Advancements in guided surgical endodontics: A scoping review of case report and case series and research implications.

This scoping review examined current case series and reports on guided surgical endodontic applications in order to provide a critical platform for future research. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews guidelines were followed. A search on PubMed and Scopus yielded 611 articles, with 17 case reports and 1 series meeting inclusion criteria. Overall, guided surgery addressed anatomical complexities, with 15 articles employing static protocols and 3 dynamic. Results showed minimal iatrogenic errors and reduced chair time, with no postoperative issues reported. Within the cases described, guided endodontic surgery exhibited satisfactory results in management of anatomical complex cases. Cost-effectiveness, the need for adequate follow-up, procedure's reproducibility and accuracy, and objective measurement of the reduction in operative times and iatrogenic errors are some of the limitations in the current reports that need to be considered for planning of future experimental and cohort studies.

Effectiveness of the platelet-rich fibrin in the control of pain associated with alveolar osteitis: a scoping review.

OBJECTIVES: The aim of this scoping review was to determine the effectiveness of the platelet-rich fibrin in the control of pain associated with alveolar osteitis. MATERIALS AND METHODS: Reporting was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. A literature search was conducted in the PubMed and Scopus databases to identify all clinical studies on the application of platelet-rich fibrin in the control of pain caused by alveolar osteitis. Data were extracted independently by two reviewers and qualitatively described. RESULTS: The initial search returned 81 articles, with 49 identified after duplicates removal; of these, 8 were selected according to the inclusion criteria. Three of the eight studies were randomized controlled clinical trials, and four were non-randomized clinical studies, two of which were controlled. One study was case series. In all of these studies, pain control was evaluated using the visual analog scale. Overall, the use of platelet-rich fibrin resulted effective in the control of pain determined by alveolar osteitis. CONCLUSIONS: Within the limits of this scoping review, the application of platelet-rich fibrin in the post-extra-extraction alveolus reduced the pain associated with alveolar osteitis in almost all the included studies. Nevertheless, high-quality randomized trials with adequate sample size are warranted to draw firm conclusions. CLINICAL RELEVANCE: Pain associated with alveolar osteitis causes discomfort to the patient and is challenging to be treated. Use of platelet-rich fibrin could be a promising clinical strategy for pain control in alveolar osteitis if its effectiveness will be confirmed by further high-quality studies.

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.

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.

Reply to Fusco et al. Is Medication-Related Osteonecrosis of the Jaws (MRONJ) Associated to Cyclin-Dependent Kinase (CDK) 4/6 Inhibitors? A Word of Cautiousness. Comment on "Marcianò et al. Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association. Int. J. Environ. Res. Public Health 2020, 17, 9509".

We read the letter from Dr. Fusco and colleagues with great interest, and we would like to thank them for the stimulating comments regarding our paper "Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association" [...].

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.

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.

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.

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.

Dentistry during the COVID-19 Epidemic: An Italian Workflow for the Management of Dental Practice.

The COVID-19 outbreak has raised concerns about infection control all over the world. Among health workers, dentists are particularly exposed to the COVID-19 infection risk. The aim of this paper is to present a workflow to manage dental procedures already in use at the Dental Unit of the University Hospital of Messina. The proposed workflow accounts for the many aspects of dental practitioners' risk in the COVID-19 era, and focuses on the assessment of patient risk level, a two-phase dental procedure management (remote and face-to-face), and the use of specific preventive measures. No cases of COVID-19 infection were detected among patients and staff of the dental unit in a two-month period of time while using this protocol. This workflow seems a promising and effective solution to manage dental procedures during the COVID-19 outbreak, and could be implemented in both public and private practices until the emergency is contained.

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.

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.

Appropriateness in Dentistry: A Survey Discovers Improper Procedures in Oral Medicine and Surgery.

OBJECTIVES: The aim of this study was to assess appropriateness of diagnostic exams, treatments, and procedures among Italian dental practitioners. MATERIALS AND METHODS: A questionnaire with multiple responses on topics of dentistry and oral medicine was administered to a sample of 198 Italian dental practitioners. Information on characteristics of the respondents was also collected. Descriptive statistics and multiple correspondence analysis (MCA) were applied. Data were analyzed using R software (version 3.3.2). RESULTS: The survey respondents included Doctors of Medicine (MD) (54/198 = 27%) with or without specialty in dentistry (33% versus 67%), Doctors of Dental Surgery (DDS) (144/198 = 73%), DDS with specialty in orthodontics (7%), and DDS with specialty in oral surgery (4%). Mandatory procedures in dental and oral medicine education and training include (a) prescription of antibiotics before/after oral surgery procedures; (b) prevention strategies for oral cancer, and (c) prescription of dental X-ray examinations (41%, 52%, and 48%, resp.). CONCLUSION: On examining the results of the survey, it is evident that information and implementation of the above mentioned procedures are crucially needed. Our results confirm the necessity to reduce inappropriate practices in dentistry, implementing formation and information, leading to correct prescriptions, and optimizing patients' oral health. This coincides with the Italian Slow Medicine program entitled "Fare di più non significa fare meglio-Choosing Wisely Italy," which has also motivated this study.

Could the Combined Administration of Bone Antiresorptive Drug, Taxanes, and Corticosteroids Worsen Medication Related Osteonecrosis of the Jaws in Cancer Patients?

