MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series.

BACKGROUND: Cancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ. METHODS: This multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients' data were retrospectively collected from the clinical charts of seven recruiting Italian centres. RESULTS: MRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandible (73.3%). The mean duration of BMAs therapy at MRONJ presentation was 34.9 months. The more frequent BMAs was denosumab (53.3%). Ten patients (66.7%) showed the following local risk factors associated to MRONJ development: periodontal disease (PD) in three cases (20%) and the remaining six (40%) have undergone PD-related tooth extractions. One patient presented an implant presence-triggered MRONJ (6.7%). In five patients (33.3%) no local risk factors were observed. CONCLUSIONS: This is the first case series that investigated BC patients under BMAs for CTIBL prevention suffering from MRONJ. These patients seem to have similar probabilities of developing MRONJ as osteo-metabolic ones. Breast cancer patients under BMAs for CTIBL prevention need a regular prevention program for MRONJ, since they may develop bone metastases and be treated with higher doses of BMAs, potentially leading to a high-risk of MRONJ.

Corrigendum: Adenosine receptor stimulation improves glucocorticoid-induced osteoporosis in a rat model.

[This corrects the article DOI: 10.3389/fphar.2017.00558.].

Impact of bisphosphonate drugs on dental implant healing and peri-implant hard and soft tissues: a systematic review.

OBJECTIVE: Implantology represents the gold standard for oral rehabilitation, unfortunately, often, despite there are no local contraindications to this type of rehabilitation, there are uncertainties regarding the general health of our patients. Many patients nowadays take bisphosphonate drugs, often without first seeking advice from an oral surgeon or a dentist. The purpose of this review is precisely to highlight any contraindications to this type of treatment reported in the literature, in patients who take or have taken bisphosphonate drugs. METHODS: For this study the scientific information sources were consulted using as search terms "("bisphosphonate AND "dental implant")", obtaining 312 results, these were subsequently skimmed according to the inclusion and exclusion criteria, and further evaluated their relevance to the study and the presence of requested outcomes. RESULTS: Only 9 manuscripts (RCTs, Multicentric studies and Clinical Trials) were included in this review, as they respected the parameters of this review, they were analyzed and it was possible to draw important results from them. Surely from this study it is understood that the use of bisphosphonate drugs does not represent an absolute contraindication to implant therapy, it is evident how adequate pharmacological prophylaxis, and an adequate protocol reduce the risks regarding implant failures. Furthermore, the values of marginal bone loss over time seem, even if not statistically significant, to be better in implant rehabilitation with bisphosphonate drugs association. Only a few molecules like risedronate, or corticosteroids, or some conditions like smoking or diabetes have shown a high risk of surgical failure. CONCLUSION: Although this study considered different studies for a total of 378 patients and at least 1687 different dental implants, showing better results in some cases for dental implant therapy in cases of bisphosphonate intake, further clinical, randomized and multicentric studies are needed, with longer follow-ups, to fully clarify this situation which often negatively affects the quality of life of our patients and places clinicians in the face of doubts.

Reduction of oxidative stress blunts the NLRP3 inflammatory cascade in LPS stimulated human gingival fibroblasts and oral mucosal epithelial cells.

The therapeutic armamentarium for the treatment of oral mucositis is very poor. Catechin and baicalin are two natural flavonoids that have been individually reported to have a curative potential. Flavocoxid is a mixed extract containing baicalin and catechin showing antioxidant effects and anti-inflammatory activity mainly due to a dual inhibition of inducible cyclooxygenase (COX-2), 5-lipoxygenase (5-LOX) and NLRP3 pathway. The aim of this study was to evaluate the anti-inflammatory and anti-oxidant effects of flavocoxid in an "in vitro" model of oral mucositis induced by triggering an inflammatory phenotype in human gingival fibroblasts (GF) and human oral mucosal epithelial cells (EC). GF and EC were challenged with lipopolysaccharide (LPS 2 µg/ml) alone or in combination with flavocoxid (32 µg/ml). Flavocoxid increased Nrf2, prompted a marked reduction in malondialdehyde levels and reduced the expression of COX-2 and 5-LOX together with PGE2, and LTB4 levels. Flavocoxid caused also a great decrease in the expression of NF-κB and turned off NLRP3 inflammasome and its downstream effectors signal, as caspase-1, IL-1ß and IL-18 in both GF and EC cells stimulated with LPS. These results suggest a correlation between oxidative stress and NLRP3 activation and indicate that flavocoxid suppresses the inflammatory storm that accompanies oral mucositis. This preclinical evidence deserves to be confirmed in a clinical setting.

