To discuss how distinct pathogenic mechanisms underlying salivary gland dysfunction may influence responsiveness to photobiomodulation (PBM) in patients with hyposalivation and xerostomia. A narrative review was conducted focusing on the biological and clinical factors potentially associated with PBM responsiveness across different etiologies of salivary gland dysfunction, including Sjögren’s disease, chemotherapy-induced dysfunction, radiation-induced salivary gland injury, and polypharmacy-associated hyposalivation. Mechanisms related to inflammation, oxidative stress, fibrosis, neurosecretory impairment, residual glandular viability, and persistence of etiological burden across different etiologies of salivary gland dysfunction were comparatively discussed. Therapeutic success assessments were also explored, emphasizing that symptom improvement and enhancement of oral quality of life may occur even in the absence of complete salivary flow normalization. In addition, the currently available evidence regarding PBM responsiveness in distinct etiological scenarios was critically presented, highlighting its heterogeneous and unbalanced distribution across conditions. Future directions involving biologically informed, individualized, and combination-based therapeutic approaches were also discussed. PBM responsiveness should not be interpreted as universally predictable across all etiologies of hyposalivation. Instead, therapeutic outcomes likely depend on several factors. Biologically informed and individualized approaches may contribute to more realistic therapeutic expectations and more personalized management strategies.
AIMS:Osteoradionecrosis (ORN) is a severe late complication of head and neck radiotherapy, often refractory to conventional treatment. Photobiomodulation therapy (PBMT) and photodynamic therapy (PDT) have shown regenerative, analgesic, and antimicrobial effects. This report aims to describe the non-invasive management of extensive mandibular ORN with intra- and extraoral fistulas using a combined PBMT-PDT protocol. CASE REPORT:A 72-year-old man previously treated with chemoradiation for laryngeal carcinoma developed chronic mandibular ORN after third molar extraction, complicated by a pathologic fracture, persistent suppuration, and failure of surgery, hyperbaric oxygen, antibiotics, and curettage. Clinical evaluation revealed intra- and extraoral suppurative fistulas and radiographic bone sequestration. A conservative regimen was initiated, consisting of weekly PBMT and PDT sessions following chlorhexidine irrigation. Over approximately one year (50 sessions), the patient reported progressive pain relief and reduced analgesic use. Complete closure of both fistulas was achieved, with recovery of soft-tissue sensitivity and radiographic resolution of sequestration. No adverse effects occurred, and the planned surgical debridement was canceled. CONCLUSION:Combined PBMT and PDT promoted complete resolution of extensive, refractory mandibular ORN using a fully non-invasive approach. This case highlights the synergistic potential of dual phototherapy as a safe and effective alternative when surgery is contraindicated or declined. Further studies are warranted to clarify underlying mechanisms and optimize treatment parameters.
INTRODUCTION:Oral mucositis (OM) remains a common and clinically significant complication of chemotherapy and radiotherapy. Current management is largely supportive, and effective local therapies remain limited. Hydrogel-based delivery systems have attracted interest because they may improve mucosal retention, protect ulcerated tissue, and enable sustained local drug release. METHODS:A systematic review of preclinical animal studies evaluating hydrogel-based interventions for oral mucositis was conducted. PubMed, Embase, and the Cochrane Library were searched, with additional gray literature screening. Data on formulation characteristics, experimental models, therapeutic outcomes, and methodological quality were extracted. Risk of bias was assessed using the SYRCLE tool. RESULTS:Eighteen studies met the inclusion criteria. Most formulations reduced lesion severity, improved histological healing, and attenuated inflammatory or oxidative markers. Multifunctional systems combining mucoadhesion with anti-inflammatory, antioxidant, or antimicrobial activity tended to show broader effects than conventional gels. However, study design, outcome reporting, and translational endpoints were heterogeneous. CONCLUSIONS:Current preclinical evidence supports hydrogels as promising local drug delivery platforms for oral mucositis. Greater standardization of models and clinically relevant endpoints will be important to support translation into human studies. PROTOCOL REGISTRATION:https://www.crd.york.ac.uk/prospero/, identifier CRD420251072050.
