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.

Cancer testis antigen (PRAME) as an independent marker for survival in oral squamous cell carcinoma (OSCC).

BACKGROUND: The objective was to assess the expression patterns of the cancer testis antigen PRAME, NY-ESO1, and SSX2 in oral squamous cell carcinoma (OSSC) and to correlate the expression with clinical and histopathological parameters including progression-free survival analysis. METHODS: The study variables of this retrospective cohort study (n = 83) included demographic data, histopathological data, and information on progression-free survival. PRAME expression patterns were rated based on immunohistochemistry on tissue microarrays (TMA). The survival rate was assessed by Kaplan-Meier method and Cox regression model. The primary predictor variable was defined as the expression of PRAME and the outcome variable was progression-free survival. RESULTS: Analysis of progression-free survival using Kaplan-Meier method showed that patients with positive expression of PRAME had lower probabilities of progression-free survival (p < 0.001). According to the Cox regression model, the level of PRAME expression had a considerable and significant independent influence on progression-free survival (positive PRAME expression increasing the hazards for a negative outcome by 285% in our sample; HR = 3.85, 95% CI: 1.45-10.2, p = 0.007). The expression of SSX2 (n = 1) and NY-ESO-1 (n = 5) in our samples was rare. CONCLUSION: PRAME is expressed in OSCC and appears to be a suitable marker of progression-free survival, correlates with severe course, and may allow identification of high-risk patients with aggressive progression.

[Management of medication-related osteonecrosis of the jaw-a review of recent study results in comparison to established strategies]. / Management von medikamentenassoziierten Kiefernekrosen ­ Ergebnisse einer Literaturanalyse neuester Studien im Vergleich zu bewährten Strategien.

BACKGROUND: Antiresorptive agents are some of the most frequently used drugs worldwide, with indications in osteology and oncology. They are generally well tolerated and display a favorable safety profile. A potentially severe unwanted side effect is medication-related osteonecrosis of the jaw (MRONJ). PURPOSE OF THIS REVIEW: This review summarizes the latest developments in etiology, diagnosis, and treatment of MRONJ, and compares new insights with established algorithms. METHODS: A systematic review of relevant studies exploring diagnostic methods, prospective management trials, and innovative studies on the pathogenesis of MRONJ published between 2016 and 2021 was performed. The study quality was assessed using the MINORS (methodological index for non-randomized studies) rating score. RESULTS AND DISCUSSION: The prevalence of MRONJ in patients undergoing treatment with antiresorptive drugs for oncological reasons is remarkable (2-12%). MRONJ prevalence in patients receiving antiresorptive drugs for the treatment of osteoporosis is much lower (0.1-1%). MRONJ treatment should be initiated early and involve a surgical approach. MRONJ treatment is safe and predictable, with long-term success rates of more than 85%.

Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinoma.

PURPOSE: To investigate the expression pattern of CD36 in a patient population with oral squamous cell carcinoma (OSCC) and to correlate CD36 expression with clinical and histopathological parameters. The hypothesis was that CD36 expression correlates with the occurrence of lymph node metastasis. METHODS: To address the study objectives, a retrospective cohort study was conducted. Study variables included demographic, histopathological and survival data. CD36 expression patterns were assessed by immunohistochemistry on tissue microarrays (TMA). Logistic regression analysis, survival analysis and Cox proportional hazards model were performed. RESULTS: High CD36 expression correlated significantly with a higher T-status, grading and occurrence of lymph node metastasis. The logistic regression with binary N status as a dependent variable showed that high CD36 expression increased the chance for lymph node metastasis 45-fold (OR = 44.7, 95% CI: 10.0-316). Patients with high CD36 expression had lower probabilities of progression-free survival. CD36 had a small and non-significant independent influence on progression-free survival. CONCLUSIONS: CD36 is expressed in OSCC and correlates with tumor grading, T-status, and especially the occurrence of lymph node metastasis. CD36 may be useful for risk stratification regarding lymph node metastasis in OSCC.