CD34 and CD105 Microvessels in Resected Bone Specimen May Implicate Wound Healing in MRONJ.

Clinical treatment outcome of MRONJ (medication-related osteonecrosis of the jaw) surgery despite radical osseous removal and primary closure healing still shows differences in terms of outcome and disease recurrence. The study aims to assess the rate of angiogenesis of MRONJ lesions in order to understand the impact of angiogenesis and neoangiogenesis status on MRONJ surgical treatment outcome. This is the first study correlating microvessel density with prognosis in MRONJ surgically-treated patients. The immunohistochemical expression of CD34 and CD105 in MRONJ specimens obtained from surgically-treated patients was evaluated. The most vascularized areas detected by CD34 and CD105 were selected and the microvessel density value of the samples was registered. Samples were retrospectively divided according to the clinical outcome of MRONJ surgical treatment, dividing patients into two groups, "healed" and "not healed". Statistical analysis was performed to assess if neovessels could influence treatment outcome in patients undergoing radical surgery. In the examined cohort, this value was highly predictive of better treatment outcome after radical surgery of MRONJ. Understanding of angiogenesis-dependent factors deserves further attention as a future target for MRONJ prevention and therapies.

Cancer Patients at Risk for Medication-Related Osteonecrosis of the Jaw. A Case and Control Study Analyzing Predictors of MRONJ Onset.

The goal of this investigation was to identify potential risk factors to predict the onset of medication-related osteonecrosis of the jaw (MRONJ). Through the identification of the multiple variables positively associated to MRONJ, we aim to write a paradigm for integrated MRONJ risk assessment built on the combined analysis of systemic and local risk factors. The characteristics of a cohort of cancer patients treated with zoledronic acid and/or denosumab were investigated; beyond the set of proven risk factors a new potential one, the intake of new molecules for cancer therapy, was addressed. Registered data were included in univariate and multivariate logistic regression analysis in order to individuate significant independent predictors of MRONJ; a propensity score-matching method was performed adjusting by age and sex. Univariate logistic regression analysis showed a significant effect of the parameters number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01-1.05; p = 0.008) and chemotherapy (OR = 0.35; 95% CI = 0.17-0.71; p = 0.008). The multiple logistic regression model showed that breast, multiple myeloma, and prostate cancer involved a significantly higher risk compared to lung cancer; a significant effect of the combined variables number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01-1.06); p-value = 0.03) and exposure to novel molecule treatment (OR = 34.74; 95% CI = 1.39-868.11; p-value = 0.03) was observed. The results suggest that a risk assessment paradigm is needed for personalized prevention strategies in the light of patient-centered care.

Molecular features and tissue engineering techniques applied to regenerative surgery: an overview of recent data.

INTRODUCTION: Regenerative procedures have become common in the medical and dentistry rehabilitation fields. Often, tissue regeneration maneuvers are necessary to rehabilitate patients in a safe and predictable manner. The aim of this narrative review was to highlight the molecular implications during regenerative surgery. EVIDENCE ACQUISITION: The analysis of the literature was conducted on the main scientific databases Pubmed, Scopus, MDPI. EVIDENCE SYNTHESIS: After a screening of 66 results only 8 were included. CONCLUSIONS: Knowing these molecular features, it is possible to highlight which are the biomaterials that offer greater potential and identify the best protocols according to the surgical needs.

Complications reported with the use of orthodontic miniscrews: A systematic review.

OBJECTIVE: The aim of this systematic review was to evaluate the complications and side effects associated with the clinical use of orthodontic miniscrews by systematically reviewing the best available evidence. METHODS: A survey of articles published up to March 2020 investigating the complications associated with miniscrew insertion, in both the maxilla and mandible, was performed using 7 electronic databases. Clinical studies, case reports, and case series reporting complications associated with the use of orthodontic miniscrew implants were included. Two authors independently performed study selection, data extraction, and risk-of-bias assessment. RESULTS: The database survey yielded 24 articles. The risk-of-bias assessment revealed low methodological quality for the included studies. The most frequent adverse event reported was root injury with an associated periradicular lesion, vitality loss, pink discoloration of the tooth, and transitory loss of pulp sensitivity. Chronic inflammation of the soft tissue surrounding the miniscrew with mucosal overgrowth was also reported. The other adverse events reported were lesion of the buccal mucosa at the insertion site, soft-tissue necrosis, and perforation of the floor of the nasal cavity and maxillary sinus. Adverse events were also reported after miniscrew removal and included secondary bleeding, miniscrew fracture, scars, and exostosis. CONCLUSIONS: These findings highlight the need for clinicians to preliminarily assess generic and specific insertion site complications and side effects.