Chronic graft vs host disease (cGVHD) is a complication associated with allogeneic hematopoietic stem cell transplantation (HSCT) that often affects the oral mucosa, causing lesions and pain. Antimicrobial photodynamic therapy (aPDT) has been proposed as a treatment for managing oral cGVHD lesions, potentially improving prognosis and leading to symptom remission. This paper presents a novel case of pediatric oral cGVHD lesions successfully treated with aPDT, alongside oral hygiene instructions and topical corticosteroid therapy. Following four sessions of aPDT, the patient reported alleviation of pain symptoms, and after ten sessions, ulcerated/erosive lesions resolved completely, with no recurrence of pain. In conclusion, in this case, aPDT was shown to be an effective adjuvant therapy for managing cGVHD lesions. This highlights the potential of aPDT as a valuable addition to the treatment regimen for oral manifestations of cGVHD, offering a promising avenue for improving patient outcomes in these cases.
Osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaws (MRONJ) are debilitating complications that compromise bone repair in patients, who have undergone radiotherapy or treatment with anti-resorptive/anti-angiogenic drugs. Once established, these lesions are difficult to manage and reduce patients' quality of life. The combination of low- and high-power lasers, through photo biomodulation therapy and antimicrobial photodynamic therapy preceding surgical laser debridement, can provide satisfactory results in the treatment of these patients. Thus, the purpose of this work is to describe three cases associating these therapies for the management and treatment of ORN and ONMRM, offering an alternative, safe and effective therapy for these conditions.
Oral mucositis (OM) and hypopharyngeal mucositis (HM) are side effects of head and neck radiotherapy. While OM has been widely discussed, HM lacks studies. Objectives were: (1) to develop a prototype with an elongated optical fiber, coupled with an existing low-power laser, to access the hypopharynx using a nasofibroscope; (2) to propose a photobiomodulation protocol for HM. An anatomical study was previously conducted on cadavers. Describing a clinical case of a 77-year-old male with squamous cell carcinoma in the aryepiglottic fold, treated with 60 Grays of radiotherapy (RTx) in 30 sessions. He received treatment 3 times weekly for OM and the proposed HM protocol. After 15 days, he developed painful OM and HM with ulceration covered by fibrinoleukocytic exudate. He completed RTx sessions without interruption or the need for a feeding tube, maintaining oral intake. Despite being in development, the prototype and protocol show promise in aiding treatment.
The therapeutic use of low-level lasers aims to promote tissue photobiomodulation without raising the local temperature. However, in darker-skin patients, melanin can increase temperature and cause adverse effects such as photosensitivity, especially in protocols with higher irradiances, such as those used in dual irradiations. Therefore, through a retrospective cohort, this project assesses the relationship between self-reported skin color and the frequency of photosensitivity in patients treated with simultaneous dual irradiation protocols at the School of Dentistry of the University of São Paulo. Data from patients treated with lasers between 2013 and 2023 were retrieved. Patients were divided into two groups based on skin color and assessed for photosensitivity after simultaneous irradiation with red and infrared wavelengths. Statistical analyses investigated the relationship between photosensitivity, skin color, patient characteristics, and delivered energy. Self-reported skin color was associated with photosensitivity, with dark-skinned patients having a three times higher risk of heating or thermal injury. The risk of clinically visible thermal injuries was nearly 12 times higher for this group compared to those with lighter skin. There was no correlation between the energy used and the degree of photosensitivity, nor was there a significant difference in energy between patients with and without photosensitivity. Self-reported skin color was associated with photosensitivity occurrence during simultaneous laser wavelengths irradiation. Further studies are needed to investigate the mechanisms underlying the relation between melanin and irradiance. Finally, individualized photobiomodulation protocols are needed to ensure patient safety and optimize the therapy's expected effects.
Background/Objectives: Oral mucositis (OM) is an extremely common and debilitating side effect in patients undergoing Hematopoietic Stem Cell Transplantation (HSCT). As such, managing this condition is an obligatory component for their supportive care. Among the available treatment options, photobiomodulation therapy has long since established itself as the most promising approach, with consistent evidence supporting its efficacy. Despite this, the clinical results of this therapy are still influenced by the chosen dosimetry parameters, as well as patient-specific factors. Therefore, this study aimed to assess which factors can continue to influence the severity and onset of OM despite the protective effect provided by the ongoing photobiomodulation therapy. Methods: To achieve this, a retrospective analysis was conducted on the medical records of 171 patients who underwent PBMT during HSCT over a two-year period at the Brazilian Institute of Cancer Control. These files were used to review clinical and laboratorial parameters, such as OM grade, serum CRP, creatinine, urea, OGT, PGT, pain levels, presence of microorganisms in cultures, type of transplant, and conditioning regimens. All of these were evaluated at two different time points: the first day of conditioning and the day of highest OM degree. The statistical analysis was then conducted to evaluate the correlation between the variables and OM grade. Results: Results showed that type of conditioning regimens, use of MTX during conditioning, presence of microorganisms in cultures, and increased serum CRP, PGT, and initial urea levels were associated with severe OM. Conclusions: Among these, the type of conditioning regimens, MTX usage, positive results in cultures, and increased PGT levels on the first day of conditioning could be considered predictive for severe OM and the worst PBMT results. Consequently, in patients exposed to additional risk factors, adjustments in dosimetry paraments of PBMT or employment of adjuvant therapies should be considered to achieve better results.