Osteonecrosis of the jaw in patients treated with denosumab: A multicenter case series.

PURPOSE: Osteonecrosis of the jaw has been recently reported in patients receiving denosumab for the treatment of metastatic bone disease and osteoporosis. It is essential to investigate this disease as a new osteonecrosis entity in order to recognize its optimal management strategies. MATERIALS AND METHODS: A total of 63 cases of denosumab-related osteonecrosis of the jaw (DRONJ) diagnosed at two clinical centres were retrospectively reviewed. Demographics, comorbidities, antiresorptive medication use, local preceding event, location, DRONJ stage, treatment and treatment outcomes were analyzed. RESULTS: In all, 69 MRONJ lesions in 63 patients were diagnosed. The mean patient age was 70 ± 9 years. Denosumab was the only received antiresorptive medication in 50.8% of the patients. Discontinuation of denosumab prior to treatment was recorded for 66.7% of the patients, with a mean period of 6 ± 3.4 months. Stage 2 was the most common stage of the disease (71%). The lesions were predominantly located in the mandible (63.5%). The most common preceding local event was extraction (55.6%). Surgical treatment was performed in 95.7% of the cases, while purely conservative treatment was performed in 4.3%. DRONJ healed after surgical treatment in 71.7% of the treated lesions. Complete mucosal healing was achieved in 77.2% of the lesions treated with fluorescence-guided surgery (17/22). Clinical characteristics and treatment outcomes were not significantly different between patients with and without previous intake of bisphosphonates. CONCLUSION: DRONJ is more prevalent at extraction and local infection sites in cancer patients. Within the limitation of this study, surgical treatment, particularly fluorescence-guided surgery, appears to be effective for the management of DRONJ. The prior use of bisphosphonates does not seem to affect severity nor the treatment success rate of DRONJ.

Mechanical and biological effects of infiltration with biopolymers on 3D printed tricalciumphosphate scaffolds.

The aim of this study was to evaluate the influence of infiltrating 3D printed (TCP) scaffolds with different biodegradable polymers on their mechanical and biological properties. 3D printed TCP scaffolds with interconnecting channels measuring 450±50 µm were infiltrated with four different biodegradable copolymers. To determine the average compressive strength, a uniaxial testing system was used. Additionally, scaffolds were seeded with MC3T3 cells and cell viability was assessed by live/dead-assay. Uninfiltrated TCP had an average compression strength of 1.92±0.38 MPa. Mechanical stability was considerably increased in all infiltrated scaffolds up to a maximum of 7.36±0.57 MPa. All scaffolds demonstrated high cell survival rates with a maximum of 94±10 % living cells. In conclusion, infiltration of 3D printed tricalcium phosphate scaffolds with biodegradable polymers significantly improved mechanical properties and biological properties were comparable to those of uninfiltrated TCP scaffolds.

Fluorescence based characterization of early oral squamous cell carcinoma using the Visually Enhanced Light Scope technique.

OBJECTIVES: Several diagnostic tools have been developed to assess benign and potentially malignant disorders of soft tissues. In this study, we aimed to assess the value of the VELscope® (Visually Enhanced Light Scope) imaging device as a technical tool to investigate malignant lesions of the oral cavity. MATERIAL AND METHODS: In this retrospective study we analyzed the photographs of 90 patients who suffered from malignant oral soft tissue lesions or carcinoma in situ (CIS) from 2008 to 2014 in the Clinic of Oral and Maxillofacial Surgery of LMU in Munich. RESULTS: In 85.6% of the cases fluorescence quenching/loss could be detected. The average value for the colour red shows a significant difference in pathologic and physiologic tissues (p = 0.007) with a higher median for pathologic tissues. For the colours green and blue our measurements show significantly higher values in the healthy tissue (p < 0.001.). The shade of red showed significantly higher values for pathologic tissues when compared to all three colours (p < 0.001). Furthermore, the shades of green and blue showed significantly lower values in the pathologic tissue (p < 0.001). CONCLUSION: In the near future, VELscope® could help to a greater extent than visual observation alone in identifying the margins of tumor resections. VELscope® still lacks the ability to identify the overall risk level of oral lesions.

