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Biomedical subjects

C Cappelli

Publications and source records attributed to C Cappelli.

16 recordsLinked to original sources

Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma.

Occlusive vasculopathy is a potential complication of radiotherapy in children with optic pathway glioma. With a median follow-up of 7 years, 13 of 69 children in this study developed clinical and radiological signs of occlusive vasculopathy after radiotherapy within a median interval of 36 months. The major risk factor was neurofibromatosis type 1. Radiotherapy should no longer be the first treatment in these settings. When radiotherapy is unavoidable, regular screening for cerebral vasculopathy is mandatory, as preventive treatment is available.

Cerebrovascular Disorders↗

Preclinical development of camptothecin derivatives and clinical trials in pediatric oncology.

Although the prognosis of childhood cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these DNA-topoisomerase I inhibitors, i.e. topotecan and irinotecan, is ongoing in paediatric malignancies. Here we review the currently available results of this evaluation. Topotecan proved to be active against several paediatric tumour xenografts. In paediatric phase I studies exploring several administration schedules, myelosuppression was dose-limiting. The preliminary results of topotecan evaluation in phase II study showed antitumour activity in neuroblastoma (response rate: 15% at relapse and 37% in newly diagnosed patients with disseminated disease) and in metastatic rhabdomyosarcoma (40% in untreated patients). Topotecan-containing drug combinations are currently investigated. Irinotecan displayed a broad spectrum of activity in paediatric solid tumour xenografts, including rhabdo-myosarcoma, neuroblastoma, peripheral primitive neuroectodermal tumour, medulloblastoma, ependymoma, malignant glioma and juvenile colon cancer. For several of these histology types, tumour-free survivors have been observed among animals bearing an advanced-stage tumour at time of treatment. The clinical evaluation of irinotecan in children is ongoing. Irinotecan undergoes a complex in vivo biotransformation involving several enzyme systems, such as carboxylesterase, UDPGT and cytochrome P450, in children as well as in adults. Preclinical studies of both drugs have shown that their activity was schedule-dependent. The optimal schedule of administration is an issue that needs to be addressed in children. In conclusion, the preliminary results of the paediatric evaluation of camptothecin derivatives show very encouraging results in childhood malignancies. The potential place of camptothecins in the treatment of paediatric malignant tumours is discussed.

Animals↗

Long-term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era.

AIM: To analyse the long-term results of conservative management with radiotherapy in patients with optic pathway tumours. DESIGN: All 69 patients were symptomatic at diagnosis and most neoplasms involved the optic chiasm and hypothalamus. RESULTS: At 10 years, overall survival and progression free survival were 83% and 65.5%, respectively. After radiotherapy, vision improved in 18 patients and remained stable in 29 other patients. Cerebrovascular complications occurred in nine of 53 patients treated with radiotherapy after a median interval of two and a half years. These complications were five times more frequent in patients with neurofibromatosis type 1 (NF1). Severe intellectual disabilities were present in 18 children, most of whom underwent irradiation at a very young age (median age, 4 years). IMPLICATIONS: Radiotherapy is a valuable treatment in terms of tumour response, visual outcome, and progression free survival. However, in young children and in patients with NF1, major sequelae are encountered and new treatment strategies should be proposed for these patients.

Adolescent↗

[The accidental diagnosis of a left atrial myxoma in an 80-year-old female].

Left atrial myxoma is usually diagnosed in patients between the ages of 30 and 60 and this diagnosis follows non-specific symptoms (i.e. temperature, anemia, weakness), and obstructive or embolic episodes. There are few cases in the literature of this disease in patients older than 80. We report the case of an 80-year-old female admitted to our institute for an episode of supraventricular tachycardia. After successful treatment of the arrhythmia using verapamil i.v., a routine echocardiographic examination showed the presence of a left atrial mass, and its appearance suggested the diagnosis of a left atrial myxoma. A CT scan and a transesophageal echocardiography confirmed the diagnosis. The patient subsequently underwent cardiac catheterization and coronary angiography. In the absence of significant lesions of the coronary artery, a decision was made to remove the myxoma surgically, based on two considerations: the good clinical status of the patient and the high current risk of peripheral embolization. The operation was successful in removing the myxoma and the patient continues to be in good clinical condition.

Aged↗

DNA-topoisomerase I, a new target for the treatment of neuroblastoma.

