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1.
J Radiat Oncol ; 4(3): 235-241, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27695605

RESUMO

OBJECTIVES: The aim of this study is to define the maximal safe radiation dose to guide further study of the GliaSite balloon brachytherapy (GSBT) system in untreated newly diagnosed glioblastoma (NEW-GBM) and recurrent high-grade glioma (REC-HGG). GBST is a balloon placed in the resection cavity and later filled through a subcutaneous port with liquid I-125 Iotrex, providing radiation doses that diminish uniformly with distance from the balloon surface. METHODS: The Adult Brain Tumor Consortium initiated prospective dose-finding studies to determine maximum tolerated dose in NEW-GBM treated before standard RT or after surgery for REC-HGG. Patients were inevaluable if there was progression before the 90-day posttreatment toxicity evaluation point. RESULTS: Ten NEW-GBM patients had the balloon placed, and 2/10 reached the 90 day timepoint. Five REC-HGG enrolled and two were assessable at the 90-day evaluation endpoint. Imaging progression occurred before 90-day evaluation in 7/12 treated patients. The trials were closed as too few patients were assessable to allow dose escalation, although no dose-limiting toxicities (DLTs) were observed. Median survival from treatment was 15.3 months (95 % CI 7.1-23.6) for NEW-GBM and 12.8 months (95 % CI 4.2-20.9) for REC-HGG. CONCLUSION: These trials failed to determine a maximum tolerated dose (MTD) for further testing as early imaging changes, presumed to be progression, were common and interfered with the assessment of treatment-related toxicity. The survival outcomes in these and other related studies, although based on small populations, suggest that GSBT may be worthy of further study using clinical and survival endpoints, rather than standard imaging results. The implications for local therapy development are discussed.

2.
AJNR Am J Neuroradiol ; 29(2): 366-72, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18055564

RESUMO

BACKGROUND AND PURPOSE: Noninvasive diagnosis of brain lesions is important for the correct choice of treatment. Our aims were to investigate whether 1) proton MR spectroscopic imaging ((1)H-MRSI) can aid in differentiating between tumors and nonneoplastic brain lesions, and 2) perfusion MR imaging can improve the classification. MATERIALS AND METHODS: We retrospectively examined 69 adults with untreated primary brain lesions (brain tumors, n = 36; benign lesions, n = 10; stroke, n = 4; demyelination, n = 10; and stable lesions not confirmed on pathologic examination, n = 9). MR imaging and (1)H-MRSI were performed at 1.5T before biopsy or treatment. Concentrations of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the lesion were expressed as metabolite ratios and were normalized to the contralateral hemisphere. Dynamic susceptibility contrast-enhanced perfusion MR imaging was performed in a subset of patients (n = 32); relative cerebral blood volume (rCBV) was evaluated. Discriminant function analysis was used to identify variables that can predict inclusion in the neoplastic or nonneoplastic lesion groups. Receiver operator characteristic (ROC) analysis was used to compare the discriminatory capability of (1)H-MRSI and perfusion MR imaging. RESULTS: The discriminant function analysis correctly classified 84.2% of original grouped cases (P < .0001), on the basis of NAA/Cho, Cho(norm), NAA(norm), and NAA/Cr ratios. MRSI and perfusion MR imaging had similar discriminatory capabilities in differentiating tumors from nonneoplastic lesions. With cutoff points of NAA/Cho < or =0.61 and rCBV > or =1.50 (corresponding to diagnosis of the tumors), a sensitivity of 72.2% and specificity of 91.7% in differentiating tumors from nonneoplastic lesions were achieved. CONCLUSION: These results suggest a promising role for (1)H-MRSI and perfusion MR imaging in the distinction between brain tumors and nonneoplastic lesions in adults.


