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).

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.

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.

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).

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

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.

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.

Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: biochemical and histopathological evaluation

Abstract The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin—the effect we tested against MTX-induced oral mucosal damage—are well known. Objective Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. Methodology In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. Results Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. Conclusion These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

Genetic polymorphisms of genes involved in oxidative stress and inflammatory management in oncopediatric patients with chemo-induced oral mucositis

Abstract Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines contribute to the amplification of the immune response. Objective: To investigate the possible associations of rs4880 (superoxide dismutase 2, SOD2 47 C/T), rs7943316 (catalase, CAT −21 A/T), rs1800629 (tumor necrosis factor α, TNF- α −308 G/A), and rs1800795 (interleukin 6, IL-6 −174 G/C) polymorphisms with chemo-induced OM occurrence and severity in oncopediatric patients. Methodology: We conducted a single-center, observational cross-sectional study with sample collection of oral epithelial cells from 95 children and adolescents with hematological cancers who underwent chemotherapy, followed by genomic DNA extraction. Single-nucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Demographic data and information concerning OM occurrence were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was obtained from appropriately-filled Oral Assessment Guide records. Descriptive and inferential statistics were conducted with Student's T test, chi-squared test, and Fisher's exact test, with p≤0.05. Results: The mean age was 10 years-old and most patients were male individuals (57.89%). Female sex was considered a protective factor for OM occurrence (OR=4.83; CI=[1.14; 16.57]). The AA genotype for CAT was the most frequent amongst individuals with severe OM (p=0.04). The GA genotype for TNF- α was the most frequent amongst individuals without severe OM (p=0.03). For SOD2 and IL-6 , the most frequent genotypes were CT and GG respectively for all groups (p>0.05). Conclusion: The AA genotype for CAT −21 A/T was a tendency among the group with severe OM. Data on TNF- α −308 G/A were inconclusive. No associations were detected for SOD2 47 C/T and IL-6 −174 G/C polymorphisms in oncopediatric patients with chemo-induced oral mucositis.

Low level laser therapy versus benzydamin in prevention and treatment of oral mucositis induced by anticancer treatments (clinical and biochemical study) / Terapia a laser de baixa intensidade versus benzidamina na prevenção e tratamento da mucosite oral induzida por terapia oncológica

Objective: In this study, patients undergoing neck and head radiotherapy (RT) with or with no chemotherapy were contrasted to the low-level laser therapy (LLLT) efficacy against benzydamine hydrochloride in treating and preventing oral mucositis (OM) (CHT). Material and Methods: This study included 90 individuals with neck and head cancer who were undergoing radiotherapy (RT) individually or in mixture with chemotherapy (CHT), varying in age from 18 to 80 years. Three equal groups were randomly formulated: Group, I patients were using oral care only, Group II patients were using benzydamine hydrochloride mouth rinse, and Group III patients were medicated by using low-level laser therapy. The National Institute of Cancer-Common Toxicity Criteria (NIC-CTC) and the World Health Organization (WHO) were used to rate the severity of OM, and the pain was validated utilizing a visual analog scale (VAS). The salivary level of tumor necrotic factor-α (TNF- α) was assayed. Results: As per WHO and NIC, the grade of oral mucositis at the end of cancer treatment was less in the LLLT group than in the other two groups. The alteration in TNF- α level was not significant. The laser group is more liable to have less salivary levels of the pro-inflammatory cytokines TNF- α . Conclusion: The incidence of oral mucositis severity has seemed to be reduced due to the prophylactic use of benzydamine hydrochloride and laser therapy protocols. However, laser therapy was more efficient in controlling the shape and progression of OM (AU)