This review aimed to determine whether photobiomodulation therapy (PBMT) is a safe and effective alternative for treating and preventing OM in children. The database search was carried out on PubMed, Embase, and Cochrane. Gray literature was also consulted through Google Scholar. Among 20 studies included, no adverse effect was reported, and only one study did not show any evidence of benefit from the use of PBMT. The analgesic effect of PBMT was emphasized and its action in accelerating the healing process and reducing the severity, duration and even incidence of OM was also noted. Evidence was found to encourage the use of PBMT to treat OM in pediatric patients. Higher quality studies must be developed in order to clarify the PBMT prophylactic effect and the best protocols for each clinical situation. The protocol of this review was registered on PROSPERO (CRD42023418109).
Background Photobiomodulation therapy (PBMT) has been employed for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing treatment. However, information about the survival of patients receiving PBMT is still lacking. Therefore, the aim of this study was to correlate the survival of patients who either received or did not receive PBMT, combined with cancer treatments, and to assess whether the number of PBMT sessions had a positive impact on survival. Methods The records of 751 patients seen at Hospital de Caridade São Vicente de Paulo diagnosed with head and neck cancer, treated by D.L.P., the sole operator of PBMT, between 2000 and 2016, were analyzed. The median survival rates were compared by analyzing diagnostic staging, the combination of cancer treatments, and the number of PBMT sessions. Correlation analyses were performed to assess the interactions between the number of PBMT sessions and survival. Results PBMT increased survival by 55.14%, from 1.07 (Without PBMT) to 1.66 years (With PBMT) for the total population and more significantly in Group 41 (stages III and IV, radiation therapy/chemotherapy, with more than five PBMT sessions), the median survival value of 1.83 years, which represents a 66.36% higher survival rate. In all the analyzed populations, the larger number of sessions was associated with better survival. In terms of survival, advanced stages III and IV almost equated with stages I and II in the absence of PBMT. Conclusions PBMT seems to interfere with the survival of patients with head and neck cancer, corroborating its recommendation for the treatment of mucositis, but further research is needed to investigate possible synergistic effects between PBMT and cancer treatments.
Introduction: Osteoradionecrosis (ORN) is a secondary complication from radiotherapy, which is difficult to manage and significantly reduces the life quality of the affected patients. Case Report: A 59-year-old female patient, diagnosed with infiltration by squamous cell carcinoma in the left cervical region, underwent adjuvant cervical-facial radiotherapy with a total dose of 66.6 Gy of radiation. Eight years after the diagnosis, the patient underwent multiple extractions and, subsequently, the installation of osseointegrated implants, evolving to extensive intraoral bone exposure associated with oral cutaneous fistula. The patient was initially exposed to photobiomodulation therapy (PBMT), with a low-power laser at wavelengths of 660 nm and 808 nm, and thereafter to antimicrobial photodynamic therapy (aPDT). After an improvement in the clinical condition and resolution of the oral cutaneous fistula, a surgical procedure with the Er: YAG laser was performed to remove the remaining necrotic bone. Once the ORN condition was completely treated, the patient's oral rehabilitation was implemented by the installation of an upper mucous-supported total prosthesis and a lower implant-supported prosthesis. Conclusion: The patient is in a clinical follow-up and has no signs of bone necrosis recurrence, suggesting that low and high-power laser treatment can be an effective therapeutic alternative to resolve this condition.
Ramsay-Hunt syndrome is an infectious disease associated with the varicella-zoster virus, and peripheral facial palsy is often one of its clinical manifestations. This case report describes a patient diagnosed with Ramsay-Hunt syndrome who developed peripheral facial palsy and was treated by photobiomodulation therapy. A 26-year-old woman developed a lack of facial mobility on the right side, asymmetry, otalgia, dysgeusia, and dry eyes, leading to the diagnosis of Ramsay-Hunt syndrome. Her peripheral facial palsy was classified as moderately severe according to the House-Brackmann scale. Acyclovir, prednisone, and physiotherapy sessions were prescribed to manage peripheral facial palsy. In the absence of a clinical response to the proposed therapies, photobiomodulation therapy was employed using the parameters: 780 nm, 100 mW, 3 J/point, and 30.48 J/cm2. After five sessions of photobiomodulation therapy, complete recovery of facial movement was observed. Photobiomodulation therapy treated peripheral facial palsy effectively, allowing a fast recovery and avoiding irreversible sequelae in a patient with Ramsay-Hunt syndrome.
