Submitted by Maike Costa (maiksebas@gmail.com) on 2016-03-10T13:51:10Z No. of bitstreams: 1 arquivo total.pdf: 3557745 bytes, checksum: 98f718f8cb5615bad9f455c64f590693 (MD5) / Made available in DSpace on 2016-03-10T13:51:10Z (GMT). No. of bitstreams: 1 arquivo total.pdf: 3557745 bytes, checksum: 98f718f8cb5615bad9f455c64f590693 (MD5) Previous issue date: 2015-12-03 / Severe oral mucositis constitutes a condition that often affects children and adolescents undergoing chemotherapy. This study aimed to construct statistical models for onset of severe oral mucositis in cancer pediatric patients from own variables of the patient and related to chemotherapy treatment regimen in order to guide the oral health decision making in disease prevention the oral mucosa during chemotherapy. This is a longitudinal, prospective and observational study, where oral mucositis was monitored during chemotherapy in 105 children and adolescents assisted in Napoleão Laureano Hospital between april 2013 and july 2015. It was evaluated by multiple regression binary logistic the association of different variables to the occurrence of severe oral mucositis (MOG) in accordance with the identification indicated by Oral Assessment Guide (OAG) modified in 10 different evaluation periods from the start of chemotherapy. Analyses were performed by the backward method, the R (3.1.3) software, adopting a 5% significance level. Over the 10 consecutive weeks of evaluation, it was observed that: in the 1st week of chemotherapy, being female (OR = 5.84), black skin color (OR=14.85) as well as be taking chemotherapy the class of antimetabolites (OR = 3.52), depending on the increase of time after drug administration (OR=1.13), were risk factors for the occurrence of MOG, whereas in the 2nd week, risk was associated with the fact that the child / adolescent be black skin color (OR=3.53). In the 3rd week, be blood group type B (OR=4.19) was a risk factor, while the increase in blood creatinine, a protective factor (OR = 0.67).In the 4th week, time since last chemotherapy was a protective factor (OR=0.92), as well as 8 weeks (OR=0.93). On the 5th week of chemotherapy, the use of chemotherapeutic agents from the class of natural products (OR=0.19) was considered a protective factor, while the increase in the number of platelets (OR=1.04) was considered a risk factor. In the 6th week, so chemotherapy Antimetabolites type (OR=5.80), and the increase of leukocytes (OR=1.06) and blood creatinine (OR=1.60) were considered risk factors, as well as also the increase of creatinine 7 review period (OR=1.46). For the first 8 weeks of chemotherapy pediatric cancer patients was possible to build predictive models for the occurrence of severe oral mucositis from the patient's own variables and related to chemotherapy treatment regimen. It was concluded that own patient factors such as being female, color black skin, blood group type B and increase in blood creatinine level were associated with increased odds of patients presenting to MOG. As for the treatment, the more likely development of MOG were related to chemotherapy class of Antimetabolites. / A mucosite oral severa ou grave se constitui em uma condição que, frequentemente, acomete crianças e adolescentes em tratamento quimioterápico. Esse estudo objetivou a construção de modelos estatísticos para o surgimento da mucosite oral grave em pacientes pediátricos oncológicos, a partir de variáveis próprias do paciente e relacionadas ao regime de tratamento quimioterápico, de forma a orientar a tomada de decisão em saúde bucal na prevenção de agravos à mucosa oral durante a quimioterapia. Trata-se de um estudo longitudinal, prospectivo, observacional, onde a mucosite oral foi monitorada durante o tratamento quimioterápico de 105 crianças e adolescentes assistidos no Hospital Napoleão Laureano entre abril de 2013 e julho de 2015. Avaliou-se, mediante regressão logística binária múltipla, a associação de diferentes variáveis à ocorrência de mucosite oral grave (MOG), de acordo com a identificação indicada pelo Oral Assessment Guide (OAG) modificado, em 10 diferentes períodos de avaliação, a partir do início da quimioterapia. As análises foram realizadas pelo método de backward, no software R (3.1.3), adotando-se um nível de significância de 5%. Ao longo das 10 semanas consecutivas de avaliação, observou-se que: na 1ª semana de quimioterapia, ser do sexo feminino (OR=5,84), de cor de pele negra (OR=14,85), bem como estar tomando quimioterápicos da classe dos Antimetabólitos (OR=3,52), a depender do aumento do tempo após a administração dos fármacos (OR=1,13), constituíram fatores de risco para a ocorrência de MOG, ao passo que, na 2ª semana, o risco esteve associado ao fato de a criança/adolescente ser de cor de pele negra (OR=3,53). Na 3ª semana, ser do grupo sanguíneo tipo B (OR=4,19) constituiu um fator de risco, enquanto que o aumento da creatinina no sangue, um fator de proteção (OR=0,67). Na 4ª semana, tempo desde a última quimioterapia constituiu um fator de proteção (OR=0,92), assim como na 8ª semana (OR=0,93). Na 5ª semana de quimioterapia, o uso de quimioterápicos da classe dos Produtos naturais (OR=0,19) foi considerado um fator de proteção, enquanto que o aumento no número de plaquetas (OR=1,04) foi considerado um fator de risco. Na 6ª semana, tanto os quimioterápicos do tipo Antimetabólitos (OR=5,80), quanto o aumento de leucócitos (OR=1,06) e da creatinina no sangue (OR=1,60) foram considerados fatores de risco, assim como também o aumento da creatinina no 7º período de avaliação (OR=1,46). Para as 8 primeiras semanas de quimioterapia de pacientes pediátricos oncológicos foi possível a construção de modelos preditivos para a ocorrência de mucosite oral grave a partir de variáveis próprias do paciente e relacionadas ao regime de tratamento quimioterápico. Concluiu-se que, fatores próprios do paciente, como ser do sexo feminino, de cor de pele negra, do grupo sanguíneo tipo B e com aumento no nível sanguíneo de creatinina estiveram relacionados à maior chance de os pacientes apresentarem a MOG. Já quanto ao tratamento, as maiores chances de desenvolvimento do MOG estiveram relacionadas ao uso de quimioterápicos da classe dos Antimetabólitos.

