Treatment of medication-related osteonecrosis of the jaw with cell therapy.

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) poses a significant challenge considering the absence of a "gold standard" treatment. Cell-based therapy and tissue engineering offer promising therapeutic alternatives. This study aimed to harness the regenerative properties of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) for MRONJ treatment. AT-SVF contains mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC), which promote bone formation, while the L-PRF scaffold can serve as a three-dimensional scaffold for the AT-SVF and support tissue healing through growth factor release. Materials and methods: The protocol involved applying autologous AT-SVF within an L-PRF matrix following surgical debridement. Age, gender, body mass index, comorbidities, underlying oncological condition, prescribed antiresorptive treatment: BP or DMB, antiresorptive treatment duration, antiresorptive treatment potential discontinuation, number of MRONJ lesion, MRONJ location, MRONJ stage, MRONJ trigger factor were assessed for each patient. Patients underwent the procedure and were monitored for a minimum of 6 months based on clinical, biological and medical imaging criteria. Results: Nine patients, with a total of ten MRONJ lesions, participated in the study. Six patients were female, and three were male, with a mean age of 68 ± 8 years. Four patients had multiple myeloma (MM), three had metastatic breast cancer, and two had metastatic prostate cancer. Seven MRONJ cases were classified as stage II, and three were classified as stage III. Soft tissue completely healed within a month after treatment in nine cases, with no clinical improvement observed in the remaining case. During follow-up, no sign of MRONJ recurrence was observed. Tridimensional medical imaging revealed bone healing 6 months after the surgical procedure. Immunophenotyping confirmed the presence of MSC and EPC in the AT-SVF: 12,6 ± 4,5% CD31+, 20.5 ± 7,8% CD34+, 34,4 ± 7,3% CD146+ and 54,6 ± 7,4% CD45+. Conclusion: This prospective study introduces a potential new treatment approach for MRONJ using autologous AT-SVF within an L-PRF scaffold. Our results are encouraging and suggest the need for further investigation with a larger patient cohort to better understand the underlying mechanisms.

Preventive and Therapeutic Effect of Metformin in Head and Neck Cancer: A Concise Review.

BACKGROUND: Head and neck cancer (HNC) is a complex affection. Nowadays, conventional treatments are associated with many side effects, reducing the patient's quality of life. Recent studies suggest that metformin, a first-line treatment for diabetes, could decrease cancer incidence and improve cancer-related survival rates. METHODS: This systematic review summarizes important data from studies evaluating metformin's contribution to preventing and treating HNC. RESULTS: The results suggest a protective effect of metformin in HNC. However, no consensus has been found on its therapeutic effects. Metformin seems to confer an improved cancer-related survival rate in a diabetic population, but compared to a non-diabetic population, the review could not identify any advantages. Nevertheless, no studies presented a negative impact. CONCLUSION: In conclusion, the results of this systematic review suggest that HNC patients may benefit from metformin. Indeed, it would reduce the HNC incidence. However, more studies are required to evaluate the effect on cancer-related survival rates.

Antibiotic Use in Patients Undergoing Complex Clean-Contaminated Head and Neck Surgery: A Prospective Study.

Aims and Objectives: Oncological surgery of the upper aerodigestive tract is a complex procedure and often includes neck dissection and flap reconstruction. It can be complicated by severe surgical site infection (SSI) leading to flap necrosis, delayed wound healing, and increasing mortality and morbidity. The purpose of this study is to perform a systematic descriptive analysis and to evaluate the effect of our adapted antibiotic regimen strategy on postoperative outcomes. Materials and Methods: A prospective cohort analysis of 47 patients undergoing major clean-contaminated head and neck surgery was conducted at the Cervicomaxillofacial Surgery Department (Saint-Pierre Hospital), between 2019 and 2022. The patients were divided into two groups: group I, which received a short-term postoperative antibiotic regimen for 24 h, and group II, which received a more extended postoperative antibiotic course for more than 24 h. Antibioprophylaxy amoxicillin and clavulanate were administered intravenously 30-60 min before making the incision. The antibiotic regimen was continued after surgery. The prognostic significance of the antibiotic regimen on postoperative outcomes, including clinical signs of infection and biological markers such as white blood cells count, and C-reactive protein levels was evaluated using univariate analysis. Results: Eighteen patients developed SSIs. All of these infections were grade 2 and were treated with antibiotics. After univariate analysis, only a history of hypothyroidism seems to be a predictor of SSI (P = 0.038). No significant difference was found in terms of onset and hospital stay when we compared the patients who received antibiotics for 24 h or more. Moreover, the rate of multidrug-resistant bacteria was not different in both groups. Conclusions: Our results suggest that postoperative antibiotics for more than 24 h do not confer benefit in terms of SSI. Oncological patients undergoing complex clean-contaminated head and neck surgery are often suffering from infectious complications and, despite the absence of guidelines, practicians should consider these findings in their decision-making.