DNA-topoisomerase I is the nuclear target of new anticancer drugs, namely camptothecin and its derivatives. In order to establish the rational basis for their clinical development in paediatric oncology, the antitumour activity of irinotecan (CPT-11) and topotecan, two camptothecin water-soluble derivatives, was studied in nude mice bearing neuroblastoma xenografts. The panel was composed of 4 previously established subcutaneous xenograft lines (IGR-N835, IGR-N91, IGR-NB3, IGR-NB8) that exhibited the common biological markers of poor prognosis in children (MYCN amplification, 1p deletion, paradiploidy and/or MDR1 overexpression). Irinotecan and topotecan were administered i.v. or i.p. over 5 consecutive days in animals bearing tumours. Irinotecan (40 mg/kg/day) induced 20-100% complete regressions with tumour growth delays ranging from 20 to 46 days. Two out of 10 IGR-N91 bearing animals were tumour free more than 120 days after treatment with the top dose (50 mg/kg/day). Topotecan (2.7 mg/kg/day) induced 0-67% complete regressions with tumour growth delays ranging from 23 to 50 days. One out of 8 IGR-NB3 bearing mice was tumour free at the end of the experiment. The antitumour activity of both drugs was clearly sustained at a lower dose level. Topoisomerase I activity was assayed in 15 neuroblastomas, 3 ganglioneuroblastomas and 2 normal adrenal glands, using a DNA relaxation assay. Topoisomerase I activity ranged from 69 to 1304 arbitrary units/mg of protein, and was significantly higher in immature neuroblastomas than in ganglioneuroblastomas and adrenal glands. In conclusion, irinotecan and topotecan are active against neuroblastoma xenografts. Their target is expressed in patients' tumour samples. Clinical development of topoisomerase I inhibitors in children with neuroblastoma is warranted.

Adrenal Glands↗

Clinical features and biological markers of brain tumors.

Brain tumors represent a wide and important field of oncology. Their incidence has increased in the last twenty years but the reason for this, as well as the etiopathogenesis of these tumors, has not been clearly understood yet. In the first part of this paper we have divided brain tumors on a topographic basis in neoplasms which develop in the posterior fossa, in the midbrain and in the hemispheres; the clinical characteristics of the most frequent tumors are also analysed. Particular attention has been given to neoplasms in children. In the second part we deal with the two most useful methods of diagnosis and classification of brain tumors: immunoistochemical markers and biochemical markers.

Adult↗

The hepatic malignant mesenchymoma: a case report.

We report a case of hepatic mesenchymoma in an 8-year-old girl who presented with abdominal pain and ultrasonographic diagnosis of hepatic echinococcosis. Due to the good general condition of the patient and the diagnostic confirmation of liver hydatid disease by the CT scan, antiparasitic therapy with albendazole was started. After 1 month of therapy the girl's general condition worsened as did the ultrasonographic picture. On laparatomy a large cystic mass was observed within the right hepatic lobe and was removed. Pathological examination of the mass excluded an echinococcal cyst and demonstrated a malignant hepatic mesenchymoma.

Child↗

A two-year study of enteric infections associated with diarrhoeal diseases in children in urban Somalia.

A hospital-based systematic sample of 1667 children with severe diarrhoeal disease was studied in Mogadishu, Somalia, throughout 1983 and 1984. One or more enteric pathogens were found in 61% of the patients. Rotavirus (25%), enterotoxigenic Escherichia coli (11%), Shigella spp. (9%), Aeromonas hydrophila (9%), Giardia lamblia trophozoites (8%), Campylobacter jejuni (8%), and Vibrio cholerae non-O1 (6%) were the most frequently identified pathogens. Age-specific detection rates of enteric pathogens and helminths, seasonal patterns, and relationship of some specific infections with feeding status and main clinical features have been defined for all the sample examined.

Adolescent↗

Chemotherapy in low-grade astrocytoma management.

The role of chemotherapy (CHT) in the management of low-grade astrocytoma (LGA) is still unclear. Nineteen children with nonresectable symptomatic LGA were treated with carboplatin (CBDCA) and etoposide (E). There were 15 newly diagnosed cases and 4 were relapses; 6 of the children were under 5 years old. In all children radiological evaluation by CT scan and/or MRI was performed after four courses of CHT. We observed complete response (CR)+ minor response (MR) in 37% of these cases and an improvement in neurological symptoms in 63%. Radiological evaluation performed in 6 patients who received CHT for longer periods (8-12 courses) showed major responses (CR+PR) in 67%. Local radiotherapy (40 Gy) was administered after CHT in 14 cases, but in 3 of these radiotherapy was delayed for 2 years. Five patients did not receive radiotherapy. The overall survival was 58% after an average follow-up of 60 months. All patients with brain stem tumors died of progressive disease even though 3 of these had shown clinical improvement after chemotherapy. In conclusion, in the treatment of nonresectable symptomatic LGA, CHT with CBDCA associated with E can be used to postpone radiotherapy in young children and even to avoid radiotherapy in some cases.

Adolescent↗

Crohn disease of the small bowel: spiral CT evaluation after oral hyperhydration with isotonic solution.

