Dental consensus on HSCT - Part II: dental Care during HSCT

ABSTRACT During the state of immune vulnerability in hematopoietic stem cell transplantation (HSCT), the patient has an increased risk of developing a vast number of complications, including severe problems in the oral cavity. These situations require professional oral care to act in the diagnosis and treatment of these conditions, as well as to develop prevention protocols to minimize patient's complications. Oral mucositis, opportunistic infections, bleeding, specific microbiota, taste, and salivary alterations are complications that can occur during HSCT and interfere with various aspects, such as pain control, oral intake, nutrition, bacteremia and sepsis, days of hospitalization and morbidity. Several guidelines have been published to address the role of professional oral care during the HSCT, we describe a consensus regarding these recommendations.

Ação da própolis no manejo de lesões não infecciosas em cavidade oral: uma revisão integrativa / The effects of Propolis in the management of non-infectious lesions in the oral cavity: an integrative review

ntrodução: a própolis é um produto natural que apresenta inúmeras propriedades terapêuticas, dentre elas a ação cicatrizante e anti-inflamatória. Diversos estudos têm sugerido o seu emprego no manejo da mucosite oral (MO) e de lesões ulceradas em mucosa bucal. A MO é uma inflamação da mucosa oral, resultante do tratamento quimio e/ou radioterápico. Já as lesões ulceradas caracterizam-se como um distúrbio ulcerativo inflamatório doloroso. Objetivo: discutir a ação da própolis sobre a prevenção e cicatrização de lesões de origem não infecciosa que acometem a cavidade oral. Metodologia: trata-se de uma revisão integrativa da literatura em que foram utilizadas as bases de dados LILACS, PubMed, SciELO e Cochrane, por meio do cruzamento dos descritores em português: "própolis", "úlceras orais" e "mucosite oral"; e em inglês: "propolis", "oral ulcer" e "mucositis". Os seguintes critérios de inclusão foram estabelecidos: ensaios clínicos e revisões sistemáticas, na íntegra, escritos em inglês ou português, entre 2005 e 2018, que utilizaram a própolis de forma tópica ou sistêmica. Resultados: foram incluídos um total de 10 estudos, onde 2 abordaram o uso da própolis em úlceras orais e 8 tiveram como foco a aplicação deste agente no manejo da MO. Quanto ao desfecho, a aplicação da própolis na mucosite se mostrou eficaz em 7 dos 8 estudos. Já se tratando de úlceras orais, a administração deste agente foi efetiva nos 2 estudos. Conclusão: os estudos analisados demostraram que a própolis apresenta propriedades capazes de favorecer a prevenção e cicatrização de lesões de MO e úlceras orais.

Introduction: propolis is a natural product that has numerous therapeutic properties, including healing and anti-inflammatory action. Several studies have suggested its use in the management of oral mucositis (OM) and ulcerated lesions in the oral mucosa. OM is an inflammation of the oral mucosa resulting from chemotherapy and/or radiotherapy. Whereas ulcerated lesions are characterized as a painful inflammatory ulcerative disorder. Objective: to discuss the action of propolis on the prevention and healing of non-infectious lesions that affect the oral cavity. Methodology: this is an integrative literature review in which LILACS, PubMed, SciELO and Cochrane databases were used, by crossing descriptors in Portuguese: "própolis", "úlceras orais" and "mucosite oral"; and in English: "propolis", "oral ulcer" and "mucositis". The following inclusion criteria were established: clinical trials and systematic reviews, in full, written in English or Portuguese, between 2005 and 2018, which used propolis topically or systemically. Results: a total of 10 studies were included, where 2 addressed the use of propolis in oral ulcers and 8 focused on the application of this agent in the management of OM. As for the outcome, the application of propolis in mucositis proved to be effective in 7 of the 8 studies. As for oral ulcers, the administration of this agent was effective in both studies. Conclusion: the analysed studies demonstrated that propolis has properties capable of help the prevention and healing of OM lesions and oral ulcers.

Update on the treatment of chemotherapy and radiotherapy-induced buccal mucositis: a systematic review / Actualización en el tratamiento de la mucositis oral inducida por quimioterapia y radioterapia: una revisión sistemática

ABSTRACT Oral mucositis (OM) is a frequent complication in cáncer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa, sometimes provoking severe consequences such as eating limitations, difficulty in speaking, and possibly superinfection. Aim: The aim of this review was to update the evidence published during the last five years on the treatment of oral mucositis induced by radiotherapy and/or chemotherapy in patients with cancer. Materials and Method: A search was conducted in Pubmed, Scielo and Scopus, using the search terms mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, with Mesh terms and free terms, from 2017 to January 2023. The systematic review was conducted in accordance with the PRISMA guidelines. Results: A total 287 articles were retrieved, of which 86 were selected by title and abstract, and 18 were included after full-text analysis. The most frequently assessed variables were OM severity, pain intensity and healing time. Treatment types were diverse, and included drugs, mouthwashes, medicines based on plant extracts, cryotherapy and low-intensity laser therapies. Conclusión: Dentoxol mouthwashes, Plantago major extract, thyme honey extract, zinc oxide paste, vitamin B complex combined with GeneTime, and the consumption of L-glutamine are effective in diminishing the severity of OM. Pain intensity was lower with doxepin mouthwashes and diphenhydramine-lidocaine-antacid mouthwashes.

RESUMEN La mucositis oral (MO) es una complicación frecuente en pacientes oncológicos sometidos a quimioterapia o radioterapia. Se manifiesta como una inflamación de la mucosa oral, provocando en ocasiones graves consecuencias como limitaciones en la alimentación, dificultad para hablar y posiblemente sobreinfección. Objetivo: El objetivo de esta revisión fue actualizar la evidencia publicada durante los últimos cinco años sobre el tratamiento de la mucositis oral inducida por radioterapia y/o quimioterapia, en pacientes con cáncer. Materiales y Método: Se realizó una búsqueda en Pubmed, Scielo y Scopus, con las palabras de búsqueda mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, utilizando términos Mesh y libres, de 2017 a enero de 2023. La revisión sistemática se realizó de acuerdo con los lineamientos de declaración del PRISMA. Resultados: Se obtuvieron un total de 287 artículos, de los cuales 86 fueron seleccionados por título y resumen y finalmente 18 fueron incluidos por texto completo. Las variables evaluadas con mayor frecuencia fueron la severidad de la MO, la intensidad del dolor y el tiempo de cicatrización. Los tipos de tratamientos fueron diversos, desde medicamentos, colutorios bucales, medicamentos a base de extractos de plantas, crioterapia y terapias con láser de baja intensidad. Conclusiones: Los enjuagues bucales de Dentoxol, extracto de Plantago major, extracto de miel de tomillo, pasta de óxido de zinc, mezcla de compuestos de vitamina B combinados con GeneTime y el consumo de L-glutamina son efectivos para disminuir la severidad de la MO. La intensidad del dolor fue menor con los colutorios de doxepina y también con los colutorios de difenhidramina-lidocaína-antiácido. Palabras clave: mucositis bucal;cáncer;quimioterapia;radioterapia;tratamiento

