Audiological monitoring of cisplatin exposed patients

Cisplatin is an antineoplasic drug, which has ototoxicity as a side effect. The goals of this paper were to evaluate the audiological behavior in osteosarcoma patients treated with cisplatin and to verify which evaluation method is the best for early detection of drug induced hearing loss. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: 13 patients, that received four cisplatin cycles of 120 mg/m²/cycle divided in two days (60 mg/m²/day), were evaluated prior to start of chemotherapy, prior to each scheduled course and at the end of treatment. It was performed the pure tone audiometry (250 to 18000 Hz) and the transitory and distortion product otoacoustic emission (TOAE and DPOAE). RESULTS: In the mean values, it was observed hearing loss, after 480 mg/m² cumulative cisplatin dosage, beginning at 8 kHz. At the individual values, it was observed that 15,3% had mild to moderate hearing loss beginning at 3kHz, 15,3% beginning at 4 kHz, 15,3% beginning at 6 kHz and 15,3% beginning at 8 kHz. TOAE did not show changes before the audiometry. DPOAE showed smaller amplitude after the cycles of cisplatin, but this change happened together with the audiometry - not prior. CONCLUSION: The high frequency audiometry was more efficient to detect early ototoxicity. TOAE and DPOAE can be used as complement tests. All cisplatin exposed patients showed high frequency hearing loss, 30,6% showed hearing loss in important frequencies (3 and 4 kHz) for speech comprehension.A cisplatina é um agente quimioterápico que apresenta dentre seus efeitos colaterais a ototoxicidade. Este estudo teve como objetivos avaliar a audição de pacientes portadores de osteossarcoma expostos à cisplatina e verificar qual o método de investigação mais adequado para identificar precocemente as alterações auditivas induzidas por drogas ototóxicas. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: 13 indivíduos portadores de osteossarcoma que receberam quatro ciclos de cisplatina de 120 mg/m²/ciclo, fracionados em dois dias de aplicação (60 mg/m²/dia), foram submetidos à avaliação audiológica - audiometria tonal liminar (250 a 18000 Hz) e emissões otoacústicas transitórias (EOAT) e por produto de distorção (EOAPD) - antes do início do tratamento e após cada ciclo de cisplatina. RESULTADOS: Observou-se, nos valores médios, perda auditiva após a dose cumulativa de 480 mg/m² a partir de 8 kHz. Quanto aos valores individuais, 15,3% dos pacientes apresentaram perda auditiva de grau leve a moderado a partir de 3 kHz, 15,3% a partir de 4 kHz, 15,3% a partir de 6 kHz e 15,3% a partir de 8 kHz. Não foi observada redução na amplitude das EOAT precocemente à alteração dos limiares nas altas freqüências. Houve redução da amplitude das EOAPD concomitante ao aumento do limiar de audibilidade. CONCLUSÃO: A audiometria de altas freqüências é mais efetiva na detecção precoce da perda auditiva induzida por cisplatina. As EOAT e EOAPD podem ser usadas como complemento à avaliação audiométrica. Todos os pacientes expostos à cisplatina têm perda auditiva nas altas freqüências, e destes, 30,6% tem perda auditiva a partir das freqüências de 3 e 4 kHz consideradas importantes para a compreensão da fala.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Distúrbios da Comunicação HumanaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Instituto de Oncologia PediátricaUNIFESP, EPM, Depto. de Otorrinolaringologia e Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPM, Instituto de Oncologia PediátricaSciEL

Autologous stem cell transplantation for the treatment of pediatric solid tumors in Brazil

Hosp Clin, Pediat Oncol Unit, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, GRAACC, Pediat Oncol Inst, São Paulo, BrazilHosp AC Camargo Fund Antonio Prudente, Dept Pediat, São Paulo, BrazilSanta Casa de São Paulo, Pediat Hematol & Bone Marrow Transplantat Unit, São Paulo, BrazilUniversidade Federal de São Paulo, GRAACC, Pediat Oncol Inst, São Paulo, BrazilWeb of Scienc

