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PURPOSE: To assess the self-reported oral health and oral health-related quality of life of patients diagnosed with hemato-oncological disease. PATIENTS AND METHODS: Data was collected through a digital questionnaire in collaboration with the Dutch patient organization Hematon. The questionnaires EORTC-QLQ-C30, EORTC-QLQ-OH15, shortened Xerostomia Inventory (XI), and the OHIP-14 were used. RESULTS: Seven hundred five patients were included (52.5% female, mean age 63.2 ± 10.1). The majority was diagnosed more than 2 years ago (86%) and had received treatment (81%) for their disease. Lymphoma, leukemia, and multiple myeloma were the most frequent malignancies. Chemotherapy alone, chemotherapy in combination with targeted therapy or immunotherapy, and myeloablative chemotherapy followed by autologous stem cell transplantation were the most common treatment modalities. The XI identified that 40.5% met the criteria for xerostomia. Other complaints included mouth soreness and sensitivity, gingival pain and bleeding, problems with teeth or with an ill-fitting denture. Despite reporting oral complaints, most patients experienced a rather good OH-QoL. A high xerostomia score led to a significantly lower OH-QoL. Female gender, history of stem cell transplantation, radiation to head and neck, and multiple daily medication use were significant predictors of xerostomia. CONCLUSION: Patients with hematologic malignancies frequently reported a dry mouth and other oral complaints including mouth soreness and sensitivity, gingival pain and bleeding, and problems with teeth. Despite these oral complaints, most patients experienced a relatively good OH-QoL. Future longitudinal studies are needed, and health professionals should have an active role in providing oral supportive care based on patients' individual needs.
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Neoplasias Hematológicas , Salud Bucal , Calidad de Vida , Xerostomía , Humanos , Femenino , Masculino , Persona de Mediana Edad , Salud Bucal/estadística & datos numéricos , Anciano , Xerostomía/etiología , Neoplasias Hematológicas/terapia , Encuestas y Cuestionarios , Autoinforme , Adulto , Países BajosRESUMEN
Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described.
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Neoplasias , Glándulas Salivales , Xerostomía , Humanos , Glándulas Salivales/fisiopatología , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Neoplasias/terapia , Xerostomía/terapia , Xerostomía/etiología , Xerostomía/fisiopatología , Radioterapia/efectos adversos , Calidad de Vida , Animales , Inmunoterapia/efectos adversos , Antineoplásicos/efectos adversosRESUMEN
OBJECTIVES: This study aimed to integrate radiomics and dosiomics features to develop a predictive model for xerostomia (XM) in nasopharyngeal carcinoma after radiotherapy. It explores the influence of distinct feature extraction methods and dose ranges on the performance. MATERIALS AND METHODS: Data from 363 patients with nasopharyngeal carcinoma were retrospectively analyzed. We pioneered a dose-segmentation strategy, where the overall dose distribution (OD) was divided into four segmental dose distributions (SDs) at intervals of 15 Gy. Features were extracted using manual definition and deep learning, applying OD or SD and integrating radiomics and dosiomics, yielding corresponding feature scores (manually defined radiomics, MDR; manually defined dosiomics, MDD; deep learning-based radiomics, DLR; deep learning-based dosiomics, DLD). Subsequently, 18 models were developed by combining features and model types (random forest and support vector machine). RESULTS AND CONCLUSION: Under OD, O(DLR_DLD) demonstrated exceptional performance, with an optimal area under the curve (AUC) of 0.81 and an average AUC of 0.71. Within SD, S(DLR_DLD) surpassed the other models, achieving an optimal AUC of 0.90 and an average AUC of 0.85. Therefore, the integration of dosiomics into radiomics can augment predictive efficacy. The dose-segmentation strategy can facilitate the extraction of more profound information. This indicates that ScoreDLR and ScoreMDR were negatively associated with XM, whereas ScoreDLD, derived from SD exceeding 15 Gy, displayed a positive association with XM. For feature extraction, deep learning was superior to manual definition.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Dosificación Radioterapéutica , Xerostomía , Humanos , Xerostomía/etiología , Carcinoma Nasofaríngeo/radioterapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Nasofaríngeas/radioterapia , Adulto , Anciano , Aprendizaje Profundo , RadiómicaRESUMEN
