Antiresorptive therapy in combination with radiation results in enhanced risk for necrosis and associated complicatifions.

OBJECTIVE: Patients exposed to a combination of antiresorptive medication and radiotherapy of the head and neck area developing necrosis of the jaw in the course of treatment are extremely rare. Therefore, the aim of this study was to identify the outcome and complications in this highly vulnerable patient cohort. STUDY DESIGN: Seventeen patients who received both antiresorptive treatment and radiotherapy (medication-related osteonecrosis of the jaw/osteoradionecrosis = the [MRONJ/ORN] group) in the head and neck area were enrolled in this study. Included patients were treated in our department between 2005 and 2022. Four hundred twenty-four patients with MRONJ (the MRONJ group) and 138 patients with ORN of the jaw were enrolled as two control groups (the ORN group). Demographic data, lesion localization, date of primary diagnosis, clinical symptoms, type of therapy (surgical or non-surgical), details on antiresorptive treatment, outcome, and complications were recorded. RESULTS: Pathological fractures, continuity resection, and recurrence appear more often in patients who receive a combination of antiresorptive treatment and radiotherapy in the head and neck area compared with patients undergoing only one of these treatments. There was a statistically significant difference (P < .001) between the MRONJ/ORN group and the MRONJ group and the MRONJ/ORN group and the ORN group considering recurrence, fracture, and continuity resection. Patients with ORN combined with MRONJ have a 4-times higher risk for developing recurrence compared with patients with MRONJ and a 1.5-times higher risk for recurrence compared with patients with ORN. Jaw fracture and continuity resection appear more often in patients with MRONJ/ORN. CONCLUSIONS: Patients under antiresorptive therapy in combination with radiation therapy in the head and neck area have a higher risk for developing complications in case of osteonecrosis of the jaw. Therefore, a strict follow-up care schedule is highly recommended.

Intra-flap recurrence of an oral squamous cell carcinoma after curative resection and reconstruction with a free flap.

Intra-flap recurrence after reconstruction is a possible complication in oral squamous cell carcinoma (OSCC) after curative resection and reconstruction with a free flap. Abstract: This case report describes an intra-flap recurrence after tumor resection and reconstruction with a latissimus dorsi flap due to OSCC. We report a 58-year-old female patient who underwent curative resection of a squamous cell carcinoma in the oral cavity and submental area and reconstruction with a latissimus dorsi free flap. Thirteen months after the operation, the patient presented with lung metastases and, 22 months after the operation, a metastatic lesion in the flap's central area with no sign of recurrence in the primary resection site occurred. The patient died 25 months after the initial operation due to the rapid progression of the disease and further distant metastases. To our knowledge, similar cases do not exist in the literature. This is the first reported case of intra-flap metastasis after surgical treatment of OSCC.

Pre- and Post-Operative Quality of Life in Patients with Osteoradionecrosis of the Jaw.

Osteoradionecrosis of the jaw (ORNJ) is a feared complication following radiation therapy performed for oncological treatment of head and neck cancers (HNC). To date, there is no clear evidence regarding the impact of surgical treatment of ORNJ on the quality of life (QoL) of affected patients. However, understanding the significance of the surgical treatment approach and its effects on QoL is an essential factor in the decision-making process for optimal, individualized therapy. In this prospective clinical study, QoL was assessed in relation to health related QoL (HRQoL) and oral health related QoL (OHQoL) before and after surgical treatment of ORNJ using standardized questionnaires (EORTC QLQ-C30, QLQ-HN35, OHIP-14). The overall QoL scores as well as individual domains of the collected scales regarding functional and symptom-related complaints were statistically analyzed. Subgroups concerning age, gender, different risk factors and type of ORNJ therapy were compared using Kruskal Wallis test. In addition, clinical and demographic patient data were collected and analyzed. QoL improvement correlated with the type of surgical ORNJ and the length of hospitalization. Better QoL scores were achieved post-operatively regarding different symptoms like pain, swallowing and mouth opening. Long-term effects of radiation therapy remained visibly restrictive to QoL and worsen over time.

Prognostic role of lymph node micrometastasis in oral and oropharyngeal cancer: A systematic review.

BACKGROUND: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. METHODS: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. RESULTS: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. CONCLUSION: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.

[Update of the S3-guideline on diagnostics, prophylaxis and treatment of osteoporosis]. / Update der S3-Leitlinie Diagnostik, Prophylaxe und Therapie der Osteoporose.

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years.

Sclerotic bone: a sign of bone reaction in patients with medication related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.

