Geometric Cuts by an Autonomous Laser Osteotome Increase Stability in Mandibular Reconstruction With Free Fibula Grafts: A Cadaver Study.

BACKGROUND: Nonunion and plate exposure represent a major complication after mandibular reconstruction with free fibula flaps. These drawbacks may be resolved by geometric osteotomies increasing intersegmental bone contact area and stability. PURPOSE: The aim of this study was to compare intersegmental bone contact and stability of geometric osteotomies to straight osteotomies in mandibular reconstructions with free fibula grafts performed by robot-guided erbium-doped yttrium aluminum garnet laser osteotomy. STUDY DESIGN, SETTING, SAMPLE: This cadaveric in-vitro study was performed on fresh frozen human skull and fibula specimens. Computed tomography (CT) scans of all specimens were performed for virtual planning of mandibular resections and three-segment fibula reconstructions. The virtual planning was implemented in a Cold Ablation Robot-guided Laser Osteotome. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: For predictor variables, straight and geometric puzzle-shaped osteotomies were designed at resection of the mandible and corresponding fibula reconstruction. MAIN OUTCOME VARIABLES: The primary outcome variable was the stability of the reconstructed mandible investigated by shearing tests. Moreover, secondary outcome variables were the duration of the laser osteotomies, the contact surface area, and the accuracy of the reconstruction, both evaluated on postsurgical CT scans. COVARIATES: Covariables were not applicable. ANALYSES: Data were reported as mean values (± standard deviation) and were statistically analyzed using an independent-sample t-test at a significance level of α = 0.05. Root mean square deviation was tested for accuracy. RESULTS: Eight skulls and 16 fibula specimens were used for the study. One hundred twelve successful laser osteotomies (96 straight and 16 geometrical) could be performed. Geometric osteotomies increased stability (110.2 ± 36.2 N vs 37.9 ± 20.1 N, P < .001) compared to straight osteotomies. Geometric osteotomy of the fibula took longer than straight osteotomies (10.9 ± 5.1 min vs 5.9 ± 2.2 min, P = .028) but could provide larger contact surface (431.2 ± 148.5 mm2 vs 226.1 ± 50.8 mm2, P = .04). Heat map analysis revealed a mean deviation between preoperational planning and postreconstructive CT scan of -0.8 ± 2.4 mm and a root mean square deviation of 2.51 mm. CONCLUSION AND RELEVANCE: Mandibular resection and reconstruction by fibula grafts can be accurately performed by a Cold Ablation Robot-guided Laser Osteotome without need for cutting guides. Osteotomy planning with geometric cuts offers higher stability and an increased bone contact area, which may enhance healing of the reconstructed mandible.

Treatment of extracapsular fractures of the mandibular condylar process: A retrospective evaluation of 377 cases.

BACKGROUND/AIM: Mandibular condylar fractures represent 25%-35% of all mandibular fractures. Despite profound research, there is still a controverse debate about treating these fractures conservatively or by open reduction and internal fixation (ORIF). The aim of this study is to analyse the outcome after open and closed treatment of extracapsular mandibular condyle fractures regarding general characteristics, post-treatment malocclusion, facial nerve palsy (FNP), maximum mouth opening (MMO) and parotid complications. METHODS: A retrospective cohort of 377 fractures (350 open, 27 closed treatment) was reviewed by reference to clinical and radiological pre- and postoperative documentation. Follow-up period was 12 months. Pearsons' chi-square-test, correlations, Kruskal-Wallis test and t-test were carried out for statistical analysis. RESULTS: The dominant type of fracture was type II in Spiessl and Schroll classification (50.1%). In the open treated fractures, the most common approach was retromandibular transparotid (91.7%). Post-treatment malocclusion occurred in 18.0% and was significantly increased in bilateral fractures (p = .039), in luxation fractures (p = .016) and in patients with full dentition (p = .004). After open reduction and internal fixation (ORIF), temporary FNP was documented in 7.1% whereas a permanent paresis occurred in 1.7%. FNP was significantly associated with high fractures (p = .001), comminution (p = .028) and increased duration of surgery (p = .040). Parotid complications were significantly associated with revision surgery (p = .009). Post-treatment reduction of MMO mainly occurred in female patients (p < .001) as well as in patients with bilateral fractures (p < .001), high fractures (p = .030) and concomitant mandibular (p = .001) and midfacial fractures (p = .009). CONCLUSION: Malocclusion seems to be the most frequent long-term complication after open reduction and osteosynthesis of extracapsular mandibular condyle fractures. We suggest ORIF by a transparotid approach to be an appropriate treatment with a low complication rate regarding especially FNP for extracapsular fractures of the mandibular condyle.