BACKGROUND: The aim of this study was to describe salivary flow rate, subjective oral dryness and dental caries 5 years post haematopoietic cell transplantation (HCT). METHODS: HCT survivors of a previous longitudinal observational cohort study in the Netherlands (the H-OME study) were invited to participate in this additional follow-up after 5 years (the HOME2 study). During the additional follow-up appointment, stimulated (SWS) and unstimulated whole saliva (UWS) was collected, participants rated subjective oral dryness on a 0 - 10 scale, and caries lesions were assessed. Furthermore, dental records, including treatments and radiographs, were requested for the 5 years preceding and the 5 years following transplantation. Paired t-tests were performed to determine changes in UWS and SWS flow rates and subjective oral dryness from pre-HCT, and to compare the number of caries-related dental treatments (restorations, endodontic treatments or extractions) before and after HCT. Hyposalivation of UWS (< 0.2 mL/min) and SWS (< 0.7 mL/min) at 3 and 12 months, was used to explore the predictive potential of hyposalivation on a high dental treatment need (> 3 treatments) over the 5 years post-HCT. RESULTS: Five years post-HCT, 39 HCT survivors were included. The mean UWS flow rate was 0.36 mL/min (SD 0.26) and the mean SWS flow rate 1.02 (SD 0.57); survivors were diagnosed with a median of 0 dentine lesions (range 0 - 12) and 73% reported a subjective oral dryness score ≥ 1. Survivors underwent a median of 3 (range 0 - 20) dental treatments during the 5 years following transplantation. The mean difference in UWS 5 years post-HCT compared to pre-HCT was 0.03 (95% CI: -0.07 - 10.12), the mean difference for SWS was -0.18 (95% CI: -0.45 - 0.08) and for subjective oral dryness 1.2 (95% CI: 0.2 - 2.1). In the 5 years post-HCT, non-significantly more treatments were performed compared to the 5 years pre-HCT (mean difference: 0.5, 95%CI: -1.2 - 2.2). Seventy eight percent of patients with hyposalivation of SWS at 12 months had a high dental treatment need, compared with 38% with no hyposalivation. CONCLUSIONS: Five years post-HCT, mean UWS and SWS flow rates were not significantly different from pre-HCT levels but subjective oral dryness scores were elevated.
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Caries Dental , Trasplante de Células Madre Hematopoyéticas , Xerostomía , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Caries Dental/etiología , Xerostomía/etiología , Xerostomía/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Longitudinales , Saliva/metabolismo , Tasa de Secreción , Países Bajos , AncianoRESUMEN
BACKGROUND: Xerostomia is a pathological condition characterized by decreased salivation due to salivary gland dysfunction and is frequently attributed to irreversible damage as a side effect of radiation therapy. Stem cell-derived organoid therapy has garnered attention as a promising avenue for resolving this issue. However, Matrigel, a hydrogel commonly used in organoid culture, is considered inappropriate for clinical use due to its undefined composition and immunogenicity. In this study, we aimed to develop a method for culturing collagen-based human salivary gland organoids (hSGOs) suitable for clinical applications and evaluated their therapeutic effectiveness. METHODS: Human salivary gland stem cells were isolated from the salivary gland tissues and cultured in both Matrigel and collagen. We compared the gene and protein expression patterns of salivary gland-specific markers and measured amylase activity in the two types of hSGOs. To evaluate the therapeutic effects, we performed xenogeneic and allogeneic transplantation using human and mouse salivary gland organoids (hSGOs and mSGOs), respectively, in a mouse model of radiation-induced xerostomia. RESULTS: hSGOs cultured in Matrigel exhibited self-renewal capacity and differentiated into acinar and ductal cell lineages. In collagen, they maintained a comparable self-renewal ability and more closely replicated the characteristics of salivary gland tissue following differentiation. Upon xenotransplantation of collagen-based hSGOs, we observed engraftment, which was verified by detecting human-specific nucleoli and E-cadherin expression. The expression of mucins, especially MUC5B, within the transplanted hSGOs suggested a potential improvement in the salivary composition. Moreover, the allograft procedure using mSGOs led to increased salivation, validating the efficacy of our approach. CONCLUSIONS: This study showed that collagen-based hSGOs can be used appropriately in clinical settings and demonstrated the effectiveness of an allograft procedure. Our research has laid the groundwork for the future application of collagen-based hSGOs in allogeneic clinical trials.
