Avaliação do Efeito do Laser Preventivo na Mucosite Oral Quimioinduzida em Pacientes Submetidos a Altas Doses de Metotrexato / Evaluation of the Effect of Preventive Laser on Chemo-induced Oral Mucositis in Patients Submitted to High Doses of Methotrexate / Evaluación del Efecto del Láser Preventivo em la Mucositis Oral Inducida por Quimioterapia en Pacientes Sometidos a Altas Dosis de Metotrexato

Introdução: A quimioterapia, uma das formas de tratamento de neoplasias malignas, tem sua administração associada a inúmeras drogas, sendo uma delas o metotrexato (MTX), de alta toxicidade, responsável por inúmeros fatores agravantes para a saúde e bem-estar do paciente. Uma das principais complicações é a mucosite oral, manifestação clínica resultante do tratamento oncológico que pode interferir no tratamento e na cura. Objetivo: Avaliar, comparativamente, por meio de um estudo retrospectivo, o efeito do laser preventivo na ocorrência da mucosite oral quimioinduzida em pacientes com osteossarcoma não metastático submetidos a altas doses de MTX, bem como a intensidade da mucosite oral, utilizando o laser preventivo após os ciclos quimioterápicos contendo o medicamento MTX nos pacientes atendidos no Hospital de Câncer infantojuvenil de Barretos/SP. Método: Estudo de coorte com coleta retrospectiva em prontuários. Os pacientes foram divididos em dois grupos, um submetido à terapia profilática com laser de baixa intensidade após infusão do MTX e outro grupo não submetido a essa terapia. Resultados: Os dados obtidos mostraram que houve redução da gravidade da mucosite oral com o uso da laserterapia preventiva, com resultados estatisticamente significativos (p<0,001), corroborando os resultados encontrados na literatura. Conclusão: O uso da laserterapia é uma terapêutica auxiliar importante na prevenção e na redução da severidade da mucosite oral em pacientes submetidos a altas doses de MTX, diminuindo o número de internações por mucosite e os atrasos no protocolo terapêutico, o que reduz gastos e melhora o prognóstico para o paciente.

Introduction: Chemotherapy, one of the treatments for malignant neoplasms, is associated to innumerous drugs, one of them methotrexate (MTX), of high toxicity, responsible for several health damages and impact on the patient's well-being. One of the main complications is oral mucositis, a clinical manifestation resulting from the oncologic treatment that can interfere in the treatment and cure. Objective: To evaluate comparatively through a retrospective study, the effect of preventive laser in the occurrence of chemo-induced oral mucositis in patients with non-metastatic osteosarcoma submitted to high doses of methotrexate (MTX), and the intensity of oral mucositis, using the preventive laser after the chemotherapy cycles containing the drug methotrexate (MTX) in the patients treated at the Child and Adolescent Cancer Hospital of Barretos/SP. Method:Retrospective cohort study with charts review. The patients were divided in two groups, one submitted to low-intensity laser prophylaxis therapy after infusion of MTX and another group not submitted to prophylactic therapy. Results: The data obtained showed that preventive laser-therapy reduced the severity of oral mucositis with statistically significant results (p<0.001), corroborating the results found in the literature. Conclusion: The use of laser therapy is an important auxiliary therapy in the prevention and reduction of severity of oral mucositis in patients submitted to high doses of MTX, reducing the number of hospitalizations and delays in therapeutic protocol, which reduces costs and improves the patient prognosis.