Risk factors for lymph node metastases of facial cutaneous squamous cell carcinoma.

PURPOSE: Determining the risk factors for lymph node metastases of facial cutaneous squamous cell carcinoma and identifying their value for predicting nodal spread. MATERIAL AND METHODS: Data on 99 patients were examined retrospectively. Conditions such as tumor staging, tumor thickness, location, histological grading, R1-resection, local recurrence, lymph node metastases, and neurovascular and lymphovascular invasion were evaluated. Statistical analysis was performed using a logistic regression analysis and Fisher's test. RESULTS: Logistic regression analysis indicates that poor differentiation, R1-resection, and periorbital location are high risk factors for nodal spread in facial cutaneous squamous cell carcinoma. CONCLUSION: Patients who show poorly differentiated facial cutaneous squamous cell carcinoma and/or have had previous R1-resection might benefit from treatment of regional lymph nodes.

Repair of large saddle defects of the mandibular ridge using dual growth factor release-An experimental pilot study in minipigs.

AIM: To test the hypothesis that the addition of small amounts of rhVEGF to rhBMP2 in a polymer carrier can accomplish equivalent repair effect as a reduced dosage of rhBMP2 compared to rhBMP2 alone. MATERIALS AND METHODS: Defects were created bilaterally in the mandibles of 18 minipigs. In 12 test animals, defects were filled with 0.5 g particulate PDLLA/CaCO3 composite loaded with 400 µg rhBMP2/50 µg rhVEGF165 on one side and 800 µg rhBMP2 on the other. After 4 and 13 weeks, the animals were evaluated each for area of new bone formation (mm²) and bone density (area %). RESULTS: Area of newly formed bone was higher in defects with carriers loaded with 400 µg rhBMP2 50 µg VEGF165 than in defects with 800 µg rhBMP2 after 4 weeks (11.97 versus 7.97 mm²; p = 0.043) and 13 weeks (72.48 versus 62.2 mm²; p = .028). Defects filled with blank carrier exhibited less bone after 13 weeks (42.75 mm²; p = .039 and .020 respectively). CONCLUSIONS: Delivery of rhBMP2 from a polymer carrier can improve repair of large saddle defects of the mandibular ridge. Addition of small amounts of rhVEGF can increase bone formation and at the same time reduce the dosage of rhBMP2.

Role of microbiological culture and polymerase chain reaction (PCR) of actinomyces in medication-related osteonecrosis of the jaw (MRONJ).

We hypothesized that local infection plays a critical role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). Recent developments in molecular methods have revolutionized new approaches for the rapid detection of microorganisms including those difficult to culture. The aim of our study is to identify the bacterial profiles in MRONJ by microbiological culture and polymerase chain reactions (PCR). A retrospective analysis was performed on MRONJ patients from 2008 to 2014. The bacterial profile from MRONJ bone samples was determined using microbiological culture and PCR. Ninety five patients fulfilled the inclusion criteria with mean age of 69.85 ± 8.71 years. A female predilection was detected. The mandible was more commonly affected than maxilla. Tooth extraction was the frequent triggering factor. Breast cancer was the primary cause for administration and intravenous bisphosphonates were the most commonly administrated antiresorptive drugs. The majority of patients were classified as stage 2. Posterior teeth were most commonly affected. Based on bone culture results, the most common microorganism were both actinomyces and mixed flora. PCR confirmed the presence of actinomyces in 55 patients. Our data suggest that PCR might be an innovative method for detection of microorganisms difficult to culture using traditional microbiological techniques.

Mesenchymal stem cell proliferation and mineralization but not osteogenic differentiation are strongly affected by extracellular pH.