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Organoides , Glándulas Salivales , Xerostomía , Xerostomía/terapia , Xerostomía/etiología , Humanos , Glándulas Salivales/efectos de la radiación , Animales , Ratones , Colágeno/metabolismo , Diferenciación Celular , Laminina/química , Proteoglicanos/metabolismo , Combinación de MedicamentosRESUMEN
INTRODUCTION: Oral health problems appear in up to 80 % of palliative care patients. Almost all of these patients suffer from a dry mouth which is often the result of medication side effects. Even though a dry mouth is not a disease by itself, it enhances the risk of developing other more serious oral lesions and diseases. Stomatitis, an inflammatory response to radio- or oncological treatment induced lesions, is very painful and may interfere severely with the ingestion of food and fluids. Finally, oral fungal infections are very common in immunosuppressed patients. Each of these entities comes with specific symptoms and signs which may impair food and fluid intake but also have consequences on the quality of life in these patients. Hence, a systematic and standardized evaluation is essential and can be accomplished with little effort by all health care professionals.
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Cuidados Paliativos , Estomatitis , Humanos , Cuidados Paliativos/métodos , Estomatitis/terapia , Estomatitis/etiología , Estomatitis/diagnóstico , Xerostomía/etiología , Xerostomía/terapia , Mucosa Bucal/patología , Calidad de Vida , Enfermedades de la Boca/terapia , Enfermedades de la Boca/etiologíaRESUMEN
Sjögren's disease is one of the most common systemic autoimmune diseases with hallmark features of sicca (dryness) symptoms of the eyes and mouth. There are a variety of ways to quantify xerostomia. α-Amylase is an enzyme secreted by the pancreas and salivary glands. While not specific to salivary glands, it may be measured as a surrogate marker of their output. Therefore, in this short investigation, we determined if there were any associations of serum α-amylase with subjective and objective markers of xerostomia. This investigation found a correlation between objective and subjective markers of xerostomia and α-amylase which suggests that measuring this analyte is a novel adjunct to qualifying xerostomia in the clinic.
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Biomarcadores , Síndrome de Sjögren , Xerostomía , Humanos , Xerostomía/sangre , Xerostomía/etiología , Xerostomía/diagnóstico , Síndrome de Sjögren/sangre , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/complicaciones , Biomarcadores/sangre , Femenino , Persona de Mediana Edad , Masculino , alfa-Amilasas/sangre , Valor Predictivo de las Pruebas , Adulto , AncianoRESUMEN
Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice (n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs.