OBJETIVO: O estudo foi conduzido para determinar o quanto o Laser de Baixa Intensidade (LBI), em adição com um protocolo de higiene oral, pode reduzir a duração da mucosite oral (MO) induzida por quimioterapia e/ou radioterapia. PACIENTES E MÉTODOS: Um ensaio clínico randomizado placebo controlado foi desenvolvido utilizando o LBI ou controle (sham-treatment) em 2 centros de tratamento do câncer - a Unidade de Oncologia Pediátrica do Hospital de Clínicas de Porto Alegre (HCPA) e a Unidade de Oncologia do Hospital São Vicente de Paulo de Passo Fundo (HSVP). Pacientes em tratamento quimioterápico e/ou radioterápico entre os meses de outubro de 2005 e maio de 2006 foram elegíveis tão logo desenvolvessem MO. Os pacientes receberam intervenção por 5 dias. O grupo LBI foi tratado com GaAlAs, comprimento de onda: 830nm (infravermelho), potência: 100mW, dose: 4J/cm2 e o grupo controle com o sham-treatment. O grau de MO foi avaliado clinicamente através da escala da World Health Organization - National Cancer Institute - Common Toxicity Criteria (WHO-NCI-CTC). RESULTADOS: Os resultados foram expostos de acordo com cada centro envolvido. UOP - HCPA: vinte e um pacientes desenvolveram MO no grupo pediátrico e foram submetidos à análise; 18 (86%) pacientes possuíam diagnóstico de leucemia ou linfoma e 3 (14%) de tumores sólidos. A média de idade foi de 8,2 (± 3,1) anos. Nove pacientes foram randomizados no grupo laser e doze no grupo sham-treatment. A MO foi mensurada quando os sintomas foram manifestados em cada paciente, sendo a duração e o grau de MO graduados diariamente até a completa cicatrização das lesões. No dia 7 após o diagnóstico da MO, 11% dos pacientes permaneciam com lesões no grupo laser e 75% no grupo sham-treatment (P=0,029). No grupo tratado com laser a média de duração da MO foi de 5,8 ± 2 dias e no grupo sham-treatment 8,9± 2,4 dias (P=0,004). UO-HSVP: trinta e quatro pacientes desenvolveram MO no grupo dos adultos e foram submetidos à análise; 22 (65%) dos pacientes possuíam diagnóstico de tumores sólidos e 12 (35%) de leucemia ou linfoma. A média de idade foi de 41 (± 20 anos). 18 pacientes foram randomizados no grupo laser e 16 no grupo sham-treatment. A MO foi mensurada quando os sintomas foram manifestados em cada paciente, sendo a duração e o grau de MO graduados diariamente até a completa cicatrização das lesões. No dia 7 após o diagnóstico da MO, 32% dos pacientes permaneciam com lesões no grupo laser e 94% no grupo sham-treatment (P=0,001). No grupo tratado com laser a média de duração da MO foi de 6,8 ± 2,2 dias e no grupo sham-treatment 11,5± 3,5 dias (P<0,001). CONCLUSÃO: Este estudo demonstrou evidências que a laserterapia em adição com um protocolo de higiene oral pode reduzir a duração da MO induzida por quimioterapia e radioterapia. Em decorrência destes achados, esta modalidade de tratamento pode ser difundida e aplicada no intuito de promover qualidade de vida aos pacientes durante os tratamentos quimioterápicos e radioterápicos. / BACKGROUND: The study was conducted to determine whether Low level laser therapy (LLLT) in addition to oral care can reduce the duration of chemotherapy and/or radiotherapy induced oral mucositis (OM). PROCEDURE: A placebo-controlled randomized study was carried out using LLLT or placebo (sham-treatment) in two centers of cancer treatment - Pediatric Oncology Unit (POU) of HCPA and Oncology Unit (OU) of HSVP. Patients treated with chemo and/or radiotherapy between Oct, 2005 and May, 2006 were eligible as soon as they developed OM. Patients received intervention for 5 days. The LLLT group was treated with Laser GaAlAs, wavelenght: 830nm (infrared), power: 100mW, dose: 4J/cm2 and the control group with sham-treatment. The grade of OM was clinically assessed by the WHONCI- CTC scale. RESULTS: Results were showed according with the center. POU-HCPA: Twenty-one patients developed OM in the children group and were submitted for analysis; 18 (86%) patients had a diagnosis of leukemia or lymphoma and 3(14%) had solid tumors. The mean age was 8.2 (± 3.1) years. Nine patients were randomized in the laser group and twelve patients in the placebo-control group. OM was measured when symptoms were manifest and the duration of OM and the grade of lesions found in each patient were recorded at the start of laser therapy and daily until complete healing of the lesions. On day 7 after OM diagnosis, 11% of patients presented lesions in laser group and 75% of patients in the sham-treatment group (P=0.029). In the group treated with laser the mean of OM duration was 5.8 ± 2 days and in the sham-treatment group 8.9± 2.4 days (P=0.004). OU-HSVP: Thirty-four patients developed OM and were submitted for analysis; 22 patients (65%) had diagnosis of solid tumors and 12 (35%) leukemia or lymphoma. The mean age was 41 (± 20) years. Eighteen patients were randomized in the laser group and 16 patients in the placebo-control group. Once OM was diagnosed, the patients had daily OM grading assessments before laser application, and thereafter until complete healing process of lesions. On day 7 after OM diagnoses , 32% of patients presented lesions in laser group and 94% of patients in the sham-treatment group (P=0.001). In the laser group the mean of OM duration was 6.8 ± 2.2 days and in the sham-treatment group was 11.5 ± 3.5 days (P<0.001). CONCLUSION: Our study has shown evidence that laser therapy in addition to oral care can decrease the duration of chemotherapy induced OM. It should encourage clinicians to use this technique to improve quality of life of cancer patients during the oncology treatment.