Assuntos
Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Prótons , Adulto , Idoso , Encefalopatias/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
3.
Pediatr Neurosurg ; 34(5): 229-34, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11423771

RESUMO

Pilocytic astrocytoma (PA) is the most common childhood brain tumor. In cases where the tumor progresses or recurs following primary surgical resection, the appropriate treatment is unclear. Options include chemotherapy, radiation therapy, surgical resection or a combination thereof. To analyze the utility of further surgery, we performed a retrospective, single-institution review of pediatric patients with recurrent PAs from 1990 to 1999 who were treated with a second surgical resection. Patients were excluded if they received adjuvant chemotherapy or radiation therapy. Twenty cases were identified. Tumor locations included: cerebral hemisphere (3), cerebellum (7), optic pathway/hypothalamus (5), thalamus (1) and brainstem (4). The indication for 4 surgeries included an enlarging tumor-associated cyst. At second surgery, 10 of 20 patients had a gross total resection (GTR), 2 a near total resection (NTR), and the remaining 8 patients had a subtotal resection (STR). No patients have died. Two of 10 tumors after GTR, 0 of 2 tumors after NTR, and 7 of 8 tumors after STR had second recurrence/progression at a mean of 15 months (range 4-33 months) following second surgery. The remaining 11 patients are recurrence/progression-free at a mean of 40.7 months (range 19-119 months). Surgery for tumors or midline structures rarely resulted in a GTR (1 of 10 cases). Surgery for tumors located in the cerebral hemispheres or cerebellum resulted in GTR or NTR in all cases and can result in long periods of progression-free survival without further adjuvant treatment.


Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Encéfalo/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adolescente , Astrocitoma/patologia , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Humanos , Lactente , Recidiva Local de Neoplasia/patologia , Reoperação/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
4.
Cancer Res ; 60(22): 6307-10, 2000 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11103789

RESUMO

Local delivery of carmustine (BCNU) via biodegradable polymers prolongs survival against experimental brain tumors and in human clinical trials. O6-benzylguanine (O6-BG), a potent inhibitor of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), has been shown to reduce nitrosourea resistance and, thus, enhance the efficacy of systemic BCNU therapy in a variety of tumor models. In this report, we demonstrate that O6-BG can potentiate the activity of BCNU delivered intracranially via polymers in rats challenged with a lethal brain tumor. Fischer 344 rats received a lethal intracranial challenge of 100,000 F98 glioma cells (F98 cells have significant AGT activity, 328 fmol/mg protein). Five days later, animals receiving an i.p. injection of O6-BG (50 mg/kg) 2 h prior to BCNU polymer (3.8% BCNU by weight) implantation had significantly improved survival (n = 7; median survival, 34 days) over animals receiving either O6-BG alone (n = 7; median survival, 22 days; P = 0.0002) or BCNU polymer alone (n = 8; median survival, 25 days; P = 0.0001). Median survival for the control group (n = 8) was 23.5 days. Moreover, there was no physical, behavioral, or pathological evidence of treatment-related toxicity. These findings suggest that O6-BG can potentiate the effects of interstitially delivered BCNU and, for tumors expressing significant AGT, may be necessary for the BCNU to provide a meaningful therapeutic benefit. Given the clinical use of BCNU polymers against malignant gliomas, concurrent treatment with O6-BG may provide an important addition to our therapeutic armamentarium.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Carmustina/farmacologia , Inibidores Enzimáticos/farmacologia , Glioma/tratamento farmacológico , Guanina/análogos & derivados , Guanina/farmacologia , Animais , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/enzimologia , Carmustina/administração & dosagem , Implantes de Medicamento , Sinergismo Farmacológico , Inibidores Enzimáticos/administração & dosagem , Glioma/enzimologia , Gliossarcoma/tratamento farmacológico , Gliossarcoma/enzimologia , Guanina/administração & dosagem , Humanos , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/enzimologia , O(6)-Metilguanina-DNA Metiltransferase/antagonistas & inibidores , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Ratos , Ratos Endogâmicos F344 , Técnicas Estereotáxicas , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Cancer ; 89(7): 1569-76, 2000 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-11013373