Osteossarcoma - quimioterapia intra-arterial e fatores prognósticos

BV UNIFESP: Teses e dissertaçõe

Results of the brazilian osteosarcoma: prognostic factors and impact on survival

Proposta: avaliar o impacto da quimioterapia e cirurgia na evolução dos pacientes com osteossarcoma (OS) de extremidades e identificar fatores prognósticos. Pacientes e métodos: um total de 225 pacientes portadores de OS de extremidades metastáticos e não metastáticos que foram registrados em 2 estudos consecutivos planejados e implementados pelo Grupo Brasileiro para Tratamento de Osteossarcoma (GBTO) foram avaliados. Os estudos foram conduzidos entre outubro de 1991 e julho de 1999. Resultados: a sobrevida global e a sobrevida livre de eventos a 5 anos foi 50,1 por cento e 39 por cento respectivamente e para os não metastáticos 60,5 por cento e 45,5 por cento. A análise multivariada documentou as seguintes variáveis que estão associadas com uma sobrevida mais curta, metástases ao diagnóstico (RP = 3,9, pBV UNIFESP: Teses e dissertaçõe

Use of plasma exchange in methotrexate removal in a patient with osteosarcoma and acute renal insufficiency

Acute renal failure induced by methotrexate (MTX) can be lethal because renal excretion of the drug can be delayed. Pre-existing renal impairment, abstention, or underdosage of folinic acid and inadequate hydration facilitate toxicity. the prolonged high serum levels of MTX result in severe mucositis and pancytopenia, but strategies useful to accelerate MTX removal have not been universally accepted. We report a case of a 13-year-old girl with osteosarcoma who was treated with high-dose MTX because of thoracic tumor recurrence. No side effects were observed after 2 cycles of high-dose MTX; however, after the third cycle there was a delayed MTX elimination followed by clinical toxicity. Forty hours post-MTX infusion the serum level of MTX was 5.39 x 10(-4) mol/L. Treatment was based on symptomatic measures, such as maintenance of an abundant and alkaline diuresis and parenteral administration of folinic acid. Concomitantly, plasma exchange was employed to accelerate MTX removal and reduce its toxicity. After 24 days, she was discharged from the hospital, and her renal function recovered gradually. (C) 2003 Wiley-Liss, Inc.Universidade Federal de São Paulo, Hematol & Transfus Med Serv, Escola Paulista Med, BR-04024002 São Paulo, BrazilGRAAC, IOP, Pediat Oncol Inst, São Paulo, BrazilUniversidade Federal de São Paulo, Hematol & Transfus Med Serv, Escola Paulista Med, BR-04024002 São Paulo, BrazilWeb of Scienc

Quantitative analysis of circulating CD34+cells as a guide for peripheral blood stem cell(PBSC) collections by leukapheresis

UNIFESP, GRAACC, Pediat Oncol Inst, Sao Paulo, BrazilSirio Libanes HOsp, Sao Paulo, BrazilSanta Paula Hosp, Sao Paulo, BrazilUNIFESP, GRAACC, Pediat Oncol Inst, Sao Paulo, BrazilWeb of Scienc

Vancomycin serum concentrations in pediatric oncologic/hematologic intensive care patients

BACKGROUND: Usual treatment regimens with vancomycin often fail to provide adequate serum levels in patients with severe infections. METHODS: Retrospective analysis of vancomycin trough serum measurements. The following parameters were calculated by Bayesian analysis: vancomycin clearance, distribution volume, and peak estimated concentrations. The area under the concentration curve (AUC) (total daily dose/24 h clearance of vancomycin) was used to determine the effectiveness of treatment through the ratio of AUC/minimum inhibitory concentration (MIC) above 400, using MIC = 1 µg/mL, based on isolates of Staphylococci in cultures. RESULTS: Sixty-one vancomycin trough measurements were analyzed in 31 patients. AUC/MIC > 400 was obtained in 34 out of 61 dosages (55.7%), but the mean vancomycin dose required to achieve these levels was 81 mg/kg/day. In cases where the usual doses were administered (40-60 mg/kg/day), AUC/MIC > 400 was obtained in nine out of 18 dosages (50%), in 13 patients. Trough serum concentrations above 15 mg/L presented a positive predictive value of 100% and a negative predictive value of 71% for AUC/MIC > 400. CONCLUSION: Higher than usual vancomycin doses may be required to treat staphylococcal infections in children with oncologic/hematologic diseases. Since the best known predictor of efficacy is the AUC/MIC ratio, serum trough concentrations must be analyzed in conjunction with MICs of prevalent Staphylococci and pharmacokinetic tools such as Bayesian analysis