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Oral mucositis (OM) induced by antineoplasic drugs is an important, dose-limiting, and costly side effect of cancer therapy. Calotropis procera is a plant plant constitutively produces abundant latex that is reported to possess anti-inflammatory, bacteriolytic, insecticidal, analgesic properties. The present work aimed to describe the effect of laticifer proteins of Calotropis procera (LP) in the expression of pro-inflammatory cytokines and inducible enzymes, such as, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the model of OM in Hamsters. OM was induced by two intraperitoneal (i.p.) administrations of 5-Fluorouracil (5-FU) on the 1st and 2nd days (60 and 40 mg/kg, respectively) in hamsters (n=5). LP (0,25; 1; 5 E 25 mg / kg) was injected i.p. 24h before and 24h after mechanical trauma of the cheek pouches. Control group received only saline. On the 10th day, the animals were sacrificed and tissues from the cheek pouches were harvested. Macroscopical and histopathological (inflammatory cell infiltration, edema, hemorrhage and the formation of ulcerations and abscess) analysis as well as immunohistochemistry for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 was performed in the cheek pouch tissue. Kruskal Wallis/Dunn was used as statistical tests. P<0.05 was accepted. Ethics Committee 036/10. The LP significantly inhibited macroscopical and histopathological parameters when compared to control group with maximum effect in macroscopic scores reaching 75% and 66% of maximum effect at the histopathological evaluation. The MPO activity was also significantly inhibited by LP in 91% at the same dose (p<0,001) and also inhibited the lost weight of 5- FU induced-oral mucositis. The cheek pouches of hamsters submitted to OM showed marked immunostaining for TNF-&#61537;, IL-1&#946;, iNOS and COX-2 on inflamed conjunctive (Cj) and epithelial (Ep) tissue compared with the cheek pouches of the normal control group. LP caused considerable reduction in the immunostaining for TNF-&#61537; (62%,Cj; 70%,Ep), IL-1&#946; (87%,Cj; 80%,Ep), iNOS (82%Cj; 52%Ep) and COX-2 (70%,Cj; 100%,Ep) in the check pouches tissue when compared with the group of animals subjected to experimental mucositis that received saline instead of LP. These findings show anti-inflammatory effects of LP in 5-FU-induced OM. The protective effect could be supported by the reduction of the expression of pro-inflammatory cytokines, such as TNF-&#61537; and IL-1&#946; and the enzymes iNOS and COX-2. The protective mechanism appears to involve inhibition of the expression of iNOS, COX-2, TNF-&#61537;, and IL- 1&#946;. / Mucosite oral (MO) induzida por drogas antineoplÃsicas à um importante fator limitante da dose e efeitos colaterais da terapia do cÃncer. Calotropis procera à uma planta que produz lÃtex constitutivamente abundante que à relatado possuir propriedades antiinflamatÃrias, bactericidas, inseticidas, analgÃsicas. O presente trabalho teve como objetivo descrever o efeito das proteÃnas do lÃtex da Calotropis procera (LP) na expressÃo de citocinas prÃ-inflamatÃrias (TNF-&#945; e IL-1&#61538;) e enzimas induzÃveis, como, ciclooxigenase-2 (COX-2) e Ãxido nÃtrico sintase induzÃvel (NOSi) no modelo de MO em hamsters. A mucosite oral foi induzida por duas administraÃÃes intraperitoneal (i.p) de 5-fluorouracil (5-FU) no 1  e 2 dias nas doses de 60 e 40 mg/kg, respectivamente nos animais (n = 5). As LP (0,25; 1; 5 E 25 mg/kg) foi injetado via i.p. 24h antes e 24h apÃs o trauma mecÃnico da mucosa jugal. O grupo controle recebeu apenas soluÃÃo salina. No 10 dia, os animais foram sacrificados e os tecidos da mucosa jugal foram colhidos. Foram realizadas no tecido mucosa jugal as anÃlises macroscÃpicas e histopatolÃgicas (infiltraÃÃo de cÃlulas inflamatÃrias, edema, hemorragia e à formaÃÃo de ulceraÃÃes e abscessos), bem como a imunohistoquÃmica para TNF-&#945;, IL-1&#946;, NOSi e COX-2. Foram utilizados Kruskal Wallis / Dunn como testes estatÃsticos, onde P <0,05 foi aceito. O estudo foi submetido ao Comità de Ãtica sob o protocolo 036/10. Observou-se que a LP inibiu significativamente parÃmetros macroscÃpicos e histopatolÃgicos, quando comparado ao grupo controle, com efeito mÃximo nos escores macroscÃpicos atingindo 75% e 66% do efeito mÃximo na avaliaÃÃo histopatolÃgica. A atividade de Mieloperoxidase (MPO) tambÃm foi significativamente inibida por LP em 91% com a mesma dose (p <0,001) quando comparado ao grupo controle e tambÃm inibiu a perda de peso em animais submetidos a mucosite oral e tratados com LP. A mucosa jugal dos animais submetidos a MO mostrou imunomarcaÃÃo para TNF-&#945;, IL-1&#946;, NOSi e COX-2 na conjuntiva inflamada (Cj) e tecido epitelial (Ep) em comparaÃÃo com o tecido jugal do grupo normal. LP causou reduÃÃo considerÃvel na imunomarcaÃÃo para TNF-&#945; (62%, Cj, 70%, Ep), IL-1&#946; (87%, Cj, 80%, Ep), NOSi (82% Cj; Ep 52%) e COX -2 (70%, Cj, 100%, Ep) no tecido jugal quando comparado com o grupo de animais submetidos à mucosite experimental que receberam salina, em vez de LP. Esses achados demonstram efeitos anti-inflamatÃrios de LP em MO induzida por 5-FU. O efeito protetor poderia ser suportado pela reduÃÃo da expressÃo das citocinas prÃ-inflamatÃrias, como TNF-&#945; e IL-1&#946; e na expressÃo de enzimas COX-2 e NOSi. O mecanismo de proteÃÃo parece envolver a expressÃo inibitÃria da NOSi, COX-2, TNF-&#945; e IL-1&#946;.