The first quantitative histomorphological analyses of bone vitality and inflammation in surgical specimens of patients with medication-related osteonecrosis of the jaw.

BACKGROUND: The purpose of the study was to categorize the vitality and inflammation of resected bone of patients with medication-related osteonecrosis of the jaw (MRONJ) and to correlate the grade of inflammation with the surgical success. METHODS: This prospective study includes 44 patients with stage III MRONJ. Necrotic bone was resected in a block fashioned way. After demineralization and staining, histological analyses were performed by measuring the areas of necrotic, vital, and regenerative bone. Areas of chronic and acute inflammation were categorized as non, mild, moderate, and severe and were correlated with surgical success and parameters of inflammation in blood plasma (C-reactive protein and leukocytes). RESULTS: An average area of 59.0% was necrotic in the examined specimen. Vital bone was measured with an average area of 40.9%. The stage of chronic inflammation correlated with the amount of vital bone (P < .001) and the success of surgery (P = .002). If acute inflammation was dominant, chronic inflammation areas were found less while necrotic areas were observed more (P < .001). Also, the risk of relapses, wound healing disorders, and the level of C-reactive protein were elevated if acute inflammation was severe or moderate (P = .031). Areas of bone regeneration were seen only in 11.3% of vital bone areas and occurred independently of infection stages. CONCLUSION: If possible, surgery should be delayed in patients with signs of severe acute inflammation. Patients may profit from prolonged pre-operative antibiotic therapy to reduce the level of acute inflammation.

A prospective clinical pilot study on the effects of a hydrogen peroxide mouthrinse on the intraoral viral load of SARS-CoV-2.

OBJECTIVES: SARS-CoV-2 is mainly transmitted by inhalation of droplets and aerosols. This puts healthcare professionals from specialties with close patient contact at high risk of nosocomial infections with SARS-CoV-2. In this context, preprocedural mouthrinses with hydrogen peroxide have been recommended before conducting intraoral procedures. Therefore, the aim of this study was to investigate the effects of a 1% hydrogen peroxide mouthrinse on reducing the intraoral SARS-CoV-2 load. METHODS: Twelve out of 98 initially screened hospitalized SARS-CoV-2-positive patients were included in this study. Intraoral viral load was determined by RT-PCR at baseline, whereupon patients had to gargle mouth and throat with 20 mL of 1% hydrogen peroxide for 30 s. After 30 min, a second examination of intraoral viral load was performed by RT-PCR. Furthermore, virus culture was performed for specimens exhibiting viral load of at least 103 RNA copies/mL at baseline. RESULTS: Ten out of the 12 initially included SARS-CoV-2-positive patients completed the study. The hydrogen peroxide mouthrinse led to no significant reduction of intraoral viral load. Replicating virus could only be determined from one baseline specimen. CONCLUSION: A 1% hydrogen peroxide mouthrinse does not reduce the intraoral viral load in SARS-CoV-2-positive subjects. However, virus culture did not yield any indication on the effects of the mouthrinse on the infectivity of the detected RNA copies. CLINICAL RELEVANCE: The recommendation of a preprocedural mouthrinse with hydrogen peroxide before intraoral procedures is questionable and thus should not be supported any longer, but strict infection prevention regimens are of paramount importance. TRIAL REGISTRATION: German Clinical Trials Register (ref. DRKS00022484).

Implant survival or implant success? Evaluation of implant-based prosthetic rehabilitation in head and neck cancer patients-a prospective observational study.

