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J Pritchard

Publications and source records attributed to J Pritchard.

At least 109 records · Page 6Linked to original sources
PubMed1995

Results of the United Kingdom Children's Cancer Study Group first Wilms' Tumor Study.

PURPOSE: The first United Kingdom Children's Cancer Study Group (UKCCSG) Wilms' Tumor Trial (UKW1) applied treatment regimens stratified by stage and histology in accordance with National Wilms' Tumor Study (NWTS) criteria, seeking to reduce treatment of low-stage, favorable-histology (FH) tumors without impairing survival and to improve prognosis of stage III and IV (FH) and unfavorable-histology (UH) tumors with more intensive chemotherapy. PATIENTS AND METHODS: Three hundred eighty-four consecutively diagnosed patients with Wilms' tumor were recruited from the 20 UKCCSG centers and Oslo, Norway, between January 1980 and June 1986. The regimen for stage I patients was vincristine (Vcr) only, while stage II patients received Vcr and dactinomycin (Act-D). Stage III patients received three-drug therapy and stage IV and UH patients four-drug regimens. Act-D was given as pulsed doses of 1.5 mg/m2 every 3 or every 6 weeks. No lung irradiation was used in stage IV patients. No randomized comparisons were attempted. End points were survival and event-free survival (EFS). RESULTS: Survival at 6 years in FH patients was 96% for stage I, 93% for stage II, 83% for stage III, 65% for stage IV, and 50% for UH patients of all stages. CONCLUSION: Vcr alone is as effective for stage I FH tumors as the two-drug regimen used in the NWTS and International Society of Pediatric Oncology (SIOP) studies. Fractionation of Act-D is unnecessary. The poorer results for stage IV FH and UH patients compared with the NWTS may be due to treatment differences, such as the use of lung irradiation for stage IV FH patients in NWTS3, and/or to case selection bias.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Successful in vivo immunolocalization of Langerhans cell histiocytosis with use of a monoclonal antibody, NA1/34.

The antibody NA1/34 is a murine monoclonal antibody directed against the CD1a surface antigen expressed on normal Langerhans cells, cortical thymocytes, and on lesional cells in Langerhans cell histiocytosis (LCH). Our hypothesis was that NA1/34 would localize sites of disease activity in patients with multisystem LCH. To test this hypothesis, indium 111-labeled NA1/34 was administered to five patients with multisystem LCH and serial gamma scans were obtained for up to 120 hours. Serial serum samples were obtained from one patient for analysis of anti-mouse Ig antibody and NA1/34 levels. Direct and indirect immunofluorescence staining for CD1a and NA1/34 were performed on a tissue biopsy specimen from one patient after administration of the antibody. The 1- and 4-hour scans showed distribution of antibody in the blood pool, but in later scans localization of the antibody was noted in areas of known disease activity in all five patients. Bony lesions, previously seen on skeletal radiographs, were especially well identified. Serum kinetics studies showed clearance of the antibody from the blood pool within 12 hours of administration. Direct binding of NA1/34 to lesional cells was demonstrated by direct immunofluorescence. The only adverse effect was urticaria in one patient. We conclude that NA1/34 localizes disease activity in vivo in bones of patients with LCH with minimal toxic effects. An evaluation of its role in determining disease extent ("staging") and in treatment is now needed.

Adult↗
PubMed1994

Molecular genetic analysis of chromosome 11p in familial Wilms tumour.

In the family reported here, a mother and both of her children developed a Wilms tumour, and all three tumours were of the relatively rare monomorphous epithelial histopathological subtype. Using restriction fragment length polymorphism analysis, both sibs were shown to inherit the same maternal allele from the 11p13 region but different maternal alleles from the 11p15 region. Using a combination of single-strand conformation polymorphism (SSCP) and polymerase chain reaction (PCR) sequencing techniques, no mutations were identified in the WT1 tumour-suppressor gene from the 11p13 region, but a novel polymorphism was identified in exon 1. mRNA expression studies using the insulin-like growth factor II (IGF-II) gene, located in 11p15, showed that there was no relaxation of imprinting at this locus. There was also no evidence of loss of heterozygosity on the long arm of chromosome 16. These findings indicate that the WT1 and IGF-II genes, together with the long arm of chromosome 16, are not directly implicated in tumorigenesis in this Wilms family, but that a recombination event has occurred on the short arm of chromosome 11.

Adult↗
PubMed1994

Bladder and kidney function after cure of pelvic rhabdomyosarcoma in childhood.

Eleven survivors of pelvic rhabdomyosarcoma underwent bladder function studies and upper urinary tract evaluation at a mean of 6.6 years after completion of therapy, which included a conservative, bladder-sparing surgical policy. Primary tumour sites were: bladder base/prostate, 6; bladder dome, 1; vagina, 2; and pelvic side wall, 2. Seven children (five bladder base/prostate, one vagina and one pelvic side wall tumours) had received irradiation to the pelvis with external beam alone, brachytherapy or both. All seven of these patients had markedly reduced functional bladder capacity (11-48% of mean expected value for age) and abnormal voiding patterns, though bladder compliance was not reduced and bladder emptying was almost complete in five cases. Four of these children also had upper tract dilatation and two required reconstructive bladder surgery because of severe bilateral hydronephrosis. By contrast, each of four children treated without radiotherapy had a normal functional bladder capacity and a normal voiding pattern. all survivors of pelvic rhabdomyosarcoma, especially those who have received radiotherapy, should be carefully monitored for dysfunction of both lower and upper urinary tracts. The frequency-volume voiding chart is a sensitive and easily accomplished method of assessing bladder function in these patients.

