Mucositis manifesting as diarrhoea is a common side effect of chemotherapy which remains poorly understood. It is one of a number of manifestations of alimentary mucositis, which affects the entire gastrointestinal tract. The exact number of patients that are affected by diarrhoea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be afflicted. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning diarrhoea is based on clinical observations, with very little basic research existing. However, from the research conducted, it is likely that the intestinal microflora and mucins play a role in the development of chemotherapy-induced diarrhoea. This thesis will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhoea (CID). Furthermore it will explore the potentially important relationship between intestinal microflora, the luminal environment and the subsequent development of chemotherapy-induced mucositis and diarrhoea. 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (p<0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells, suggesting 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects, and in particular may contribute to the development of chemotherapy-induced mucositis. Irinotecan causes cholinergic and delayed onset diarrhoea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Diarrhoea was observed in treated rats, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora), suggesting that irinotecan-induced diarrhoea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished. Mucus production appears to be increased after irinotecan treatment, which may contribute to the development of diarrhoea. Goblet cells were demonstrated to decrease significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. This indicates that irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. To determine if the changes to the intestinal microflora caused by chemotherapy could be translated to the clinic, a pilot clinical study was carried out. Sixteen patients experiencing CID were recruited to the study with two control subjects. A large proportion of patients (75%) demonstrated a reduced anaerobic component of their faecal microflora. A reduced diversity of species was also observed in patients. The majority of patients exhibited decreases in Clostridium spp., Lactobacillus spp. and Bifidobacterium spp., whilst all patients exhibited decreases in Bacteroides spp. and Enterococcus spp. Patients receiving antibiotics did not exhibit any marked differences to patients not receiving antibiotics. This indicates that the results observed in the animal studies are clinically relevant, and further research into this area should be undertaken. CID is associated with marked changes in the intestinal microflora. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. In conclusion, there is clear evidence demonstrating chemotherapy treatment results in changes to the intestinal microflora and mucin secretion, which may be responsible in part for the development of severe mucositis and diarrhoea. Irinotecan toxicity may be compounded by the increase in β-glucuronidase producing bacteria. The intestinal flora of cancer patients experiencing CID is also noticeably different to that of healthy subjects. Irinotecan causes changes to mucin secretion, and the specific expression of Muc2, Muc4 and Klf4, suggesting that secretory control by the enteric nervous system may also be affected by chemotherapy. This research has extended the understanding of chemotherapy-induced mucositis and diarrhoea, complex side effects of chemotherapy. However, new areas for future research have also been identified. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352119 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009

Thesis (doctoral)--Rijksuniversiteit Groningen, 1989. / Includes bibliographical references.

Thesis (doctoral)--Rijksuniversiteit Groningen, 1989. / Includes bibliographical references.