Introducción: La quimioterapia, es uma de las formas de tratamiento de las neoplasias malignas, tiene su administración asociada a numerosas drogas siendo una de ellas el metotrexato (MTX), de alta toxicidad, responsable de numerosos factores agravantes para la salud y bienestar del paciente. Una de las principales complicaciones es la mucositis oral, manifestación clínica resultante del tratamiento oncológico que puede interferir en el tratamiento y cura. Objetivo: Evaluar, comparativamente, a través de um estudio retrospectivo, el efecto del láser preventivo em la aparición de la mucositis oral quimio inducida em pacientes com osteosarcoma no mestastásico sometido a altas dosis de MTX, bien como la intensidade de la mucositis oral, utilizando el láser preventivo después de los ciclos quimioterápicos que contiene el medicamento MTX en los pacientes antendidos en el Hospital del Cáncer Infantojuvenil de Barretos/SP. Método: Estudio de coorte con colección retrospectiva en prontuários. Los pacientes fueron divididos em dos grupos, uno sometido a terapia profiláctica con láser de baja intensidade después de la infusión de MTX y otro grupo no sometido a terapia profiláctica. Resultados: Los dados obtenidos mostraron que hubo una reducción en la severidad de la mucositis oral con el uso de la terapia láser preventiva, con resultados estáticamente significativos (p<0,001), corroborando los resultados encontrados em la literatura. Conclusión: El uso de la terapia con láser es una terapia auxiliar importante en la prevención y reducción de la severidad de la mucositis oral em pacientes sometidos a altas dosis de MTX, diminuendo el número de internaciones por mucositis y retrasos en el protocolo terapéutico, lo que reduce los gastos y mejora el pronóstico para el paciente.

Orientações odontológicas aos pacientes submetidos à quimioterapia antineoplásica / Dental guidelines for patients undergoing antineoplastic chemotherapy

Objetivo: este trabalho propõe condutas bucais aos pacientes com indicação quimioterápica, a partir de uma revisão de literatura, visto que o paciente é pouco orientado em muitos casos. Material e métodos: a busca foi realizada a partir da base de dados PubMed/Medline. Apenas estudos observacionais e revisões da literatura, em inglês, espanhol e português, publicados entre 2001 e 2019, que abordassem o tratamento antineoplásico e apresentassem complicações bucais foram incluídos. Resultados: dez artigos preencheram os critérios de inclusão. Notou-se que a maioria dos efeitos adversos cessam ao fim da quimioterapia. As principais alterações bucais observadas foram mucosite, xerostomia e candidose. Diversas alternativas terapêuticas se mostraram eficazes, sendo fundamental individualizar o paciente e propor a melhor opção para o quadro específico apresentado. Considerações finais: A participação do cirurgião-dentista na equipe oncológica é extremamente importante, realizando intervenções odontológicas e orientando os pacientes, colaborando para uma melhor qualidade de vida e contribuindo significativamente no prognóstico da doença.(AU)

Objective: This study suggests oral management for chemotherapy patients, through a literature review, considering that patients are poorly instructed in most cases. Material and methods: The search was performed in the PubMed / Medline database. Only observational studies and literature reviews in English, Spanish, and Portuguese, published between 2001 and 2019, which discussed antineoplastic treatment and presented oral complications were included. Results: Ten articles met the inclusion criteria. Most adverse effects were observed to cease at the end of chemotherapy. The main oral changes observed were mucositis, xerostomia, and candidosis. Several therapeutic alternatives seem to be effective, and it is essential to individualize the patient and propose the best option for the specific condition. Final considerations: The participation of dentists in the cancer team is extremely important for performing dental interventions, guiding patients, helping to provide a better quality of life, and contributing significantly to the prognosis of the disease.(AU)

Amifostine reduces inflammation and protects against 5-fluorouracil-induced oral mucositis and hyposalivation

Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.

Chemotherapy protocols and incidence of oral mucositis. An integrative review / Protocolos quimioterápicos e incidência de mucosite bucal. Revisão integrativa

ABSTRACT This review aimed to analyze the scientific production on severity of oral mucositis as an adverse effect of chemotherapy. To this end, we performed a search at PubMed databases combining the keywords "oral mucositis" and "chemotherapy protocol". To describe the investigation, the following variables were considered: journal, year/place, study design, sample, protocol used and incidence of oral mucositis. A total of 547 articles were retrieved, of which 26 were selected. Out of these 26, only 2 reported severity of oral mucositis; the others only reported the presence of the condition. Protocols for treating different types of carcinoma were evaluated in 16 (61.53%) studies, for hematological malignancies in 6 (23.07%), and for hematopoietic stem cell transplantation in 4 (15.4%). Protocols for hematopoietic stem cell transplantation entail a high risk for oral mucositis, just as chemotherapy with cytarabine and high-dose 5-fluorouracil, alkylating agents and platinumbased compounds. To provide the best prevention and treatment for oral mucositis, it is essential to know the chemotherapy protocols used and their effects on the oral cavity.