P-glycoprotein, erb2 and p53 expression in high-grade human osteosarcomas and their correlation with anaplasia

BACKGROUND: Osteosarcomas (OS), the most frequent primary malignant bone tumors, have aggressive local behavior and high rate of metastatization. The events that allow tumor growth and dissemination are still controversial. The studies about carcinogenesis and tumor progression in this neoplasia, which are based on c-erb-B2, P-glycoprotein (P-gp) and p53 immunoexpression, show conflicting results as to the real prognostic value and its correlations with histological parameters. Anaplasia in childhood neoplasias is a histological parameter of tumor aggressiveness and chemoresistance. In primary or metastatic OS, its meaning remains controversial. On the other hand, in other human neoplasias, c-erb-B2 expression is associated with p53, nuclear grade and other aggressiveness parameters. OBJECTIVE: The aim of the present study was to evaluate p53, c-erb-B2 and P-gp immunoexpression in OS, correlating the parameters with the presence of anaplasia. METHODS: This study included 96 pre-chemotherapy biopsies in patients with high-grade OS diagnosed between 1991 and 2000. The immunohistochemical evaluation of p53 and c-erb-B2 was carried out with the streptavidin-biotin-peroxidase technique. Cases were considered positive when there was immunoexpression in 10% or more neoplastic cells. Only membrane staining (for c-erb-B2 and P-gp), and nuclear staining (for p53) were considered positive. Anaplasia was defined as Wilms' tumor, and considered present or absent. RESULTS: Anaplasia was present in 29 out of 82 cases (35.36%); p53 immunoexpression was detected in 25 out of 60 cases (36.23%); P-gp, in 30 out of 73 cases (41.1%); and c-erb-B2, in 22 out of 55 cases (40%). The results demonstrated an association between c-erb-B2 and p53 immunoexpression (p = 0.042), p53 and parameter of anaplasia (p = 0.015), anaplasia and P-gp (p = 0.034). CONCLUSIONS: The p53, c-erb-B2 and P-gp immunoexpression is relatively frequent in high-grade, metastatic and non-metastatic OS. The results reinforce the hypotheses that in the presence of anaplasia adverse events may occur simultaneously in this neoplasm. Anaplasia may become a histological marker for P-gp and/or p53 status in some high-grade OS, and it may indicate chemoresistance. There was no positive association between p53 and P-gp.INTRODUÇÃO: Osteossarcoma (OS), o mais freqüente tumor primário maligno do osso, tem comportamento local agressivo e alto índice de disseminação sistêmica. Os eventos que permitem o crescimento e a disseminação tumoral ainda permanecem controversos. Os estudos sobre a carcinogênese e a progressão dessa neoplasia, com base na imunoexpressão de c-erb-B2, P-glicoproteína (P-gp) e p53, apresentam resultados conflitantes acerca do real valor prognóstico e suas correlações com parâmetros histológicos. A anaplasia, em neoplasias na infância, constitui parâmetro histológico de agressividade tumoral e quimiorresistência. Nos OS primários ou metastáticos, seu significado permanece controverso. Por outro lado, em outras neoplasias humanas, a expressão do c-erb-B2 relaciona-se com p53, grau nuclear e outros parâmetros de agressividade. OBJETIVO: Avaliar a imunoexpressão de p53, c-erb-B2 e P-gp em OS, correlacionando os parâmetros entre si e com a presença de anaplasia. MÉTODO: O estudo incluiu 96 biópsias pré-quimioterapia de pacientes com OS de alto grau, diagnosticados entre 1991 e 2000. A pesquisa imuno-histoquímica de p53, P-gp e c-erb-B2 foi feita pela técnica da estreptoavidina-biotina-peroxidase. Foram considerados positivos os casos onde havia imunoexpressão em 10% ou mais das células neoplásicas. Somente colorações membranosa (para cerb-B2 e P-gp) e nuclear (para p53) foram consideradas positivas. Anaplasia foi definida como no tumor de Wilms, sendo considerada presente ou ausente. RESULTADOS: Anaplasia pôde ser avaliada em 82/96 casos, estando presente em 29 (35,36%). Imunoexpressão de p53 foi detectada em 25 dos 60 casos (36,23%); de P-gp, em 30 dos 73 casos (41,1%); e de c-erb-B2, em 22 dos 55 casos (40%). Os resultados demonstraram associação entre as imunoexpressões de c-erb-B2 e p53 (p = 0,042), p53 e o parâmetro anaplasia (p = 0,015), anaplasia e Pg (p = 0.034) CONCLUSÕES: A imunoexpressão de p53, c-erb-B2 e P-gp é evento relativamente freqüente em OS de alto grau, metastáticos e não-metastáticos ao diagnóstico. Os resultados reforçam a hipótese de que nessa neoplasia na presença de anaplasia ocorrem simultaneamente eventos adversos, que atuam conjuntamente. A anaplasia constitui marcador histológico do status da P-gp e/ou do p53 em parte dos OS de alto grau e nestes talvez seja indicativa de quimiorresistência. Não houve associação positiva entre p53 e P-gp