Made available in DSpace on 2015-05-14T12:56:08Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 842543 bytes, checksum: dcc4a89c58b1a2bed72a86aa5e76dab2 (MD5) Previous issue date: 2008-12-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The aim of this study was to assess salivary EGF concentration in head and neck cancer patients and its correlation with oral mucositis. It was an observational, transversal, control-case study. Whole stimulated saliva was collected in this groups: G1 control (n=9), G2 diagnostic moment (n=13), G3 before therapy (n=11), G4 during therapy (n=13) and G5 after therapy (n=11). The samples were centrifuged and measured. The supernatant was obtained and stored at -80° C until assayed. Salivary EGF content was measured with a commercial ELISA kit (Quantikine, R & D Systems, Minneapolis, MN, E.U.A.). The salivary flow means to G1, G2, G3, G4, G5 were 1,27; 1,58; 1,70; 0,77 and 0,99 ml/min. respectively. Differences on salivary flow did not reach statistical significance in the groups (p=0,064) but there was a strong reduction in G4 and G5. In relation to EGF levels, it was seen 1624,08; 1816,63; 1905,47 and 1457,12 pg/ml, respectively. There was no significant difference in the salivary EGF levels of this patients (p=0,686) but the decreased levels in G4 was evident. There was a positive correlation between salivary flow and EGF levels in G4 and G5, but it was not statistically significant, G4 (p=0,446) and G5 (p=0,258). There was not association between EGF concentration and oral mucositis development (p=0,037), but it was significant between decreased salivary flow and mucositis (p< 0,001). It was shown that EGF levels were not influenced for the use of alcohol (p=0,792), tobacco (p=0,706) and the patient performance status (p=0,213). It was possible to conclude that radiation therapy induces reduction in salivary flow and EGF levels over time. That EGF levels decreased is influenced by low salivary flow, but there was no association between oral mucositis development and salivary EGF levels. / O presente estudo teve como objetivo verificar a concentração do EGF na saliva de pacientes com neoplasias malignas em região de cabeça e pescoço e sua possível relação com a mucosite oral e o fluxo salivar. Constituiu-se em um estudo transversal, observacional, do tipo caso-controle. As amostras de saliva estimulada foram obtidas nos seguintes grupos: G1-controle (n=9), G2- momento do diagnóstico (n=13), G3-antes da terapia (n=11), G4-durante a terapia (n=13) e G5-após a terapia (n=11), sendo as mesmas centrifugadas e mensuradas. O sobrenadante foi então armazenado a temperatura de -80 º C e, posteriormente, descongelado a temperatura ambiente e submetido a imunoensaio do tipo sanduíche, onde a concentração salivar de EGF foi determinada por um kit comercial de ELISA (Quantikine, R & D Systems, Minneapolis, MN, E.U.A.). Verificou-se médias de fluxo salivar para G-1, G-2, G-3, G-4 e G-5 de 1,27; 1,58; 1,70; 0,77 e 0,99 ml/min, respectivamente. Segundo o teste F (ANOVA) não houve diferença estatisticamente significativa entre os fluxos nesses grupos (p=0,064), embora tenha havido redução significativa no G4 e G5. Em relação ao EGF, observou-se, consecutivamente, as seguintes médias: 1624,08; 1816,63; 1905,47; 1414,87 e 1457,12 pg/ml, também não sendo observada significância estatística nas diferenças entre os grupos (p=0,686), percebendo-se diminuição em seus níveis no G4. Por meio da correlação de Pearson, observou-se correlação positiva entre as medidas de fluxo salivar e as concentrações de EGF no G4 e G5, embora sem significância estatística, G4 (p=0,446) e G5 (p=0,258). Não houve associação entre as concentrações de EGF e o desenvolvimento da mucosite oral (p=0,337), mas houve entre o fluxo salivar diminuído e a mucosite (p< 0,001). Além disso, os níveis de EGF na saliva não foram influenciados pelos hábitos de etilismo (p=0,792), tabagismo (p=0,706), ou ainda, pelo estado de saúde geral do paciente (p=0,213), segundo o t-Student. Com base nos resultados obtidos, podemos concluir que a radioterapia promoveu diminuição no fluxo salivar e nos níveis de EGF, que os níveis de EGF foram influenciados pela diminuição do fluxo salivar e que não houve associação entre o desenvolvimento da mucosite oral e a concentração de EGF na saliva.

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.