OBJECTIVES: Definition of implant success is unclear in prosthetic implant-based rehabilitation of head neck cancer patients. MATERIALS AND METHODS: Fifty-two patients with 309 inserted implants were included in this prospective observational study. Implant survival (in situ and loaded) and implant success (modified Albrektsson criteria) at 2-year follow-up were evaluated under the influence of patient- and implant-specific variables. RESULTS: Thirty-nine patients with 234 implants finished the study. Overall implant survival after 2 years was 92.3% (216/234) with an osseointegration rate of 94% (220/234). Implant success was 78.6% (184/234). Main reasons for failure were "bone resorption > 1.7mm" (n = 27, 11.5%) and "implant not in situ or not loaded" (n = 18, 7.7%). Smoking (OR 3.1, p = 0.034), bone grafts (OR 2.4, p = 0.021) and radiation dose > 60 Gy (OR 3.8, p = 0.025) revealed as significant predictors for implant failure. CONCLUSION: Implant survival differs significantly from implant success in head and neck cancer patients. Implant success is mainly determined by radiographic peri-implant bone resorption. CLINICAL RELEVANCE: Dealing with head and neck cancer patients a higher amount of peri-implant bone resorption must be taken into account and warrants for intensified implant monitoring.

The induction of cellular senescence in dental follicle cells inhibits the osteogenic differentiation.

Dental stem cells such as human dental follicle cells (DFCs) have opened new promising treatment alternatives for today's dental health issues such as periodontal tissue regeneration. However, cellular senescence represents a restricting factor to cultured stem cells, resulting in limited lifespan and reduced cell differentiation potential. Therefore, this study evaluated if and how DFCs exhibit features of cellular senescence after being expanded in cell culture. The cell proliferation of DFCs decreased, while the cell size increased during prolonged cell culture. Moreover, DFCs expressed the senescence-associated ß-galactosidase after a prolonged cell culture. The onset of senescence inhibited both the induction of osteoblast markers RUNX2 and osteopontin and the biomineralization of DFCs after stimulation of the osteogenic differentiation. In conclusion, we showed that a prolonged cell culture induces cellular senescence and inhibits the osteogenic differentiation in DFCs.

Long-term outcome and subjective quality of life after surgical treatment of lower lip cancer.

OBJECTIVES: Squamous cell carcinoma of the lower lip represents a common type of cancer with a favourable prognosis. Different types of defect reconstruction after ablative surgery are described for maintenance of patients' quality of life. MATERIALS AND METHODS: The study retrospectively evaluates the outcome of 105 patients treated for lower lip cancer. Oncological data as well as individual quality of life were investigated. RESULTS: Cervical lymph node metastases rarely occurred (7.6 %) and were correlated to larger-sized tumours (p = 0.041). Only five patients (4.8) died related to the tumour disease, especially after lymph node metastasis and tumour recurrence (p < 0.001). The 5-year rates for recurrence-free, overall and disease-specific survival were 84.5, 61.2 and 93.9 %. Tumour recurrence correlated with a resection margin of less than 0.75 cm (p = 0.089). With view to postoperative quality of life, the modified Bernard-Fries technique showed the most unfavourable results, particularly referring to sensibility, paraesthesia, lip pursing and mouth opening compared to a stair-step and/or Abbe reconstructions. CONCLUSIONS: Squamous cell carcinoma of the lower lip shows a very favourable prognosis. Neck dissection seems often negligible particularly in small tumours. Patients' functional quality of life after lip surgery depends on the size of the primary and the used technique. Stair-step and/or Abbe reconstructions should be preferred to a Bernard-Fries technique in comparable defect sizes. CLINICAL RELEVANCE: Proper treatment of lower lip cancer provides favourable prognosis and preserves patients' functional and aesthetic quality of life.

Antiresorptive agents enhance ossification of free flap reconstructions of the mandible: a radiological retrospective cohort study.

Background: The aim of this study was to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time. Methods: A total of 38 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs. The study group (n = 13) had segmental resection of the mandible and free bone flap reconstruction due to medication-related osteonecrosis of the jaw (MRONJ). The control group (noMRONJ, n = 25) comprised segmental mandibular resections and free bone flap reconstructions due to tumors, chronic osteomyelitis, or trauma without any radiation. Ossification time and influencing factors were evaluated. Results: Both duration of surgery (346 ± 90 min. vs. 498 ± 124 min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in the MRONJ group compared to the noMRONJ group. Ossification after mandibular reconstruction was significantly faster in the MRONJ study group [224 days, interquartile range (IQR) 175-287] compared to the control group (288 days, IQR 194-445; p < 0.001). Moreover, good initial contact between the segments resulted in faster ossification (p < 0.001) in the MRONJ group. Ossification rate between original and grafted bone or between grafted bone segments only did not differ in both the study and control groups (MRONJ, p = 0.705 vs. control, p = 0.292). The type of antiresorptive agent did not show any significance for ossification. The rate of wound healing disturbances did also not differ between the study and control groups (p = 0.69). Conclusion: Advanced MRONJ (stage 3) can be resected and reconstructed safely with free microvascular bone flaps. Antiresorptive agents enhance the ossification of the bone segments. Optimal initial contact of the bone segments accelerates bone healing. Surgery and hospitalization are markedly shortened in this vulnerable group of MRONJ patients compared to oncologic patients.