RESUMO Esta revisão teve como objetivo analisar a produção científica sobre a gravidade da mucosite oral como efeito adverso da quimioterapia. Para tal, nos bancos de dados do PubMed, foi realizada uma busca com a associação dos descritores "oral mucositis" com "chemotherapy protocol". Para descrição da investigação, foram consideradas como variáveis: periódico, ano/local, delineamento da pesquisa, amostra, protocolo utilizado e incidência de mucosite oral. Foram analisados 547 artigos e, destes, 26 foram selecionados. Destes 26, apenas 2 tinham como objetivo avaliar a gravidade de mucosite oral; nos outros, a mucosite oral foi apenas relatada. Protocolos para tratamento de diferentes tipos de carcinoma foram avaliados em 16 (61,53%) estudos, para neoplasias hematológicas, em 6 (23,07%), e para transplante de células tronco hematopoiéticas em 4 (15,4%). Protocolos para transplante de células tronco hematopoiéticas são de alto risco para o desenvolvimento de mucosite oral, da mesma forma que os quimioterápicos citarabina e 5-fluorouracil em altas doses, agentes alquilantes e compostos derivados da platina. A fim de oferecer prevenção e tratamento mais adequados para mucosite oral, é imprescindível que se conheçam os protocolos quimioterápicos utilizados e seus efeitos sobre a cavidade oral.

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil

Abstract Purpose: To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Methods: Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Results: Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Conclusions: Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

Effectiveness of low intensity laser therapy on oral mucositis in head and neck cancer patients / Efetividade da terapia com laser de baixa intensidade em mucosite oral de pacientes com câncer de cabeça e pescoço

Introduction: About 870,000 new cases of malignant airway and digestive tract tumor are diagnosed annually worldwide. Patients undergoing radiotherapy (RT) for head and neck develop as side effects oral mucositis and other complications that can lead to discontinuation of anticancer treatment. Aim: This study was conducted to determine whether oral care can reduce the rates of discontinuation of anticancer treatment. Method: We selected patients with carcinoma of the head and neck radiotherapy with or without chemotherapy (CT) in the Hospital São Vicente de Paulo de Passo Fundo. A total of 187 patients were evaluated and divided into two groups: Group I (patients receiving dental treatment) and Group II (patients not receiving dental treatment). Group I ­ patient were submitted to daily assessments, receiving guidance, following a protocol for dental treatment and adjuvant application of low intensity laser throughout the period they performed RT. Group II - patients were evaluated and followed only, for not allowing the proposed treatment. Results: The interruption of radiation treatment was 2.4% of the patients in Group I, and Group II 34.6%. Conclusions: prevention and early treatment of complications related to RT like oral mucositis can decrease the chance of the patient to abandon radiotherapy and consequently contribute for a better prognosis for cure and patient survival (AU)

Introdução: Cerca de 870 mil novos casos de neoplasias malignas de vias aéreas e tumores do aparelho digestivo são diagnosticados anualmente em todo o mundo. Os pacientes submetidos à radioterapia (RT) de cabeça e pescoço desenvolvem efeitos colaterais como mucosite oral e outras complicações que podem levar à interrupção do tratamento anticâncer. Objetivo: Este estudo foi realizado para determinar se cuidados bucais podem reduzir as taxas de abandono do tratamento anticâncer. Método: Foram selecionados pacientes com carcinoma de cabeça e pescoço submetidos a radioterapia (RT), com ou sem quimioterapia (QT), no Hospital São Vicente de Paulo de Passo Fundo. Um total de 187 pacientes foram avaliados e divididos em dois grupos: Grupo I (pacientes que recebem tratamento dental) e Grupo II (pacientes que não receberam tratamento dental). Os pacientes do grupo I foram submetidos a cuidados diários, recebendo orientação, seguindo um protocolo de tratamento odontológico e aplicação adjuvante do laser de baixa intensidade durante todo o período que realizaram RT. Os pacientes do grupo II foram avaliados odontologicamente e acompanhados somente. Resultados: A interrupção do tratamento com radiação foi de 2,4% dos pacientes do Grupo I e no Grupo II 34,6%. Conclusões: a prevenção e o tratamento precoce das complicações relacionadas com a RT, como mucosite oral, podem diminuir a chance de o paciente abandonar a radioterapia e, consequentemente, contribuir para um melhor prognóstico de cura e sobrevida dos pacientes (AU)