RESUMO

BACKGROUND: Brain stem tumors in children have been classified pathologically as low grade or high grade gliomas and descriptively as diffuse gliomas, intrinsic gliomas, midbrain tumors, tectal gliomas, pencil gliomas, dorsal exophytic brain stem tumors, pontine gliomas, focal medullary tumors, cervicomedullary tumors, focal gliomas, or cystic gliomas. METHODS: To search for a simplified and prognostic clinicopathologic scheme for brain stem tumors, the authors reviewed a consecutive cohort of patients younger than age 21 years with tumors diagnosed from 1980 through 1997. Pathology specimens and neuroimaging were classified by masked review. Statistical and survival analysis along with Cox proportional hazards regression was performed. RESULTS: Seventy-six patients were identified, with initial diagnostic magnetic resonance imaging available for 51 and pathology specimens for 48 patients. Twenty cases were classified histologically as pilocytic astrocytoma (PA), 14 as fibrillary astrocytoma (FA), and 14 as other tumors or indeterminate pathology. For all tumors, characteristics significantly associated with a worse survival rate were: symptom duration less than 6 months before diagnosis (P = 0.004); abducens palsy at presentation (P < 0.0001); pontine location (P = 0.0002); and engulfment of the basilar artery (P = 0.006). Pilocytic astrocytoma was associated with location outside the ventral pons (P = 0.001) and dorsal exophytic growth (P = 0.013); Fibrillary astrocytoma was associated with symptoms less than 6 months (P = 0. 006), abducens palsy (P < 0.001), and engulfment of the basilar artery (P = 0.002). Pilocytic astrocytoma showed 5-year overall survival (OS) of 95% (standard error [SE], 5%) compared with FA 1-year OS of 23% (SE, 11%;P < 0.0001). CONCLUSIONS: Brain stem tumors can be succinctly and better biologically classified as diffusely infiltrative brain stem gliomas-generally FA located in the ventral pons that present with abducens palsy, often engulf the basilar artery, and carry a grim prognosis-and focal brain stem gliomas-frequently PA arising outside the ventral pons, often with dorsal exophytic growth, a long clinical prodrome, and outstanding prognosis for survival. Our findings emphasize the individuality of PA as a distinct clinicopathologic entity with an exceptional prognosis.


Assuntos
Astrocitoma/patologia , Neoplasias do Tronco Encefálico/patologia , Adolescente , Adulto , Astrocitoma/classificação , Neoplasias do Tronco Encefálico/classificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
6.
J Urol ; 164(4): 1352-4, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10992414

RESUMO

PURPOSE: It was suggested that patients with a ventriculoperitoneal shunt are at risk for increased intracranial pressure during pneumoperitoneum. Shunt pressure monitoring and ventricular drainage to maintain normal pressure were recommended. We evaluated a series of patients with a ventriculoperitoneal shunt who underwent laparoscopic surgery to determine the clinical indications of increased intracranial pressure. MATERIALS AND METHODS: We reviewed the anesthesia records of 12 females and 6 males with a mean age of 13.2 years who had a ventriculoperitoneal shunt and underwent a total of 19 consecutive laparoscopic operations. Data on operative time, carbon dioxide level, pulse, blood pressure and any untoward anesthetic events were obtained. Postoperative records were assessed for evidence of neurological change. RESULTS: Mean operative time was 7 hours 13 minutes and estimated mean laparoscopic time was 2 hours 52 minutes. Average insufflation pressure was 16 mm. Hg (range 12 to 20). There was no evidence of a trend to combined bradycardia and hypertension or surgically related neurological deterioration and no untoward anesthetic events. Ventriculoperitoneal shunt revision was done in 3 cases, a rate consistent with that in the literature. Mean followup was 23.4 months (range 1 to 58). CONCLUSIONS: There was no evidence of clinically significant increased intracranial pressure in our series or in the literature in patients with a ventriculoperitoneal shunt who undergo laparoscopy. Invasive methods for shunt monitoring are not without risk. Routine anesthetic monitoring should remain the standard of care in the absence of clear evidence to the contrary.