Influência da via hippo no reparo da mucosite oral quimicamente induzida em modelo murino submetida a tratamento com laser, geleia real ou própolis / Influence of the hippo pathway on the repair of chemically induced oral mucositis in a murine model subjected to treatment with laser, royal jelly or propolis

A via hippo é uma via de transdução de sinal altamente conservada que está implicada no desenvolvimento, homeostase e regeneração celular/tecidual. A YAP tem papel fundamental na via hippo uma vez que junto com a TAZ ativam fatores de transcrição que levam ao crescimento, diferenciação e migração celular. O mecanismo de fosforilação da YAP/TAZ pela LATS1/LATS2 cria um sítio de ligação para manter a YAP no citoplasma (fosforilada) impedindo suas funções a nível nuclear. Diante das importantes funções desta via no reparo e crescimento tecidual, esta pesquisa avaliou se a via hippo exerceu influência na resposta ao tratamento da MO através da expressão das proteínas YAP e LATS2 em mucosite oral (MO) quimicamente induzida pelo 5- fluoracil (5-FU), em modelo murino, tratada com própolis (P), geleia real (GR) ou laser (L) comparadas ao grupo controle (C), sem tratamento. Foram utilizadas amostras de ratos machos wistar divididos nos seguintes grupos: C, P, GR e L (intraoral 6 J/cm2 ) separados em três tempos experimentais: dias 08, 10 e 14. O perfil de imunomarcação foi feito por escores padronizados entre 0 a 3 levando em consideração a marcação nuclear e/ou citoplasmática. Na análise de imunomarcação da YAP, no dia 08, o grupo controle obteve os escore 0 e 1 na maioria das amostras, já nos dias 10 e 14 a maior parte das amostras obteve os escore 2 e 3. Nos grupos experimentais (L, GR e P), o escore 2 prevaleceu em todos os tempos experimentais. Para LATS2 houve prevalência do escore 2 tanto no grupo controle quanto nos grupos teste em todos os tempos experimentais. Em relação a análise estatística da imunoexpressão da proteína YAP, verificou-se diferença estatítica significativa (p= 0,020), apenas no dia 08 entre o grupo controle comparado aos grupos experimentais (L, GR e P). Já para LATS2 nenhuma diferença estatística foi encontrada. Na avaliação estatística dos diferentes tempos experimentais dentro um mesmo grupo, só foi encontrada diferença estatística significativa no grupo laser e apenas para LATS2 (p=0,025). Adicionalmente foi realizada a correlação de spearman, entre YAP e LATS2 para todos os grupos, porém não houve associação estatística significativa. A maior imunoexpressão de YAP e LATS2 (escores 2 e 3) observada nos grupos experimentais, indica que a via hippo é ativada e parece influenciar o processo de reparo nas mucosites orais quimioinduzidas e tratadas pelos diferentes métodos (AU).

The hippo pathway is a highly conserved signal transduction pathway that is implicated in cell/tissue development, homeostasis and regeneration. YAP plays a key role in the hippo pathway since, together with TAZ, they activate transcription factors that lead to cell growth, differentiation and migration. The YAP/TAZ phosphorylation mechanism by LATS1/LATS2 creates a binding site to keep YAP in the cytoplasm (phosphorylated) preventing its functions at the nuclear level. Given the important functions of this pathway in tissue repair and growth, this research evaluated whether the hippo pathway exerted influence on the response to OM treatment through the expression of YAP and LATS2 proteins in oral mucositis (OM) chemically induced by 5-fluororacil (5- FU), in a murine model, treated with propolis (P), royal jelly (GR) or laser (L) compared to the control group (C), without treatment. Samples of male Wistar rats divided into the following groups were used: C, P, GR and L (intraoral 6 J/cm2) separated into three experimental times: days 08, 10 and 14. The immunostaining profile was performed by standardized scores between 0 to 3 taking into account nuclear and/or cytoplasmic labeling. In the YAP immunostaining analysis, on day 08, the control group obtained scores 0 and 1 in most samples, while on days 10 and 14 most samples obtained scores 2 and 3. In the experimental groups (L, GR and P), score 2 prevailed at all experimental times. For LATS2 there was a prevalence of score 2 both in the control group and in the test groups at all experimental times, showing a very heterogeneous expression. Regarding the statistical analysis of YAP protein immunoexpression, there was a statistically significant difference (p= 0.020), only on day 08 between the control group compared to the experimental groups (L, GR and P). As for LATS2, no statistical difference was found. In the statistical evaluation of the different experimental times within the same group, a statistically significant difference was only found in the laser group and only for LATS2 (p=0.025). Additionally, the Spearman correlation was performed between YAP and LATS2 for all groups, but there was no statistically significant association. The greater immunoexpression of YAP and LATS2 (scores 2 and 3) observed in the experimental groups indicates that the hippo pathway is activated and seems to influence the repair process in chemoinduced oral mucositis treated by different methods (AU).

Distribution and Drug Resistance of Pathogens in Oral Mucositis Associated with Chemotherapy in Patients with Malignant Hematopathy / 中国实验血液学杂志

OBJECTIVE@#To analyze the distribution and drug resistance of pathogens in oral mucositis associated with chemotherapy in hospitalized patients with malignant hematopathy, so as to provide scientific evidences for rational selection of antibiotics and infection prevention and control.@*METHODS@#From July 2020 to June 2022, 167 patients with malignant hematopathy were treated with chemical drugs in the Department of Hematology, Hainan Hospital, and secretions from oral mucosal infected wounds were collected. VITEK2 COMPECT automatic microbial identification system (BioMerieux, France) and bacterial susceptibility card (BioMerieux) were used for bacterial identification and drug susceptibility tests.@*RESULTS@#A total of 352 strains of pathogens were isolated from 167 patients, among which 220 strains of Gram-positive bacteria, 118 strains of Gram-negative bacteria and 14 strains of fungi, accounted for 62.50%, 33.52% and 3.98%, respectively. The Gram-positive bacteria was mainly Staphylococcus and Streptococcus, while Gram-negative bacteria was mainly Klebsiella and Proteus. The resistance of main Gram-positive bacteria to vancomycin, ciprofloxacin and gentamicin was low, and the resistance to penicillin, cefuroxime, ampicillin, cefotaxime, erythromycin and levofloxacin was high. The main Gram-negative bacteria had low resistance to gentamicin, imipenem and penicillin, but high resistance to levofloxacin, cefotaxime, cefuroxime, ampicillin and vancomycin. The clinical data of oral mucositis patients with oral ulcer (severe) and without oral ulcer (mild) were compared, and it was found that there were statistically significant differences in poor oral hygiene, diabetes, sleep duration less than 8 hours per night between two groups (P<0.05).@*CONCLUSION@#Gram-positive bacteria is the main pathogen of oral mucositis in patients with malignant hematopathy after chemotherapy. It is sensitive to glycopeptide antibiotics and aminoglycosides antibiotics. Poor oral hygiene, diabetes and sleep duration less than 8 hours per night are risk factors for oral mucositis with oral ulcer (severe).