Serious stomatitis and esophagitis: a peculiar mucous reaction induced by pegylated liposomal doxorubicin

Pegylated liposomal doxorubicin is an important antineoplastic agent with activity in a variety of solid tumors. It has a totally different profile of pharmacokinetics and toxicity compared with doxorubicin. It rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in many kinds of mucocutaneous reactions, including palmar-plantar erythrodysesthesia, diffuse follicular rash, intertrigo-like eruption, new formation of melanotic macules, stomatitis and radiation recall dermatitis. We present a rare case of multiple myeloma who immediately developed serious stomatitis and esophatitis associated with minor palmar-plantar erythrodysesthesia after a single course of pegylated liposomal doxorubicin.

New drugs, new challenges for dermatologists: mucocutaneous ulcers secondary to everolimus

Everolimus, a mammalian target of rapamycin inhibitor, is an emerging drug, which is being increasingly applied in oncology and solid organ transplantation. Oral ulcers are a frequent side effect associated with this immunosupressor. We report the case of a renal transplant recipient who developed disfiguring oral and perianal ulcers secondary to everolimus's toxicity. This is probably the first report of perianal involvement. Dermatologists need to be aware of the potential mucocutaneous adverse effects related to these new drugs that are becoming evermore common in our clinical practice.

Análise da ação do gel de plaquetas e glutamina em mucosite causada por quimioterapia induzida em ratos Wistar / Analysis of Platelet Gel Action and Glutamine in Mucositis caused by chemotherapy induced in Wistar Rats

Neste estudo avaliou-se a ação do gel de Plaquetas e da Glutamina no processo de cicatrização de lesões bucais causadas por mucosite induzida por quimioterapia em ratos Wistar. Foram utilizados 50 animais divididos em 05 grupos: um Grupo A (Gel de Plaquetas), Grupo B (Glutamina tópica), Grupo C (Glutamina gavagem), Grupo D (Glutamina + Gel de plaquetas) e Grupo E (controle +). A partir do 7o dia após a quimioterapia, avaliou-se os graus de mucosite e iniciou-se a aplicação dos medicamentos propostos para cada grupo. O sacrifício dos animais ocorreu em 5 e 10 dias após o início de aplicação dos medicamentos. Foram realizadas as biópsias da mucosa jugal e língua para análise do exame histopatológico onde se avaliou a quantidade de macrófagos, linfócitos e queratinização. Os graus de mucosite desenvolvidos na 1a e 2a fase do experimento apresentaram variação numérica importante, mas sem diferenças estatísticas significantes. Na análise histológica, resultados estatisticamente significativos foram obtidos (Fase 1) para linfócitos em mucosa jugal, onde o grupo B (glutamina) foi maior que o do grupo D (gel de plaquetas + glutamina) (p = 0,032); os linfócitos em língua do grupo A (gel de plaquetas) (p = 0,000) foi superior quando comparado com todos os outros grupos. A queratinização em mucosa jugal no grupo D (Fase 1) apresentou resultados significativamente superiores quando comparada com a queratinização dos demais grupos. A queratinização em língua no grupo D apresentou diferenças estatisticamente significantes (p = 0,000) e maior em relação aos outros grupos. Na fase 2, os macrófagos em língua tiveram resultados significantes entre os grupos A e C (p = 0,031) e A e E (p = 0,006), onde A foi maior. Diante dos resultados encontrados, concluiu-se que os biocurativos utilizados neste estudo promoveram uma maior reação inflamatória no conjuntivo e maior queratinização no epitélio. Entretanto, clinicamente, nas lesões observadas, o tempo de cicatrização foi...