Objetivo: Neste estudo, pacientes submetidos à radioterapia (RT) da cabeça e pescoço com ou sem quimioterapia foram avaliados quanto à eficácia da terapia com laser de baixa potência (LLLT) versus o cloridrato de benzidamina no tratamento e prevenção da mucosite oral (MO) (CHT). Material e Métodos: Este estudo incluiu 90 indivíduos com câncer de cabeça e pescoço submetidos à radioterapia (RT) individualmente ou em combinação com quimioterapia (QT), com idade variando de 18 a 80 anos. Três grupos iguais foram aleatoriamente formulados: os pacientes do Grupo I usaram apenas higiene bucal, os pacientes do Grupo II usaram bochechos com cloridrato de benzidamina e os pacientes do Grupo III foram medicados com terapia a laser de baixa intensidade. Foram utilizados os critérios do National Institute of Cancer-Common Toxicity Criteria (NIC-CTC) e da Organização Mundial da Saúde (OMS) para classificar a gravidade da OM, e a dor foi validada utilizando uma escala visual analógica (VAS). O nível salivar de fator necrótico tumoral-α (TNF-α) foi ensaiado. Resultados: De acordo com a OMS e NIC, o grau de mucosite oral ao final do tratamento do câncer foi menor no grupo LLLT do que nos outros dois grupos. A alteração no nível de TNF-α não foi significativa. O grupo com tratamento a laser apresentou menores níveis de citocinas pró-inflamatórias TNF-α na saliva. Conclusão: A gravidade da mucosite oral parece ser reduzida devido ao uso profilático de cloridrato de benzidamina e protocolos de laserterapia. No entanto, a laserterapia foi mais eficiente em controlar a forma e a progressão da MO. (AU)

Acute Oral Manifestations in Patients Submitted to Radiotherapy in the Head and Neck Region: Literature Narrative Review / Manifestações Orais Agudas em Pacientes Submetidos à Radioterapia em Região de Cabeça e Pescoço: Revisão Narrativa da Literatura

The use of ionizing radiation, affects not only malignant cells but also healthy tissues, and promotes several side acute or late effects in the oral cavity. Among the acute effects, oral mucositis, xerostomia, hyposalivation, dysgeusia and dysphagia present a prominent role. The present study aims to conduct a narrative literature review on radiotherapy in the head and neck region as a therapeutic modality for cancer in this region and the main acute oral manifestations and their respective treatments. This was an exploratory literature rev iew, through the database of Scielo, Pubmed, Medline and institutional websites using the crossing of the descriptors in English and Portuguese "head and neck neoplasms", "radiotherapy", "xerostomia", "dysgeusia" and "dysphagia". According to the established criteria, a total of 46 articles and 2 institutional websites were selected from the databases, and one book was added for presenting relevance on this theme. The results demonstrate that oral mucositis is the most prevalent acute effect and has a direct impact on patient's quality of life, but there is no gold standard treatment. Dysphagia, xerostomia, hyposalivation and dysgeusia are common manifestations in irradiated patients, and present several therapeutic modalities. Given the importance of side effects of radiotherapy in head and neck region, further studies are nee ded to widely disseminate acute oral manifestations in irradiated patients. (AU)

A utilização de radiação ionizante, no câncer de cabeça e pescoço, afeta não somente células malignas, mas também tecidos sadios, o que promove diversos efeitos colaterais em cavidade oral, classificados em agudos ou tardios. Dentre os efeitos agudos, a muc osite oral, xerostomia, hipossalivação, disgeusia e disfagia apresentam papel de destaque. O presente trabalho visou realizar uma revisão narrativa de literatura sobre a radioterapia em região de cabeça e pescoço como modalidade terapêutica para o câncer nesta região e as principais manifestações orais agudas decorrentes da radiação ionizante e seus respectivos tratamentos. Tratou-se de revisão de literatura do tipo exploratória, através das bases de dados da Scielo, Pubmed, Medline e sites institucionais utilizando o cruzamento dos descritores em inglês e português "neoplasias de cabeça e pescoço", "radioterapia", "mucosite oral", "xerostomia", "disgeusia" e "disfagia". De acordo com os critérios estabelecidos, um total de 46 artigos e 2 sites institucionais foram selecionados nas bases de dados, e 1 livro foi acrescentado por apresentar relevância sobre a temática em questão. Os resultados demonstram que a mucosite oral é o efeito agudo mais pre valente e apesar de ter impacto direto na qualidade de vida, não há tratamento considerado padrão ouro para esta condição. A disfag ia, xerostomia, hipossalivação e disgeusia são manifestações comuns em pacientes irradiados, e apresentam diversas modalidades terapêuticas que podem ser empregadas. Dada à importância dos efeitos colaterais da radioterapia de cabeça e pescoço, torna-se necessária a realização de mais estudos afim de divulgar amplamente as manifestações orais agudas em pacientes irradiados. (AU)