OBJETIVO: O estudo foi conduzido para determinar o quanto o Laser de Baixa Intensidade (LBI), em adição com um protocolo de higiene oral, pode reduzir a duração da mucosite oral (MO) induzida por quimioterapia e/ou radioterapia. PACIENTES E MÉTODOS: Um ensaio clínico randomizado placebo controlado foi desenvolvido utilizando o LBI ou controle (sham-treatment) em 2 centros de tratamento do câncer - a Unidade de Oncologia Pediátrica do Hospital de Clínicas de Porto Alegre (HCPA) e a Unidade de Oncologia do Hospital São Vicente de Paulo de Passo Fundo (HSVP). Pacientes em tratamento quimioterápico e/ou radioterápico entre os meses de outubro de 2005 e maio de 2006 foram elegíveis tão logo desenvolvessem MO. Os pacientes receberam intervenção por 5 dias. O grupo LBI foi tratado com GaAlAs, comprimento de onda: 830nm (infravermelho), potência: 100mW, dose: 4J/cm2 e o grupo controle com o sham-treatment. O grau de MO foi avaliado clinicamente através da escala da World Health Organization - National Cancer Institute - Common Toxicity Criteria (WHO-NCI-CTC). RESULTADOS: Os resultados foram expostos de acordo com cada centro envolvido. UOP - HCPA: vinte e um pacientes desenvolveram MO no grupo pediátrico e foram submetidos à análise; 18 (86%) pacientes possuíam diagnóstico de leucemia ou linfoma e 3 (14%) de tumores sólidos. A média de idade foi de 8,2 (± 3,1) anos. Nove pacientes foram randomizados no grupo laser e doze no grupo sham-treatment. A MO foi mensurada quando os sintomas foram manifestados em cada paciente, sendo a duração e o grau de MO graduados diariamente até a completa cicatrização das lesões. No dia 7 após o diagnóstico da MO, 11% dos pacientes permaneciam com lesões no grupo laser e 75% no grupo sham-treatment (P=0,029). No grupo tratado com laser a média de duração da MO foi de 5,8 ± 2 dias e no grupo sham-treatment 8,9± 2,4 dias (P=0,004). UO-HSVP: trinta e quatro pacientes desenvolveram MO no grupo dos adultos e foram submetidos à análise; 22 (65%) dos pacientes possuíam diagnóstico de tumores sólidos e 12 (35%) de leucemia ou linfoma. A média de idade foi de 41 (± 20 anos). 18 pacientes foram randomizados no grupo laser e 16 no grupo sham-treatment. A MO foi mensurada quando os sintomas foram manifestados em cada paciente, sendo a duração e o grau de MO graduados diariamente até a completa cicatrização das lesões. No dia 7 após o diagnóstico da MO, 32% dos pacientes permaneciam com lesões no grupo laser e 94% no grupo sham-treatment (P=0,001). No grupo tratado com laser a média de duração da MO foi de 6,8 ± 2,2 dias e no grupo sham-treatment 11,5± 3,5 dias (P<0,001). CONCLUSÃO: Este estudo demonstrou evidências que a laserterapia em adição com um protocolo de higiene oral pode reduzir a duração da MO induzida por quimioterapia e radioterapia. Em decorrência destes achados, esta modalidade de tratamento pode ser difundida e aplicada no intuito de promover qualidade de vida aos pacientes durante os tratamentos quimioterápicos e radioterápicos. / BACKGROUND: The study was conducted to determine whether Low level laser therapy (LLLT) in addition to oral care can reduce the duration of chemotherapy and/or radiotherapy induced oral mucositis (OM). PROCEDURE: A placebo-controlled randomized study was carried out using LLLT or placebo (sham-treatment) in two centers of cancer treatment - Pediatric Oncology Unit (POU) of HCPA and Oncology Unit (OU) of HSVP. Patients treated with chemo and/or radiotherapy between Oct, 2005 and May, 2006 were eligible as soon as they developed OM. Patients received intervention for 5 days. The LLLT group was treated with Laser GaAlAs, wavelenght: 830nm (infrared), power: 100mW, dose: 4J/cm2 and the control group with sham-treatment. The grade of OM was clinically assessed by the WHONCI- CTC scale. RESULTS: Results were showed according with the center. POU-HCPA: Twenty-one patients developed OM in the children group and were submitted for analysis; 18 (86%) patients had a diagnosis of leukemia or lymphoma and 3(14%) had solid tumors. The mean age was 8.2 (± 3.1) years. Nine patients were randomized in the laser group and twelve patients in the placebo-control group. OM was measured when symptoms were manifest and the duration of OM and the grade of lesions found in each patient were recorded at the start of laser therapy and daily until complete healing of the lesions. On day 7 after OM diagnosis, 11% of patients presented lesions in laser group and 75% of patients in the sham-treatment group (P=0.029). In the group treated with laser the mean of OM duration was 5.8 ± 2 days and in the sham-treatment group 8.9± 2.4 days (P=0.004). OU-HSVP: Thirty-four patients developed OM and were submitted for analysis; 22 patients (65%) had diagnosis of solid tumors and 12 (35%) leukemia or lymphoma. The mean age was 41 (± 20) years. Eighteen patients were randomized in the laser group and 16 patients in the placebo-control group. Once OM was diagnosed, the patients had daily OM grading assessments before laser application, and thereafter until complete healing process of lesions. On day 7 after OM diagnoses , 32% of patients presented lesions in laser group and 94% of patients in the sham-treatment group (P=0.001). In the laser group the mean of OM duration was 6.8 ± 2.2 days and in the sham-treatment group was 11.5 ± 3.5 days (P<0.001). CONCLUSION: Our study has shown evidence that laser therapy in addition to oral care can decrease the duration of chemotherapy induced OM. It should encourage clinicians to use this technique to improve quality of life of cancer patients during the oncology treatment.