Among bio-curatives there are those derived from the addition "in vitro" of thrombin and calcium gluconate to the platelet rich human plasma that stimulate its degranulation to releasing of growth factors acting on the healing process. Glutamine is the amino acid present in plasma and muscle tissue being considered an important energetic source for the immune system cells. Mucositis is a denomination for the changes that occur in the oral mucosa, mainly due to the cancer treatments. In this study, the action of platelet gel and Glutamine was evaluated in the oral lesions healing process caused by mucositis induced by chemotherapy in Wistar rats. 50 animals divided into 05 groups were used: A Group (Platelet Gel), B Group (Topical glutamine), C Group (Glutamine gavage), D Group (Glutamine + Platelet Gel) and E Group (control +). From the 7th day after chemotherapy, the degree of mucositis was evaluated and the proposed drug application began for each group. The animal sacrifice occurred within 5 to 10 days after the medicine application beginning. Jugal and tongue mucosa biopsies for histopathological examination analysis were carried out which evaluated the macrophages amount, lymphocytes and keratinization. The mucositis degrees developed in the 1st and 2nd phase of the experiment showed important numerical variation, but without meaningful statistical differences. In the histological analysis, statistically meaningful results were obtained (Phase 1) for lymphocytes in the jugal mucosa where the B group (glutamine) was higher than D group (platelet gel + glutamine) (p = 0,032); lymphocytes in tongue in A group (platelet gel) (p = 0,000) was higher when compared to all other groups. Keratinization in the jugal mucosa in D group (Phase 1), showed meaningfully superior results when compared to the keratinization of the other groups. The Keratinization in tongue in D group showed meaningful statistical differences (p = 0,000) and higher compared to the other...

Análise da ação do gel de plaquetas e glutamina em mucosite causada por quimioterapia induzida em ratos Wistar / Analysis of Platelet Gel Action and Glutamine in Mucositis caused by chemotherapy induced in Wistar Rats

Neste estudo avaliou-se a ação do gel de Plaquetas e da Glutamina no processo de cicatrização de lesões bucais causadas por mucosite induzida por quimioterapia em ratos Wistar. Foram utilizados 50 animais divididos em 05 grupos: um Grupo A (Gel de Plaquetas), Grupo B (Glutamina tópica), Grupo C (Glutamina gavagem), Grupo D (Glutamina + Gel de plaquetas) e Grupo E (controle +). A partir do 7o dia após a quimioterapia, avaliou-se os graus de mucosite e iniciou-se a aplicação dos medicamentos propostos para cada grupo. O sacrifício dos animais ocorreu em 5 e 10 dias após o início de aplicação dos medicamentos. Foram realizadas as biópsias da mucosa jugal e língua para análise do exame histopatológico onde se avaliou a quantidade de macrófagos, linfócitos e queratinização. Os graus de mucosite desenvolvidos na 1a e 2a fase do experimento apresentaram variação numérica importante, mas sem diferenças estatísticas significantes. Na análise histológica, resultados estatisticamente significativos foram obtidos (Fase 1) para linfócitos em mucosa jugal, onde o grupo B (glutamina) foi maior que o do grupo D (gel de plaquetas + glutamina) (p = 0,032); os linfócitos em língua do grupo A (gel de plaquetas) (p = 0,000) foi superior quando comparado com todos os outros grupos. A queratinização em mucosa jugal no grupo D (Fase 1) apresentou resultados significativamente superiores quando comparada com a queratinização dos demais grupos. A queratinização em língua no grupo D apresentou diferenças estatisticamente significantes (p = 0,000) e maior em relação aos outros grupos. Na fase 2, os macrófagos em língua tiveram resultados significantes entre os grupos A e C (p = 0,031) e A e E (p = 0,006), onde A foi maior. Diante dos resultados encontrados, concluiu-se que os biocurativos utilizados neste estudo promoveram uma maior reação inflamatória no conjuntivo e maior queratinização no epitélio. Entretanto, clinicamente, nas lesões observadas, o tempo de cicatrização foi...