Mucosite oral em pacientes com câncer de cabeça e pescoço: limitações das escalas de graduação, avaliação da terapia fotodinâmica antimicrobiana no tratamento e associação com microbioma oral / Oral mucositis in patients with head and neck cancer: limitations of grading scales, evaluation of antimicrobial photodynamic therapy in treatment and association with oral microbiome

O câncer de cabeça e pescoço (CCP) é uma das principais causas de morbidade e mortalidade em todo mundo. Cirurgia, radioterapia (RT) e quimioterapia (QT) são os principais tratamentos empregados. Contudo, pacientes submetidos a RT e QT podem apresentar complicações como mucosite oral (MO). A terapêutica mais recomendada para MO é a fotobiomodulação (FTBM). Há diversas escalas para graduação da MO, entretanto elas apresentam limitações quando aplicadas em pacientes com CCP. Por esse motivo, foi desenvolvido uma revisão da literatura para descrever as escalas mais utilizadas e apontar as limitações. Microrganismos podem agravar a cicatrização da MO. Diante disso, a terapia fotodinâmica antimicrobiana (aPDT), poderia complementar a ação da FTBM. Assim, foi realizado estudo comparativo entre o uso da FTBM isolada e FTBM + aPDT no tratamento da MO. Mudanças no microbioma oral induzidas pela RT e seu papel no agravamento das complicações, como MO, vem sendo descrito. Em razão disso, amostras da cavidade oral dos pacientes com CCP foram coletadas com swab antes da RT (T0), entre 12 e 16 Grays (Gy) (T1), entre 30 e 36 Gy (T2) e acima de 60 Gy (T3) para caracterização molecular por meio da amplificação e sequenciamento das regiões v1-v2 do gene 16S rRNA. As escalas da World Health Organization - WHO, Radiation Therapy Oncology Group - RTOG e National Cancer Institute ­ NCI foram as mais utilizadas e todas apresentaram limitações associadas principalmente com a dificuldade de diferenciar entre os sinais e sintomas da MO e os do tumor, como por exemplo a disfagia. O estudo comparativo (FTBM isolada X FTBM + aPDT) foi composto por 14 pacientes, com câncer de boca e orofaringe submetidos a RT e QT concomitantes, com 6 pacientes no grupo FTBM isolada e 8 no grupo FTBM + aPDT. A média de redução no tamanho da MO no grupo intervenção foi de 0,70 cm2 (±0,35) e 0,30 cm2 (±1,10) no grupo controle. A média de duração foi de 18,37 dias (±12,12) para o grupo intervenção e 23 dias (±14,78) para o grupo controle. O grupo intervenção teve redução média de 3,40 pontos na escala de dor (±2,44), enquanto o grupo controle teve 0,17 (±2,28). O estudo prospectivo que avaliou o microbioma oral (filo e gênero) ao longo da RT foi composto por 49 pacientes com CCP. Intrigantemente não foi observado diferença no microbioma oral dos pacientes que apresentaram MO (n=31) daqueles que não apresentaram (n=18). Interessantemente foi observado ao final da RT (T3) diminuição de Porphyromonas (p=<0.0001), Prevotella (p=0.010), Fusobacterium (p=<0.0001), gêneros associados ao câncer. Não há uma escala ideal para a avaliação da mucosite oral em pacientes com CCP. A mensuração das lesões de MO associada aos dados de dor e duração da MO pode ser uma forma mais eficaz de avaliação. A combinação de FTBM + aPDT parece ser uma abordagem promissora para descontaminar lesões de MO. Não foi observado diferença no microbioma oral de pacientes com e sem MO. Mudanças na composição do microbioma oral foram observadas durante a RT.

Head and neck cancer (HNC) is one of the main causes of morbidity and mortality worldwide. Surgery, radiotherapy (RT) and chemotherapy (CT) are the main treatments used. However, patients undergoing RT and CT may present complications such as oral mucositis (OM). The most recommended therapy for OM is photobiomodulation (PBM-T). There are several scales for grading OM, however they have limitations when applied to patients with HNC. For this reason, a literature review was developed to describe the most used scales and point out the limitations. Microorganisms can aggravate OM healing. Therefore, antimicrobial photodynamic therapy (aPDT) could complement the action of PBM-T. Thus, a comparative study was carried out between the use of PBM-T alone and PBM-T + aPDT in the treatment of OM. RT-induced changes in the oral microbiome and its role in worsening complications such as OM have been described. For this reason, samples from the oral cavity of patients with HNC were collected with a swab before RT (T0), between 12 and 16 Grays (Gy) (T1), between 30 and 36 Gy (T2) and above 60 Gy (T3) for molecular characterization through amplification and sequencing of regions v1-v2 of the 16S rRNA gene. The World Health Organization - WHO, Radiation Therapy Oncology Group - RTOG and National Cancer Institute - NCI scales were the most used and all had limitations mainly associated with the difficulty of differentiating between the signs and symptoms of OM and those of the tumor, such as example dysphagia. The comparative study (isolated PBM-T X PBM-T + aPDT) consisted of 14 patients with oral and oropharyngeal cancer who underwent concomitant RT and CT, with 6 patients in the isolated PBM-T group and 8 in the PBM-T + aPDT group. The mean reduction in OM size in the intervention group was 0.70 cm2 (±0.35) and 0.30 cm2 (±1.10) in the control group. The mean duration was 18.37 days (±12.12) for the intervention group and 23 days (±14.78) for the control group. The intervention group had an average reduction of 3.40 points on the pain scale (±2.44), while the control group had 0.17 (±2.28). The prospective study that evaluated the oral microbiome (phylum and genus) during RT consisted of 49 patients with HNC. Intriguingly, no difference was observed in the oral microbiome of patients who had OM (n=31) and those who did not (n=18). Interestingly, a decrease in Porphyromonas (p=<0.0001), Prevotella (p=0.010), Fusobacterium (p=<0.0001) was observed at the end of RT (T3), genera associated with cancer. There is no ideal scale for assessing oral mucositis in patients with HNC. Measurement of OM lesions associated with data on pain and duration of OM may be a more effective form of evaluation. The combination of PBM- T + aPDT appears to be a promising approach to decontaminate OM lesions. No difference was observed in the oral microbiome of patients with and without OM. Changes in oral microbiome composition were observed during RT.

Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis

Purpose: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. Methods: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. Results: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. Conclusions: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

Impacto na deglutição e manejo da mucosite hipofaríngea em pacientes submetidos à quimiorradioterapia na região de cabeça e pescoço: uma revisão integrativa da literatura / Management of hypopharyngeal mucositis in patients undergoing chemoradiotherapy in the head and neck region and its impact on swallowing: an integrative literature review

RESUMO Objetivo Investigar o impacto da mucosite hipofaríngea quimiorradioinduzida na deglutição e o seu manejo, a partir de uma revisão integrativa de literatura. Estratégia de pesquisa A busca e a seleção dos artigos foram realizadas nas seguintes bases de dados: PubMed, Embase, Scopus, ScienceDirect e LILACS. Critérios de seleção Os termos de busca utilizados foram ''Pharyngeal Mucositis", ''Radiotherapy" e ''Esophagitis", com auxílio do operador booleano (AND). A equação de busca utilizada foi: ''Pharyngeal Mucositis" AND "Radiotherapy" AND "Esophagitis". A seguinte questão central orientou o estudo: "Qual a forma de avaliação e manejo da mucosite hipofaríngea induzida pela radiação na região de cabeça e pescoço e seu impacto na deglutição?". Resultados Foram identificados 75 estudos, sendo que 6 foram excluídos devido à duplicidade e 60 foram excluídos por não se encaixarem nos critérios de inclusão; os artigos restantes foram lidos na íntegra e 4 foram selecionados para fazerem parte desta revisão integrativa da literatura. Conclusão Apesar da escassa literatura e das poucas informações sobre os métodos de avaliação da mucosite hipofaríngea, os artigos apontam que, independentemente da dose de radiação, a radioterapia na região cervical causa mucosite hipofaríngea. A mucosite hipofaríngea provoca grande impacto na deglutição, resultando na necessidade de uso de via alternativa de alimentação. Além da ausência de informações quanto à avaliação e graduação da mucosite hipofaríngea, os estudos não discutem o tratamento direto ou a prevenção desse tipo de doença.

ABSTRACT Purpose To investigate the impact of chemoradiation-induced hypopharyngeal mucositis on swallowing and its management, based on an integrative literature review. Research strategy Two researchers were responsible for the search and selection of articles, within the following databases: PubMed, Embase, Scopus, Science Direct, and Lilacs. Selection criteria The search terms used were "Pharyngeal Mucositis", "Radiotherapy" and "Esophagitis", with the aid of the Boolean operator (AND). The search equation used was "Pharyngeal Mucositis" AND Radiotherapy AND Esophagitis. The following central question guided the study: "What is the assessment and management of radiation-induced hypopharyngeal mucositis in the head and neck region and its impact on swallowing?" Results 75 studies were identified, of which 6 were excluded due to duplicity and 60 were excluded for not meeting the inclusion criteria; the remaining articles were read in full and 4 were selected to be part of the integrative literature review. Conclusion Despite the scarce literature and little information on methods for evaluating hypopharyngeal mucositis, the articles point out that, regardless of the radiation dose, radiotherapy in the cervical region causes hypopharyngeal mucositis. Hypopharyngeal mucositis causes a great impact on swallowing, resulting in the need to use an alternative feeding route. In addition to the lack of information regarding the assessment and grading of hypopharyngeal mucositis, the studies do not discussitsdirect treatment or prevention.

Aplicação do plasma de baixa temperatura sob pressão atmosférica como adjuvante ao tratamento da mucosite oral / Application of low temperature atmospheric pressure plasma as an adjuvant in treatment oral mucositis

A mucosite oral é um quadro clínico que acomete frequentemente pacientes sob terapia antineoplásica na região de cabeça e pescoço e caracteriza-se por ulcerações na mucosa que geram intensa dor local, odinofagia, aumento do risco de infecções, do uso de antibióticos e do tempo de hospitalização. A correlação entre mucosite oral, infecção fúngica e o potencial de disseminação fúngica sistêmica foi recentemente descrita. Apesar do impacto desse quadro clínico sobre a qualidade e tempo de vida dos pacientes oncológicos, não há consenso sobre a profilaxia e o protocolo terapêutico. O plasma de baixa temperatura sobre pressão atmosférica (LTAPP) apresenta efeito antimicrobiano, anti-inflamatório e reparador tecidual, o que sugere que possa ser promissor no tratamento da mucosite oral. Os objetivos gerais deste projeto foram divididos em dois subprojetos: 1) Definir os melhores parâmetros in vitro com efeito antifúngico e não tóxico e avaliar o LTAPP no tratamento de lesão de mucosite oral em modelo murino de mucosite por quimioterapia e 2) avaliar se o tratamento com LTAPP pode prevenir a disseminação fúngica sistêmica em ratos a partir de infecção experimental de lesões de mucosite oral por Candida albicans. Para tal, foram incluídos no estudo 100 ratos (Rattus norvegicus) com 90 a 100 dias de idade. No subprojeto 1, a lesão de mucosite oral foi induzida por administração de 5 fluorouracila (5-FU), enquanto no subprojeto 2, utilizou-se 5-FU associada à cisplatina ambas associadas à aplicação tópica de ácido acético 50%. Para o subprojeto 1, os animais foram randomicamente divididos em 2 grupos experimentais (n=30): a) Grupo mucosite; b) Grupo mucosite tratado com LTAPP, avaliados após 1, 5 e 12 dias do tratamento. Durante o período experimental, as lesões foram fotografadas e a gravidade da mucosite classificada por meio da atribuição de escores. Após a eutanásia e o processamento, os cortes histológicos corados por hematoxilina-eosina (HE) foram analisados microscopicamente. Para o subprojeto 2, o estudo de disseminação sistêmica fúngica nos grupos de mucosite infectada com C. albicans tratado ou não com LTAPP foi conduzido pelo isolamento fúngico a partir de amostras de sangue total e macerado dos órgãos. Para tanto foram estudados 2 grupos de ratos (n=20): c) Grupo mucosite infectado com C. albicans e d) Grupo mucosite infectado com C. albicans tratada com LTAPP, avaliados após 24 e 72 h do tratamento. Para ambos os projetos, o melhor parâmetro in vitro foi selecionado, isto é aquele com maior atividade antifúngica e baixa toxicidade. Dessa forma, as lesões foram expostas ao LTAPP de hélio por 5 min na distância de 1,5 cm na potência de 1 W. Os resultados in vitro mostraram que o LTAPP teve efeito antifúngico e baixa toxicidade para células de mamíferos. Os resultados in vivo mostraram que 5-FU afetou a saúde geral dos animais, evidenciada pela perda de peso corporal. Em ambos os grupos, houve reparo tecidual após 12 dias do tratamento, com resolução quase completa da lesão, o que foi corroborado pelos achados microscópicos. O grupo LTAPP exibiu uma tendência maior de redução da lesão, após 12 dias de tratamento. Além disso, o LTAPP apresentou efeito inibitório sobre C. albicans após 5 minutos, de exposição, com redução da recuperação fúngica da língua após 24 h (p<0.05). A disseminação fúngica sistêmica foi reduzida significativamente após 24 e 72 h do tratamento. Com base nos resultados obtidos, conclui-se que o LTAPP é uma ferramenta promissora para futura aplicação clínica em pacientes com mucosite oral. (AU)