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Terapia por Luz de Baja Intensidad , Animales , Ratones , Glándula Submandibular/efectos de la radiación , Glándula Submandibular/metabolismo , Saliva/metabolismo , Xerostomía/etiología , Uniones Estrechas/efectos de la radiación , Uniones Estrechas/metabolismo , Ratas , Luz VerdeRESUMEN
BACKGROUND: Radiotherapy (RT) in head and neck squamous cell cancer (HNSCC) often leads to sticky saliva and xerostomia (SSX). Dose sparing of salivary glands (SG) reduces occurrence of SSX but few studies investigated the relationship between RT dose to SG substructures and SSX. We therefore investigated this hypothesis, focusing on the parotid duct (PD). METHODS: Retrospective data was collected from 99 HNSCC patients treated at our center with (chemo-)radiotherapy (CRT). PD and other organs-at-risk (OAR) were (re-)contoured and DVHs were generated without re-planning. SSX was graded according to CTCAE v.4.03 and evaluated at acute, subacute, and two late timepoints. RESULTS: Most patients presented with loco-regionally advanced disease. In 47% of patients, up-front neck dissection preceded CRT. Weighted mean dose was 28.6 Gy for bilateral parotid glands (PG), and 32.0 Gy for PD. Acute SSX presented as grades 0 (35.3%), I (41.4%), II (21.2%) and III (2.0%). There was no association of OARs and SSX ≥ grade 2 in univariable logistic regression (LR). Multivariable LR showed statistically significant relationship of acute SSX with: PG weighted mean dose (OR 0.84, p = 0.004), contralateral PG mean dose (OR 1.14, p = 0.02) and contralateral PD planning OAR (PD PRV) mean dose (OR 1.84, p = 0.03). CONCLUSIONS: There was an association of acute SSX with dose exposure of PD PRV in multivariable regression, only. Due to statistical uncertainties and the retrospective nature of this analysis, further studies are required to confirm or reject the hypothesis.
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Neoplasias de Cabeza y Cuello , Órganos en Riesgo , Glándula Parótida , Dosificación Radioterapéutica , Carcinoma de Células Escamosas de Cabeza y Cuello , Xerostomía , Humanos , Xerostomía/etiología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Glándula Parótida/efectos de la radiación , Anciano , Neoplasias de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Órganos en Riesgo/efectos de la radiación , Adulto , Anciano de 80 o más Años , Saliva/efectos de la radiación , Traumatismos por Radiación/etiología , Carcinoma de Células Escamosas/radioterapia , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the clinical assessment of salivary gland hypofunction and xerostomia in cancer patients. METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: The objective assessment of saliva secretion involves an extra- and intra-oral clinical examination while the subjective assessment involves eliciting information on the patient's complaint of xerostomia and its impact on daily functioning. This CPS summarizes the common investigator- and patient-reported instruments used in clinical practice for assessing salivary gland hypofunction and xerostomia in cancer patients. CONCLUSION: There is a range of tools to assess salivary gland function in patients undergoing cancer therapy, patients recovering from cancer therapy, or cancer survivors. Clinicians should ideally conduct both objective and subjective measurements to ensure a clear understanding about the status of the patients in order to provide the most appropriate treatment.
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Neoplasias , Xerostomía , Humanos , Xerostomía/etiología , Xerostomía/diagnóstico , Neoplasias/complicaciones , Glándulas Salivales/fisiopatologíaRESUMEN
PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of salivary gland hypofunction and xerostomia in cancer patients. METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: Salivary gland hypofunction and xerostomia in cancer patients are managed by (i) stimulating saliva production of salivary glands with residual secretory capacity or (ii) artificial wetting of the oral and lip surfaces which can be achieved by pharmacological or non-pharmacological interventions. Pharmacological interventions encompass the use of sialagogues and sialolytics, while non-pharmacological interventions involve the use of moistening agents, mechanical, gustatory, or electrostimulation of the salivary glands. Additional treatment modalities may be incorporated in practice based on local availability and the clinician's experience. CONCLUSION: The information presented in this CPS offers clinicians convenient access to the dosages and regimens of different interventions for managing salivary gland hypofunction or xerostomia to facilitate clinical efficiency and conserve valuable time for clinicians.
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Neoplasias , Xerostomía , Humanos , Xerostomía/etiología , Xerostomía/terapia , Neoplasias/complicaciones , Glándulas SalivalesRESUMEN
Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.