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / INTRODUÃÃO: A mucosite oral (MO) à um efeito colateral frequente em pacientes sob tratamento oncolÃgico, em especial à quimioterapia (QT). Caracteriza-se por hiperemia, edema e Ãlceras em toda a cavidade oral e faringe. A importÃncia da MO à devido à dor, alteraÃÃes do paladar e infecÃÃes locais. Surge incapacidade de alimentar-se, ingerir lÃquidos, risco de infecÃÃes sistÃmicas, necessidade de interrupÃÃo da QT, necessidade de hospitalizaÃÃo, tornando o tratamento mÃrbido, dispendioso, doloroso e muitas vezes impossÃvel ou ineficaz. Ainda nÃo hà terapÃutica totalmente eficaz, com nÃvel de evidÃncia que torne a MO manejÃvel. OBJETIVOS: Avaliar os efeitos do tratamento tÃpico com duas plantas medicinais, a Myracrodruon urundeuva (aroeira) e a Aloe barbadensis (babosa) sobre o desfecho da MO experimental induzida por 5-Fluorouracil (5-FU) em hamsters, atravÃs de escores macro e microscÃpicos e avaliaÃÃo de perda ponderal. Investigar os possÃveis mecanismos envolvidos nesses efeitos, atravÃs de anÃlise da atividade de mieloperoxidase (MPO) e expressÃo tissular de TNF-alfa e iNOS. MATERIAIS E MÃTODOS: Hamsters Goldem siriam receberam injeÃÃes i. p. de 60 e 40 mg/Kg de 5-FU, nos dias 1 e 2, respectivamente. No dia 4 os animais eram anestesiados, tinham suas mucosas jugais submetidas a trauma mecÃnico (TM) com agulha de ponta romba. Em seguida, eram tratadas com gel inerte (controle), gel de aroeira a 5, 10 ou 20% (AR) ou gel de babosa (ALOE) a 25, 50 e 100% . Tais tratamentos eram realizados 2xdia atà o dia 9. Os animais eram pesados diariamente. No dia 10, ocorriam os sacrifÃcios para: 1. AnÃlise macroscÃpica das mucosas; 2. Retiradas de amostras para histopatologia, imunohistoquÃmica para e dosagem de MPO. RESULTADOS: Na anÃlise macroscÃpica, AR determinou inibiÃÃo significativa da MO (AR 5% - Md 2; AR 10% - Md 3; Controle â Md 4), ALOE tambÃm inibiu a MO (ALOE 25% - Md 1; ALOE 50% - Md 1,5; ALOE 100% - Md 1; Controle â Md 4). à histopatologia confirmou-se inibiÃÃo significativa da MO pela AR (p < 0,01) e pela ALOE a 50 e 100% ( p< 0,01). Houve tambÃm inibiÃÃo dos nÃveis de MPO pelos extratos das duas drogas e a expressÃo de TNF-alfa e iNOS tambÃm foi reduzida. Houve uma tendÃncia a uma menor perda ponderal nos grupos experimentais. CONCLUSÃES: Extratos de ALOE e AR foram capazes de inibir a MO experimental induzida por 5-FU atravÃs de aplicaÃÃes tÃpicas e tal efeito pode ser modulado por suas atividades anti-inflamatÃrias sobre a produÃÃo de citocinas envolvidas com o processo e de NO. / INTRODUCTION: Oral mucositis (OM) is a frequent dose-limiting and costly complication of antineoplastic chemotherapy. Itâs caractherized by ulcerative lesions and causes pain, restrict food and fluids oral intake and causes substancial risk for sepsis. In severe cases, hospitalization, parenteral nutrition and opiode analgesics are required. OBJECTIVES: Evaluate the effects of extracts of two herbal medicines, Aloe barbadensis Miller (Ab) and Myracrodruon urundeuva AllemÃo (Mu) on 5-fluorouracil-induced OM in hamsters. To evaluate the possible mechanisms by the extracts act, it was performed analysis of intensity of activity of myeloperoxidase (MPO) and analysis of immunohistochemistry for TNF-alpha and iNOS in mucosa specimens. METHODS: Golden siriam hamsters were submitted to intra-peritoneal 60 and 40 mg/Kg injections of 5-fluorouracil (5-FU) in day 1 and 2, respectively. On day 4, animals were submitted to anaesthesia, followed by mecanic trauma with needle to potenciate the effect of 5-FU. After that, the mucosas were treated with topical gel containing Mu extracts at 5, 10 or 20%, Ab extracts at 25, 50 or 100% (experimental groups) or carbapol gel (control group). The treatments above were mantained twice daily until day 9. On day 10 the animals were sacrified. Diferent parameters were evaluated: macroscopic and microscopic scores of OM, body mass variation and immunohistochemistry for TNF-alpha e iNOS. RESULTS: Mu significantly inhibited macroscopic oral mucositis at 5 and 10% concentrations (5% Mu â Md 2; 10% Mu â Md 3; control â Md 4, p < 0,01). Ab also inhibited OM (25% Ab â Md 1; 50% Ab â Md 1,5; 100% Ab â Md 1; control â Md 4, p < 0,001). These results were confirmed by histological analysis (5% Mu â Md 1,5; 10% Mu â Md 1; 25% Ab â Md 1; 50% Ab â Md 1,5; 100% Ab â Md 1; control â Md 2, p < 0,01). MPO activity was significantly decreased by Mu and Ab compared to control animals. Both Mu and Ab decreased expression of TNF-alpha and iNOS on tissue. It was observed a decrease on ponderal lost in experimental groups. CONCLUSIONS: Myracrodruon urundeuva and Aloe barbadensis cause important inhibitory effects in oral mucositis 5-FU induced probably by their antiinflamatory properties.