UNLABELLED: Osteomyelitis is a serious complication in oral and maxillofacial surgery affecting bone healing. Bone remodeling is not only controlled by cellular components but also by ionic and molecular composition of the extracellular fluids in which calcium phosphate salts are precipitated in a pH dependent manner. OBJECTIVE: To determine the effect of pH on self-renewal, osteogenic differentiation and matrix mineralization of mesenchymal stem cells (MSCs). METHODS: We selected three different pH values; acidic (6.3, 6.7), physiological (7.0-8.0) and severe alkaline (8.5). MSCs were cultured at different pH ranges, cell viability measured by WST-1, apoptosis detected by JC-1, senescence was analyzed by ß-galactosidase whereas mineralization was detected by Alizarin Red and osteogenic differentiation analyzed by Real-time PCR. RESULTS: Self-renewal was affected by pH as well as matrix mineralization in which pH other than physiologic inhibited the deposition of extracellular matrix but did not affect MSCs differentiation as osteoblast markers were upregulated. The expression of osteocalcin and alkaline phosphatase activity was upregulated whereas osteopontin was downregulated under acidic pH. CONCLUSION: pH affected MSCs self-renewal and mineralization without influencing osteogenic differentiation. Thus, future therapies, based on shifting acid-base balance toward the alkaline direction might be beneficial for prevention or treatment of osteomyelitis.

Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development?

INTRODUCTION: Scientific debate outlines tooth extraction as a potential trigger for the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Therefore, the aim of this study was to investigate the outcome of tooth extractions in patients receiving bisphosphonate therapy. PATIENTS AND METHODS: A retrospective cohort study was performed on patients with a history of oral or intravenous bisphosphonate administration and tooth extraction between 2007 and 2013 in a single university hospital oral and maxillofacial surgical unit. In all patients, extractions were performed according to the guidelines of the German Society of Oral and Maxillofacial Surgery. The outcome variable was the onset of typical BRONJ signs during postoperative follow-up. RESULTS: In 72 subjects (53 female, 19 male; mean age 67.5 years) receiving oral (n = 27) and/or intravenous (n = 45) bisphosphonates due to malignant tumor (n = 43) or osteoporosis (n = 29), 216 tooth extractions were performed. The mean duration of intake was 36.2 months. In 67 out of 72 patients (93.1%) and 209 out of the 216 extraction sites the postoperative course was uneventful and the wounds healed without complications. Three of the 72 patients (4.2%) developed osteonecrosis of the jaw in four of the 216 extraction sites (1.9%). Duration and route of administration, oral hygiene and steroid intake were identified as potential risk factors for the development of BRONJ. CONCLUSION: Tooth extraction in patients receiving bisphosphonates can be performed in a safe and predictable way, even in high-risk patients, when performed according to established guidelines. It is not tooth extractions themselves, but rather prevailing infectious conditions that may be a key risk factor for the development of BRONJ.

Osteoradionecrosis of the mandible: A ten year single-center retrospective study.

BACKGROUND: Numerous factors have been associated with the development of osteoradionecrosis (ORN) of the jaws. The purpose of this study was to investigate the factors that are linked to the severity of mandibular ORN. METHODS: A retrospective study was conducted which included all ORN cases treated in the Department of Oral and Maxillofacial Surgery in Munich (LMU) between 2003 and 2012. The cases were categorized according to the necrosis stage and several variables were evaluated in order to identify possible correlation between them and the severity of the necrosis. RESULTS: A total of 115 patients with 153 osteonecrosis lesions were included in the study. Twenty-three cases were of stage I, 31 were of stage II and 99 were of stage III. The initial tumors were predominantly located in the floor of the mouth, the tongue or the pharynx. Diabetes mellitus (OR: 4.955, 95% Cl: 1.965-12.495), active smoking (OR: 13.542, 95% Cl: 2.085-87.947), excessive alcohol consumption (OR: 5.428, 95% Cl: 1.622-18.171) and dental treatment and/or local pathological conditions (OR: 0.237, 95% Cl: 0.086-0.655) were significant predictors for stage III necrosis. CONCLUSIONS: The aforementioned factors are predictive of ORN severity and can guide its prophylaxis and management.