Child↗
PubMed1994

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.

Adolescent↗
PubMed1994

Haemophagocytic lymphohistiocytosis: experience at two U.K. centres.

Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of inappropriate macrophage activation. Both familial and sporadic forms, which may be infection-associated, are recognized. Between 1985 and 1991 we treated 23 cases of HLH (12 male, 11 female). There were eight familial cases, defined by a previously affected sibling and/or history of consanguinity, age 3 d to 15 months at presentation. The age of the remaining 15 cases varied from 1 month to 9.5 years. A potential viral trigger was identified in four cases (EBV, two; parvovirus B19, one; echovirus II, one) including one familial case. Six of eight (75%) patients who received supportive care alone, including all four familial cases, died within 6 months of presentation. Both long-term survivors in this group presented at an older age (7.5 and 8 years) and had proven or suspected virus-associated HLH. 15 patients were treated with etoposide (150-250 mg/m2 days 1-3 every 21 d) and methylprednisolone; 10 patients received intrathecal methotrexate in addition. In nine (60%) of these cases a complete (six) or partial (three) response was achieved, though one child suffered a fatal 'tumour lysis' syndrome. Overall mortality in the treated group was 66.6%, being highest (75%) in patients under 2 years at presentation compared to 33% in those over 2 years. Two of three familial and one of five sporadic cases relapsed and died 3 d to 20 months from diagnosis. Only one familial case survives at follow-up of 11 months. Of the five remaining survivors, two received allogeneic bone marrow transplantation (one matched related, one haploidentical) and are alive at 11 and 29 months. Three cases aged 2.5, 7.5 and 9.5 years remain in remission at 11, 20 and 25 months respectively. The high mortality of HLH supports a role for allogeneic BMT in selected cases, particularly those with a familial basis or under 2 years at presentation.

Bone Marrow↗
PubMed1994

Histiocytosis--an introduction.

The Histiocytoses are a group of rare and puzzling multisystem disorders, currently regarded as non-malignant but often treated with 'cancer chemotherapy'. In this article, the origins of histiocytes and of the Histiocyte Society's classification of the Histiocytoses are described with suggested minor modifications to the classification. The current nomenclature for the 2 principal diseases, now named 'Langerhans cell histiocytosis' and 'Haemophagocytic Lymphohistiocytosis', is less confusing than the terms originally chosen. The article sets the scene for the succeeding papers, which focus on 'Langerhans cell histiocytosis'.

Histiocytes↗
PubMed1994

Monoclonal antibody therapy in Langerhans cell histiocytosis--feasible and reasonable?

Many recent studies have demonstrated the range of disorders in which monoclonal antibodies have a clinical role. The monoclonal antibody NA1/34, directed against a surface antigen present on lesional cells ('LCH cells'), has been found to localise in vivo to sites of disease. This review explores the possible applications and limitations of monoclonal antibody based-therapy in Langerhans cell histiocytosis.

Antibodies, Monoclonal↗
PubMed1993

Testicular function following the treatment of Hodgkin's disease in childhood.

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.

Adolescent↗
PubMed1993

Chemotherapy effects on hepatoblastoma. A histological study.

The histopathological features of hepatoblastoma in 17 patients treated with preoperative chemotherapy were compared with those in 11 patients not subjected to chemotherapy during the same 11-year period. Tumor necrosis was more extensive in patients receiving preoperative chemotherapy. Two tumors, however, were apparently unaffected by chemotherapy. There was no obvious correlation between the extent of necrosis and the number of courses of chemotherapy. There also seems to be no evidence of preferential ablation of a particular morphological type of tumor. The most notable feature in cases treated with chemotherapy was the extensive presence of osteoid. Osteoid was present in 36% of untreated cases, occupying < 5% of the surface area, compared with 82% in the treated group. In seven cases, osteoid occupied > 40% of the surface area. This finding raises speculation about the role of chemotherapy in the maturation of tumors that have an inherent ability to differentiate. A long-term study is needed to clarify the prognostic significance of mature heterologous elements in hepatoblastoma.

Adolescent↗
PubMed1993

Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment.

PURPOSE AND METHODS: Based on preliminary experience, there was a need for modifications and clarifications in the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Response Criteria (INRC). In 1988, a proposal was made to establish an internationally accepted staging system for neuroblastoma, as well as consistent criteria for confirming the diagnosis and determining response to therapy (Brodeur GM, et al: J Clin Oncol 6:1874-1881, 1988). A meeting was held to review experience with the INSS and INRC and to revise or clarify the language and intent of the originally proposed criteria. Substantial changes included a redefinition of the midline, restrictions on age and bone marrow involvement for stage 4S, and the recommendation that meta-iodobenzylguanidine (MIBG) scanning be implemented for evaluating the extent of disease. Other modifications and clarifications of the INSS and INRC are presented. In addition, the criteria for the diagnosis of neuroblastoma were modified. Finally, proposals were made for the development of risk groups that incorporate both clinical and biologic features in the prediction of prognosis. The biologic features that were deemed important to evaluate prospectively included serum ferritin, neuron-specific enolase (NSE), and lactic dehydrogenase (LDH); tumor histology; tumor-cell DNA content; assessment of N-myc copy number; assessment of 1p deletion by cytogenetic or molecular methods; and TRK-A expression. RESULTS AND CONCLUSION: Modifications of the INSS and INRC made at this conference are presented. In addition, proposals are made for future modifications in these criteria and for the development of International Neuroblastoma Risk Groups.

Humans↗