Contribution of Antiangiogenic Agents to the Risk of Medication-related Osteonecrosis of the Jaw in Combination with Antiresorptive Agents: Preliminary Results in a Comparative Prospective Report of 59 Oncologic Cases.

Aim: The aim of this preliminary study was to evaluate in an oncological population the association risk of antiangiogenic (AA) agents to antiresorptive (AR) agents on the incidence and the severity of medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: In this prospective study, we reviewed the medical records and clinical variables of 59 consecutive oncologic patients who developed MRONJ. For all patients, we retrieved the following variables: age, gender, alcohol and tobacco use, type of cancer, use of corticosteroids for >3 months, history of diabetes, MRONJ staging, combination of AR and AA agents, dental history (surgery, prosthesis) or spontaneous, site of MRONJ, delay between AR and AA first intake, and MRONJ development. Patients were divided into two groups according to drugs therapy they underwent: group 1 (G1) including patients treated with AR agents alone and group 2 (G2) including patients receiving antiresorptive-antiangiogenic drugs (AR+AA). The degree and the therapeutical success were defined as primary outcomes and the number, the localization, and the delay in onset of the lesions as secondary outcomes. In order to identify predictive factors of osteonecrosis-free interval time, univariate and multivariate Cox regression was performed. Statistical tests were carried out using the IBM® SPSS® Statistics software. All reported P-values are two-tailed and were considered to be significant when less than 0.05. Results: Among the 47 patients who received AR agent alone (group 1), the mean treatment duration before diagnosis of MRONJ was 39.2 months. In the second group (n = 12), patients developed MRONJ with a comparable mean time of 55 months (P = 0.16). According to the staging of MRONJ at the time of diagnosis, no significant difference (P = 0.736) was observed between the two groups. Moreover, the treatment applied was not statistically different in both the groups and was successful in 36.17% of the patients in group 1 and 58.33% of the patients in group 2. No statistically difference was reported in both the groups (P = 0.16). After statistical analysis, no significant difference in terms of MRONJ localization (P = 0.13) was observed. Finally, the incidence of spontaneous MRONJ was comparable in both the groups. Statistical analysis revealed that total time of treatment was the only factor associated with poor osteonecrosis-free interval time (hazard ratio 0.99; P = 0.001). Interestingly, the combination of an AA and AR agent was not a significant predictor factor of the interval time before the diagnosis of osteonecrosis. Additionally, corticosteroid use, diabetes mellitus, and dental consultation before treatment were not statistically related to poorer osteonecrosis-free interval time rates. Conclusion: In our preliminary study, neither the mean treatment time duration before the diagnosis of MRONJ nor the dose delivered was different in both the groups (AR vs. AR+AA). Moreover, no significant difference was observed between both the groups regarding the localization and the staging of MRONJ at the time of diagnosis. Interestingly, our results demonstrated that the risk of spontaneous MRONJ is statistically comparable in the AR and AR-AA groups. Additionally, the addition of an AA agent did not influence the treatment applied in the two groups of patients.

Prognostic Significance of a Scoring System Combining p16, Smoking, and Drinking Status in a Series of 131 Patients with Oropharyngeal Cancers.