Assuntos
Pressão Intracraniana , Laparoscopia , Derivação Ventriculoperitoneal , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
7.
Z Gastroenterol ; 38(5): 349-55, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10875143

RESUMO

BACKGROUND AND STUDY AIMS: Attempts to standardize Helicobacter pylori (Hp) diagnosis and therapy have led to the publication of guidelines by various national gastroenterological societies in Europe and the USA. However, little information is available either regarding the compliance of gastroenterologists and referring physicians with these guidelines, or regarding the patients' perspective. PATIENTS AND METHODS: A retrospective analysis was conducted of all outpatient upper gastrointestinal endoscopy reports for a one-month period in eleven different centers (two university hospitals and nine private practice gastroenterology offices) with a total of 24 gastroenterologists. Endoscopy reports from patients wit the indications of reflux, diarrhea, and tumors were excluded. Diagnoses and treatment recommendations given by gastroenterologists were recorded. Questionnaires concerning Hp diagnosis, treatment indications and performance, and follow-up were sent to referring physicians and patients. RESULTS: A total of 772 endoscopy reports were included in the study; analyzable questionnaires were returned by 287 referring physicians (47%) and by 265 patients (59%). Gastroenterologists recommended Hp eradication in all ulcers and in 29% of gastritis/nonulcer dyspepsia (NUD) cases. Referring physicians thought that 94% of ulcers should be treated by Hp eradication, which was also considered to be an absolute and relative indication in NUD by 15% and 53% of the referring physicians, respectively. Among the patients who replied, 52% had received Hp eradication regimens; ulcers were found in 22% of the total patient group. Check-up examinations after Hp therapy were considered necessary by 75% of the referring physicians, but only 22% of the responding patients actually underwent some form of check-up (upper gastrointestinal endoscopy in 91%). CONCLUSIONS: Gastroenterologists and (to a somewhat lesser extent) referring physician appear to be following the current guidelines for Hp treatment. As expected, two thirds of referring physicians consider NUD to be absolute or relative indication for Hp eradication. Check-up examinations are apparently being performed less frequently than recommended.


Assuntos
Gastroenterologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Guias de Prática Clínica como Assunto , Encaminhamento e Consulta , Gastropatias/diagnóstico , População Urbana , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Gastroenterologia/estatística & dados numéricos , Alemanha , Infecções por Helicobacter/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Gastropatias/tratamento farmacológico , Inquéritos e Questionários , População Urbana/estatística & dados numéricos
8.
Pediatr Neurosurg ; 32(1): 24-9, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10765135

RESUMO

The mesencephalic tectal glioma is a distinctive form of brain stem glioma with an unusually benign clinical course. Periaqueductal location, lack of contrast enhancement, and long periods of stability are classic features. The clinical management of these lesions, especially at the time of radiographic enlargement varies widely in the published literature. It is unclear whether these progressive lesions need to be treated. Accordingly, clinical and radiologic features of 7 patients were reviewed, with attention to the clinical course of the disease after radiologic enlargement. The age at diagnosis ranged from 3.3 to 16.6 years. Six of 7 had MRI tumor enlargement beginning 0.3-5.7 years after initial diagnosis. One of these 6 patients had radiographic progression coupled with a new clinical symptom which was treated with stereotactic radiation therapy. The remaining 5 patients with MRI progression and normal neurological exams were not treated and remain free of new neurologic deficits 1.8-6.9 years after the first radiographic tumor enlargement. The results suggest that pediatric tectal gliomas are a very low-grade lesion. Conservative management in the absence of new clinical symptoms could be argued, reserving radiotherapy or chemotherapy for clinical progression.


Assuntos
Astrocitoma/diagnóstico , Astrocitoma/fisiopatologia , Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/fisiopatologia , Mesencéfalo , Adolescente , Idade de Início , Astrocitoma/complicações , Neoplasias do Tronco Encefálico/complicações , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Análise de Sobrevida , Tomografia Computadorizada por Raios X
9.
J Neurosurg ; 87(1): 103-5, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9202274

RESUMO

This 9-year-old boy with a history of behavioral problems and worsening psychosis responded initially to treatment with haloperidol. However, a magnetic resonance image obtained as part of his psychiatric evaluation revealed an anterior third ventricle tumor and mild-to-moderate hydrocephalus. The resected tumor was found on pathological examination to be a choroid plexus papilloma. The patient had an uneventful postoperative course and remained free of psychosis or mood disorder at 1-year follow-up examination.