Among bio-curatives there are those derived from the addition "in vitro" of thrombin and calcium gluconate to the platelet rich human plasma that stimulate its degranulation to releasing of growth factors acting on the healing process. Glutamine is the amino acid present in plasma and muscle tissue being considered an important energetic source for the immune system cells. Mucositis is a denomination for the changes that occur in the oral mucosa, mainly due to the cancer treatments. In this study, the action of platelet gel and Glutamine was evaluated in the oral lesions healing process caused by mucositis induced by chemotherapy in Wistar rats. 50 animals divided into 05 groups were used: A Group (Platelet Gel), B Group (Topical glutamine), C Group (Glutamine gavage), D Group (Glutamine + Platelet Gel) and E Group (control +). From the 7th day after chemotherapy, the degree of mucositis was evaluated and the proposed drug application began for each group. The animal sacrifice occurred within 5 to 10 days after the medicine application beginning. Jugal and tongue mucosa biopsies for histopathological examination analysis were carried out which evaluated the macrophages amount, lymphocytes and keratinization. The mucositis degrees developed in the 1st and 2nd phase of the experiment showed important numerical variation, but without meaningful statistical differences. In the histological analysis, statistically meaningful results were obtained (Phase 1) for lymphocytes in the jugal mucosa where the B group (glutamine) was higher than D group (platelet gel + glutamine) (p = 0,032); lymphocytes in tongue in A group (platelet gel) (p = 0,000) was higher when compared to all other groups. Keratinization in the jugal mucosa in D group (Phase 1), showed meaningfully superior results when compared to the keratinization of the other groups. The Keratinization in tongue in D group showed meaningful statistical differences (p = 0,000) and higher compared to the other...

Toxicidad severa asociada a metotrexato: caso clínico / Severe toxicity associated with methotrexate: clinical case

El metotrexato (MTX) es un agente anti folato con actividad antineoplásica e inmunosupresora que ha alcanzado gran aceptación y uso debido a su eficacia en distintos desórdenes reumatológicos. Sin embargo, tiene el potencial para causar complicaciones serias y, a veces, mortales, principalmente hematológicas, hepáticas o pulmonares. Los factores de riesgo para el desarrollo de pancitopenia incluyen edad avanzada, alteración de la función renal, niveles bajos de ácido fólico y uso concomitante de otros fármacos que modifiquen el metabolismo del folato. Presentamos un caso de pancitopenia severa y estomatitis, secundaria a una dosis estándar de MTX, en una paciente de 53 años de edad, con Artritis Reumatoídea (AR) de 10 años de evolución y enfermedad renal crónica en hemodiálisis trisemanal. Es muy importante prestar atención a los factores de riesgo asociados a la aparición de efectos adversos antes de iniciar terapia con MTX en pacientes reumatológicos. Además, los pacientes con MTX deben ser monitorizados durante su tratamiento para identificar efectos adversos hematológicos severos, como la pancitopenia.

Methotrexate (MTX) is an agent for anti-folate with antineoplastic activity and immunosuppressive that has achieved wide acceptance and use due to its efficacy in various rheumatologic disorders. However, it has the potential to cause complications serious and sometimes deadly, primarily hematologic, hepatic or pulmonary. The factors of risk for the development of pancytopenia include advanced age, renal function, low levels of folic acid and concomitant use of other drugs that alter the metabolism of folate. We present a case of severe pancytopenia and stomatitis, secondary to a standard dose of MTX in patient of 53 years, with rheumatoid arthritis (RA) of 10 years of evolution and chronic kidney disease on hemodialysis immediately. It is very important to pay attention to the risk factors associated with the occurrence of adverse effects, before initiating therapy with MTX in rheumatologic patients. In addition MTX patients should be monitored during treatment to identify severe haematological adverse effects such as pancytopenia.

Metotrexate como inductor en la producción de citocinas proinflamatorias en células epiteliales / Methotrexate as inducer of proinflammatory cytokines by epithelial cells

El metotrexate (MTX) es uno de los medicamentos frecuentemente utilizados en el cáncer infantil señalándose además, como agente citotóxico de la mucosa bucal, que puede desencadenar el proceso inflamatorio e incremento de la vascularidad en los tejidos epiteliales durante las fases iniciales de la mucositis oral. El presente trabajo tiene como objetivo determinar la producción de citocinas proinflamatorias IL-1b, IL-6 y TNF-a en cultivos de células epiteliales tratadas con MTX. Se realizaron cultivos de células epiteliales de laringe humana obtenidas de la línea celular Hep-2, con diferentes dosis de MTX en distintos tiempos de incubación, y a su vez se analizó la citotoxicidad del fármaco mediante el ensayo colorimétrico, el cual se basa en la reducción metabólica del bromuro de 3-(4,5- dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT), y la producción de citocinas proinflamatorias mediante el ensayo inmuno enzimático indirecto (ELISA). En cuanto a los resultados se observó, que los cultivos de células Hep-2 presentaron aumento en la producción de las citocinas proinflamatorias a las 72 horas al utilizar las dosis de 0.32µM MTX. Estos resultados sugieren que la dosis y el tiempo de exposición del MTX alteran la fisiología de las células epiteliales humanas, lo cual podrían desempeñar un papel importante durante las fases de iniciación y de desarrollo de la mucositis oral.