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Biomarcadores , Canales Iónicos , Glándulas Salivales , Canales Iónicos/metabolismo , Canales Iónicos/genética , Biomarcadores/metabolismo , Glándulas Salivales/metabolismo , Glándulas Salivales/efectos de la radiación , Animales , Xerostomía/etiología , Xerostomía/metabolismo , Ratones , Masculino , Regulación hacia Arriba/efectos de la radiación , Humanos , Ratones Endogámicos C57BLRESUMEN
Background: Diabetes Mellitus is a chronic disease characterized by uncontrolled blood sugar levels, which lead to end-organ damage. While the diagnosis and treatment of its complications have been extensively studied, the effect of Hyperbaric Oxygen Therapy (HBO2) on diabetes-related oral complications remains unexplored. Aim: This prospective clinical study aims to investigate the effect of HBO2 on diabetes-related oral complications. Methods: Twenty patients diagnosed with diabetic foot ulcers and scheduled for HBO2 were included in this study. We recorded stimulated and unstimulated saliva pH, buffering capacity, flow rate, and subjective symptoms such as dry mouth, halitosis, taste loss, difficulty swallowing, and clinical examination findings before HBO2 and after the 21st session. Results: Upon comparing the findings, we observed a significant decrease in dry mouth and halitosis, periodontal disease severity, and healing of candida-related stomatitis and angular cheilitis. Despite not reaching statistical significance for other saliva parameters, the unstimulated salivary flow rate increased to normal limits (0.3-0.4 ml/min) in 6 out of 8 patients with a flow rate of less than 0.25 ml/min. Conclusion: Our study investigated the effect of HBO2 on diabetes-related oral complications for the first time, highlighting symptomatic relief for dry mouth and halitosis. Although our results are insufficient to report a definitive benefit, they underscore the need for further research on the oral health effects of HBO2.
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Pie Diabético , Halitosis , Oxigenoterapia Hiperbárica , Saliva , Xerostomía , Humanos , Oxigenoterapia Hiperbárica/métodos , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Xerostomía/etiología , Xerostomía/terapia , Pie Diabético/terapia , Pie Diabético/etiología , Anciano , Saliva/química , Halitosis/etiología , Halitosis/terapia , Concentración de Iones de Hidrógeno , Enfermedades Periodontales/terapia , Enfermedades Periodontales/etiología , Estomatitis/etiología , Estomatitis/terapia , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Trastornos del Gusto/etiología , Trastornos del Gusto/terapia , Adulto , Tasa de SecreciónRESUMEN
BACKGROUND: One of the main side effects of radiation therapy to the head and neck region is altered taste sensation. This causes significant morbidity and has profound effects on the quality of life (QoL) of patients. While radiation-associated toxicities like xerostomia and dysphagia are part of large investigations, data on taste impairment is sparse. Small cohort sizes in the majority of studies and a variety of analysis methods limit our current understanding of the underlying processes. None of the studies published to date used a taste-specific QoL questionnaire with differentiation of the different taste qualities (e.g. sour, bitter). Furthermore, data regarding the correlation of taste impairment with radiation-associated change in saliva composition is currently not available. The aim of the TASTE study is to fill this gap. Based on the acquired data, a normal tissue complication probability (NTCP) model for late radiation-associated taste impairment will be developed. METHODS: In this prospective, observational multicenter study 150 head and neck cancer patients undergoing radiation therapy will be recruited and undergo repetitive (semi-) objective and subjective assessment of their taste, smell and salivary function (questionnaires, taste and smell assessment, saliva analysis). Primary endpoint will be patient-reported taste impairment 12 months post radiation therapy using a standardized questionnaire. Secondary endpoints will include taste impairment measured using taste strips at 12 months and 2 years post radiation therapy. Differences between subgroups (radiation side, chemotherapy, etc.) and changes over time will be assessed while adjusting for confounding factors (e.g. age, sex, smoking history). DISCUSSION: This study sets out to further our understanding of taste impairment in patients undergoing radiation therapy to the head and neck region with the goal to prevent this common side effect in future patients. The results of the study may be used to evaluate taste-preserving radiotherapy for patients with head and neck cancer, which may significantly reduce the long-term burden in this patient cohort.
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Neoplasias de Cabeza y Cuello , Calidad de Vida , Saliva , Trastornos del Gusto , Gusto , Femenino , Humanos , Masculino , Neoplasias de Cabeza y Cuello/radioterapia , Estudios Prospectivos , Traumatismos por Radiación/etiología , Radioterapia/efectos adversos , Saliva/efectos de la radiación , Saliva/metabolismo , Encuestas y Cuestionarios , Trastornos del Gusto/etiología , Trastornos del Gusto/diagnóstico , Xerostomía/etiología , Xerostomía/diagnósticoRESUMEN
Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.