Introdução: o tratamento oncológico em crianças inclui frequentemente quimioterapia e/ou radioterapia que podem determinar alterações à cavidade bucal que consequentemente predispõem à intercorrências estomatológicas. Objetivo: verificar as condições de saúde bucal em crianças e adolescentes portadores de neoplasias, no momento do diagnóstico, e sua relação com as complicações estomatológicas após intervenção odontológica. Metodologia: foram incluídas crianças e adolescentes portadores de neoplasias atendidas no Serviço de Oncologia Pediátrica do HCPA, durante o período de maio de 2011 a dezembro de 2012. Através de critérios específicos, os pacientes foram alocados em dois grupos, de acordo com as condições de saúde bucal, em Favorável e Desfavorável no momento do diagnóstico. A análise das condições de saúde bucal foi relacionada com os desfechos mucosite, infecções odontogênicas, gengivite, cistos de erupção e pericoronarite durante os primeiros seis meses de tratamento oncológico. Foram feitas associações com o potencial tóxico da QT, Gênero, Faixa Etária, RT de cabeça e pescoço, tempo até a primeira intercorrência e óbito. Análise estatística utilizou o teste Qui–quadrado para comparação de variáveis categóricas entre os dois grupos, Mann-Whitney para comparação da graduação de mucosite entre os dois grupos, Kaplan Meier para análise do tempo até o surgimento dos desfechos e Regressão de Cox para cálculo da probabilidade estimada de ocorrência dos desfechos. Resultados: foram incluídos 65 pacientes, sendo 36 meninos, 32 com Saúde Bucal Favorável e 33 com Saúde Bucal Desfavorável. No total foram realizadas 839 avaliações. O grupo Favorável apresentou menos infecções odontogênicas (P 0,003) que o grupo Desfavorável. No total foram realizadas 839 avaliações. O grupo Favorável apresentou menos infecções odontogênicas (P 0,003) que o grupo Desfavorável. Houve um aumento significativo de MO nos pacientes tratados com drogas com alto risco para mucosite (P 0,001). Os dados sugerem que o grupo Desfavorável apresenta mais infecções tanto durante o tratamento utilizando drogas de Alto Risco (26,1%) como Baixo Risco (40%) para a MO. A incidência de MO foi maior entre os pacientes da faixa etária de dentição permanente (13 a 18 anos) 82,4%, assim como entre os pacientes do gênero masculino (80,6%). A ocorrência de Infecção Odontogênica foi mais presente entre pacientes na faixa etária de dentição permanente (41,2%) e entre pacientes do gênero feminino (41,4%). O índice CPOD dos pacientes do grupo Desfavorável foi 3,57, considerado alto para risco de cárie na população estudada. Os índices de placa visível e sangramento gengival reforçaram as diferenças entre os dois grupos. Conclusões: os pacientes oncológicos pediátricos são expostos à toxicidade das drogas quimioterápicas e consequentemente estão suscetíveis aos riscos decorrentes de processos infecciosos. As infecções com origem na cavidade bucal são frequentes nesta população e sua prevenção está diretamente ligada aos protocolos de higiene bucal e tratamento odontológico. Os estudos com intervenção odontológica em pacientes pediátricos em tratamento oncológico são muito limitados e a nossa pesquisa tem importante papel para identificação do perfil destes pacientes e suas necessidades. Os resultados obtidos serão fundamentais para a elaboração de protocolos e estratégias de atendimento direcionadas a esta população. / Introduction: cancer treatment in children often includes chemotherapy and / or radiotherapy that can determine changes in the oral cavity which consequently predispose to complications Stomatological. Objective: To verify the conditions of oral health in children and adolescents with cancer, at the time of diagnosis, and their relation to complications Stomatological after dental intervention. Methodology: included children and adolescents with cancer treated at the Pediatric Oncology Unit of the HCPA, during the period from May 2011 to December 2012. Through specific criteria, patients were divided into two groups, according to the oral health conditions in Favorable and Unfavorable at diagnosis. The analysis of the oral health status was related outcomes mucositis, dental infections, gingivitis, pericoronitis and eruption cysts during the first six months of cancer treatment. Associations were made with the toxic potential of QT, Gender, Age Group, RT head and neck, time to first complication and death. Statistical analysis included the chi-square test to compare categorical variables between the two groups, Mann - Whitney test to compare the degree of mucositis between the two groups, Kaplan Meier analysis of time to the emergence of outcomes and Cox regression to calculate the estimated probability of occurrence of outcomes. Results: 65 patients were included, 36 boys , 32 with Oral Health Favorable and Unfavorable 33 with Oral Health . In total we performed 839 evaluations. The Favorable group had fewer dental infections (P 0.003 ) than the group Unfavorable . A significant increase OM in patients treated with drugs with high risk for mucositis (P 0.001). Data suggest that the most unfavorable group has infections during the treatment using both drugs High Risk (26.1%) and low risk (40 %) for the MO. The incidence of OM was higher among patients in the age group of permanent dentition (13- 18 years) 82.4%, and among male patients (80.6%). The occurrence of odontogenic infection was higher among patients aged permanent dentition (41.2%) and among female patients (41.4%). The DMFT Unfavorable group of patients was 3.57, considered high risk for caries in the population studied. The visible plaque index and gingival bleeding reinforced the differences between the two groups. Conclusions: The pediatric oncology patients are exposed to the toxicity of chemotherapy drugs and thus are susceptible to risks from infectious processes. Infections originating in the oral cavity are common in this population and its prevention is directly linked to the protocols of oral hygiene dental treatment. Studies of dental intervention in pediatric cancer treatment are very limited and our research has an important role to identify the profile of these patients and their needs. The results will be fundamental to the development of protocols and service strategies directed toward this population.

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.