Methotrexate (MTX), a drug commonly used in childhood cancer, has also been indicated as a cytotoxic agent of the oral mucosa, which can trigger the inflammatory process and increase the vascularity of epithelial tissues during the early stages of oral mucositis. The aim of this study was to determine the production of proinflammatory cytokines IL-1b, IL-6 y TNF-a in epithelial cell cultures treated with MTX. Epithelial cells of human larynx, obtained from the cell line Hep-2, were cultured with different doses of MTX during different incubation times. The drug cytotoxicity was analyzed by means of the colorimetric test, which is based on the metabolic reduction of the bromide of 3-(4, 5-dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT); and the proinflammatory cytokines production by the test enzyme-linked immunosorbent assay (ELISA). Cultures of HEp-2 cells showed increased production of proinflammatory cytokines at 72 hours with 0.32µM of MTX. These results suggest that depending on the dose and exposure time, MTX alters the physiology of human epithelial cells, which may play an important role during the phases of initiation and development of oral mucositis.

Effect of laser phototherapy in the prevention and treatment of chemo-induced mucositis in hamsters

The aim of this study was to investigate the effect of laser phototherapy (LPT) in the prevention and/or treatment of oral mucositis induced by 5-fluorouracil (5-FU; Eurofarma, São Paulo, Brazil) in hamsters. Ninety-six hamsters were divided into four groups (n = 24): Control (no treatment); Preventive [LPT from day (D) D-5 to D+5]; Therapeutic (LPT from D+5 to D+15); and Combined (preventive plus therapeutic LPT from D-5 to D+15). The animals received an intraperitoneal injection of 5-FU on Days 0 and 2. The pouch mucosa was scratched on Days 3 and 4. The irradiation parameters were: indium-gallium-aluminum-phosphide (InGaAlP) diode laser (MM Optics, São Carlos, Brazil) (660 nm), beam area of 0.036 cm2, 40 mW, 1.11 W/cm2, 6.6 J/cm2, power density applied daily of 39.6 J/cm2, in punctual mode (six points and six seconds per point) and contact mode, one application per day. The animals were sacrificed on Days 0, 5, 10 and 15 (n = 6) and weighed, and the pouch mucosa was removed for histopathological analysis. Clinical and corresponding histological scores were compared using ANOVA and Tukey's test (p ≤0.05). Similar weight losses ranging from 5% to 10% occurred in all groups. The therapeutic group had significantly lower clinical and histological scores than the other groups at Day 10. This study showed that positive effects on oral mucositis management were obtained only when LPT was applied in the therapeutic protocol (from D+5 to D+15 after chemotherapy).

Tratamiento y prevención de la mucositis oral asociada al tratamiento del cáncer / Treatment and prevention of cáncer treatment related oral mucositis

One ofthe most common and troublesome complications ofmodern intensive anticancer treatments is oral mucositis. The purpose ofthis review is to summarize current evidente and clinical guidelines regarding its prevention and therapy. The use of keratinocyte growth factor-1, supplementary glutamine and other recently developed treatment modalities are discussed. The injury ofthe oral mucosa caused by antineoplastic agents promotes the local expression of múltiple pro-inflammatory and pro-apoptotic molecules and eventually leads to the development of ulcers. Such lesions predispose patients to several infectious and nutritional complications. Also, they lead to modification of treatment schedules, potentially affecting overall prognosis. Local cryotherapy with ice chips and phototherapy with low energy láser may be useful as preventive measures. Mouthwashes with allopurinol and phototherapy with low energy láser can be used as treatment. In radiotherapy, special radiation administration techniques should be used to minimize mucosal injury. Pain control should always be optimized, with the use ofpatient controlled analgesia and topical use of morphine. Supplemental glutamine should not be used outside of research protocols. Lastly, thorough attention should bepaid to general care and hygiene measures.