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A mucosite ou estomatite oral (MO), que consiste na resposta inflamatÃria da mucosa oral à aÃÃo de drogas ou radioterapia, onstitui-se num efeito colateral debilitante, sendo uma complicaÃÃo potencialmente sÃria, dose-limitante que tem impacto tanto no controle local quanto na sobrevida e qualidade de vida de pacientes oncolÃgicos. O objetivo deste trabalho foi desenvolver um modelo de MO induzida por radioterapia (RXT) em aparelho de megavoltagem - cobalto-60 (MV - Co60) e avaliar o papel protetor do agente inibidor de citocinas, pentoxifilina (PTX). Foram utilizados 156 hÃmsters Golden Siriam machos com massa corpÃrea mÃdia de 139 gramas. Os animais foram submetidos à RXT da mucosa jugal, utilizando aparelho de MV - Co60. A irradiaÃÃo foi realizada no dia um com campo direto e colocaÃÃo de bolus sobre a mucosa e dose Ãnica de 35 Gy. No quarto dia foram feitas irritaÃÃes mecÃnicas (IM) na mucosa jugal irradiada, como fator potencializador da MO. Os animais foram observados por um perÃodo de 16 dias, ao longo do qual a mucosa foi avaliada macroscopicamente considerando os aspectos de hiperemia, Ãreas hemorrÃgicas, Ãlceras e abscessos. Em dias prÃ- determinados (7, 10, 13 e 16 dias), os animais foram sacrificados e as mucosas removidas e processadas para anÃlise histopatolÃgica (infiltrado celular, dilataÃÃo e ingurgitamento vascular, hemorragia, edema, Ãlceras e abscessos), dosagem da mieloperoxidase e detecÃÃo de TNF-&#945; por imunohistoquÃmica. Antes do sacrifÃcio, foi colhido sangue para contagem total e diferencial de leucÃcitos. Os animais foram pesados diariamente e avaliados quanto as suas respectivas variaÃÃes da massa corpÃrea e realizado tambÃm estudo da curva de sobrevida. No 13 dia, observou-se o pico de intensidade dos achados inflamatÃtios. A PTX foi utilizada nas doses de 5, 15 e 45 mg kg-1sc, 1 h antes da radioterapia e, diariamente,por 13 dias. Observou-se que a induÃÃo da MO causou lesÃes significantes a partir do 7 dia,atingindo pico entre os dias 13 e 16, com aumento significante de marcaÃÃo de TNF-&#945;, sem alteraÃÃo do hemograma dos animais. Contudo, a induÃÃo da MO causou perda significante de peso a partir do 5 dia, mantendo-se estÃvel atà o 13 dia, quando, entÃo se observou queda acentuada e significante da sobrevida dos animais atà o 16 dia. A PTX (15 mg kg-1) foi capaz de reduzir hiperemia, hemorragia, Ãlceras e abscessos (0; 0-2), quando comparada a animais com MO nÃo tratados (salina) com PTX (3; 2-3) (p<0,05). Estes dados foram confirmados pela anÃlise histopatolÃgica das mucosas, onde PTX 15 mg kg-1 (1; 1-3) reduziu o infiltrado inflamatÃrio, dilataÃÃo e ingurgitamento vasculares, edema, Ãlceras e abscessos, quando comparada aos animais que receberam apenas Salina (3; 1-3) (p<0,05). Ainda, PTX 15 mg kg-1reduziu, a marcaÃÃo do TNF-&#945; nas mucosas com MO, quando comparada aos animais nÃo tratados. A PTX nÃo alterou o hemograma, nem a variaÃÃo de massa corpÃrea observada na MO. Em resumo, o modelo de MO induzido por radioterapia de megavoltagem e irritaÃÃo mecÃnica em hamster foi desenvolvido e em concordÃncia ao modelo descrito na literatura por ortovoltagem, mostra caracterÃsticas que em muito se assemelham à mucosite oral humana, em termos de achados macroscÃpicos, histopatolÃgicos e bioquÃmicos, portanto, se prestando para o estudo de novas drogas capazes de combatÃ-la. Quanto à aÃÃo da PTX, foi observado um efeito protetor deste agente na dose de 15 mg kg-1, confirmado pela avaliaÃÃo do mediador inflamatÃrio TNF-&#945; e tambÃm um possÃvel efeito de radiossensibilizaÃÃo na dose de 45 mg kg1 / The oral mucositis (OM) consists of an inflammatory esponse of the oral mucosa to the drugs or radiation therapy and is a deleterious side effect and a potential serious complication,limiting-dose and impacting the local control, overall survival and quality of life in oncology patients. The objective of this study was to develop a OM model radio-induced (RXT) by amegavoltage machine â cobalt unit (MV - 60Co) and evaluate the protector role of the cytokinesinhibitor agent, pentoxyfilline (PTX). For this purpose, 146 male Golden Siriam Hamsters withme dium body mass of 139 grams were used. On the first day, the animals were exposed tomegavoltage irradiation in a cobalt unit, with a single fraction of 35 Gy. A irradiation field was opened to the oral mucosa and it was used a bolus on it. After the 4th day of irradiation, a mechanical scratching (MS) was done over the irradiated oral mucosa for nhancing the OM.The animals were observed for 16 days period in which the oral mucosa was evaluated macroscopically considering the clinical aspects of hyperemia, bleeding areas, ulcers and infections. In pre-determined days (days 7, 10, 13 and 16), the animals were sacrificed and the oral mucosa removed to be analyzed under the histopathological aspects (cellular effusion,vascular dilatation, bleeding, edema, ulcers and infection), mieloperoxidase dosage and TNF-&#945; detection by munohistochemical stain. Before the animals were sacrificed, a blood sample was drawn to count the white cells. The animals were daily weighed and evaluated about their bodymass variations and a survival curve was taken. On the 13th day, it was observed the highest inflammatory finding. The PTX was used in the following doses: 5, 15 and 45 mg kg-1 sc, one hour before the irradiation and daily, for 13 days. It was observed that the induced OM was greatly significant after the 7th day, with the higher findings of TNF-&#945; without blood counting changes between 13 to 16 days. The weight loss was detected after the 5th day and remained stable till 13th day when it was noticed a highly significant weight loss and survival till the 16th day. The PTX (15 mg kg-1) was able to reduce the hyperemia, bleeding, ulcers and infection (0; 0-2) when compared to the animals that received only saline solution (3; 1-3) (p < 0,05). The PTX 15 mg kg-1 reduced the TNF-&#945; stain in the oral mucosa with OM when compared to the animals that were not treated. The PTX altered neither the blood counting nor the body mass in the OM group. In summary, the OM model induced by megavoltage irradiation and mechanical scratching in hamsters was developed accordingly to the model designed to ortovoltage studies in the literature, shows close relationship to the human oral mucosa changes, macroscopically, histopathologically and biochemically, and it can be used in the study of new drugs to prevent mucositis. About the PTX action, it was observed the protector effect of this agent in the 15 mg kg-1 dosage, confirmed by the evaluation of the TNF-&#945; and its possible radiation sensitivity effect in the 45 mg kg-1 dosage

