Onset of MRONJ in Breast Cancer Patients after Switching from Low to High Dose of Bone Modifying Agents Due to Bone Metastases Development: A Single Center Retrospective Cohort Study

Background: Medication-Related Osteonecrosis of the Jaw (MRONJ) is an adverse drug reaction mainly associated to bone modifying agents (BMAs). Breast cancer (BC) is the most frequent cancer worldwide. Its therapy can cause cancer treatment-induced bone loss (CTIBL), commonly treated with BMAs. The aims of this retrospective study are: to describe characteristics of BC patients under BMAs for CTIBL; to record any switch to high-dose BMAs; to assess MRONJ onset and to identify any factors associated with it. Patients: Authors included patients referred for MRONJ prevention to the Unit of Oral Medicine (University Hospital of Palermo). Results: Fourteen female BC patients under low-dose BMAs for CTIBL were eligible (mean age 66.6 years). Four patients switched to high-dose BMAs for bone metastases. In two of the four, MRONJ developed: one case, in the mandible (risedronate for 48 months then Xgeva® for 60 months); the other case, in the maxilla (Prolia® for 20 months then zoledronate for 16 months). Conclusion: It can be theorized that BC patients under BMAs for CTIBL are likely to have MRONJ risk similar to osteo-metabolic patients. These patients need more careful monitoring of oral health since they may switch, for preventing or treating bone metastases, to heavier BMAs therapy, thus increasing their risk of MRONJ

Salivary Biomarkers for Oral Squamous Cell Carcinoma Diagnosis and Follow-Up: Current Status and Perspectives

Oral cancer is the sixth most common cancer type in the world, and 90% of it is represented by oral squamous cell carcinoma (OSCC). Despite progress in preventive and therapeutic strategies, delay in OSCC diagnosis remains one of the major causes of high morbidity and mortality; indeed the majority of OSCC has been lately identified in the advanced clinical stage (i.e., III or IV). Moreover, after primary treatment, recurrences and/or metastases are found in more than half of the patients (80% of cases within the first 2 years) and the 5-year survival rate is still lower than 50%, resulting in a serious issue for public health. Currently, histological investigation represents the “gold standard” of OSCC diagnosis; however, recent studies have evaluated the potential use of non-invasive methods, such as “liquid biopsy,” for the detection of diagnostic and prognostic biomarkers in body fluids of oral cancer patients. Saliva is a biofluid containing factors such as cytokines, DNA and RNA molecules, circulating and tissue- derived cells, and extracellular vesicles (EVs) that may be used as biomarkers; their analysis may give us useful information to do early diagnosis of OSCC and improve the prognosis. Therefore, the aim of this review is reporting the most recent data on saliva biomarker detection in saliva liquid biopsy from oral cancer patients, with particular attention to circulating tumor DNA (ctDNA), EVs, and microRNAs (miRNAs). Our results highlight that saliva liquid biopsy has several promising clinical uses in OSCC management; it is painless, accessible, and low cost and represents a very helpful source of diagnostic and prognostic biomarker detection. Even if standardized protocols for isolation, characterization, and evaluation are needed, recent data suggest that saliva may be successfully included in future clinical diagnostic processes, with a considerable impact on early treatment strategies and a favorable outcome

Commonalities between ENT Specialists and Oral Medicine Experts: Old HPV Diseases and New Oral HPV-Cancer along the Borders

A human papillomavirus (HPV) infection is globally one of the most common causes of sexually transmitted infections of the mucous membranes (genital, anal and oral). Over the last decade, an increasing number of young patients have been infected due to the changes in sexual habits in the general population. The majority of the lesions are benign; however, substantial scientific evidence has suggested a role for the HPV family in the carcinogenesis of squamous cell carcinoma (SCC). It is proposed that dentists, in addition to ENT specialists, should apply standardized management protocols in order to construct a well-defined pathway in terms of diagnosis, which is based on a PCR diagnostic technique and the management of those lesions

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

Ranula: Modified Micro-Marsupialization: Case Report and Review of Literature

Introduction: Ranula is a limited mucus retention on the floor of mouth. Due to the young age of patients, over the years, attempts were made to find minimally invasive and effective surgical techniques. To date, however, there is still no gold standard. The modified micro-marsupialization is an effective and minimally invasive technique, with minimal risk of relapse, although there are very few reports about it. Case report: A 12-year-old male presented to our ENT Clinic with a rounded swelling with regular and defined margins, measuring 4x3 cm, soft and painless, non-compressible and bluish. Clinical diagnosis of ranula was made and a modified micro-marsupialization was performed: eight interrupted sutures using silk 3-0 were placed perpendicularly to the major axis of the lesion, from one side of the lesion to the other, without reaching the underlying tissue. No sutures were lost during follow-up, no complications occurred. Complete healing was reached after removing sutures on the 30th postoperative day. At 6 months control no relapse was observed. Conclusion: Modified micro-marsupialization is strongly indicated and recommended, especially in pediatric patient, due to its low invasiveness and its very low relapse rate. The poor case history found in the literature is probably an indication of the lack of knowledge of modified micro-marsupialization which, in our opinion, could be considered the gold standard