Oral mucositis is a clinical condition that frequently affects patients undergoing antineoplastic therapy in the head and neck region and is characterized by mucosal ulcerations that generate intense local pain, odynophagia, increased risks of infections, use of antibiotics and the length of hospital stay. The correlation among oral mucositis, fungal infection and the potential for systemic fungal dissemination has recently been described. Despite the impact of this clinical condition on the quality and life expectancy of cancer patients, there is no consensus on prophylaxis and the therapeutic protocols. Low temperature atmospheric pressure plasma (LTAPP) has antimicrobial, anti-inflammatory and tissue repairing effects, which suggests that it can be promising in the treatment of oral mucositis. The general objectives of this project were divided into two subprojects: 1) Define the best antifungal and non-toxic in vitro parameters and to evaluate the application of LTAPP in the treatment of oral mucositis in murine model for chemotherapy, and 2) to evaluate whether treatment with LTAPP can prevent systemic fungal dissemination in rats from experimental infection of oral mucositis lesions by Candida albicans. A total of 100 rats (Rattus norvegicus) aged 90 to 100 days were included in the study. In subproject 1, oral mucositis lesion was induced by administration of only 5- fluorouracil (5-FU), while in subproject 2, administration and systemic administration of 5-FU associated with cisplatin, both associated with topical application of 50% acetic acid. For subproject 1, the animals were randomly divided into 2 experimental groups (n=30):a) Mucositis group and b) Mucositis group treated with LTAPP evaluated after 1, 5 and 12 days of treatment. During the experimental period, the lesions were photographed, and the severity of mucositis was classified into scores. After euthanasia and processing, the histological cuts stained by hematoxylin-eosin (HE) were analyzed. For subproject 2, the study of fungal systemic dissemination in groups of mucositis infected with C. albicans treated or not with LTAPP was conducted by fungal isolation from whole blood and macerated organs. Therefore, 2 groups of rats (n=20) were studied: c) Mucositis group infected with C. albicans and d) Mucositis group infected with C. albicans treated with LTAPP, evaluated after 24 and 72 h of treatment. For both subprojects, the best in vitro parameter was selected, that is, the one with the greatest antifungal effect and low toxicity. Thus, the lesions were exposed to helium LTAPP for 5 min at a distance of 1.5 cm at power of 1 W. In vitro results showed that LTAPP has an antifungal effect and low toxicity. In vivo results showed that 5-FU affected the general health of animals evidenced by body weight loss. In both groups, there was tissue repair after 12 days of treatment, with almost complete resolution of the lesion, which was corroborated by the microscopic findings. LTAPP group showed a greater trend of reduction of lesion, after 12 days of the treatment. Furthermore, LTAPP showed inhibitory effect on C. albicans after 5 min of exposition, with reduction in fungal recovery from the tongue after 24 h (p<0.05). Reduction in fungal dissemination was observed after 24 and 72 h of LTAPP treatment (p<0.05). Based on the obtained results, it was concluded that LTAPP is a promising tool for future clinical application in patients with oral mucositis.(AU)

Oral Mucositis in Children with Leukemia Undergoing Chemotherapy: A Case Series

ABSTRACT Objective: To report nine cases of pediatric patients with Acute Lymphoid Leukemia (ALL) or Acute Myeloid Leukemia who developed severe oral mucositis (SOM) at the first week of chemotherapy. Material and Methods: The cases were selected from a sample of 105 children followed for 10 consecutive weeks. Hematological and personal data were obtained from the patient's medical records. The oral cavity was examined weekly using the modified Oral Assessment Guide. Results: More of the patients were male (55.6%), had black/brown skin (55.6%), with ALL (66.7%), and the mean age was 5.55. Two patients had values below normal for leukocytes, platelets, and creatinine over the follow-up. However, all patients showed changes in the normality of hematological data in most weeks. The most used chemotherapeutic agents were aracytin, etoposide, and methotrexate, known for their high stomatotoxic potential. Patients had 2 to 6 (mean of 4) episodes of SOM and 4 to 7 (mean of 5.5) episodes of OM. One patient at week 7, one patient at week 5, and one patient at weeks 2 and 10 did not have OM. Saliva (84 times) and lips (44 times) were the most affected items. Conclusion: The patients showed oscillations in the severity of oral mucositis and hematological parameters over the follow-up. All patients were exposed to stomatotoxic drugs during the initial phase of cancer treatment.

Desafios terapêuticos da mucosite oral em oncopediatria / Therapeutic challenges of oral mucositis in pediatric oncology

O Neuroblastoma (NB) é uma neoplasia do sistema nervoso simpático, e o segundo tumor sólido maligno extracraniano mais comum da infância. Na terapia antineoplásica, complicações orais podem ser observadas, dentre elas a mucosite oral (MO). Trata-se de uma inflamação aguda da mucosa, proveniente da toxicidade dos quimioterápicos. Este relato de caso enfatiza o manejo da MO, bem como sua influência na condição sistêmica e qualidade de vida. Paciente do sexo feminino, nove anos, apresentou recidiva de NB metastático, após tratamento de primeira linha. Admitida na unidade hospitalar para tratamento oncológico na enfermaria de pediatria oncológica, queixando-se de dor intensa em cavidade bucal e orofaringe, associada a pancitopenia severa febril. Ao exame físico apresentava disfagia e déficit ponderal grave, que debilitava a deglutição da própria saliva. O exame intraoral revelou lesões de MO grau 3, segundo a Organização Mundial de Saúde (OMS), em lábios, gengiva anterior e orofaringe. O tratamento consistiu em remoção de debris local, higiene da cavidade bucal com clorexidina 0,12% e utilizando haste flexível de algodão estéril tipo "Swab", visando controle microbiano local, diariamente. Além disso, foi aplicado no leito eritematoso e hemorrágico fotobiomodulação (660 nm, 50 mW, 2 J/cm2, 90 segundos) pontualmente nas áreas do leito da lesão e em varredura na região de orofaringe (sessões intercaladas). Foi prescrito acetato de racealfatocoferol (vitamina E) para ação antioxidante e hidratação dos lábios. Concomitante a mucosite, a paciente apresentou pancitopenia febril severa, sendo necessário uso de cefepima 150 mg/kg/dia, com coleta prévia de hemoculturas, fator estimulador de colônias de granulócitos, Fluconazol, hidratação e suporte nutricional. As hemoculturas foram negativas. As consequências da mucosite contribuíram para desnutrição e piora da qualidade de vida. Conclui-se que a intervenção odontológica em interdisciplinaridade, possibilitou o restabelecimento físico e emocional, possibilitando melhor uma qualidade de vida da paciente (AU).