Progress of Ossification after Mandibular Reconstruction by Free Fibula Flap Depending on Different Timing of Radiotherapy: A Retrospective 3D Analysis by CT Scans.

Background: The aim of this study was to evaluate the difference between pre- and post-operative radiotherapy on the progress of ossification after free fibula flap reconstruction of the mandible using three-dimensional (3D) analysis. Methods: A total of 38 free fibula reconstructions of the mandible were evaluated retrospectively for ossification between bone segments by measuring Hounsfield Units (HU) in at least two postoperative computer tomography scans (average of 2.4 scans per patient; around the 5th, 12th, 16th, and 19th month postoperative). Three subgroups were created according to the time of irradiation: preoperative radiotherapy (preORT) (n = 11), postoperative radiotherapy (postORT) (n = 16), and patients without any radiation therapy (n = 11) as the control group (noRT). HU in eight regions of interest (ROI) and overlapping surfaces between segments per contact point, as well as influencing factors, were analyzed. Results: The fastest progress in gain of HU ossification with a difference of 0.30 HU/day was observed in noRT compared to preORT (p = 0.002). postORT was -0.24 HU/day slower than preORT (p = 0.005). Original and grafted bone showed a significantly slower HU uptake than between two graft segments with -84.18 HU/day (p < 0.001). Moreover, a larger initial overlapping surface between the segments in cm2 resulted in a higher rise of HU/day (p < 0.001). Conclusions: 3D analysis of post-reconstructive CT scans shows prolonged ossification of mandible reconstructions by free fibula after head and neck radiation. The effect is distinct in cases with post-operative adjuvant radiotherapy. The effects of radiotherapy on ossification may be minimized by a larger initial contact surface and improved operational techniques. Moreover, HU longitudinal measurements and 3D analysis offer new perspectives for clinical evaluation of successful bony healing.

Patient's Perception of Outcome after Extracapsular Fractures of the Mandibular Condyle Differs from Objective Evaluation-Experience of a Third-Level Hospital.

Background: The aim of this study is to assess patients' subjective perception of treatment outcome after extracapsular fractures of the mandibular condyle. Methods: A questionnaire survey regarding facial nerve palsy (FNP), malocclusion, pain, reduction in maximum mouth opening (MMO) and further discomfort after 3, 6, and 12 months was carried out. Patients aged 18 or more presenting with an extracapsular condylar fracture between 2006 and 2020 were identified by purposive sampling Questionnaires were received from 115 patients. Fractures were classified on the basis of the pre-treatment imaging, the way of treatment was obtained from patients' medical records. Data were analyzed using Pearsons' chi-square-test, descriptive statistics and Student's t-test. Results: 93.0% of the fractures were treated by open reduction and internal fixation (ORIF). MMO reduction was the most common post-treatment complication (55.6%). ORIF was associated with less pain after 3 months (p = 0.048) and lower VAS scores compared to conservative treatment (p = 0.039). Comminuted fractures were more frequently associated with post-treatment malocclusion (p = 0.048), FNP (p = 0.016) and MMO reduction (p = 0.001). Bilateral fractures were significantly accompanied by malocclusion (p = 0.029), MMO reduction (p = 0.038) and pain occurrence (p < 0.001). Conclusions: Patients report less pain after ORIF. Comminuted and bilateral fractures seem to be major risk factors for complications. Subjective perception of complications after extracapsular condylar fractures differs from objectively assessed data.

Rigid matrix supports osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHED).