SIRT2 and SIRT3 expression correlates with redox imbalance and advanced clinical stage in patients with multiple myeloma.

OBJECTIVES: Sirtuins comprise seven family elements (SIRT1-7) involved in various cell signalling pathways comprising cancer inhibition and tumorigenesis. The present study aims to evaluate SIRT2 and SIRT3 gene expression and potential redox reactions in patients with multiple myeloma (MM) at onset and its correlation with disease status, extent and presence of organ damage secondary to myeloma. DESIGN & METHODS: Total RNA was extracted from 17 MM patients and 10 controls to assess gene expression using real-time PCR. The NAD+/NADH ratio as well as the levels of glutathione peroxidase (GPx) and hydrogen peroxide (HP) in peripheral blood mononuclear cells (PBMCs) were determined using established biochemical assays. RESULTS: SIRT2 and SIRT3 expression is reduced in MM patients compared to healthy controls. Correlational analysis demonstrated that SIRT2 reduction is associated with advanced clinical stage and with more advanced bone lesions than in the remaining patients. SIRT3 expression is correlated with lytic bone lesions. Biochemical analysis indicated an imbalance of oxidative stress biomarkers with low concentrations of the antioxidant enzyme GPx, low amounts of NAD + and higher concentrations of pro-oxidant enzyme HP in PBMCs of MM patients compared to controls. Moreover, MM patients with bone lesions had lower concentrations of NAD + and GPx in PBMCs than patients without signs of bone disease. In addition, MM patients had higher quantities of intracellular HP than controls. CONCLUSIONS: Our results demonstrate that SIRT2 and SIRT3 are downregulated in MM and that lower concentrations correlate with an advanced stage of disease and redox imbalance. We conclude that SIRT2 and SIRT3 together with oxidative stress biomarkers, may be useful for improved risk stratification of MM patients.

Clinical validation of 13-gene DNA methylation analysis in oral brushing samples for detection of oral carcinoma: Italian multicenter study.

BACKGROUND: The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. METHODS: Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. RESULTS: DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative. CONCLUSION: These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.

Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association.

The purpose of the present study was to estimate the prevalence of cyclin-dependent kinase (CDK) 4/6 inhibitors use among cancer patients from the medication-related osteonecrosis of the jaw (MRONJ) cohort of the University of Messina. We retrospectively reviewed the records of all patients with either intravenous bisphosphonates or denosumab-related MRONJ reported in the electronic health records of the Unit of Oral Surgery, School of Dentistry, University of Messina between the first quarter of 2018 and the first quarter 2020 to identify eligible patients. We observed six cases of MRONJ associated with CDK4/6 inhibitors concomitantly with intravenous bisphosphonates and/or denosumab in breast cancer patients. The CDK4/6 inhibitors registered were palbociclib (n = 5) and abemaciclib (n = 1). Data of cancer patients diagnosed with MRONJ in the same period (n = 10) were extracted for comparison. The comparative assessment with this group of patients showed a similar distribution of MRONJ stage ranged and clinical course after treatment. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and close monitoring. The role of premedication dental evaluation as a prevention strategy has been acknowledged for cancer patients about to initiate intravenous bisphosphonates and/or denosumab for treatment of bone metastasis, but additional attention should be paid to whom are assuming CDK4/6 inhibitors because of their oral adverse events.

Comparison between Additive and Subtractive CAD-CAM Technique to Produce Orthognathic Surgical Splints: A Personalized Approach.

The present study aimed to evaluate the accuracy of digitally designed surgical splints generated with milling technology (material subtractive procedure) and with 3D printing technology (material additive procedure) through a customized approach in the planning of surgical orthognathic splints. Cone beam computed tomography (CBCT) examinations and scanned dental models of 10 subjects who had required surgical treatment of skeletal malocclusion were included. Simulation of the orthognathic surgery was performed according to dento-skeletal and aesthetic characteristics of the subjects and the visual treatment objective (VTO), using Dolphin3D software (Dolphin Imaging, version 11.0, Chatsworth, CA, USA). Afterward, the Appliance Designer software (3Shape A/S, Copenhagen, Denmark) was used to digitally design the surgical splints that were generated twice using laser stereolithography technology (DWS 0.29D, DWS, Vicenza, Italy) and milling technology (Sirona inLab MC X5). Finally, each physical splint was digitalized using a desktop scanner (D500 3D, 3Shape A/S, Copenhagen, Denmark) in order to perform deviation analysis using the original project as a reference. The relative percentage of matching (trueness) was calculated (Geomagic Control X software (3D Systems, version 2018.1.1, 3D Systems, Rock Hill, SC, USA). An Independent Student's t-test was used to statistically analyze the data. The milled splints showed a lower value of root to mean square (RMS) relative to the original project (0.20 mm ± 0.018) compared to the prototyped splints (0.31 ± 0.021) (p < 0.001). According to the present findings, surgical splints generated with milling technology present higher trueness compared with 3D printing technology.