Orientador: Jair Cortez Montovani / Banca: Mariza Akemi Matsumoto / Banca: José Vicente Tagliarini / Resumo: A cavidade oral é um local potencial de complicações em pacientes imunossuprimidos podendo ser um importante local de agentes causadores de infecções sistêmicas, o que pode contribuir para a perda do transplante de célulastronco hematopoéticas, ou mesmo para o óbito do paciente. OBJETIVOS: Apresentar um modelo de avaliação para identificação de potenciais riscos das doenças orais em pacientes imunossuprimidos antes e após transplante de célulastronco hematopoéticas. O presente estudo é clínico, prospectivo, com modelo de coorte temporal longitudinal, realizado no período de julho de 2007 a dezembro de 2008 no Hospital Amaral Carvalho em Jaú/SP. Foram incluídos 65 pacientes divididos em 2 grupos de acordo com o tipo de transplante (alogênico e autológo), maiores de 18 anos, de ambos os sexos, portadores de doenças hematológicas malignas ou não, e que se submeteram ao transplante de células-tronco hematopoéticas no período acima citado. Foram feitas 3 avaliações odontológicas: no período pré-transplante (momento 1), uma semana após a infusão das célulastronco (momento 2) e cem dias pós-transplante (momento 3). Os dados de cada momento foram correlacionados de acordo com a pontuação obtida e os indivíduos foram classificados como grau de risco leve, moderado, grave e gravíssimo no momento 1 e graus de toxicidade leve, moderado, grave e gravíssimo nos momentos 2 e 3 para as complicações clínicas da cavidade oral. As alterações patológicas da boca mais frequentes foram as gengivites, pericoronarite de 3º molar e próteses nos três momentos. Porém, nos momentos 2 e 3 a principal causa do aumento da toxicidade associada a imunossupressão foi a mucosite. Mesmo em indivíduos classificados com grau leve, quando tinham mucosite em graus variados o período de internação hospitalar era maior o mesmo ocorrendo para as recidivas e óbitos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Oral cavity is a potential site for complications in immunosuppressed patients and it can be an important center of causative agents of systemic infections, which can contribute to the loss of hematopoietic stem cell transplantation, or even to patient's death. To present an assessment model for identifying the potential risks of oral diseases in immunosuppressed patients, before and after the hematopoietic stem cell transplantation. This is a clinical, prospective study with model of longitudinal temporal cohort performed from July/2007 to December/2008, at the Amaral Carvalho Hospital, Jau, São Paulo. The sample comprised 65 patients who were divided into 2 groups according to transplant type (allogenous and autologous), older than 18 years old, both sexes, with or without malignant hematopoietic diseases, and who undergone hematopoietic stem cell transplantation during the aforementioned period. Three dental assessments were executed: at pretransplantation (Time 1), at one week after stem cell infusion (Time 2), and at 100-day post-transplantation (Time 3). Data of each time were correlated according to the score obtained, and the individuals were classified in: mild, moderate, severe, and very severe risk groups at Time 1; and, in mild, moderate, severe and very severe toxicity levels at Time 2 and 3, regarding to clinical complications of oral cavity. The most frequent pathological conditions were: gingivitis, pericoronaritis due to third molar, and presence of prosthesis, at three times. However, at Time 2 and 3, the main cause of the increase of toxicity associated to immunosuppression was mucositis. Even when mild-risk individuals exhibited mucositis at several levels, the hospital stay length was higher, as well as the relapses and deaths. In the identification of oral diseases in patients who will undergo hematopoietic stem cell transplantation, mucositis accounted... (Complete abstract click electronic access below) / Mestre