Low-level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients

Objective: A pilot clinical study was conducted to evaluate the efficacy and feasibility of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy (CT)-induced oral mucositis (OM) in young patients.Background Data: Besides compromising the patient's nutrition and well-being, oral mucositis represents a portal of entry into the body for microorganisms present in the mouth, which may lead to sepsis if there is hematological involvement. Oncologic treatment tolerance decreases and systemic complications may arise that interfere with the success of cancer treatment. LLLT appears to be an interesting alternative to other approaches to treating OM, due to its trophic, anti-inflammatory, and analgesic properties.Materials and Methods: Patients undergoing chemotherapy (22 cycles) without mucositis were randomized into a group receiving prophylactic laser-irradiation (group 1), and a group receiving placebo light treatment (group 2). Patients who had already presented with mucositis were placed in a group receiving irradiation for therapeutic purposes (group 3, with 10 cycles of CT). Serum granulocyte levels were taken and compared to the progression of mucositis.Results: in group 1, most patients (73%) presented with mucositis of grade 0 (p = 0.03 when compared with the placebo group), and 18% presented with grade 1. in group 2, 27% had no OM and did not require therapy. in group 3, the patients had marked pain relief (as assessed by a visual analogue scale), and a decrease in the severity of OM, even when they had severe granulocytopenia.Conclusion: the ease of use of LLLT, high patient acceptance, and the positive results achieved, make this therapy feasible for the prevention and treatment of OM in young patients.Universidade Federal de São Paulo, Inst IOP GRAACC, São Paulo, BrazilNUPEN, Res & Educ Ctr Photo Therapy Hlth Sci, São Paulo, BrazilUniversidade Federal de São Paulo, GRAACC, Inst Pediat, IOP, São Paulo, BrazilUniversidade Federal de São Paulo, Inst IOP GRAACC, São Paulo, BrazilUniversidade Federal de São Paulo, GRAACC, Inst Pediat, IOP, São Paulo, BrazilWeb of Scienc

Protocol for a tumor tissue bank

A Tumor Bank with systematic organization of data allows for the carrying out of cancer research with sound and scientific conclusions. The need thus arises for a specific protocol whose main advantage would be that of adding qualified donor information to tumor samples used in research. The purpose of this study was to develop a simple, reliable, and replicable procedures protocol to acquire and store samples of musculoskeletal tumors. The basis for the planning of this protocol comprises the information gathered in the literature relating to tumor tissue banks from 1969 to 2005. The paper describes the capture, storage, and donor background. The tumor bank with an efficient protocol allows to store both healthy and neoplastic tissue, and to record information relating to patients with neoplastic lesions. Furthermore, it enables supplying tissue samples in ideal research conditions.Um banco de tumores com organização sistematizada das informações permite a elaboração de pesquisas em câncer com conclusões sólidas e científicas. Assim, há a necessidade de um protocolo específico, cuja principal vantagem seria a de agregar informações qualificadas sobre o doador às amostras tumorais utilizadas para a pesquisa. O objetivo deste trabalho foi desenvolver um protocolo de procedimentos simples, confiável e reproduzível, para adquirir e armazenar amostras de tumores do sistema músculo-esquelético. O planejamento deste protocolo tem como base os dados da literatura relacionada a bancos de tecidos neoplásicos, no período de 1969 a 2005. Descreve a captação, armazenamento das amostras e o histórico do doador. O banco de tumores com um protocolo eficiente permite armazenar amostras de tecido normal e neoplásico, além de registrar dados referentes a pacientes com lesões neoplásicas. Além disso, possibilita o fornecimento, aos pesquisadores em câncer, de amostras de tecido em condições ideais para a pesquisa