Patogenia y tratamiento de la mucositis asociada al tratamiento de radioterapia y/o quimioterapia en pacientes con cáncer de cabeza y cuello / Pathogenesis and treatment of mucositis associated with radiotherapy and / or chemotherapy treatment in patients with head and neck cancer / Patogênese e tratamento da mucosite associada ao tratamento com radioterapia e / ou quimioterapia em pacientes com câncer de cabeça e pescoço

Resumen: La mucositis es un efecto adverso frecuente e invalidante en los pacientes oncológicos que reciben tratamiento de Radioterapia y Quimioterapia a altas dosis y muchas veces lleva a la suspensión del tratamiento. Si bien es una entidad que tiene gran relevancia en los pacientes e importante impacto económico en las instituciones de salud, no existen tratamientos claramente establecidos ni eficaces para mejorar esta condición. El objetivo de esta revisión es analizar la evidencia disponible en el tratamiento de la mucositis, y el respaldo científico e impacto que tienen conductas habitualmente tomadas en su tratamiento.

Abstract: Mucositis is a frequent and disabling adverse effect in cancer patients who received radiation therapy and chemotherapy at high doses and often discontinues treatment. Although it is an entity that has great relevance in patients and an important economic impact in health institutions, there are no clearly established or modified treatments to improve this condition. The objective of this review is to analyze the available evidence in the treatment of mucositis, and the scientific support and impact of behaviors commonly taken in its treatment.

Resumo: A mucosite é um efeito adverso frequente e incapacitante em pacientes com câncer que receberam radioterapia e quimioterapia em altas doses e muitas vezes interrompe o tratamento. Embora seja uma entidade que tenha grande relevância nos pacientes e um importante impacto econômico nas instituições de saúde, não existem tratamentos claramente estabelecidos ou modificados para melhorar essa condição. O objetivo desta revisão é analisar as evidências disponíveis no tratamento da mucosite, o suporte científico e o impacto das condutas comumente adotadas no seu tratamento.

Mucositis Oral: Actualización en el Diagnóstico, Prevención y Tratamiento

RESUMEN: La mucositis oral (MO) es la reacción secundaria aguda más frecuente en la cavidad oral y tracto gastrointestinal en pacientes oncológicos sometidos a quimioterapia o radioterapia de cabeza y cuello que incide negativamente en la calidad de vida del paciente. Su tratamiento requiere de un manejo multidisciplinario con el objetivo de minimizar la incidencia y severidad de esta patología. El desconocimiento parcial respecto de su etiopatogenia imposibilita la realización de protocolos para el manejo de esta complicación. Si bien existe evidencia científica respecto a las alternativas de prevención y tratamiento, éstas dependen de la evaluación individual que haga el clínico con cada paciente. A continuación, se presenta una revisión bibliográfica actualizada de la literatura científica publicada y se discuten aquellos aspectos más relevantes en torno a la prevención y tratamiento de la mucositis oral.

ABSTRACT: Oral mucositis (OM) is the most common acute secondary reaction in the oral cavity and gastrointestinal tract in cancer patients undergoing chemotherapy or radiotherapy to the head and neck, which adversely affects the patient's quality of life even at the risk of death. This requires multidisciplinary knowledge and management in order to minimize the incidence and severity of this pathology. The partial lack of knowledge regarding its etiopathogenesis makes it impossible to establish standardized guidelines for the management of this complication. Although there is scientific evidence regarding prevention and treatment alternatives, these depend on the individual evaluation of each patient and the clinical scenario in which they are presented. An updated review of the published scientific literature is presented below and those aspects most relevant to the prevention and treatment of oral mucositis are discussed.

Correlation between changes of oral bacterial flora and radiation-induced oral mucositis during radiotherapy for head and neck / 中华放射肿瘤学杂志