BACKGROUND: Tobacco and alcohol are two main risk factors associated with head and neck squamous cell carcinoma (HNSCC). Studies showed that human papillomavirus (HPV) plays a role in the etiology of this cancer. HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients present in general a better response to conventional therapy and better overall survival (OS). However, OSCC is a heterogeneous disease regarding treatment. This study aimed to identify more effective prognostic factors associated with a poor clinical outcome for OSCC patients to improve treatment selection. MATERIALS AND METHODS: OSCC patients diagnosed between 2007 and 2017, in two Belgian hospitals, were included. Demographic and clinicopathologic data were extracted from medical records. HPV status was determined through p16 immunohistochemistry. Univariable and multivariable Cox proportional hazard regression analyses allowed to identify variables prognostic for OS and recurrence-free survival (RFS). Kaplan-Meier survival curves have been assessed for survival. RESULTS: The study included 131 patients. Statistics showed that monotherapies were significantly associated with a shorter OS; p16 overexpression was significantly associated with a weak consumption of tobacco or alcohol, and a high p16 expression was significantly associated with both longer RFS and OS. The study validated that tobacco and alcohol consumption were significantly correlated with poorer RFS and poorer OS. Only p16 expression trended to be significant for RFS when compared to smoking and drinking habits, while p16 upregulation and alcohol use were both vital for OS indicating that p16 is an independent and significant prognostic factor in OSCC patients. Finally, a scoring system combining p16, tobacco, and alcohol status was defined and was significantly associated with longer RFS and longer OS for nonsmoker and nondrinker p16-positive OSCC patients. CONCLUSIONS: This study confirmed that the overexpression of the p16 protein could be viewed as a factor of good prognosis for RFS and OS of OSCC patients. The prognostic significance of a scoring system combining p16 expression, smoking, and drinking status was evaluated and concluded to be a more effective tool to determine therapeutic orientations based on the risk factors for better treatment relevance and survival.

Survival and treatment outcome of head and neck cancer patients with pulmonary oligometastases.

OBJECTIVES: The purpose of this study was to determine the outcome of head and neck squamous cell carcinoma (HNSCC) patients developing lung metastasis. DESIGN: Retrospective study. PARTICIPANTS: HNSCC patients with lung metastasis treated between 2001 and 2018 were included. MEAN OUTCOMES MEASURES: Statistical analyses described the relationship between patient survival, treatment efficacy and pulmonary metastasis occurrence. RESULTS: One hundred HNSCC patients were included in the study. The median overall survival (OS) was 21 months. The median recurrence-free survival (RFS) was seven months. Patient survival with only lung metastases was significantly longer compared to patients with lung metastases and lymph nodes involvement or other metastases. Moreover, patients with a single metastasis had longer post-RFS and OS than patients with multiple metastases. The local control of metastasis was better when patients presented only lung metastases, and it was more effective in single metastasis. The surgery allowed better metastases local control than supportive care or radio and/or chemotherapy. In case of specific therapy, pulmonary resection was associated with a longer post-RFS and a longer OS compared to supportive care or radio and/or chemotherapy. CONCLUSIONS: We confirmed, in the current study, the significant survival benefit for HNSCC patients treated by surgery for their pulmonary metastasis. While treatment of multiple metastases required palliative chemotherapy or best supportive care in most of the cases, specific surgical treatment in selected HNSCC patients should be considered.

Unilateral chronic maxillary rhinosinusitis after bone maxillary graft for dental implant placement: A case report.

Odontogenic chronic maxillary rhinosinusitis has to be suspected in patient with a history of dental implant placement just after bone maxillary graft.

Bisphosphonate-related osteonecrosis of the jaw and its associated risk factors: a Belgian case series.

OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BROJ) is a serious oral complication of bisphosphonate (BP) treatment involving the exposure of necrotic maxillary or mandibular bone. Our purpose is to describe the clinical presentation of 34 cases of BROJ and to identify potential risk factors. STUDY DESIGN: A retrospective study was performed in four Belgian institutions. METHODS: Complete medical histories were recorded and analyzed. These data include age, gender, initial disease requiring BP, type and duration of BP treatment, symptomatology and location of BROJ, prior dental procedures, treatment of the BROJ and treatment outcome, and radiographic, histological, and microbiological data. RESULTS: Bisphosphonates (BP) were used in the management of disseminated cancers in 30 patients (88.5% of total studied), while four patients received BP due to osteoporosis (11.5%). The most frequently used BP was zoledronic acid in 29 patients (83%). Microbiological data obtained in 25 patients demonstrated that 72% of these patients were infected or colonized by an actinomyces. Eight of the 14 patients (57%) who received only medical treatment were cured. Of the 20 patients who underwent surgical treatments, only four were completely cured (20%). BROJ lesions smaller than 1 cm are associated with better prognosis in terms of treatment outcomes (P = .0009). Local treatments combined with long-term antibiotics are also correlated with better prognosis (P = .02). CONCLUSIONS: Lesions smaller than 1 cm and lesions that were subject to medical treatments are associated with a better outcome. Surgical treatments appear to be non-beneficial for BROJ.