Assuntos
Ventrículos Cerebrais , Neoplasias do Plexo Corióideo/psicologia , Glioma/psicologia , Transtornos Psicóticos/etiologia , Criança , Neoplasias do Plexo Corióideo/diagnóstico , Neoplasias do Plexo Corióideo/cirurgia , Glioma/diagnóstico , Glioma/cirurgia , Humanos , Hidrocefalia/etiologia , Imageamento por Ressonância Magnética , Masculino
11.
Eur J Gastroenterol Hepatol ; 8(4): 343-9, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8781903

RESUMO

BACKGROUND: Helicobacter pylori infection is associated with gastric ulcer disease in about 75% of cases. OBJECTIVE: The aim of this study was to determine whether H. pylori eradication reduces gastric ulcer relapse rates. DESIGN: The study was randomized, controlled, multicentric and investigator blinded, and was conducted at three university hospitals, two teaching hospitals, and by six practising gastroenterologists. METHODS: During a period of 1 year 152 patients with gastric ulcers were randomly assigned to one of two treatment regimens: omeprazole 20 mg daily in the morning for 8 weeks (74 patients), or bismuth subsalicylate 600 mg three times daily for 8 weeks combined with 500 mg amoxicillin twice daily and 1000 mg tinidazole twice daily for the first 10 days (triple therapy) (78 patients). Follow-up examinations were performed 6, 12 and 18 months after treatment and whenever ulcer symptoms occurred. RESULTS: Of the 152 randomized patients five were excluded because of gastric cancer, 10 missed follow-up examinations and seven receiving triple therapy terminated treatment because of side effects. Of the remaining 130 patients, five of 69 (7.2%) in the omeprazole and six of 61 (9.8%) in the triple group were H. pylori negative. After 8 weeks' therapy, the gastric ulcer was healed in 85.9% (omeprazole) and in 81.8% triple) in H. pylori-positive patients, and in 80% (omeprazole) and 16.7% (triple) in H. pylori-negatives. H. pylori was eradicated in 8.1% of the patients who received omeprazole monotherapy and in 78.2% receiving triple therapy, and in 8.1% and 69.4% in an intention-to-treat analysis. The subsequent relapse rates during a follow-up period of 12 months were 50% in the omeprazole group and 4% in the triple group. Gastric ulcer relapse was observed in 49% of patients who were H. pylori positive and in 2% who were H. pylori negative after treatment. CONCLUSION: The data show that the presence of H. pylori is an important predictor of gastric ulcer relapse and that eradication of H. pylori may heal gastric ulcer disease.


Assuntos
Amoxicilina/uso terapêutico , Antiulcerosos/uso terapêutico , Bismuto/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Omeprazol/uso terapêutico , Compostos Organometálicos/uso terapêutico , Penicilinas/uso terapêutico , Salicilatos/uso terapêutico , Úlcera Gástrica/microbiologia , Tinidazol/uso terapêutico , Adulto , Idoso , Biópsia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Mucosa Gástrica/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Recidiva , Úlcera Gástrica/prevenção & controle , Fatores de Tempo
12.
Int J Cancer ; 62(5): 605-9, 1995 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-7665233