Neuroblastoma (NB) is a neoplasia of the sympathetic nervous system and the second most common extracranial malignant solid tumor in childhood. In antineoplastic therapy, oral complications can be observed in antineoplastic therapy, among them oral mucositis (OM). It is an acute mucosa inflammation resulting from the toxicity of chemotherapy drugs. This case report emphasizes the management of OM and its influence on the systemic condition and quality of life. A female patient, nine years old, presented a recurrence of metastatic NB after first-line treatment. She was admitted to the hospital unit for oncological therapy in the pediatric oncology ward, complaining of severe pain in the oral cavity and oropharynx associated with severe febrile pancytopenia. On physical examination, she presented dysphagia and severe weight deficit, which weakened the swallowing of her saliva. According to the World Health Organization (WHO), the intraoral exam revealed third-grade OM lesions on the lips, anterior gum, and oropharynx. Treatment consisted of removing local debris, cleaning the oral cavity with 0.12% chlorhexidine, and using a flexible, sterile cotton swab, aiming for daily local microbial control. In addition, photobiomodulation (660 nm, 50 mW, 2 J/cm2, 90 seconds) was applied to the erythematous and hemorrhagic bed, punctually in the areas of the lesion and sweeps in the oropharynx region (interspersed sessions). Racealphatocopherol acetate (vitamin E) was prescribed for antioxidant action and lip hydration. Concomitant with mucositis, the patient had severe febrile pancytopenia, requiring cefepime 150 mg/kg/day, with previous collection of blood cultures, granulocyte colony-stimulating factor, fluconazole, hydration, and nutritional support. Blood cultures were negative. The consequences of mucositis contributed to malnutrition and worsened quality of life. It is concluded that the interdisciplinary dental intervention enabled physical and emotional restoration, enabling a better quality of life for the patient (AU).

Can NLR be a biomarker for mucositis and gvhd in patients undergoing allogeneic HSCT?

Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment for many diseases; however, it can induce complications such as Oral Mucositis (OM) and Graft-versus- Host Disease (GVHD). The neutrophil-lymphocyte ratio (NLR) is a peripheral biomarker of systemic inflammation and an independent prognostic factor for several inflammatory diseases. Aim: This study aimed to evaluate the association of NLR with OM and GVHD in patients undergoing allogeneic HSCT. Methods: Patients who underwent allogeneic HSCT at the Bone Marrow Transplant Service of the Hospital de Clínicas Complex of the Federal University of Paraná were included in the study. Socio-demographic data and blood counts were collected from patients' medical records. The NLR was calculated and associated with OM and GVHD. Results: 45 patients were included in the study. Although NLR was higher in patients with OM and oral GVHD, no statistical difference was observed, and no relationship between OM and GVHD with NLR could be stated. Conclusion: Although both OM and GVHD are associated with an inflammatory response as well as the immune system, it was not associated with NLR. Further investigation considering other variables related to HSCT might find possible associations, as it could favor patient management and prevention

Oral mucositis and microbial status in acute lymphoblastic leukemia subjects undergoing high-dose chemotherapy

Aim: To assess oral microbial status in patients with acute lymphoblastic leukemia (ALL) undergoing high-dose chemotherapy and to unravel possible associations between nosocomial pathogens and the establishment of chemotherapy-induced oral mucositis (CIOM). Methods: Oral mucosa, saliva, and peripheral blood samples were collected from 46 ALL subjects one day prior to chemotherapy (D0) and 2 weeks after treatment initiation (D14). Clinical intraoral inspection was performed by a single practitioner, with mucositis classification performed according to the WHO oral toxicity scale. Blood components were quantified by automatic flow cytometry, while oral Staphylococcus aureus and Pseudomonas aeruginosa were detected by Polymerase Chain Reaction with species-specific primers. Associations among bacteria and clinical findings were determined by Fisher's Exact test, longitudinal bacterial changes by paired Macnemar, and correlations among blood parameters and mucositis status or bacteria via Mann-Whitney. Results: S. aureus displayed higher detection rates at D14 (p < 0.05) and was positively associated with mucositis, adoption of a non-solid diet (all p < 0.001), nausea and fever (all p < 0.05). Conversely, P. aeruginosa did not correlate to CIOM clinical parameters. At the systemic standpoint, lower hemoglobin levels associated with CIOM and fever events (all p < 0.01). Conclusion: The study evidences S. aureus as a potential pathogen in ALL-CIOM, reaffirming microbial control as an important preventive measure during high-dose immunosuppressive therapy. The weight of non-white-blood-cell parameters should be validated as novel CIOM biomarkers in prospective research

Chemotherapy-induced oral mucositis induced by low dose methotrexate: a case report and literature review / 口腔疾病防治

Objective@# To investigate the diagnosis and treatment for oral mucositis induced by low-dose methotrexate and to provide a reference for clinicians@*Methods @# A case of severe chemotherapy-induced oral mucositis caused by short-term use of low-dose methotrexate (the maximum cumulative dose within 1 week) was reported and reviewed in combination with the literature.@*Results@# The patient was treated with low-dose methotrexate (2.5 mg orally every other day at weeks 1, 2, and 4; the third week, 2.5 mg each time for 3 consecutive days for twice, with a maximum cumulativedose of 15 mg within a week). After irregular medication for approximately three weeks, the patient gradually developed severe erosion of the lips, pain, difficulty eating, and skin erosion on both legs. Methotrexate was stopped after admission, and local symptomatic treatments such as Kangfuxin solution were given. Recombinant human granulocyte colony-stimulating factor was used systemically when combined with neutropenia. After treatment, the chemotherapy-induced oral mucositis and skin lesions were improved. A literature review shows that chemotherapy-induced oral mucositis is a toxic reaction to high-dose methotrexate, while cases of severe chemotherapy-induced oral mucositis caused by low-dose methotrexate are rare. Studies have found that the more risk factors patients have, such as poor local oral conditions and systemic diseases such as liver and kidney dysfunction and diabetes, the higher the risk of chemotherapy-induced oral mucositis. Clinicians should cooperate with dentists to address oral diseases as much as possible before using chemotherapy drugs. In addition, when ordering patients to take methotrexate, we should pay attention to the patient's general condition and susceptibility factors, standardize the frequency and dose of administration, adopt personalized treatment plans, and give patients detailed medication education to prevent the occurrence of adverse consequences caused by medication errors. If methotrexate poisoning occurs, the drug should be stopped in time, detoxification and active symptomatic and supportive treatment should be given. Basic oral care, cryotherapy, laser therapy, nutritional support and analgesic drugs are common treatments for chemotherapy-induced oral mucositis. Systemic administration of granulocyte colony-stimulating factor may be considered when accompanied by neutropenia.@*Conclusion@# It is necessary to be alert to the occurrence of severe chemotherapy-induced oral mucositis caused by low-dose methotrexate in clinical practice.