PURPOSE: Our aim was to evaluate the accuracy of spiral CT study of small-bowel Crohn disease with use of oral hyperhydration with isoosmotic solution. METHOD: We prospectively analyzed 33 consecutive patients and 10 control subjects with spiral CT after oral administration of 2,000 ml of polyethylene glycol electrolyte-balanced solution. The CT diagnoses were compared with the results of conventional radiologic oral barium examination (33 cases), ileum colonoscopy (8 cases), and surgery (4 cases). RESULTS: The final diagnoses were Crohn disease (14 cases), no small-bowel disease (16 cases), cancer of ileocecal valve (1 case), carcinosis of mesenteric root (1 case), and intestinal lymphangiectasia (1 case). In the control group, no abnormalities of the small bowel were found. The sensitivity of spiral CT was 85.7%, specificity 100%, positive predictive value 100%, negative predictive value 90%, and diagnostic accuracy 93.9%. CONCLUSION: Our method allowed adequate distension of the small bowel for spiral CT studies, thus resulting in a safe and effective alternative to small-bowel spiral CT enema, which can be used in patients that refuse the nasojejunal balloon catheter.

Adolescent↗

Ten-day schedule oral etoposide therapy in advanced childhood malignancies.

PURPOSE: The activity of etoposide (VP-16) has been demonstrated to be schedule-dependent. Several studies have been conducted on the efficacy and safety of different schedules of VP-16 both in adults and in children, but the optimal schedule has not been determined. METHODS: In the current study, the feasibility and effectiveness of prolonged oral VP-16 in children with high-risk malignancies were evaluated. Between April 1995 and February 1999, 15 pretreated patients with high-risk tumors received oral VP-16. The schedule of therapy was oral VP-16 50 mg/m2/day for 10 consecutive days and 1-week interval between cycles. Therapy was stopped after 1 year of treatment or at time of progressive disease or possible surgery. All patients had received parenteral VP-16 in their earlier chemotherapy. RESULTS: Twelve patients were evaluable for tumor response. After 2 to 4 months of treatment, one patient had complete remission (CR), two had partial response (PR), two had minor response (MR), two had mixed response (MxR), three had stable disease (SD), and two had progressive disease (PD). A useful palliative effect was noted in patients with stable disease. In three patients, oral VP-16 was administered for maintenance therapy. After an average follow-up of 27.5 months (range, 7-41 months), five patients are alive without disease (in three, total surgery was performed after VP-16 therapy) and three patients are alive with disease. Six patients died of progressive disease, and one died of promyelocytic leukemia. One patient had Grade 34 thrombocytopenia; in the remaining patients, no acute toxicity was observed during treatment. CONCLUSIONS: This schedule of oral VP-16 produced CRs, PRs, and MRs in medulloblastoma, neuroblastoma, teratocarcinoma, and ependymoma. Stable disease was observed in three patients, one with an Askin tumor, one with medulloblastoma, and one with hepatoblastoma. Given the possible leukemogenic risk, this schedule should be used as a palliative form of therapy or in patients with poor prognosis..

Administration, Oral↗

Hyperthyroidism and concurrent thyroid cancer.

AIMS AND BACKGROUND: The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid malignancy in endemic goiter areas and review the current literature on the subject. METHODS: During the period January 1984 to June 1998, 1853 patients were examined for hyperthyroidism at the Spedali Civili Hospital of Brescia, Italy; 512 (27.6%) subjects underwent surgery. Of these patients 108 (21%) had Graves' disease, 251 (49%) multinodular toxic goiter (MTG) and 153 (30%) uninodular toxic goiter (UTG). RESULTS: Malignancy was found in 24 (4.7%) patients: 19 females and 5 males with a mean age of 52.2 years (range, 21-76 years). The frequency of cancer in Graves' disease was 6.4%, 5 females and 2 males; in MTG 3.9%, 2 females and 8 males, and in UTG 4.4%, 7 females and 1 male. CONCLUSIONS: Our data confirm previous reports on the frequency of thyroid cancer in hyperthyroidism. This association is more relevant than previously suspected. The frequent coexistence of hyperthyroidism and neoplasia, demonstrated by our study and the most recent literature, underlines the importance of studying and excluding the possibility of neoplastic degeneration by means of a systematic approach.

Adult↗

Flow cytometric and molecular analysis of proliferative activity and DNA content in neuroblastoma: presence of stationary cells in S-phase.

Twenty-nine previously untreated neuroblastomas were analyzed for DNA content and percentage of cells in S-phase, both determined by flow cytometry, and N-myc oncogene copy number. Twelve of them were also tested for histone H3 transcript levels as a marker of actual proliferative activity. A significantly higher S-phase fraction was associated with advanced stages of disease, unfavorable (i.e., near-diploid and near-tetraploid) DNA content, and N-myc amplification. The occurrence of six tumors with a remarkable (greater than or equal to 10%) S-phase fraction but lacking histone H3 transcripts suggests the presence of stationary S-phase cells in neuroblastoma.

Cell Division↗