RESUMO

Camptothecin, a naturally occurring inhibitor of the DNA-replicating enzyme topoisomerase I, demonstrated promising anti-tumor activity in pre-clinical testing; however, because of unexpected toxicity and low anti-tumor effects in the initial clinical trials, further testing was discontinued. We hypothesized that local controlled delivery of camptothecin sodium would achieve effective concentrations in brain tumors without the observed systemic side effects, thereby allowing this novel drug to be used to treat patients with malignant gliomas. To test this hypothesis, we evaluated the sensitivity of rat glioma lines and established human glioma lines to camptothecin in vitro. We found that the LD90 for the established rat and human lines was 0.3 to 1.4 microM after a 1 hr exposure and decreased to less than 0.1 microM after continuous exposure for 7 days. We loaded camptothecin into a controlled-release polymer (ethylene-vinyl acetate co-polymer; EVAc) and showed by high-pressure liquid chromatography that controlled release occurred over at least 21 days. We then tested camptothecin against 9L gliosarcoma, implanted into the brain of Fischer 344 rats. Five days after tumor implantation, animals were treated with camptothecin delivered either systemically or locally by release from EVAc. Local controlled delivery by the polymer significantly extended survival: 59% of the treated animals were long-term survivors (> 120 days) compared to 0% of controls. Systemic administration did not extend survival compared to controls. We compared the efficacy of camptothecin delivered locally with a polymer to camptothecin injected directly into the tumor. Camptothecin increased survival only when delivered locally by polymer.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Camptotecina/administração & dosagem , Gliossarcoma/tratamento farmacológico , Inibidores da Topoisomerase I , Animais , Preparações de Ação Retardada , Injeções Intralesionais , Masculino , Polímeros , Ratos , Ratos Endogâmicos F344 , Análise de Sobrevida
13.
J Neurosurg ; 82(4): 635-40, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7897527

RESUMO

This study was designed to explore the question of whether minocycline, a semisynthetic tetracycline shown to inhibit tumor-induced angiogenesis, could control the growth of the rat intracranial 9L gliosarcoma. Minocycline was tested alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vivo. Treatment was started at the time of intracranial implantation of 9L gliosarcoma into male Fischer 344 rats, 5 days later, or after tumor resection. Minocycline was delivered locally with a controlled-release polymer or systemically by intraperitoneal injection. Systemic minocycline did not extend survival time. Local treatment with minocycline by a controlled-release polymer implanted at the time of tumor implantation extended median survival time by 530% (p < 0.001) compared to treatment with empty polymer. When treatment was begun 5 days after tumor implantation, minocycline delivered locally or systemically had no effect on survival. However, after tumor resection, treatment with locally delivered minocycline resulted in a 43% increase in median survival time (p < 0.002) compared to treatment with empty polymer. Treatment with a combination of minocycline delivered locally in a controlled-release polymer and systemic BCNU 5 days after tumor implantation resulted in a 93% extension of median survival time compared to BCNU alone (p < 0.002). In contrast, treatment with a combination of systemic minocycline and BCNU did not increase survival time compared to systemic BCNU alone. These results demonstrate that minocycline affects tumor growth when delivered locally and suggest that minocycline may be a clinically effective modulator of intracranial tumor growth when used in combination with a chemotherapeutic agent and surgical resection.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Gliossarcoma/tratamento farmacológico , Minociclina/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Carmustina/uso terapêutico , Terapia Combinada , Preparações de Ação Retardada , Gliossarcoma/mortalidade , Gliossarcoma/patologia , Gliossarcoma/cirurgia , Masculino , Transplante de Neoplasias , Ratos , Ratos Endogâmicos F344
14.
Ann N Y Acad Sci ; 732: 263-72, 1994 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-7526758

RESUMO

The exponential growth of solid tumors depends upon induction of new vessel growth, a process mediated by diffusable angiogenic factors produced by tumor cells. By inhibiting angiogenesis, it is now possible to modulate tumor growth and metastasis in laboratory animals. The first described inhibitor of angiogenesis was a protein derived from cartilage. Other important classes of antiangiogenic agents include angiostatic steroids combined with heparin or heparin derivatives, and the synthetic derivatives of fumigallin. As the mechanisms of action of these and other angiostatic agents are being elucidated, it is becoming apparent that many modulators of collagen metabolism inhibit angiogenesis and may offer clinically useful anticancer treatments. Minocycline and other tetracycline derivatives with anticollagenase properties have been shown to be potent inhibitors of angiogenesis. These agents, when administered with other standard cancer therapies, help prolong survival in laboratory animals with solid tumors. Further studies of these biologic response modifiers of tumor progression are under way in the hope that they will offer effective new treatments for cancer in humans.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Graxos Insaturados/uso terapêutico , Neoplasias/irrigação sanguínea , Neovascularização Patológica/prevenção & controle , Tetraciclinas/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Cartilagem/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Colágeno/antagonistas & inibidores , Cicloexanos , Humanos , Neoplasias/patologia , Neoplasias/terapia , Sesquiterpenos
15.
J Neurosurg ; 80(2): 283-90, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8283268