The effect of frontal trauma on the edentulous mandible with four different interforaminal implant-prosthodontic anchoring configurations. A 3D finite element analysis.

PURPOSE: The present three-dimensional (3D) finite element analysis (FEA) was aimed to assess the biomechanical effects and fracture risks of four different interforaminal implant-prosthodontic anchoring configurations exposed to frontal trauma. MATERIAL AND METHODS: A symphyseal frontal trauma of 1 MPa was applied to four dental implant models with different configurations (two unsplinted interforaminal implants [2IF-U], two splinted interforaminal implants [2IF-S], four unsplinted interforaminal implants[ 4IF-U], four splinted interforaminal implants [4IF-S]. By using a 3D-FEA analysis the effective cortical bone stress values were evaluated in four defined regions of interest (ROI) (ROI 1: symphyseal area; ROI 2: preforaminal area; ROI 3: mental foraminal area; and ROI 4: condylar neck) followed by a subsequent intermodel comparison. RESULTS: In all models the frontal traumatic force application revealed the highest stress values in the condylar neck region. In both models with a four-implant configuration (4IF-U, 4IF-S), the stress values in the median mandibular body (ROI 1) and in the condylar neck region (ROI 4) were significantly reduced (P <0.01) compared with the two-implant models (2IF-U, 2IF-S). However, in ROI 1, the model with four splinted implants (4IF-S) showed significantly (P < 0.01) reduced stress values compared to the unsplinted model (4IF-U). In addition, all models showed increased stress patterns in the area adjacent to the posterior implants, which is represented by increased stress values for both 2IF-U and 2IF-S in the preforaminal area (ROI 3) and for the four implant-based models (4IF-U, 4IF-S) in the mental foraminal area. CONCLUSION: The configuration of four splinted interforaminal implants showed the most beneficial distribution of stress pattern representing reduced stress distribution and associated reduced fracture risk in anterior symphysis, condylar neck and preforaminal region.

X-Linked Hypophosphatemia: Does Targeted Therapy Modify Dental Impairment?

X-linked hypophosphatemia is a rare, hereditary disorder that significant influences teeth and alveolar bone. The first clinical sign leading to the diagnosis of X-linked hypophosphatemia is often dental impairment with dental abscesses and dentin mineralization defects. Genetic analysis helped find the responsible gene and therefore opened up new ways of therapeutically managing X-linked hypophosphatemia. The human monoclonal antibody Burosumab represents a milestone in the targeted therapy of this hereditary disease by directly addressing its pathophysiology. Targeted therapy has been shown to improve skeletal impairment, pain, and phosphate metabolism. However, the influence of this new therapy on dental impairment has only been addressed in a few recent studies with varying results. Therefore, in this review, we aim to summarize the dental phenotype and analyze the different treatment modalities with a focus on dental impairment.

New insights into redox-related risk factors and therapeutic targets in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral cavity accounting for 90 % of oral cancer with a global incidence of 350.000 new cases per year. Curative resection along with adjuvant radiation therapy or a combination of radiotherapy with chemotherapy remain as gold standard in treating OSCC. Still, local recurrence, lymph nodal recurrence, and complications of radiation remain the main cause of tumor-related mortality. Reactive oxygen species are not only correlated to the etiology of OSCC due to oxidative DNA damage, lipid peroxidation or effecting signal transduction cascades that effect cell proliferation and tumorigenesis, but are also of great interest in the therapy of OSCC patients. As induced oxidative stress can be used therapeutically for the induction of tumor cell death, redox targets might be a therapeutic addition to the conventional treatment options. In this review, we discuss markers of impaired redox homeostasis as well as potential redox-related treatment targets in OSCC.

[Update of the S3-guideline on diagnostics, prophylaxis and treatment of osteoporosis]. / Update der S3-Leitlinie Diagnostik, Prophylaxe und Therapie der Osteoporose.

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years.

Comparison of alternative N-staging models in patients with oral cancer. Is nodal yield or burden the most critical parameter?