Stem cell fate can be induced by the grade of stiffness of the extracellular matrix, depending on the developed tissue or complex tissues. For example, a rigid extracellular matrix induces the osteogenic differentiation in bone marrow derived mesenchymal stem cells (MSCs), while a softer surface induces the osteogenic differentiation in dental follicle cells (DFCs). To determine whether differentiation of ectomesenchymal dental precursor cells is supported by similar grades of extracellular matrices (ECMs) stiffness, we examined the influence of the surface stiffness on the proliferation and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHED). Cell proliferation of SHED was significantly decreased on cell culture surfaces with a muscle-like stiffness. A dexamethasone-based differentiation medium induced the osteogenic differentiation of SHED on substrates of varying mechanical stiffness. Here, the hardest surface improved the induction of osteogenic differentiation in comparison to that with the softest stiffness. In conclusion, our study showed that the osteogenic differentiation of ectomesenchymal dental precursor cells SHED and DFCs are not supported by similar grades of ECM stiffness.

Recurrent osteomyelitis with proliferative periostitis after segmental resection and reconstruction of the mandible: a case report.

A 50-year-old patient presented with a two-year history of chronic osteomyelitis of the left mandibular body. It was treated by wide segmental resection of the left hemimandible and reconstruction with a free vascularized fibular graft. Six months after surgery, the patient returned with pain, swelling, and moth-like lesions in the transplant in combination with appositional bone formation surrounding the ossified fibular bone. Radiographic and histological examination led to the diagnosis of a recurrent osteomyelitis with proliferative periostitis affecting the resected and reconstructed mandible. Application of ibandronate led to a significant symptom decrease.

The Folded Radial Forearm Flap in Lip and Nose Reconstruction-Still a Unique Choice.

(1) Background: The radial forearm flap (RFF) has evolved as the flap of choice for intraoral mucosal reconstructions, providing thin and pliable skin with a safe blood supply. Perforator flaps such as the anterolateral thigh (ALT) flap are increasingly being discussed for the same applications. (2) Methods: Patient history, treatment details, and outcome of 12 patents with moderate to extended defects of the lip and/or nose area that were reconstructed by a folded radial forearm flap were retrospectively evaluated for oncologic and functional outcomes. (3) Results: The mean oncologic and functional follow-up were 21.1 (min. 3.8; max. 83.3) and 31.2 (min. 6; max. 96) months, respectively. All flaps survived without revision. In eight cases, major lip defects were reconstructed by an RFF; in six patients, the palmaris longus tendon was included for lip suspension. The functional results in terms of eating, drinking, and mouth opening were good in five cases, while three patients were graded as fair due to moderate drooling. In seven cases, the major parts of the nose were reconstructed with two good and five fair (nostril constriction in three cases) functional results. (4) Conclusions: The folded RFF remains a unique free flap option for complex three-dimensional lip and nose reconstructions in terms of flexibility, versatility, and robustness.

Novel Three-Dimensional and Non-Invasive Diagnostic Approach for Distinction between Odontogenic Keratocysts and Ameloblastomas.

Aim of this study was to demonstrate the diagnostic ability to differentiate odontogenic keratocysts (OKCs) from ameloblastomas (AMs) based on computed tomography (CT) or cone beam computed tomography (CBCT) scans. Preoperative CT and CBCT scans from 2004 to 2019 of OKCs and AMs were analyzed in 51 participants. Lesions were three-dimensionally (3D) assessed and Hounsfield units (HU) as well as gray scale values (GSV) were quantified. Calculated HU spectra were compared within the same imaging modalities using unpaired t-tests and correlated with participants characteristics by calculating Pearsons correlation coefficients. Within the CT scans, AMs had highly significantly higher HU values compared to OKCs (43.52 HU and 19.79 HU, respectively; p < 0.0001). Analogous, within the CBCT scans, AMs had significantly higher GSV compared to OKCs (-413.76 HU and -564.76 HU, respectively; p = 0.0376). These findings were independent from participants' gender and age, anatomical site, and lesion size, indicating that the HU- and GSV-based difference reflects an individual configuration of the lesion. HU and GSV spectra calculated from CT and CBCT scans can be used to discriminate between OKCs and AMs. This diagnostic approach represents a faster and non-invasive option for preoperative diagnosis of such entities and has potential to facilitate therapeutic decision making.

Elective Tracheotomy in Patients Receiving Mandibular Reconstructions: Reduced Postoperative Ventilation Time and Lower Incidence of Hospital-Acquired Pneumonia.