RESUMO

Sustained drug delivery by biodegradable polymer devices can increase the therapeutic efficacy of drugs by producing high local tissue concentrations over extended periods of time. It has been shown previously that implantation of controlled-release polymers impregnated with the nitrosourea carmustine (BCNU) extended the period of survival in rats bearing the 9L glioma compared with similar rats treated with systemically administered BCNU. This study evaluated the effect on the monkey brain of interstitial delivery of BCNU by the biodegradable polyanhydride copolymer poly[bis(p-carboxyphenoxy)propane]anhydride (PCPP) and sebacic acid (SA) in a 20:80 formulation (PCPP:SA). The effect of combining interstitial BCNU with radiation therapy was also evaluated. Eighteen male cynomolgus monkeys were randomly assigned to one of four groups: a control group; a group with implantation of empty polymer; a group with implantation of BCNU-loaded polymer; and a group with implantation of empty polymer in the right hemisphere and BCNU-loaded polymer in the left hemisphere, followed by irradiation. The effects were evaluated radiologically and histologically at specified times. A local reaction by the brain to the polymer was found, which was greater when the polymer contained BCNU. Local cerebral edema was observed radiographically on postoperative Day 14 and had resolved by Day 72. Histologically, a subacute cellular inflammatory response was seen on postoperative Day 16, which had changed to a chronic inflammatory response by Day 72. In the group with radiation therapy administered to the hemisphere bearing BCNU-loaded polymer, only localized pathological changes were detected. In all animals, brain distant from the polymer implantation site was normal. No neurological or general deleterious effects were seen in any of the animals. It is concluded that the interstitial delivery of BCNU by the polyanhydride polymer PCPP:SA is safe in the primate brain and that concomitant radiation therapy did not lead to any adverse effects. These experimental findings are important to an understanding of the clinical effects of PCPP:SA implants in treating brain diseases.


Assuntos
Neoplasias Encefálicas/terapia , Carmustina/administração & dosagem , Ácidos Decanoicos/administração & dosagem , Ácidos Dicarboxílicos , Implantes de Medicamento , Glioma/terapia , Polímeros/administração & dosagem , Animais , Edema Encefálico/induzido quimicamente , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Ácidos Decanoicos/efeitos adversos , Combinação de Medicamentos , Encefalite/induzido quimicamente , Glioma/diagnóstico , Glioma/tratamento farmacológico , Glioma/radioterapia , Macaca fascicularis , Masculino , Veículos Farmacêuticos , Polímeros/efeitos adversos
16.
Curr Opin Neurol Neurosurg ; 5(6): 808-12, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1467571

RESUMO

Glial tumors remain challenging problems for the clinician and researcher. Despite more aggressive therapy, the majority of these tumors recur locally. This review will provide an update on the new strategies being developed to treat gliomas. Advances in our understanding of the biology of glial tumors will provide new targets at which to direct therapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Glioma/tratamento farmacológico , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/efeitos da radiação , Neoplasias Encefálicas/patologia , Carmustina/administração & dosagem , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimioterapia Adjuvante , Terapia Combinada , Glioma/patologia , Glioma/radioterapia , Humanos
17.
Leber Magen Darm ; 17(1): 47-9, 1987 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-3561143

RESUMO

Yet within the last years adenomas were described in the duodenum, which are frequently found in the colon. The incidence of the lesions in the routine endoscopy of the upper GI-tract was estimated to be 0.23% for tubulo-villous and 0.86% for all adenoma. This case report describes an unusual flat tubulovillous adenoma with cellular atypia covering nearly the whole duodenal bulb which was endoscopically diagnosed.