nÃo hà / A mucosite oral (MO) à um efeito colateral freqÃente e dose limitante da terapia do cÃncer, caracterizada por intensa reaÃÃo inflamatÃria na mucosa e formaÃÃo de Ãlceras na cavidade orofarÃngea. O objetivo deste trabalho foi avaliar o efeito da atorvastatina (ATV), droga utilizada para reduzir os nÃveis sÃricos de colesterol e que tem atividade antiinflamatÃria, na mucosite oral induzida por 5-fluorouracil (5-FU) em hamsters Golden Sirian. A mucosite oral foi induzida pela administraÃÃo intraperitoneal (i.p.) de 5-FU no 1 e 2 dias do experimento (60 e 40 mg/kg, respectivamente), com subseqÃentes escoriaÃÃes na mucosa jugal, no quarto dia. Os animais foram tratados intraperitonealmente (i.p.) com ATV 1, 5 ou 10 mg/kg ou salina ou salina/etanol 5% vol/vol 30 minutos antes de cada injeÃÃo do 5-FU e diariamente por 5 ou 10 dias. Os animais foram sacrificados no 5 ou 10 dia e amostras de mucosa jugal e dos principais ÃrgÃos vitais foram coletados para anÃlise histopatolÃgica. A determinaÃÃo dos nÃveis de TNF-&#945;, IL-1&#946;, nitrito, grupos sulfidrilas nÃo proteicos (NP-SH), ensaio da mieloperoxidase (MPO), imunohistoquÃmica para TNF-&#945;, Ãxido nÃtrico sintase induzida (iNOS), NF-KB-p50, NF-kB-p50 NLS (sequÃncia de localizaÃÃo nuclear) e a expressÃo do NF-kB-p50 por Western Blot foram outros parÃmetros avaliados em amostras coletadas da mucosa jugal dos animais. O sangue foi coletado para leucograma, anÃlise dos parÃmetros bioquÃmicos e anÃlise da bacteremia. Atorvastatina nas doses de 1 e 5 mg/kg reduziu o dano na mucosa e a inflamaÃÃo, bem como os nÃveis de citocinas, nitrito e a atividade da MPO no 5 e 10 dia da MO. Ademais, atorvastatina 1 e 5 mg/Kg diminuiu a marcaÃÃo imunohistoquÃmica para TNF-&#945;, NOSi, NF-kB-p50, NF-kB-p50 NLS, bem como a expressÃo do NF-kB-p50 na mucosa jugal dos hamsters submetidos a MO, no 5 dia. ATV 1 mg/Kg aumentou os nÃveis de NP-SH na mucosa jugal dos animais, quando comparado com os grupos 5-FU no 10 dia da MO. A associaÃÃo de ATV 5 mg/Kg e 5-FU diminuiu a taxa de sobrevida, amplificou a leucopenia dos animais, aumentou os nÃveis sÃricos de transaminases e causou lesÃo hepÃtica. NÃs tambÃm detectamos a presenÃa de bacilos Gram negativos no sangue de 100% dos animais tratados com ATV 5mg/Kg + 5-FU. Esses resultados sugerem que a atorvastatina previne o dano na mucosa oral e a inflamaÃÃo associada com MO induzida por 5-FU, entretanto a combinaÃÃo de altas doses de ATV com 5-FU induz hepatotoxicidade, amplificaÃÃo da leucopenia e bacteremia, que merecem atenÃÃo e futuros estudos em humanos. / Oral mucositis (OM) is a frequent side effect and dose-limiting of cancer therapy, characterized by intense inflammatory mucosal reaction and formation of ulcers in oropharyngeal cavity. The aim of this study was to evaluate the effect of atorvastatin (ATV) â cholesterol lowering drug with anti-inflammatory activity - in oral mucositis induced by 5-fluorouracil (5-FU) in Golden Sirian hamsters. Oral mucositis was induced by intraperitoneal (i.p.) administration of 5-FU in the first and second days of experiment (60 and 40 mg/kg i.p., respectively), with subsequent excoriations of the cheek pouch mucosa on the fourth day. The animals were treated by intraperitoneal route (i.p.) with ATV 1, 5 or 10 mg/kg or saline or saline and 5% vol/vol ethanol 30 min before 5-FU injection and daily for 5 or 10 days. The animals were sacrificed on the 5th or 10th day and samples of cheek pouches and major vital organs were removed for histopathological analysis. The determination of TNF-&#945;, IL-1&#946;, nitrite, non-protein sulfhydryl group (NP-SH) levels, myeloperoxidase (MPO) assay, immunohistochemistry for TNF-&#945;, induced nitric oxide synthase (iNOS), NF-kB-p50, NF-kB-p50 NLS and the expression of NF-kB-p50 by Western Blot were other parameters evaluated in the samples collected from the oral mucosa of animals. Blood was collected for a leukogram, analysis of biochemical parameters and analysis of bacteremia. Atorvastatin at doses of 1 and 5 mg/kg reduced mucosal damage and inflammation, as well as the levels of cytokines, nitrite, and myeloperoxidase activity on the 5th and 10th day of OM. Moreover, ATV 1 and 5 mg/kg decreased the immunohistochemical staining for TNF-&#945;, iNOS, NF-kB-p50, NF-kB-p50 NLS and expression of NF-kB-p50 of the cheek pouch mucosa on the 5th day of OM. ATV at 1 mg/kg increased cheek pouch NP-SH when compared to 5-FU groups on the 10th day of OM. The association of ATV 5 mg/kg and 5-FU decreased the survival rate, amplified the leukopenia of animals, increased transaminase serum levels and caused liver lesions. We also detected the presence of Gram negative bacillus in the blood of 100% of the animals treated with ATV 5 mg/kg + 5-FU. These results suggest that atorvastatin prevent mucosal damage and inflammation associated with 5-FU-induced OM, but the association of a higher dose of ATV with 5-FU induced hepatotoxicity, amplified leucopenia and bacteremia, which deserves attention and further research in humans.