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.
(1) Background: Thyroid tissue ablation with radioactive iodine (RAI) has been successfully used in the treatment of differentiated thyroid cancers. However, as a side effect, RAI may induce salivary gland (SG) hypofunction, which has been alternatively managed with photobiomodulation therapy (PBMT). In our study, we assessed the effects of RAI on the SGs and further analyzed whether PBMT can minimize tissue damage. (2) Methods: Balb/c mice were allocated into three groups, as follows: RI, submitted to RAI orally; RIL, similar to RI, but with PBMT for SG hypofunction; and C, control group. The animals were euthanized on days 0, 10, and 90 after RAI. (3) Results: A decrease in tri-iodothyronine (T3) and thyroxine (T4) serum levels was observed both in the RI and RIL groups. In addition, a decrease in SG weight and morphological alterations were shown in the RI group throughout the experimental period, as well as a significant increase in total protein and peroxidase concentrations, and catalase activity. On day 90, the RI group presented less collagen and fewer sodium/iodine channels, with higher rates of cell apoptosis. Pertechnetate (Na99mTcO4) uptake was also affected in the RI group in all experimental times. Interestingly, although the RIL group also presented some alterations regarding these parameters, they were not statistically different from those of the C group on day 90. (4) Conclusions: Our results provide evidence that RAI induces harmful effects on the SGs, which can be successfully managed with PBMT.
The association of more than one wavelength for photobiomodulation therapy (PBMT) to treat oral mucositis (OM) is unusual in the literature. Thus, this study aims to compare the simultaneous irradiation effects with their isolated application to treat OM. In order of that, 48 male Syrian hamsters were divided into 4 groups: Chemotherapy (Ch), which received only a OM induction protocol (5-fluorouracil chemotherapy and superficial oral mucosa scratches); red laser (RL), which received the OM induction and a PBMT protocol at 660 nm; infrared laser (IRL), which received the OM induction, and a PBMT protocol at 808 nm; and the RL + IRL group, which received the simultaneous application, of 660 and 808 nm wavelengths. Clinical (OM grade classification), histological (light microscopy analysis with H&E and collagen staining), immunohistochemical (TNF-α expression), and biochemical (TNF-α and hydroxyproline concentration) analyzes were performed after 7 and 10 days. Mainly on the 10th day, the RL and IRL groups showed lower OM grades and faster microscopic repair process, with greater expression of collagen fibers and lower TNF-α levels, besides the higher hydroxyproline concentrations, mainly in comparison with the Ch group. In conclusion, in this study, the simultaneous protocol did not present superior results than the isolated irradiations.
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.
Several oral lesions related to COVID-19 have been described in the scientific literature. The COVID-19 pandemic highlighs importance of supportive protocols, which can reduce the inflammation and aid in tissue repair in severe cases. Photobiomodulation therapy (PBMT) alone or in combination with antimicrobial photodynamic therapy (aPDT) can be used to manage orofacial lesions in confirmed cases of COVID-19. Here, we sought to describe the clinical presentation and specificities of three cases in which aPDT and PBMT were used to manage orofacial lesions in patients with COVID-19. The laser protocols were effective with improvement of the orofacial lesions within a few days.