Preclinical and Clinical Applications of Biomaterials in the Enhancement of Wound Healing in Oral Surgery: An Overview of the Available Reviews.

Oral surgery has undergone dramatic developments in recent years due to the use of biomaterials. The aim of the present review is to provide a general overview of the current biomaterials used in oral surgery and to comprehensively outline their impact on post-operative wound healing. A search in Medline was performed, including hand searching. Combinations of searching terms and several criteria were applied for study identification, selection, and inclusion. The literature was searched for reviews published up to July 2020. Reviews evaluating the clinical and histological effects of biomaterials on post-operative wound healing in oral surgical procedures were included. Review selection was performed by two independent reviewers. Disagreements were resolved by a third reviewer, and 41 reviews were included in the final selection. The selected papers covered a wide range of biomaterials such as stem cells, bone grafts, and growth factors. Bioengineering and biomaterials development represent one of the most promising perspectives for the future of oral surgery. In particular, stem cells and growth factors are polarizing the focus of this ever-evolving field, continuously improving standard surgical techniques, and granting access to new approaches.

Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference-held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)-after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw.

Bisphosphonates (BPs) are inhibitors of osteoclast-mediated bone resorption used for the treatment of multiple myeloma (MM) patients with osteolytic lesions. Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is an infrequent drug-caused adverse event of these agents. Long noncoding RNAs (lncRNAs) are a set of more than 200 base pairs, noncoding RNA molecules, which are critical posttranscriptional regulators of gene expression. Our study was aimed at evaluating 17 lncRNAs, whose targets were previously validated as key elements in MM, bone metabolism, and angiogenesis in MM subjects without BONJ (MM group), in MM subjects with BONJ (BONJ group), and a group of healthy controls (CTRL group). Our results demonstrated a different lncRNA profile in BONJ patients compared to MM patients and controls. Two lncRNAs (DANCR and MALAT1) were both downregulated compared to controls and MM, twelve (HOTAIR, MEG3, TP73-AS1, HOTTIP, HIF1A-AS2, MANTIS, CTD-2201E18, CTD1-2003C8, R-471B22, RP1-43E13, RP11-553L6.5, and RP1-286D6) were overexpressed in MM with BONJ, and one (H19) was upregulated compared with only MM. Two lncRNAs (JHDMD1 and MTMR9LP) had higher expression, but these differences were not statistically significant. The examined lncRNAs target several genes and metabolic pathways. An altered lncRNA signature could contribute to the onset of BONJ or have a protective action. Targeting these lncRNAs could offer a possibility for the prevention or therapy of BONJ.

Oral Surgical Management of Bone and Soft Tissues in MRONJ Treatment: A Decisional Tree.

BACKGROUND: The aim of the present work was to analyze a 10-year retrospective series of surgically treated medication-related osteonecrosis of the jaws (MRONJ) cases, reporting the clinical outcome and success rate for each adopted procedure in order to draw a treatment algorithm that is able to standardize clinical decision making and maximize the success of oral surgical treatment of MRONJ. METHODS: Different surgical approaches were categorized taking into consideration two variables a) hard tissue management (defined as debridement, saucerization or marginal resective surgery of maxillary necrotic bone) and b) soft tissue management (defined as type of flap design and related modality of wound-healing). RESULTS: For the retrospective cohort study, 103 MRONJ patients were enrolled and a total of 128 surgical procedures were performed. The role of radical-intended surgery using local flaps in MRONJ treatment was investigated, as well as palliative treatments. All stage I-II patients completely healed when a combination of radical necrotic bone surgery associated with a first intention healing of soft tissues was obtained. In stage III, when a patient was not eligible for maxillo-facial surgery, the use of palliative surgical strategies was effective in symptom relief in order to maintain a better quality of life for the duration of the patient's life. CONCLUSIONS: Oral surgery with radical intent associated with a flap design able to ensure first intention healing might represent a valid option for the majority of MRONJ patients. The designed decision tree allows clinicians to assess individual surgical approaches for MRONJ treatment in accordance with patient-centered outcomes and surgical skills.