Mucosite oral induzida por radiação: uso de fatores de crescimento e de laser / Radiation-induced oral mucositis: the use of growth factors and laser

Dosagens de radiação em torno de 50 a 70 Gy são consideradas de risco para o desenvolvimento de mucosite oral. Foi realizado um levantamento da literatura relacionada com a mucosite oral induzida por radiação em humanos na base de dados MEDLINE, tendo como critério inicial a seleção de artigos completos publicados em inglês de 1995 a 2005. Foram identificados 40 trabalhos relevantes, dos quais apenas 17 apresentavam evidências científicas sobre o uso local de fatores de crescimento e do laser de baixa potência como modalidades terapêuticas para a mucosite oral. A maioria dos autores considerava o sistema de gradação em escores preconizado pela Organização Mundial da Saúde como o mais adequado para a classificação do grau de evolução desta complicação oral. Observou-se, a partir da análise realizada, que o uso local de fatores de crescimento e do laser de baixa potência pode reduzir a severidade da mucosite oral induzida por radiação, favorecendo a proliferação celular e, consequentemente, a indução do reparo da mucosa e contribuindo para melhorar a qualidade de vida dos pacientes.

Radiation doses of 50 to 70 Gy may cause oral mucositis. The MEDLINE database was searched for full articles published in English from 1995 to 2005 on radiation-induced oral mucositis in humans. Forty relevant articles were found and of these, only 17 presented scientific evidence of the use of growth factors and low-power laser administered locally as treatment options for oral mucositis. Most authors considered the World Health Organization's grading system the most appropriate for classifying the grade of this oral complication. Review of these articles revealed that growth factors and low-power laser used locally can reduce the severity of radiation-induced oral mucositis, stimulating cell proliferation and consequently, promote healing. This helps to better the quality of life of these patients.

Reações tegumentares adversas relacionadas aos agentes antineoplásicos: parte I / Adverse mucocutaneous reactions to chemotherapeutic agents: part I

O tratamento local e sistêmico das neoplasias pode causar alterações na pele, membranas mucosas, cabelos e unhas. O diagnóstico preciso e o tratamento adequado destes efeitos colaterais requerem conhecimento dos padrões das reações adversas mais comuns para as medicações que o paciente está utilizando. O dermatologista deve estar familiarizado com as manifestações tegumentares das neoplasias, bem como com os efeitos adversos mucocutâneos dos tratamentos antineoplásicos.

The local and systemic treatment of tumors can cause changes in the skin, mucous membranes, hair and nails. Accurate diagnosis and appropriate treatment of side effects require knowledge about the patterns of the most common adverse reactions to drugs the patient may be using. The dermatologist must be familiar with the manifestations of certain soft tissue neoplasms, as well as with the adverse mucocutaneous forms of cancer treatment.

Complicações orais decorrentes da terapia antineoplásica / Oral complications of cancer therapy

É comum, em pacientes oncológicos submetidos à terapia antineoplásica, o desenvolvimento de complicações orais agudas ou tardias. Esses distúrbios na integridade e função da cavidade bucal se devem ao fato de que a radioterapia e quimioterapia não são capazes de destruir as células tumorais sem lesionar células normais. Dentre as complicações orais encontram-se a mucosite, xerostomia, disgeusia, as infecções fúngicas, bacterianas e virais, as cáries de radiação, trismo, osteorradionecrose, neurotoxicidade, e, em pacientes pediátricos, o comprometimento da formação óssea, muscular e dentária. Esses efeitos geralmente variam a cada paciente dependendo de variáveis do tratamento, do paciente e do tumor. O objetivo do presente trabalho foi apresentar as complicações orais decorrentes da terapia antineoplásica bem como a importância da atuação do cirurgião-dentista nesse contexto. Através da literatura pesquisada, foi possível concluir que é imprescindível que os pacientes oncológicos sejam acompanhados antes, durante e após a terapia antineoplásica a fim de que o cirurgião-dentista possa elaborar um plano de tratamento adequado às suas necessidades, de forma a prevenir ou controlar a ocorrência dessas complicações.