AbstractIntroduction: Various methods of analysis for the assay of chemotherapeutic agent 5-Fluorouracil (5-FU) in human and animal biological fluids have previously been reported. However, there is no standardization for detecting 5-FU in the hamsters’ saliva that received the chemotherapeutic agent. Objective: Considering that the administration of 5-FU in some way changes the morphology and function of the salivary glands, and that the presence of the chemotherapeutic agents in the oral mucosa may lead to some oral complications, the aim of this study was to determine the presence of 5-FU in the hamsters’ saliva that received the chemotherapeutic agent, by means of the High Performance Liquid Chromatography technique (HPCL) since this animal model is used in studies of 5-FU induced oral mucositis and glandular hypofunction. Methods: Twelve animals were divided into 4 groups: CP and CPI, in which the animals received pilocarpine (CP) or pilocarpine + isoproterenol (CPI) and the chemotherapy vehicle intraperitoneally; and Groups QP and QPI, in which the animals received the same secretagogues listed above, and the chemotherapeutic agent 5-FU, respectively. After the secretagogue administration, saliva was collected from all the animals for a period of 60 mins. Subsequently, the saliva was frozen at -80 ˚C for later determination of the chemotherapeutic agent by HPLC. After the the chromatograms analysis, and based on the results obtained, it was possible to identify the presence of 5-FU in the saliva samples from hamsters that received the chemotherapeutic agent intraperitonally, by the HPLC technique. Keywords: Antimetabolites. Chromatography, High Pressure Liquid. Saliva ResumoVários métodos de análise para o ensaio do quimioterápico 5-Fluorouracil (5-FU) em fluidos biológicos de humanos e animais, foram previamente relatados. No entanto, não há uma padronização para detecção de 5-FU na saliva de hamsters que receberam o quimioterápico. Considerando que a administração do 5-FU altera de alguma maneira a morfologia e função das glândulas salivares, e que a presença do quimioterápico na mucosa oral pode levar a algumas complicações orais, este trabalho teve como objetivo de determinar a presença de 5-FU na saliva de hamsters que receberam o quimioterápico pela técnica de Cromatografia Líquida de Alta Eficiência (CLAE), uma vez que este modelo animal é usado nos estudos com mucosite oral e hipofunção glandular, induzidas por 5-FU. Doze animais foram divididos em 4 grupos: CP e CPI, onde os animais receberam intraperitonealmente pilocarpina (CP) ou pilocarpina + isoproterenol (CPI) e o veículo do quimioterápico, e os grupos QP e QPI, onde os animais receberam, respectivamente, os mesmos secretagogos listados acima e o quimioterápico 5-FU. Após a administração do secretagogo, foi coletada a saliva de todos os animais, por um período de 60 min. Em seguida, a saliva foi congelada a -80 ˚C para posterior determinação do quimioterápico por CLAE. Após análise dos cromatogramas, e com base nos resultados obtidos, foi possível identificar a presença do 5-FU nas amostras de saliva de hamsters que receberam o quimioterápico via intraperitoneal pela técnica da CLAE. Palavras-chave: Antimetabólitos. Cromatografia Líquida de Alta Pressão. Saliva
Oral surgical procedures are a great challenge in cancer patients, especially those with pancytopenia, given the risk of both hemorrhage and opportunistic infection. Thus, we report herein a case of a patient with refractory acute myeloid leukemia, severe pancytopenia, and some episodes of febrile neutropenia, who presented asymptomatic, bilateral lesions on the tongue, requiring excisional biopsy. Considering the high risk of bleeding, surgical intervention was proposed with a high-power laser (HPL) at the bedside. There was no considerable bleeding and stitches were not needed. Within 48 h postoperatively, the patient reported neither pain nor further bleeding and her tongue presented normal function. The patient was under a follow-up period of about 8 months, with no lesion relapse. The HPL seems to be of great value for preventing excessive bleeding and late infection in patients with pancytopenia submitted to minor oral surgeries.
Objetivo: Proponer el uso del láser de baja potencia extraoral para el tratamiento de la odinofagia asociada a mucositis hipofaríngea radio inducida. La odinofagia se caracteriza por dolor al tragar, que a menudo requiere cambios en la dieta, lo que impacta directamente en la calidad de vida del paciente. Material y métodos: La investigación fue un estudio observacional descriptivo con reporte de series de casos clínicos. Se realizó aplicación de fotobiomodulación extraoral para tres pacientes con odinofagia asociada a mucositis oral e hipofaríngea. Se utilizó la terapia con láser de baja potencia (Therapy XT DMC®), con λ808nm, 100 mW de potencia y 4J de energía, 40 segundos por punto. Se recopilaron, transcribieron y revisaron cualitativamente los informes de tres pacientes que se sometieron a tratamiento. Los puntos de aplicación del láser se propusieron a partir de un estudio anatómico previo en cadáveres, que buscó identificar la mejor zona de aplicación del láser extraoral en la región cervical para llegar a la hipofaringe. Resultados: Los pacientes informaron una reducción de la odinofagia y una mayor comodidad con el uso de este tratamiento en el trígono carotídeo. Conclusión: El trígono carotídeo resultó ser la mejor región extraoral para la aplicación de láser para llegar a la región hipofaríngea. El uso de láser de baja potencia aplicado en esta región redujo la odinofagia de los pacientes. Se necesitan más estudios para evaluar la capacidad analgésica de este tratamiento.