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V Castel

Publications and source records attributed to V Castel.

At least 19 recordsLinked to original sources
PubMed1998

Pediatric brain tumors: loss of heterozygosity at 17p and TP53 gene mutations.

Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) have demonstrated material losses of 17p, the region that contains the TP53 gene, as the most frequent abnormality. Mutations in the TP53 gene are, however, very rare in these tumors. These findings strongly suggest that another, as yet unidentified, gene on 17p may be involved. We performed a search for loss of heterozygosity (LOH) on 17p by microsatellite markers on 26 childhood CNS tumors as well as TP53 gene mutations (exons 5-8) by single-strand conformational polymorphism analysis on 41 pediatric brain tumor samples of distinct histologic types. LOH was detected in 10 cases: 7 PNET, 2 astrocytomas, and 1 glioblastoma multiforme. In 4 of the PNETs the losses were limited to more distal markers. On the other hand, TP53 mutations were detected in 6 of 41 samples studied. Our results not only confirm the low penetrance of the TP53 gene on pediatric CNS tumors, but also provide further evidence of a putative tumor suppressor gene distal to TP53, between markers (D17S938, D17S926) and 17pter, specifically taking part in the development of PNET.

Adolescent↗
PubMed1998

Surgical treatment for neuroblastoma: complications during 15 years' experience.

BACKGROUND/PURPOSE: Surgery plays an important role in neuroblastoma treatment. Although influence of resectability in survival has been studied deeply, reports about surgical complications are scant. The authors analyze retrospectively their experience in neuroblastomas (NB) diagnosed from 1980 to 1995. METHODS: Clinical variables such as age, stage, location, presurgical chemotherapy, type, and extent of surgery were studied. Complications were classified according to the following criteria: time, type of surgery, and extent of resection. RESULTS: Seventy-eight NB patients had surgery performed in our hospital. Mean age at diagnosis was 2.4 years (range, 0 to 11 years); 33 patients were under 1 year of age. Sixty-eight percent of the patients had advanced disease. Abdominal tumors were predominant. Sixty-three percent of the patients had chemotherapy before surgery, with shrinkage of the tumor in most of the cases (88%). Eighty-six surgical procedures were performed, 29 initially and 57 delayed. Complete resection was reached in 52 patients, partial in 19 patients, and seven patients underwent biopsy only. There were 42 surgical complications. Three of them were considered extremely serious (one death caused by cardiac arrest, one tumoral rupture, and one great vessel injury). Nephrectomies (n = 12) were the most frequent intraoperatory complications. Bernard-Horner syndrome (n = 5) and pleural effusions (n = 5) predominated in the postoperative period. CONCLUSIONS: (1) Surgery in NB can be performed safely. (2) Nephrectomies can be necessary to achieve complete resection in some abdominal tumors. (3) Nephrectomies, Bernard-Horner syndrome, and pleural effusions were the most frequent complications in our patients. (4) Presurgical chemotherapy can lead to a wider and safer removal of locally advanced tumors.

Adrenal Gland Neoplasms↗
PubMed1998

A novel TP53 germ-line mutation identified in a girl with a primitive neuroectodermal tumor and her father.

A search of TP53 mutations was undertaken in a series of 51 pediatric brain tumors. The only germ-line mutation was detected in a 9-year-old girl with a PNET. Her family history was unremarkable for neoplastic disease, except for the paternal grandfather, who died of a gallbladder carcinoma at an advanced age. The mutation was a thymine deletion at the first base of codon 241, leading to termination codon at position 246 that has not previously been reported. This mutation was found to be inherited from the proband's father, who was healthy at age 40. In the tumoral sample, loss of heterozygosity in several 17p markers was found, the only TP53 allele preserved in the tumor was the mutated one. The presence of two short tandem repeats and two different palindromic sequences spanning the deletion lead us to propose the predisposition of this region to forming a complex secondary structure during replication. Consequently, it could have facilitated the present deletion. Furthermore, six other short deletions affecting--partially or totally--the region implicated in the folding model that we propose have been described in the literature. These findings confirm that this sequence represents a hotspot of deletion in the TP53 gene.

Child↗
PubMed1998

[Central nervous system tumors in children less than three years of age].

OBJECTIVE: Central nervous system (CNS) tumors are the most frequent solid tumors in children. Twelve to twenty percent are diagnosed in patients younger than two years of age and these patient present more morbidity and mortality due to the illness and the treatment itself. PATIENTS AND METHODS: A retrospective study of CNS tumors in children younger than three years of age diagnosed in our hospital between 1985 and 1995 was carried out. RESULTS: We treated 21 patients between 1985 and 1995. There were 10 male and 11 females. The mean age was 20.3 months (range: 0-32 months). The mean time between symptoms and treatment was 2.4 months (range: 0-18 months). The most common symptoms included ataxia, nausea and vomits. The most common locations of the tumor were: infratentorial (57.1%) and supratentorial (38.1%). Complete surgery was performed in 3 patients, subtotal in 10, partial in 5, and a biopsy in 2. The anatomical-pathological diagnosis was: astrocytoma (6), ependinoma (5), meduloblastoma (4), ganglioglioma (1), neuroblastoma (1), and primitive neuroectodermic tumor (1). We could not document the histology in 3 patients. Ten patients received chemotherapy that was well tolerated and 14 received radiotherapy whose sequels were updated. The mean follow-up period was 44.42 months (range: 0-136 months). Overall survival was 42.86%. There were no statistically significant differences in survival between those who were irradiated and those who were not, nor between those with supra-or infratentorial tumors. CONCLUSIONS: CNS tumors in children younger than three years of age have a worse prognosis than in older children. New therapeutic schedule with chemotherapy are being tested to avoid radiotherapy side-effects.