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Neoplasias de Cabeza y Cuello , Mitocondrias , Glándulas Salivales , Xerostomía , Xerostomía/etiología , Xerostomía/prevención & control , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/efectos de la radiación , Neoplasias de Cabeza y Cuello/radioterapia , Glándulas Salivales/efectos de la radiación , Glándulas Salivales/efectos de los fármacos , Glándulas Salivales/patología , Traumatismos por Radiación/prevención & control , Traumatismos por Radiación/etiología , Animales , Radioterapia/efectos adversos , Radioterapia/métodos , Calidad de VidaRESUMEN
Although SARS-CoV-2 induces mucin hypersecretion in the respiratory tract, hyposalivation/xerostomia has been reported by COVID-19 patients. We evaluate the submandibular gland (SMGs) pathogenesis in SARS-CoV-2-infected K18-hACE2 mice, focusing on the impact of infection on the mucin production and structural integrity of acini, ductal system, myoepithelial cells (MECs) and telocytes. The spike protein, the nucleocapsid protein, hACE2, actin, EGF, TNF-α and IL-1ß were detected by immunofluorescence, and the Egfr and Muc5b expression was evaluated. In the infected animals, significant acinar hypertrophy was observed in contrast to ductal atrophy. Nucleocapsid proteins and/or viral particles were detected in the SMG cells, mainly in the nuclear membrane-derived vesicles, confirming the nuclear role in the viral formation. The acinar cells showed intense TNF-α and IL-1ß immunoexpression, and the EGF-EGFR signaling increased, together with Muc5b upregulation. This finding explains mucin hypersecretion and acinar hypertrophy, which compress the ducts. Dying MECs and actin reduction were also observed, indicating failure of contraction and acinar support, favoring acinar hypertrophy. Viral assembly was found in the dying telocytes, pointing to these intercommunicating cells as viral transmitters in SMGs. Therefore, EGF-EGFR-induced mucin hypersecretion was triggered by SARS-CoV-2 in acinar cells, likely mediated by cytokines. The damage to telocytes and MECs may have favored the acinar hypertrophy, leading to ductal obstruction, explaining xerostomia in COVID-19 patients. Thus, acinar cells, telocytes and MECs may be viral targets, which favor replication and cell-to-cell viral transmission in the SMG, corroborating the high viral load in saliva of infected individuals.
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COVID-19 , Receptores ErbB , SARS-CoV-2 , Glándula Submandibular , Xerostomía , COVID-19/patología , COVID-19/virología , COVID-19/metabolismo , Animales , Glándula Submandibular/virología , Glándula Submandibular/patología , Glándula Submandibular/metabolismo , SARS-CoV-2/fisiología , Ratones , Xerostomía/etiología , Xerostomía/patología , Xerostomía/virología , Xerostomía/metabolismo , Receptores ErbB/metabolismo , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Mucina 5B/metabolismo , Células Acinares/patología , Células Acinares/metabolismo , Células Acinares/virología , Interleucina-1beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Modelos Animales de EnfermedadRESUMEN
PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of oral manifestations of chronic graft-versus-host-disease (cGVHD). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and table to generate a short manual about the best standard of care. RESULTS: The treatment goals in oral cGVHD are to relieve pain and xerostomia, improve oral function, prevent secondary infection, prevent deterioration of the dentition, and detect malignant transformation as early as possible. The prevention and treatment measures for oral mucosal lesions, hypofunction of the salivary glands, and sclerodermatous changes in the oral and perioral tissues are detailed, as well as the possible complications and side effects of these interventions. CONCLUSIONS: Patients post allogeneic hematopoietic cell transplantations, with cGVHD manifest in the oral and perioral tissues, should be regularly monitored and treated as needed by an oral care practitioner. This CPS provides the clinician with practical tools for examining, preventing, and treating the various sequalae that may affect the oral cavity in these patients.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedades de la Boca , Enfermedad Injerto contra Huésped/terapia , Enfermedad Injerto contra Huésped/etiología , Humanos , Enfermedades de la Boca/etiología , Enfermedades de la Boca/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Crónica , Xerostomía/etiología , Xerostomía/terapiaRESUMEN