BACKGROUND: There is increasing evidence in the literature that alternative N-classification systems offer a simpler and more precise risk stratification than the current N- classification in patients with oral squamous cell carcinoma. The purpose of this study is to compare three broadly proposed models incorporating lymph node ratio, log odds of positive lymph nodes and number of positive lymph nodes regarding disease-free and overall survival. METHODS: This is a retrospective study of patients treated in a single center between 2013 and 2019. Cox proportional hazard models, Kaplan Meier curves, the long rank test and the area under the curve were implemented to compare the risk-stratification ability of the three models. Moreover, a hazard ratio plot was calculated to investigate the association between nodal yield and disease-free survival. RESULTS: 231 patients were included. All three proposed N-models were significantly correlated to the patient's prognosis in the multivariate analysis. Pairwise comparisons between the groups showed that the current pN classification offers the worst stratification and that the model incorporating the number of positive lymph nodes had a better performance for predicting both endpoints. Finally, a decrease in hazard ratio was observed with each additional lymph node removed up to the number of 39 lymph nodes. CONCLUSIONS: The model incorporating the nodal burden offered a better predictive ability. The current N-classification cannot adequately identify patients with different prognosis. A non-linear relationship was found between nodal yield and survival, which could be the disadvantage of the lymph node ratio and log odds models.

Metastases of OSCC Based on Oral Lichen Ruber Planus.

Oral lichen ruber planus (OLP) is a poorly understood chronically inflammatory disease of the oral mucosa. Malignant transformation into oral squamous cell carcinoma (OSCC) is reported in between 1-2% of cases in the literature. After malignant transformation, surgical treatment-meaning tumor resection combined with neck dissection-is recommended. The recommended extent of treatment is controversial in the literature because this kind of OSCC is often a highly differentiated tumor with a lower risk for lymph nodal spreading. This study aims to overview 103 patients treated in our department due to OLP. The primary outcome parameter was the development of metastases in OLP patients compared to a group of OSCC patients without OLP and the comparison of survival in between both groups. Statistical analysis showed a significantly lower risk for patients with OSCC and with OLP for lymph nodal spreading (p = 0.013). Patients with OSCC and without OLP had a 4.76-higher risk for lymph nodal spreading. On the other hand, second metachronous tumor occurred more often in patients with OSCC and OLP. Overall, OSCC based on OLP occurs more often in female patients, is more highly differentiated and comes with a lower risk for metastases but has a higher risk for second metachronous tumors. Therefore, special attention should be paid to patients with OSCC based on OLP when planning adjuvant therapy and clinical follow-up. The indication for postoperative radiation should be made cautiously in this case, and clinical controls should be performed more closely due to the risk of recurrent disease or tumors at different locations.

Fibrous Dysplasia of the Jaw: Advances in Imaging and Treatment.

A total of 7% of all benign bone lesions are diagnosed as fibrous dysplasia (FD). The symptoms of FD of the jaw range from asymptomatic to dental anomalies, pain and facial asymmetry. Due to its resemblance to other fibro-osseous bone lesions, misdiagnosis often occurs and can lead to inadequate treatment. Particularly in the jaw, this lesion does not become quiescent during puberty, making fundamental knowledge about the diagnosis and treatment of FD crucial. Mutational analysis and nonsurgical approaches offer new diagnostic and therapeutic options. In this review, we examine the advances and the difficulties of the diagnosis and the various treatment modalities of FD of the jaw in order to capture the current scientific knowledge on this bone disease.

Accuracy of maxillary positioning using computer-designed and manufactured occlusal splints or patient-specific implants in orthognathic surgery.

OBJECTIVE: To determine the accuracy of maxillary positioning using computer-designed and manufactured occlusal splints or patient-specific implants in orthognathic surgery. MATERIAL AND METHODS: A retrospective analysis of 28 patients that underwent virtually planned orthognathic surgery with maxillary Le Fort I osteotomy either using VSP-generated splints (n = 13) or patient-specific implants (PSI) (n = 15) was conducted. The accuracy and surgical outcome of both techniques were compared by superimposing preoperative surgical planning with postoperative CT scans and measurement of translational and rotational deviation for each patient. RESULTS: The 3D global geometric deviation between the planned position and the postoperative outcome was 0.60 mm (95%-CI 0.46-0.74, range 0.32-1.11 mm) for patients with PSI and 0.86 mm (95%-CI 0.44-1.28, range 0.09-2.60 mm) for patients with surgical splints. Postoperative differences for absolute and signed single linear deviations between planned and postoperative position were a little higher regarding the x-axis and pitch but lower regarding the y- and z-axis as well as yaw and roll for PSI compared to surgical splints. There were no significant differences regarding global geometric deviation, absolute and signed linear deviations in the x-, y-, and z-axis, and rotations (yaw, pitch, and roll) between both groups. CONCLUSIONS: Regarding accuracy for positioning of maxillary segments after Le Fort I osteotomy in orthognathic surgery patient-specific implants and surgical splints provide equivalent high accuracy. CLINICAL RELEVANCE: Patient-specific implants for maxillary positioning and fixation facilitate the concept of splintless orthognathic surgery and can be reliably used in clinical routines.

Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model).

Background and Objectives: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising theory suspects infectious stimuli and local acidification with adverse effects on osteoclastic activity as crucial steps of MRONJ etiology. Clinical evidence showing a direct association between MRONJ and oral infections, such as periodontitis, without preceding surgical interventions is limited. Large animal models investigating the relationship between periodontitis and MRONJ have not been implemented. It is unclear whether the presence of infectious processes without surgical manipulation can trigger MRONJ. The following research question was formulated: is there a link between chronic oral infectious processes (periodontitis) and the occurrence of MRONJ in the absence of oral surgical procedures? Materials and Methods: A minipig large animal model for bisphosphonate-related ONJ (BRONJ) using 16 Göttingen minipigs divided into 2 groups (intervention/control) was designed and implemented. The intervention group included animals receiving i.v. bisphosphonates (zoledronate, n = 8, 0.05 mg/kg/week: ZOL group). The control group received no antiresorptive drug (n = 8: NON-ZOL group). Periodontitis lesions were induced by established procedures after 3 months of pretreatment (for the maxilla: the creation of an artificial gingival crevice and placement of a periodontal silk suture; for the mandible: the placement of a periodontal silk suture only). The outcomes were evaluated clinically and radiologically for 3 months postoperatively. After euthanasia a detailed histological evaluation was performed. Results: Periodontitis lesions could be induced successfully in all animals (both ZOL and NON-ZOL animals). MRONJ lesions of various stages developed around all periodontitis induction sites in the ZOL animals. The presence of MRONJ and periodontitis was proven clinically, radiologically and histologically. Conclusions: The results of this study provide further evidence that the infectious processes without prior dentoalveolar surgical interventions can trigger MRONJ. Therefore, iatrogenic disruption of the oral mucosa cannot be the decisive step in the pathogenesis of MRONJ.

Recent Advances, Systemic Therapy, and Molecular Targets in Adenoid Cystic Carcinoma of the Head and Neck.

With an incidence of 3-4.5 cases per million, adenoid cystic carcinoma (ACC) of the head and neck is one of the most common tumors of the parotid and sublingual salivary glands. In the clinical course, ACC is shown to have an aggressive long-term behavior, which leads to the fact that radical surgical resection of the tumor with tumor-free margins remains the "gold standard" in treating ACC. Particle radiation therapy and systemic molecular biological approaches offer new treatment options. However, risk factors for the formation and prognosis of ACC have not yet been clearly identified. The aim of the present review was to investigate long-term experience of diagnosis and treatment as well as risk and prognostic factors for occurrence and outcome of ACC.

Platelet-rich fibrin vs. buccal advancement flap for closure of oroantral communications: a prospective clinical study.

OBJECTIVES: The primary aim was to evaluate the success of the defect closure (tight or open) of oroantral communications (OAC) after treatment with platelet-rich fibrin (PRF) clots or a buccal advancement flap (BAF). Secondary outcome measurements were the evaluation of the wound healing, the displacement of the mucogingival border (MGB), and the pain level. MATERIAL AND METHODS: Fifty eligible patients with an OAC defect larger than 3 mm were randomly assigned to either PRF (test group, n = 25) or BAF (control group, n = 25) for defect closure. In a prospective follow-up program of 21 days, the defect closure healing process, the wound healing course using Landry's wound healing index (score: 0-5), the displacement of the MGB, and the postoperative pain score were evaluated. RESULTS: Five patients in each group were lost to follow-up resulting in 40 patients (20 in each group) for continuous evaluation. On postoperative day 21 (study endpoint), no difference regarding success rate (defined as closure of OAC) was noticed between the test (90%; 18/20) and control group (90%; 18/20). A univariate analysis showed significant differences for age and defect size/height for the use of PRF between successful-tight and open-failed defect healing. At the final evaluation, a significantly (p = 0.005) better wound healing score, a lower displacement of the MGB as well as lower pain-score were seen for the use of PRF. CONCLUSIONS: Based on the findings of the current study, the use of platelet-rich fibrin represents a reliable and successful method for closure of oroantral communications. The use of PRF clots for defect filling is associated with lowered pain levels and less displacement of the mucogingival border. CLINICAL RELEVANCE: The defect size should be taken into account when choosing the number and size of PRF plugs.