ß-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors.

Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of ß-Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 µg/mL) alone or in combination with BCP; a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-κB and STAT-3 and in reduced mRNA levels of PPARγ and PGC-1α. BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting.

Role of Local Flaps to Achieve Primary Wound Closure in Medication-Related Osteonecrosis of the Jaws Osseous-Resective Surgery.

The aim of the present work is to evaluate the most suitable surgical technique in relation to location and extent of medication-related osteonecrosis of the jaws (MRONJ) through comparison of success rate between the routinely used mucoperiostal flaps and different local flaps designs and propose a standardization of surgical procedures according to MRONJ stage and localization with 2 objectives: to provide the surgeon with an algorithm of treatment according to MRONJ localization and extension; to maximize the success of surgical treatment.Thirteen consecutive patients affected by focal MRONJ were surgically treated with radical osteotomy at the Center for Treatment of the Osteonecrosis of the Jaws (University of Messina, Italy).Initial defects were classified according to the classification of the Italian Societies of Oral Medicine and Maxillofacial Surgery (the SICMF-SIPMO staging system) which consider not only bone exposure but also radiological bone involvement. Treatment outcome was retrospectively assessed according to the different adopted surgical procedure: mucoperiostal flaps (GROUP A) advanced mucoperiostal flaps or rotation flaps (GROUP B) local flaps (GROUP C).Outcome after surgical treatment of focal MRONJ was positive in every group irrespective of MRONJ localization and extension. This may be due to the appropriate selection of surgical procedure.The results obtained demonstrated that focal MRONJ surgical treatment is a reliable procedure irrespective of the initial clinical situation. Radical osteotomy combined with appropriate selection of soft tissue management is crucial.

Early Diagnosis on Oral and Potentially Oral Malignant Lesions: A Systematic Review on the VELscope® Fluorescence Method.

The fluorescence method is an innovative technique used by pathologists for examining body mucosa, and for the abnormalities tissue screening, potentially leading to the earlier discovery of pre-cancer, cancer or other disease processes. The early detection is one of the best mechanisms for enabling treatment success, increasing survival rates and maintaining a high quality of life. The purpose of this review is to evaluate the clinical efficiency of this diagnostic tool applied to the oral cavity (VELscope®). A literature systematic review has been performed. The initial research provided 53 results after applying the inclusion and exclusion criteria, and after a manual screening of the abstracts by the authors, only 25 results were eligible for review. The results and data contained in all the researches, no older than 10 years, were manually evaluated, and provided useful information on this diagnostic method. The VELscope® mean value about sensitivity and specificity resulted of 70.19% and 65.95%, respectively, by results analysis, but despite this some studies disagree about its clinical effectiveness, and this diagnostic method is still much debated in scientific and clinical medical literature. Surely being able to have efficient and effective tools from this point of view could help the clinician in the diagnosis, and also make timelier the pharmacological or surgical therapy, improving the quality of life of the patient, and in some cases guaranteeing a longer survival term.

Role of Antioxidants in Minor Salivary Glands Cancer in the Elderly.

BACKGROUND: Minor salivary gland tumors (MSGTs) are infrequent, representing 10% to 15% of all salivary neoplasms. Despite this low frequency, a significant increase in the incidence of these tumors has been reported in the lasts 30 years. While tumors of the salivary glands can appear at any age, different authors consider the peak of incidence to be associated with old age (60+). The etiopathogenesis of MSGTs remains unclear. In this context, the aim of this study was to explore the hypothesis that age-related changes in salivary antioxidant capacity are involved in the pathogenesis of minor salivary glands tumors to identify possible preventive measures.Furthermore the study aimed to describe the clinico-pathological features of a multi-institutional case series of MSGTs which results are consistent with data in the literature. METHODS: An electronic search of the English language literature was performed using PubMed and Google scholar (). Databases were screened for papers using a number of search strings constructed using relevant terms (minor salivary glands tumors, elderly, diet, antioxidant, saliva, salivary glands). RESULTS: According to the world literature, the peak of incidence of MSGTs is between the fifth and seventh decades of life. To date, the only confirmed risk factor for salivary gland tumors is the exposure to ionizing radiation. The significantly reduced salivary antioxidant capacity in old people may explain the higher prevalence of these tumors in the elderly population. CONCLUSIONS: Further investigation is required to determine the real etiopathogenesis of MSGTs and why these tumors result more frequent in elderly patients.