Assuntos
Neoplasias Duodenais/patologia , Pólipos Intestinais/patologia , Idoso , Duodenoscopia , Epitélio/patologia , Humanos , Masculino
18.
Dtsch Med Wochenschr ; 112(2): 53-6, 1987 Jan 09.
Artigo em Alemão | MEDLINE | ID: mdl-3492353

RESUMO

With the spread of coloileoscopy, solitary colon ulcers are being diagnosed more frequently nowadays. Their clinical significance consists in the differential diagnosis of gastrointestinal bleeding and abdominal pain. Whereas they were formerly diagnosed surgically only in complications such as perforation or massive hemorrhage, they are mainly discovered coloscopically today and are characterized by a course which can be controlled conservatively. The characteristics appear to be essentially unchanged: sex ratio (about 1:1), age peak (in the fifth decade of life), age distribution (20-80 years), in occasional cases up to four ulcers, diameter (a few millimeters up to about three cm) and localization (Bauhin's valve 58%, ascending colon 13%, cecum and sigmoid colon 10%). The histological investigation of biopsies reveals mainly unspecific alterations. The pathogenesis is mostly unknown, but above all ischemia, drugs and inflammatory processes are suspected to be the cause.


Assuntos
Doenças do Colo/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Biópsia , Colo/patologia , Doenças do Colo/complicações , Doenças do Colo/patologia , Colonoscopia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/patologia , Humanos , Íleo/patologia , Úlcera/complicações , Úlcera/diagnóstico , Úlcera/patologia
19.
Endoscopy ; 17(5): 182-5, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3876926

RESUMO

In a prospective study, the occurrence of angiodysplasia was investigated by total colonoscopy in 1938 patients. Angiodysplasia was found in 59 patients, i.e. 3%. 12 out of 59 patients were admitted for acute or chronic peranal hemorrhage or anemia. 47 out of 59 patients were asymptomatic. The site of the lesions was as follows: cecum 37%, ascending colon 17%, transverse colon 7%, descending colon 7%, sigmoid colon 18% and rectum 14%. Histological confirmation was obtained in 15 out of 37 biopsies. The endoscopic appearance was variable, most of the vascular dilatations being smaller than 5 mm (n = 47), with a homogeneous (n = 35) or inhomogeneous (n = 24) structure and a regular (n = 34) or irregular (n = 25) border. The lesions were single (n = 34) as well as multiple (n = 25), they were usually flat (n = 54), seldom slightly prominent (n = 5). Concomitant pathological findings in the bowel were diagnosed in 33 out of 59 patients: diverticula in 32%, adenomas in 24% and carcinomas in 8.5%. Right hemicolectomy for bleeding angiodysplasia is indicated only if endoscopic therapy has failed and other colorectal sources of bleeding, and especially angiodysplasia in the left colon and rectum have been excluded by endoscopy or angiography.


Assuntos
Vasos Sanguíneos/patologia , Colo/irrigação sanguínea , Reto/irrigação sanguínea , Adolescente , Adulto , Idoso , Colectomia , Colo/cirurgia , Colonoscopia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reto/cirurgia , Procedimentos Cirúrgicos Vasculares
20.
Dtsch Med Wochenschr ; 109(41): 1549-52, 1984 Oct 12.
Artigo em Alemão | MEDLINE | ID: mdl-6479056

RESUMO

In a prospective study, angiodysplasias were looked for in 824 patients during total coloscopy. Such angiodysplasias were discovered in 30 patients (3.6%). The endoscopic morphology varied, most of the angiodysplasias being smaller than 5 mm (23 patients), with a homogeneous structure in 19, spider-like extensions in only 11 patients. In 13 patients there were multiple angiodysplasias. Two or more segments of the colon were affected in 7 patients. Site of lesions was as follows: in 19 patients in the caecum and/or ascending colon; descending colon, sigmoid and/or rectum in 16; transverse colon in 3 patients. Histological confirmation was obtained in 9 of 20 patients who had a biopsy. Right-sided colectomy for bleeding angiodysplasias (resulting in anaemia) is indicated only if endoscopic coagulation has failed and other colorectal sources of bleeding (neoplasm, diverticulum or polyp) and especially angiodysplasias in the left colon or rectum have been excluded by endoscopy or angiography.


Assuntos
Vasos Sanguíneos/anormalidades , Colo/irrigação sanguínea , Reto/irrigação sanguínea , Adolescente , Adulto , Idoso , Ceco/irrigação sanguínea , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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