BACKGROUND: Few studies have examined health related Quality of Life (HR-QoL) during the treatment of head and neck cancer (HNC) with even fewer focusing on the impact of oral mucositis (OM) on HR-QoL. Studies performed during treatment of HNC makes it possible to follow fluctuations in HR-QoL, OM and other treatment related side effects. The aim was to prospectively analyze HR-QoL, changes in clinical variables and the impact of OM on HR-QoL during HNC treatment. MATERIALS AND METHODS: Patients were recruited before commencing curative cancer treatment and were given professional oral care weekly during oncologic treatment. HR-QoL was reported before, during (week 2, 4 and 6) and three months after treatment using the EORTC Quality of Life questionnaires C30 and H&N35 and the stimulated whole salivary secretion rate was determined at the same time-points. OM (erythema and ulceration) was registered using the Oral Mucositis Assessment Scale (OMAS), at baseline, weekly during treatment and post treatment. Differences in HR-QoL between different timepoints were analyzed. To analyze the impact of OM on HR-QoL the patients were categorized into two groups: no/mild OM (OMAS ulceration score 0-1) or severe OM (OMAS ulceration score ≥ 2) and HR-QoL was compared between the two OM groups at three timepoints during treatment. RESULTS: Fifty-seven patients (43 men, 14 women), with a mean age of 58 years were included. Patients reported progressively impaired HR-QoL, with peak issues noted at weeks 4 and 6, particularly in social eating, senses, appetite loss, sticky saliva, and decreasing salivary secretion rates were determined. Patients with severe OM reported worse HR-QoL compared to those with no/mild OM. Persistent problems 3 months post treatment were appetite loss, dry mouth, senses (smell and taste) and problems with social eating. CONCLUSION: Patients experienced exacerbated symptoms and problems weeks 4 and 6 of oncological treatment, especially among those with severe OM, stressing the importance of clinically monitoring the patients to reduce and alleviate their symptoms. Persistent problems three months post treatment are likely associated with the reduced salivary secretion rate indicating that patients should be monitored also after completed oncological treatment.
Asunto(s)
Neoplasias de Cabeza y Cuello , Salud Bucal , Calidad de Vida , Estomatitis , Humanos , Estomatitis/etiología , Estomatitis/psicología , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/psicología , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/terapia , Anciano , Adulto , Xerostomía/psicología , Xerostomía/etiología , Estudios de Seguimiento , Saliva/metabolismo , Saliva/química , Salivación/efectos de los fármacos , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor (VEGF) antibodies, such as ranibizumab (RBZ), have been used to treat diabetic retinopathy, their effects on the salivary glands are unknown. This study evaluated the effects of RBZ on salivary glands to reduce inflammation and restore salivary function in a mouse model of type 2 diabetes. METHODS: Male KK-Ay mice with type 2 diabetes (10-12 weeks old) were used. The diabetes mellitus (DM) group received phosphate-buffered saline, while the DM + RBZ group received an intraperitoneal administration of RBZ (100 µg/kg) 24 h before the experiment. RESULTS: Ex vivo perfusion experiments showed a substantial increase in salivary secretion from the submandibular gland (SMG) in the DM + RBZ group. In addition, the mRNA expression levels of TNF-α and IL-1ß were considerably lower in this group. In contrast, those of aquaporin 5 were substantially higher in the DM + RBZ group, as revealed by quantitative reverse transcription PCR. Furthermore, the number of lymphocyte infiltration spots in the SMG was notably lower in the DM + RBZ group. Finally, intracellular Ca2+ signaling in acinar cells was considerably higher in the DM + RBZ group than that in the DM group. CONCLUSION: Treating a type 2 diabetic mouse model with RBZ restored salivary secretion through its anti-inflammatory effects.