NN Vf at diagnosis of ALL indicating possibly prior exposure to a mutagen or defective DNA repair involving erythroid stem cells. We conclude that a raised Vf detected by the GPA assay can act as a marker for the development of secondary induced leukaemia and can be used to screen individuals at a known high risk of this complication.

The United Kingdom children's cancer study group—the first 20 years of growth and development

THE LATE 1960s and early 1970s were a time of rapid progress in the treatment of childhood cancer, particularly in North America and Western Europe. The impact of multicentre clinical trials run by the Children’s Cancer Study Group (CCSG, now CCG) and Pediatric Oncology Group (POG) in the U.S. disseminated widely the benefits of the treatment advances pioneered in some of the individual major cancer centres. In Europe, the International Society of Paediatric Oncology (SIOP) drew together researchers from the main centres in the same way and provided an annual forum to update results from their own trials and the major U.S. trials, in particular those of the Intergroup (Wilms’, rhabdomyosarcoma, Ewing’s) studies. Young investigators interested in paediatric malignancy were able to use the contacts made within SIOP to arrange training opportunities across international boundaries and on their return to their home institution invigorated them with new ways of thinking about old problems. In the U.K. a few multicentre clinical trials took place under the auspices of the Medical Research Council (for leukaemias, Wilms’ tumour and osteosarcoma) and some major centres contributed actively to SIOP trials on rhabdomyosarcoma and medulloblastoma. However, it became increasingly apparent that a new national organisation was required if children nationwide were going to benefit promptly from the advances being made. On 14 January 1977, a meeting was held in the Birmingham Children’s Hospital at which 14 members from 7 paediatric oncology units agreed to form the UKCCSG. This core group, which was augmented by invited representatives of 6 other units, was multidisciplinary and included paediatric oncologists, haematologists, surgeons, radiotherapists and pathologists. Half of its original members are still active participants of the group 20 years later. The membership of the UKCCSG now totals 220 full and associate members, 20 affiliates (consultants in shared care centres), 24 corresponding (overseas), 6 honorary and 17 junior members (trainees). At that inaugural meeting, the aims of the group were agreed to include the establishment of cooperative groups