Study of application of 3D printed oral stents in radiotherapy for head and neck malignancies / 中华放射肿瘤学杂志

Objective:To analyze the dosimetric differences between 3D printed oral stents and corked oral stents in the target area and perioral organ at risk (OAR) in radiotherapy for head and neck cancer, and the effectiveness in reducing acute adverse reactions associated with radiotherapy.Methods:A total of 58 patients with head and neck cancer admitted to Department of Oncology of Affiliated Hospital of North Sichuan Medical College were selected and divided into experimental group (Group A, n=28, wearing 3D printed oral stents during radiotherapy) and control group (Group B, n=30, wearing corked oral stents during radiotherapy) in this retrospective cohort study. The incidence of radiotherapy - induced oral mucositis (RTOM), xerostomia and oropharyngeal mucosal pain was compared between two groups. Meanwhile, informed consent was obtained from 21 patients in Group A. Using the self control method, each patient wore a 3D printed oral stent (Group C) and a corked oral stent (Group D) to make two radiotherapy plans. The differences in the conformity index (CI), homogeneity index (HI) and exposure dose of OAR (D max, D mean) in the target area were analyzed between two groups. SPSS 25.0 statistical software was used for statistical analysis. Measurement data were expressed as Mean±SD. Comparison between two groups was conducted by paired t-test or repeated measurement analysis. Count data were expressed as ratio. Comparison between two groups was performed by Chi - square test or Fisher's exact test. P<0.05 was considered as statistically significant difference. Results:The severity of RTOM ( P<0.05), oropharyngeal mucosal pain ( P=0.004) and xerostomia score ( P<0.001) in Group A were significantly lower than those in Group B. There was no significant difference in the HI and CI of the target area between Group C and Group D (both P>0.05). The D max ( P=0.014, 0.009) and D mean ( P<0.001, P=0.033) of the upper lip and the affected buccal mucosa in Group C were significantly lower than those in Group D. Conclusion:3D printed oral stents obtain favorable HI and CI in radiotherapy for head and neck cancer, significantly reduce the irradiated dose to perioral OAR, and effectively lower the incidence and mitigate the severity of acute RTOM, xerostomia and oropharyngeal mucosal pain associated with radiotherapy.

O odontólogo frente aos cuidados paliativos na oncologia / The dental surgeon facing palliative care in oncology: a literature review / El odontólogo ante los cuidados paliativos en oncología

Cuidados paliativos são um conjunto de procedimentos ofertados ao paciente por uma equipe multidisciplinar com objetivo de garantir bem-estar, autonomia,conforto e alívio de sintomas decorrentes de doença ou tratamento quando a cura é impossibilitada. O câncer representa uma das doenças que possuem chances de evoluir o paciente ao estágio terminal, momento em que cuidados paliativos são indicados e necessários. Dentro da equipe responsável, o cirurgião-dentista atua na prevenção, diagnóstico e tratamento de lesões expressas no sistema estomatognático que se manifestam estimuladas pelo câncer ou pelos tratamentos utilizados. O objetivo desta pesquisa é destacar a função do odontólogo dentro da equipe multidisciplinar paliativista para pacientes oncológicos. Trata-se de uma revisão bibliográfica sistemáticada literatura. Foram feitas buscas nas plataformas Biblioteca Virtual em Saúde (BVS) e Scientific Electronic Library Online (SciELO) e após aplicação dos critérios de inclusão e exclusão foram selecionados 14 artigos. A literatura evidencia que alterações orais estão relacionadas com o curso da neoplasia ou seu tratamento; as lesões mais descritas foram: mucosite, xerostomia, candidíase, cárie, periodontite e osteorradionecrose. Isso faz com que o paciente sofra limitações em realizar atividades básicas, alterando negativamente a sua qualidade de vida. A complexidade da manifestação oral pode interromper o tratamento antineoplásico. As medidas de enfrentamento mais empregadas para a saúde bucal do paciente oncológico são a laserterapia, bochechos com clorexidina 0,12%, instrução de higiene oral, uso de anti-inflamatórios, analgésicos e antifúngicos. A atuação do odontólogo na equipe multidisciplinar oncológica paliativista é indispensável para o controle das manifestações orais.

Palliative care comprises a set of procedures offered by a multidisciplinary team to patients who cannot be cured, aiming to restore and ensure well-being, autonomy, independence, comfort and relief from symptoms resulting from illness or treatments. Cancer commonly leads the patient to the terminal stage, and at this stage palliative care is indicated and necessary. Composing the multidisciplinary team, the dentist works in the prevention, diagnosis and treatment of injuries that arise in the stomatognathic system, which manifest themselves due to cancer or its treatments. The objective of this research was to highlight the work of the dentist in the multidisciplinary team of palliative care for cancer patients. This is a systematic bibliographic review of the literature, with an integrative character. Study searches were performed in the Virtual Health Library (VHL) and Scientific Electronic Library Online (SciELO). After applying the inclusion and exclusion criteria, 14 articles were selected. Results showed that oral alterations are completely related to the development of the neoplasm or its treatment; the most described lesions were: mucositis, xerostomia, candidiasis, osteoradionecrosis, radiation caries and periodontitis. These injuries make the patient suffer limitations to perform basic activities, such as eating or communicating, negatively altering their quality of life. The complexity of the oral manifestation can determine the interruption of the anticancer treatment. The most used coping measures for the oral healthof cancer patients are: low- potency laser therapy, mouthwash with 0.12% chlorhexidine, instructionin oral hygiene and use of anti-inflammatory, analgesic and antifungal drugs. The role of dentists in the multidisciplinary palliative oncology team is essential for the control of oral lesions.