Age Factors↗
PubMed1995

Treatment of stage III neuroblastoma with emphasis on intensive induction chemotherapy: a report from the Neuroblastoma Group of the Spanish Society of Pediatric Oncology.

From October 87 to April 92, 172 children were admitted in the N-I-87 protocol of the Spanish Society of Pediatric Oncology for the diagnosis and treatment of neuroblastoma. Forty-eight were considered Evans stage III, 33 of them being older than 1 year. All children were treated with induction chemotherapy (IC) and surgery. IC consisted of three courses of high-dose cisplatin-VM-26 alternating with three further courses of cyclophosphamide-doxorubicin (CAD). Infants less than 1 year received the same drugs at lower doses. After surgery, maintenance chemotherapy was administered to all children during 14 months. It consisted of four pairs of drugs rotated every 4 weeks. Radiotherapy was administered exclusively to patients older than 1 year with residual tumor after IC and surgery. Response was evaluated after IC and surgery. In children older than 1 year, response was obtained in 28/33 (88%). Fifteen of them (47%) achieved complete remission (CR), seven (22%) good partial response (GPR), six (19%) partial response (PR); and in three patients (9%) there was progressive disease (PD). Actuarial survival at 48 months was 0.60 +/- 0.10 and EFS was 0.61 +/- 0.12. Audiologic impairment was considered the worst toxicity. In children less than 1 year the response rate to IC and surgery was 93% (14/15); nine infants obtained complete response and four had GPR. Only one patient experienced PD in the first 6 months of therapy and died. The other 14 are alive and well at a mean follow-up time of 48 months. Chemotherapy toxicity was mild and reversible.

Adolescent↗
PubMed1995

Neuroblastoma IV-S followed by extra-adrenal pheochromocytoma 15 years later.

Common origin of sympathoblasts and pheochromoblasts from the neural crest cells is generally accepted. Neuroblastoma and pheochromocytoma result from an abnormal proliferation of these committed cells. They are included in the group of neuroendocrine neoplasms, formerly named Apudomas. Previous reports of mixed tumours of neuroblastoma and pheochromocytoma, and ganglioneuroma and pheochromocytoma, support this hypothesis. A case of extra-adrenal pheochromocytoma in an adolescent who 15 years before was successfully treated for a stage IV-S neuroblastoma without evidence of primitive tumour is reported. Two hypothesis are formulated: (1) the second neoplasm may have arisen from the unlocated primitive tumour, probably silent evolution could be due to its maturation into ganglioneuroma-pheochromocytoma; (2) taken into account a common origin of both neoplasms, the patient may have a genetic predisposition to develop neuroendocrine tumours. Whatever the mechanism, second neoplasms, as the case reported, late relapses, and late toxic effects may justify long follow-up of neuroblastoma survivors.

Adolescent↗
PubMed1995

The treatment of advanced neuroblastoma. Results of the Spanish Neuroblastoma Study Group (SNSG) studies.

The Spanish Neuroblastoma Study Group has conducted a study on advanced neuroblastoma (N-I-87), which included 33 stage III and 60 stage IV neuroblastoma children more than 1 year of age, enrolled between October 1987 and April 1992. They were staged according to Evans and treated with induction chemotherapy (IC) consisting of 3 courses of cyclophosphamide-doxorubicin alternating with 3 of high-dose cisplatin-teniposide. Evaluation after IC and surgery demonstrated an overall response rate of 88% for stage III and 69% for stage IV. In the latter, complete responses and good partial responses were 33 and 14%, respectively. After surgery, children received maintenance chemotherapy (all stage III except 2 and 30 stage IV) or autologous bone marrow transplantation (ABMT) (11 stage IV), the distribution was not randomised. Probability of survival at 5 years was 0.60 +/- 0.12 for stage III and 0.24 +/- 0.07 for stage IV. A significant difference in survival at 5 years was found between "good responders" and "non-responders" to initial chemotherapy.

Adolescent↗
PubMed1994

Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry.

This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary.

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↗
PubMed1992

Acute nonlymphoblastic leukemia in children treated for acute lymphoblastic leukemia with an intensive regimen including teniposide.

Some cases of conversion from acute lymphoblastic leukemia (ALL) to acute nonlymphoblastic leukemia (ANLL) at relapse have been reported recently. We report three cases initially diagnosed as having ALL and showing morphological, cytochemical, and immunophenotypic features of ANLL at relapse (lineage switch). Conversion was observed among 14 patients who developed bone marrow relapse while undergoing intensive treatment with our ALL protocol, which includes teniposide, and that had been administered to 62 patients. The three cases converted at first relapse, with a mean time of 20 months (13-29 months). Clinical and immunologic characteristics of T-cell leukemia were present in one patient. Changes documented in cytogenetic studies are discussed. The underlying mechanisms for the lineage switch remain unclear as does its relation with mixed lineage leukemias, but we believe that drugs employed in our therapy protocol could have had an influence on this conversion.

Child, Preschool↗