The study presents a report of 58 metastatic cancer patients who developed osteonecrosis of the jaws after being treated with zoledronic acid and taxanes, plus corticosteroids. A retrospective analysis of data registered in the archives of two Italian osteonecrosis of the jaws treatment centers, who are based at the University of Messina and at the University of Palermo, was performed in order to study, in these patients, demographic data and characteristics such as frequency of cancer location, lines of therapy, frequency of cancer drugs, presence/absence of oral trigger, number, location, and stage of jaw osteonecrosis. It was found that the majority of patients developed advanced stages of osteonecrosis, frequently complicated with infection. It was hypothesized that the concurrent administration of chemotherapeutic agents could be eventually considered as a factor able to allow a faster worsening of the clinical manifestation through the exacerbation of soft tissue defects, due to chemotherapy drugs.

Impact of electro-neuro-feedback on postoperative outcome of impacted lower third molar surgery.

OBJECTIVE: The purpose of this study was to evaluate the impact of a treatment with electro-neuro-feedback (ENF), a portable transcutaneous electrical nerve stimulation (TENS) device, on the clinical outcome and inflammatory biochemical parameters related to the impacted lower third molar surgery. MATERIALS AND METHODS: A randomized, split-mouth, and single-blind study was conducted on 32 patients requiring lower third molars extractions and referred to the Oral Surgery Unit of the School of Dentistry of the University of Messina. Every patient underwent surgical removal of both lower third molars. The first extraction included a placebo (electrodes placement with turned-off device) treatment following the surgery, while the second had the ENF used next to the avulsion and the following days. Clinical parameters were collected 4 days before, immediately after, 2, 4, and 7 days after the surgical procedure. Biochemical parameters were obtained 1 day before the surgical removal and 7 days after. Data were processed using Wilcoxon-Mann-Whitney test, with significance being set at P < 0.05. RESULTS: Clinical outcome parameters showed a significant improvement after the ENF treatment, while considered inflammatory markers expressed different patterns. CONCLUSIONS: ENF, a reliable portable TENS device, has demonstrated to be a useful tool in the managing of the postsurgical phases, reducing edema, pain, and consequent pain-killers consumption.

Treatment of Medication-Related Osteonecrosis of the Jaw and its Impact on a Patient's Quality of Life: A Single-Center, 10-Year Experience from Southern Italy.

INTRODUCTION: No official guidelines are available for the management of medication-related osteonecrosis of the jaw (MR-ONJ). The additional benefit of surgery after pharmacological treatment is debated by both clinicians and patients. OBJECTIVE: The aim of this study was to evaluate the changes in patients' MR-ONJ-related quality of life (QoL) after pharmacological treatment with or without surgery in a large cohort affected by MR-ONJ. METHODS: Anonymized data on patients diagnosed with MR-ONJ were extracted from the database of the Osteonecrosis of the Jaw Treatment Center (University of Messina, Italy) in the years 2005-2015. QoL was evaluated at the moment of MR-ONJ diagnoses (T0), after pharmacological treatment with or without surgery (T1 and T2, respectively), based on scores from the European Organisation for Research and Treatment of Cancer (EORTC) QOL Module for Head and Neck Cancer (global oral health status [GOHS]) and a visual analog scale (VAS), stratified by indication for use. RESULTS: Among 100 patients, 36% were affected by osteoporosis (OSTEO group) and 64% were affected by cancer (ONC group). Considering T0, QoL scores were higher in the OSTEO group then in the ONC group. At T1, GOHS and VAS increased in both groups (OSTEO group: +9.9% and +39.9%; ONC group: +35.4 and +97.2%, respectively). Pharmacological treatment was effective in reducing pain (OSTEO group: -22.0%; ONC group: -44.8%), and social contact troubles (OSTEO group: -40.3%; ONC group: -26.7%). At T2, GOHS and VAS further increased. Scores related to 'pain' and the troubles related to the 'social dimension' also decreased (OSTEO group: -91.3% and -72.0%; ONC group: 50.8% and -16.4%, respectively). CONCLUSIONS: MR-ONJ-related QoL increased after pharmacological treatment and, more notably, after surgery, which may offer benefits to selected patients. QoL data may help clinicians in promoting tailored management of MR-ONJ.

Oral-Health-Related Quality of Life After Surgical Treatment of Osteonecrosis of the Jaws.

The aim of this study is to analyze the clinical outcome and the change in oral-health-related quality of life (QoL) of osteoporotic patients affected by medication-related osteonecrosis of the jaws (MRONJ). Forty-one patients, consecutively treated for a 10-year period, were retrospectively analyzed. All the patients underwent a marginal osseous resective jaw surgery. A clinical 12 months postoperative evaluation has been performed and the complete mucosal healing, the absence of swelling and suppuration, and no signs of disease recurrence were defined like success parameters. Quality-of-life surveys tests like EORTC QQ-C30 and QLQ-HN35 appendices in conjunction with a perceived oral health visual analog scale (VAS) were administered before (time of diagnosis of MRONJ) and after surgery (at least 6 months) in order to record the different oral health status of the treated patients. The majority of MRONJ-diagnosed patients complained symptoms like pain, eating discomfort, and sense problems, with occasional involvement of the social dimension. There was a prevalence of troubles with social eating and social contact.The complete mucosal healing was achieved in 100% of the patients and the administered survey tests reported a significant improvement in all the investigated spheres. Similarly, an increased mean score of perceived oral health VAS was reported.Marginal-resective surgery of the necrotic jaw bone can be an effective treatment of osteoporotic patients affected by localized MRONJ. Quality-of-life parameters are demonstrated to be useful for recording the patient-centered outcome of MRONJ treatment.