Introdução: o tratamento oncológico em crianças inclui frequentemente quimioterapia e/ou radioterapia que podem determinar alterações à cavidade bucal que consequentemente predispõem à intercorrências estomatológicas. Objetivo: verificar as condições de saúde bucal em crianças e adolescentes portadores de neoplasias, no momento do diagnóstico, e sua relação com as complicações estomatológicas após intervenção odontológica. Metodologia: foram incluídas crianças e adolescentes portadores de neoplasias atendidas no Serviço de Oncologia Pediátrica do HCPA, durante o período de maio de 2011 a dezembro de 2012. Através de critérios específicos, os pacientes foram alocados em dois grupos, de acordo com as condições de saúde bucal, em Favorável e Desfavorável no momento do diagnóstico. A análise das condições de saúde bucal foi relacionada com os desfechos mucosite, infecções odontogênicas, gengivite, cistos de erupção e pericoronarite durante os primeiros seis meses de tratamento oncológico. Foram feitas associações com o potencial tóxico da QT, Gênero, Faixa Etária, RT de cabeça e pescoço, tempo até a primeira intercorrência e óbito. Análise estatística utilizou o teste Qui–quadrado para comparação de variáveis categóricas entre os dois grupos, Mann-Whitney para comparação da graduação de mucosite entre os dois grupos, Kaplan Meier para análise do tempo até o surgimento dos desfechos e Regressão de Cox para cálculo da probabilidade estimada de ocorrência dos desfechos. Resultados: foram incluídos 65 pacientes, sendo 36 meninos, 32 com Saúde Bucal Favorável e 33 com Saúde Bucal Desfavorável. No total foram realizadas 839 avaliações. O grupo Favorável apresentou menos infecções odontogênicas (P 0,003) que o grupo Desfavorável. No total foram realizadas 839 avaliações. O grupo Favorável apresentou menos infecções odontogênicas (P 0,003) que o grupo Desfavorável. Houve um aumento significativo de MO nos pacientes tratados com drogas com alto risco para mucosite (P 0,001). Os dados sugerem que o grupo Desfavorável apresenta mais infecções tanto durante o tratamento utilizando drogas de Alto Risco (26,1%) como Baixo Risco (40%) para a MO. A incidência de MO foi maior entre os pacientes da faixa etária de dentição permanente (13 a 18 anos) 82,4%, assim como entre os pacientes do gênero masculino (80,6%). A ocorrência de Infecção Odontogênica foi mais presente entre pacientes na faixa etária de dentição permanente (41,2%) e entre pacientes do gênero feminino (41,4%). O índice CPOD dos pacientes do grupo Desfavorável foi 3,57, considerado alto para risco de cárie na população estudada. Os índices de placa visível e sangramento gengival reforçaram as diferenças entre os dois grupos. Conclusões: os pacientes oncológicos pediátricos são expostos à toxicidade das drogas quimioterápicas e consequentemente estão suscetíveis aos riscos decorrentes de processos infecciosos. As infecções com origem na cavidade bucal são frequentes nesta população e sua prevenção está diretamente ligada aos protocolos de higiene bucal e tratamento odontológico. Os estudos com intervenção odontológica em pacientes pediátricos em tratamento oncológico são muito limitados e a nossa pesquisa tem importante papel para identificação do perfil destes pacientes e suas necessidades. Os resultados obtidos serão fundamentais para a elaboração de protocolos e estratégias de atendimento direcionadas a esta população. / Introduction: cancer treatment in children often includes chemotherapy and / or radiotherapy that can determine changes in the oral cavity which consequently predispose to complications Stomatological. Objective: To verify the conditions of oral health in children and adolescents with cancer, at the time of diagnosis, and their relation to complications Stomatological after dental intervention. Methodology: included children and adolescents with cancer treated at the Pediatric Oncology Unit of the HCPA, during the period from May 2011 to December 2012. Through specific criteria, patients were divided into two groups, according to the oral health conditions in Favorable and Unfavorable at diagnosis. The analysis of the oral health status was related outcomes mucositis, dental infections, gingivitis, pericoronitis and eruption cysts during the first six months of cancer treatment. Associations were made with the toxic potential of QT, Gender, Age Group, RT head and neck, time to first complication and death. Statistical analysis included the chi-square test to compare categorical variables between the two groups, Mann - Whitney test to compare the degree of mucositis between the two groups, Kaplan Meier analysis of time to the emergence of outcomes and Cox regression to calculate the estimated probability of occurrence of outcomes. Results: 65 patients were included, 36 boys , 32 with Oral Health Favorable and Unfavorable 33 with Oral Health . In total we performed 839 evaluations. The Favorable group had fewer dental infections (P 0.003 ) than the group Unfavorable . A significant increase OM in patients treated with drugs with high risk for mucositis (P 0.001). Data suggest that the most unfavorable group has infections during the treatment using both drugs High Risk (26.1%) and low risk (40 %) for the MO. The incidence of OM was higher among patients in the age group of permanent dentition (13- 18 years) 82.4%, and among male patients (80.6%). The occurrence of odontogenic infection was higher among patients aged permanent dentition (41.2%) and among female patients (41.4%). The DMFT Unfavorable group of patients was 3.57, considered high risk for caries in the population studied. The visible plaque index and gingival bleeding reinforced the differences between the two groups. Conclusions: The pediatric oncology patients are exposed to the toxicity of chemotherapy drugs and thus are susceptible to risks from infectious processes. Infections originating in the oral cavity are common in this population and its prevention is directly linked to the protocols of oral hygiene dental treatment. Studies of dental intervention in pediatric cancer treatment are very limited and our research has an important role to identify the profile of these patients and their needs. The results will be fundamental to the development of protocols and service strategies directed toward this population.

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.