Objective:To investigate the correlation between the changes of oral bacterial flora during head and neck radiotherapy and radiation-induced oral mucositis (ROM).Methods:The oral bacterial samples of patients with nasopharyngeal carcinoma and accompanying family members were obtained before and at the end of radiotherapy and subjected to high-throughput sequencing. C57BL/6 mice were used to establish the ROM models. On the 9 th day after radiotherapy, oral bacterial samples were collected in the radiotherapy group and the negative control group. On the 3 rd, 5 th, 7 th, and 9 th days post-radiotherapy, the tongue tissues were obtained from another batch of mice in the negative control and radiotherapy groups. Inflammatory factors were detected with PCR and HE staining was performed. Results:The oral bacterial diversity of patients after radiotherapy significantly differed from that of patients before radiotherapy and their accompanying family members before and after radiotherapy in Observed species, Chao1, Simpson index (all P<0.05). There was a significant difference in Shannon index between the severe and mild ROM patients ( P=0.036). LEfSe analysis showed that patients with severe ROM had higher levels of g_ Streptococcus and f_ Streptococcus, and lower levels of f_ Familyxl, g_ Gemini and o_ Bacillus. The Simpson index and PCoA results in the oral bacterial samples significantly differed between the negative control and radiotherapy groups (all P<0.05). Conclusions:Radiotherapy can disrupt the balance of bacterial flora. The dysregulated oral bacterial flora is closely associated with the aggravation of ROM.

The role of Toll-like receptors in chemoradiotherapy-induced gastrointestinal mucositis / 口腔疾病防治

@#Mucositis is a common gastrointestinal complication in cancer patients undergoing chemoradiotherapy, including oral mucositis and gastrointestinal mucositis, with clinical manifestations of oral ulcers, vomiting, diarrhea and pain that seriously reduce the quality of life of patients and even affect anticancer therapy. Toll-like receptor (TLR) are important receptors involved in innate immunity and in the development of chemoradiation-induced mucositis by mediating the effect between microorganisms and the host. A comprehensive understanding of the role of TLR in mucositis is helpful to guide the prevention and treatment of mucositis. This paper reviews the available studies on TLR and mucositis. The results of the literature review indicate that different TLR have different roles in chemoradiation-induced mucositis: TLR2 is an important receptor in the inflammatory cascade of chemoradiation-induced mucositis; TLR4 activation can increase gastrointestinal mucosal inflammation and lead to oral epithelial ulceration; TLR5 agonists can reduce the degree of radiation-induced mucositis damage; and antagonizing or knocking out TLR9 can reduce chemoradiation-induced gastrointestinal mucositis. However, no TLR agonists or inhibitors have yet been applied in clinical practice, and additional studies are needed to explore the role of different TLR in mucositis in the future to provide a reference for the precise prevention and treatment of chemoradiation-induced mucositis.

Research progress on probiotics for the prevention and treatment of oral and gastrointestinal chemoradiotherapy mucositis / 口腔疾病防治

@#http://www.kqjbfz.com/article/2021/2096-1456/2096-1456-29-8-567.shtml

Research progress on biomarkers related to radiotherapy and/or chemotherapy-induced oral mucositis / 口腔疾病防治

@#Radiotherapy and/or chemotherapy-induced oral mucositis is a common oral complication in tumor patients undergoing radiotherapy and/or chemotherapy, which seriously compromises patients’ quality of life and even affects anti-tumor treatment. Biomarkers are signal indicators that appear at different biological levels before or during disease. A comprehensive understanding of the biomarkers associated with oral mucositis contributes to the early identification of high-risk patients with oral mucositis and aids in the screening of patients prone to develop severe oral mucositis, guiding the prevention and treatment of oral mucositis. This article reviews the existing biomarkers associated with oral mucositis. The literature review results showed that the biomarkers associated with oral mucositis included growth factors, inflammatory cytokines, genes, plasma antioxidants, and pro-apoptotic proteins/inhibitor of apoptosis proteins. These biomarkers can be used to predict the risk of oral mucositis or facilitate early discrimination of patients prone to exhibit severe radiotherapy and/or chemotherapy-induced oral mucositis. EGF, TNF-α, IL-6, IL-1β and CRP can be used to predict and evaluate the risk and development of oral mucositis, whereas genes such as excision repair cross complementing 1(ERCC1), X-ray repair cross complementing 1(XRCC1), methylenetetrahydrofolate reductase (MTHFR) and tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) have been focus of research in recent years. The genotypes and expression levels of some of these genes exhibit variable capacities to predict the risk and severity of oral mucositis. However, no biomarkers have been used in clinical practice, and more studies are needed in the future to verify the reliability and accuracy of these biomarkers, to provide a reference for the early accurate prevention and treatment of radiation and chemotherapy oral mucositis.