Los cuidados paliativos son un conjunto de procedimientos ofrecidos al paciente por un equipo multidisciplinar con el objetivo de garantizar el bienestar, la autonomía, el confort y el alivio de los síntomas derivados de la enfermedad o del tratamiento cuando la curación es imposible. El cáncer representa una de las enfermedades que tienen posibilidades de evolucionar al paciente hasta la fase terminal, momento en el que los cuidados paliativos son indicados y necesarios. Dentro del equipo responsable, el cirujano dentista actúa en la prevención, diagnóstico y tratamiento de las lesiones expresadas en el sistema estomatognático que se manifiestan estimuladas por el cáncer o por los tratamientos utilizados. El objetivo de esta investigación es destacar la función del odontólogo dentro del equipo paliativo multidisciplinar para pacientes oncológicos. Se trata de una revisión bibliográfica sistemática. Se realizaron búsquedas en las plataformas Virtual Health Library (BVS) y Scientific Electronic Library Online (SciELO) y tras aplicar los criterios de inclusión y exclusión, se seleccionaron 14 artículos. La literatura muestra que las alteraciones orales están relacionadas con el curso del cáncer o su tratamiento; las lesiones más comúnmente descritas fueron: mucositis, xerostomía, candidiasis, caries, periodontitis y osteorradionecrosis. Esto hace que el paciente sufra limitaciones para realizar actividades básicas, alterando negativamente su calidad de vida. La complejidad de la manifestación oral puede interrumpir el tratamiento antineoplásico. Las medidas de afrontamiento más utilizadas para la salud bucodental de los pacientes con cáncer son la terapia láser, los enjuagues bucales con clorhexidina al 0,12%, las instrucciones de higiene bucodental y el uso de fármacos antiinflamatorios, analgésicos y antifúngicos. La actuación del odontólogo en el equipo multidisciplinar de oncología paliativa es fundamental para el control de las manifestaciones orales.

Severe oral mucositis relating to pain and worse oral condition among patients with solid tumors undergoing treatment with FOLFIRI and 5-FU: a retrospective study

ABSTRACT BACKGROUND: There is a need for studies that correlate the severity of oral mucositis (OM) with chemotherapy protocols, transient myelosuppression and oral health. OBJECTIVE: To analyze the severity of OM among individuals with solid tumors during hospitalization and its correlation with the type of chemotherapy, myelosuppression and oral health condition. DESIGN AND SETTING: Retrospective study at a public hospital in Bauru, state of São Paulo, Brazil, that is a regional referral center. METHODS: Individuals diagnosed with solid malignant tumors who received chemotherapy during hospitalization for completion of the antineoplastic treatment cycle or who presented complications resulting from this were assessed. RESULTS: Twenty-eight individuals (24.3%) manifested some degree of OM. The most prevalent degrees of OM according to the World Health Organization (WHO) and modified WHO classification were grades 2 (11.3%) and 5 (4.3%), respectively. It was observed that the higher the OM-WHO (P < 0.001; r = 0.306) and modified OM-WHO (P < 0.001; r = 0.295) classifications were, the greater the oral pain reported by the individuals was. Presence of mucositis in the upper lip and buccal mucosa contributed to increased severity of OM and worsening of swallowing during hospitalization. Thus, severe OM was associated with use of the FOLFIRI protocol (folinic acid, fluorouracil and irinotecan). CONCLUSION: Individuals with tumors who presented severe OM had greater severity of oral pain and worse oral health. Use of the FOLFIRI protocol was associated with higher prevalence of severe OM, while use of 5-fluorouracil (5-FU) was correlated with worse oral condition.

Mycoplasma pneumoniae?induced rash and mucositis: A new entity

Mycoplasma pneumoniae is a well-known cause of community-acquired pneumonia, mostly associated with dermatological manifestations especially with mucosal involvement and targetoid cutaneous lesions. For many years, it was considered among the spectrum of erythema multiforme. Recently, some authors have recommended the creation of a new syndrome called “mycoplasma-induced rash and mucositis.” This new syndrome has distinct epidemiological, clinical and histological features making it different from drug-induced Stevens-Johnson syndrome, toxic epidermal necrosis and erythema multiforme. Herein, we report two patients with acute Mycoplasma pneumoniae respiratory tract infection presenting severe mucocutaneous lesions in accordance with this new syndrome.

Oral Manifestations of Erythema Multiforme due to Methotrexate Intoxication

ABSTRACT: To report a rare case of erythema multiforme (EM) associated with methotrexate (MTX) with cutaneous and oral manifestations and to compare it to existing cases in which MTX was not used for cancer treatment. A 56-years- old female, in physical examination skin lesions and multiple oral ulcers associated with pain during manipulation were observed, and underwent treatment for rheumatoid arthritis with Methotrexate 2.5mg. During examination patient-reported that 15 days ago she had undergone a rheumatoid factor examination, doubling the MTX dosage (10mg / day) without doctor's consent. The diagnostic hypothesis of EM. The medical conduct consisted of the suspension of MTX and prescription of a vitamin complex with folinic acid. Local dental therapy for to control oral lesions, pain control and lip hydration was performed using low-level laser therapy (Twin Laser, P: 40mW, T: 50s, DE: 50J / cm), benzydamine hydrochloride spray, purified lanolin for lip dryness, and toothpaste without sodium lauryl sulfate to prevent burning. After 12 days, there was significant remission of oral and skin signs and symptoms, which confirmed the diagnosis was EM due to MTX intoxication. Thorough clinical evaluation and anamnesis favored diagnosis and early multi-professional management provided remission of oral and skin lesions, prevented systemic complications.

RESUMEN: El objetivo de este trabajo fue informar un caso raro de eritema multiforme (EM) asociado a metotrexato (MTX) con manifestaciones cutáneas y orales y compararlo con casos existentes en los que no se utilizó MTX para el tratamiento del cáncer. Caso clínico: Mujer de 56 años, en el examen físico se observaron lesiones cutáneas y múltiples úlceras de la cavidad oral asociadas a dolor durante la manipulación.Se sometió a tratamiento para la artritis reumatoide con metotrexato 2,5 mg. Durante el examen, la paciente informó que hacía 15 días se había sometido a un examen de factor reumatoide, duplicando la dosis de MTX (10 mg / día) sin el consentimiento del médico. La hipótesis diagnóstica de EM. La conducta médica consistió en la suspensión de MTX y prescripción de un complejo vitamínico con ácido folínico. La terapia dental local para el control de las lesiones orales, el control del dolor y la hidratación de los labios se realizó mediante terapia con láser de bajo nivel (Twin Laser, P: 40mW, T: 50s, DE: 50J / cm), aerosol de clorhidrato de bencidamina, lanolina purificada para la sequedad de labios y pasta de dientes sin lauril sulfato de sodio para evitar quemaduras. Después de 12 días, hubo una remisión significativa de los signos y síntomas orales y cutáneos, lo que confirmó el diagnóstico de ME por intoxicación por MTX. La evaluación clínica exhaustiva y la anamnesis favorecieron el diagnóstico y el manejo multiprofesional precoz proporcionó la remisión de las lesiones orales y cutáneas, evitando además complicaciones sistémicas.

Curcuma longa extract protects against 5-fluorouracil-induced oral mucositis in hamsters

Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1ß and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1ß (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.