Considerando a mucosite oral (MO) e a hipofunção das glândulas salivares (HGS) consequências debilitantes da quimioterapia (QT), este trabalho teve como objetivo induzir, em hamsters, MO e HGS, através do quimioterápico 5- Fluorouracil (5-FU), e comparar, através de análises clínicas, bioquímicas e histológicas, diferentes fototerapias no tratamento da MO, assim como o efeito do laser no tratamento da HGS. Cento e oitenta animais foram divididos em dois grupos, controle e experimental, onde, o grupo controle foi subdividido em grupo C, o qual recebeu somente anestesia/veículo de diluição do quimioterápico e o CQ, o qual recebeu anestesia/quimioterapia e indução da MO. O grupo experimental foi também subdividido em grupo L: com indução de MO e tratamento com LED, 630nm, 1,2J/cm2; LA: MO e tratamento com laser de alta potência (LAP), 808nm, 10J/cm2; LB: MO e tratamento com laser de baixa potência (LBP), 660nm, 6J/cm2 e o LG: sem MO e tratamento com LBP, 780nm, 5J/cm², na região das glândulas salivares (GS) submandibulares (GSSM) e sublinguais GSSL). A MO foi induzida através de ranhuras após QT e foi avaliada, clinicamente, através de escalas específicas. Os animais foram sacrificados após 5, 7 e 10 dias de experimento e a mucosa oral e as GS removidas para análises bioquímicas (TNF- e análise de proteína total, LDH e parâmetros do sistema antioxidante, respectivamente) e histológicas (análise por microscopia de luz e imuno-histoquímica para as amostras de mucosa, e por microscopia de luz, eletrônica de transmissão e imunocitoquímica para as amostras de GS). Após análises estatísticas, os resultados clínicos, bioquímicos e histológicos mostraram que os tratamentos com LBP e LED foram eficazes no tratamento da MO, com diminuição da concentração de TNF- no dia 7 (p<0.05) e completa cicatrização das lesões ao termino do experimento, com maior formação de tecido de granulação e angiogênese. Além disso, a expressão de citoqueratina 10, analisada por imunohistoquímica, apresentou-se menos intensa comparada ao grupo CQ. O LAP não prejudicou a cicatrização final da MO quando comparada ao grupo CQ. O LBP também se mostrou eficaz para a HGS causada pelo 5-FU, uma vez que os parâmetros estudados para o grupo LG foram similares para os animais do grupo C na maior parte dos tempos experimentais. A HGS do grupo CQ foi representada por importantes alterações morfológicas, estruturais e bioquímicas, como a atrofia das unidades secretoras terminais, aumento do estroma glandular na GS sublingual e alterações na expressão de EGF, NGF e PIP2 nas GSSM, assim como alteração na expressão de mucina e p16 nas GSSL. De acordo com as análises bioquímicas, foram observadas alterações na atividade das enzimas antioxidantes catalase, peroxidase e superóxido dismutase e da atividade da enzima lactato desidrogenase (p<0.05) tanto para a GSSM quanto para a GSSL. Com base nos resultados, podemos concluir que as fototerapias com LBP e LED diminuem a severidade da MO por acelerar a reparação tecidual e diminuir o processo inflamatório, assim como o LBP é eficaz no tratamento da HGS induzida pelo quimioterápico 5-FU. / Considering oral mucositis (OM) and salivary glands hipofunction (SGH) debilitating consequences of chemotherapy (CT), the aim of this study was to compare, through clinical, biochemical and histological analysis, different photherapies on the treatment of OM and SGH induced by injections of the chemotherapic agent 5-Fluorouracil in hamsters. One-hundred-eighty animals were divided into two groups, control and experimental, which were subdivided in group C: anesthesia/chemotherapy vehicle and CQ: anesthesia, chemotherapy/OM induction, for control group and in group L: anesthesia, chemotherapy/OM and phototherapy with LED (1,2 J/cm², 1.2 J of total energy), LA: anesthesia, chemotherapy/OM and phototherapy with highpower laser (HPL) (10 J/cm², 10 J of total energy), LB: anesthesia, chemotherapy/OM and phototherapy with low-power laser (LPL) (6 J/cm², 1.2 J of total energy) and LG: anesthesia, chemotherapy and phototherapy with LPL (5 J/cm2) on salivary gland (SG) (submandibular and sublingual) areas for experimental group. The OM was induced by slots on oral mucosa, which were performed after chemotherapy treatment. The OM was analyzed through specific clinical scales and after 5, 7 and 10 days, the animals were sacrificed and the oral mucosa and submandibular and sublingual glands removed for biochemical (TNF- and total protein concentration, LDH and antioxidant system parameters, respectively) and histological (light microscopy and immune-histochemical for OM samples, and light microscopy, electronic transmission and immunocitochemical for SG samples) analysis. After statistical analysis, the clinical, biochemical and histological results showed Led and LPL as efficient treatments for OM, with decrease of TNF- concentration on day 7 (p<0.05) and complete lesions healing on last day of experiment, showing increase of granulation tissue and new blood vessels formation. In agreement, the citokeratin 10 expression by immunehistochemistry, showed less intensity when was compared with CQ group. The HPL had no interference on OM final healing in comparison with CQ group. The LPL also showed good results on treatment of SGH induced by 5- FU. The SGH on CQ group included important morphological, structural and biochemical changes, as acinar atrophy, increase of glandular stroma on sublingual glands and important changes for EGF, NGF and PIP2 expression on submandibular glands, and for mucin and p16 gene expression on sublingual glands. Furthermore, the biochemical analysis showed changes on antioxidant enzime system activity, catalase, peroxidase and superoxide dismutase, and also for dehidrogenase lactate activity (p<0.05). The results of the present study suggest the phototherapies with LPL and LED where efficient on decrease of OM severity, accelerating tissue repair and decreasing the inflammatory process, as well as, the LPL efficient as treatment of SGH induced by 5-FU.

Introduction: Oral mucositis is an inflammatory and frequently ulcerative side effect of cancer therapy, which has been identified by patients as the most debilitating side effect of their treatment. Mucositis is a dose limiting toxicity which exerts a substantial clinical and economic impact and negatively affects patient quality of life. The patient experience of mucositis is under-reported in the literature. To date, no interventions have been identified that have proven successful in the prevention of mucositis for patients receiving all types of therapy. Vitamin E has shown conflicting results in clinical trials. This thesis combines appraisal of the literature and empirical research,and uses lessons learned from previous studies together with the results of a feasibility study to identify a best practice model for future trials. Methods: The Cochrane risk of bias (ROB) instrument was used to assess the ROB in the studies included in the Cochrane prevention review. A sensitivity analysis was conducted after studies assessed at unclear or high risk of overall bias were excluded. A systematic review of assessment instruments was conducted which identified 50 instruments. Consideration of the appropriateness of these instruments for the use in a clinical trial for the prevention of mucositis was based on the practicality, comparability, and reproducibility, and the impact of these instruments on patients. Three of these instruments were chosen for use in a clinical trial of adults undergoing stem cell transplant. Finally, a feasibility study was designed, developed and conducted which investigated vitamin E for the prevention of mucositis in patients undergoing conditioning for bone marrow transplantation. Through lessons learned from previous studies, consultations with medical professional, the MHRA, ethics committee and suppliers, a protocol was developed for a double blind RCT. The process of gaining MHRA and ethical approval, and the repackaging of intervention and placebo products to meet MA-IMP requirements are described. Results: 130 articles were assessed for risk of bias. Only ten studies were assessed as being at low overall risk of bias. Blinding of outcome assessors and adequate allocation concealment were identified to be important considerations in the planning of future studies. Although only nine patients were recruited into the feasibility study, a number of issues affecting the design and conduct of future trials were identified. Recruitment in particular was identified to be problematic. Strategies for overcoming this problem in future trials were discussed. The methods of blinding and allocation concealment employed were found to be feasible for use in future trials. Expected adverse events patients undergoing stem cell transplantation were also reported. Conclusion: Further studies are required to investigate interventions for the prevention of mucositis. It is of upmost importance that these trials are rigorous in both their methodology and subsequent reporting in order to elicit the maximum benefit for patients taking part in clinical trials, and future patients undergoing therapy for cancer.

No description available.