Elective tracheotomy (ET) secures the airway and prevents adverse airway-related events as unplanned secondary tracheotomy (UT), prolonged ventilation (PPV) or nosocomial infection. The primary objective of this study was to identify factors predisposing for airway complications after reconstructive lower ja surgery. We reviewed records of patients undergoing mandibulectomy and microvascular bone reconstruction (N = 123). Epidemiological factors, modus of tracheotomy regarding ET and UT, postoperative ventilation time and occurrence of hospital-acquired pneumonia HAP were recorded. Predictors for PPV and HAP, ET and UT were identified. A total of 82 (66.7%) patients underwent tracheotomy of which 12 (14.6%) were performed as UT. A total of 52 (42.3%) patients presented PPV, while 19 (15.4%) developed HAP. Increased operation time (OR 1.004, p = 0.005) and a difficult airway (OR 2.869, p = 0.02) were predictors, while ET reduced incidence of PPV (OR 0.054, p = 0.006). A difficult airway (OR 4.711, p = 0.03) and postoperative delirium (OR 6.761, p = 0.01) increased UT performance. HAP increased with anesthesia induction time (OR 1.268, p = 0.001) and length in ICU (OR 1.039, p = 0.009) while decreasing in ET group (HR 0.32, p = 0.02). OR for ET increased with mounting CCI (OR 1.462, p = 0.002) and preoperative radiotherapy (OR 2.8, p = 0.018). ET should be strongly considered in patients with increased CCI, preoperative radiotherapy and prolonged operation time. ET shortened postoperative ventilation time and reduced HAP.

OSCC in Never-Smokers and Never-Drinkers Is Associated with Increased Expression of Tumor-Infiltrating Lymphocytes and Better Survival.

The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers/never-drinkers and smokers/drinkers. Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers/drinkers and never-smokers/never-drinkers. Associations of smoking/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers/never-drinkers was associated with the female gender (p < 0.001). Never-smokers/never-drinkers were older at diagnosis than smokers/drinkers (p < 0.001). Never-smokers/never-drinkers had more tumors in the maxilla, mandible, and tongue (p < 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers/never-drinkers (p < 0.001). Perineural invasion was more common in smokers/drinkers (p = 0.039). Never-smoking/never-drinking was associated with better overall survival (p = 0.004) and disease-specific survival (p = 0.029). High CD4+ T cell infiltration was associated with never-smoking/never-drinking (p = 0.008). Never-smokers/never-drinkers also showed increased CD8+ T cell infiltration (p = 0.001) and increased FoxP3+ Treg infiltration (p = 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking/never drinking (p = 0.005). To conclude oral squamous cell carcinoma of the never-smokers/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment.

Adjuvant Radiotherapy in Patients with Squamous Cell Carcinoma of the Oral Cavity or Oropharynx and Solitary Ipsilateral Lymph Node Metastasis (pN1)-A Prospective Multicentric Cohort Study.

(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.

Socioeconomic influence on treatment and outcome of patients with oral cancer in Germany.

PURPOSE: To illustrate the influence of different socioeconomic factors on the treatment and outcome of patients in Germany with oral cancer. METHODS: In this retrospective single-center study, 400 patients of our department of oral and maxillofacial surgery with primary cases of oral cancer were included. Preoperative diagnostics, occupational groups, and marital and health insurance status were evaluated. Overall and disease-specific survival were analyzed. Occupations were distinguished in 5 groups (unemployed, physically light workers, physically hard worker, university graduate, and freelancer). Data were adjusted to covariables like tumor size, positive lymph nodes, age, alcohol, or tobacco abuse. RESULTS: There was no differences between private and statutory insured patients concerning overall (p = 0.858) or disease-specific survival (p = 0.431). Private insured patients received more preoperative PET-CT (p = 0.046) and had a better dental status (p = 0.006). The occupational groups showed also no differences in survival (p = 0.963). The hospitalization of freelancers was in average 2 days shorter. Physically hard workers were diagnosed with bigger tumors (p = 0.018) and consumed more tobacco and alcohol. The 5-year survival rate of married patients was approximately 20% points better than not married patients, without showing a significant difference over the entire observation time (p = 0.084). CONCLUSION: In our cohort, socioeconomic factors have just a limited influence on the survival or treatment of patients with oral cancer. A sufficient statutory health insurance system is a reasonable explanation for this.

Influence of Radiotherapy on Ossification of Vascularized Osseous Reconstruction of the Jaw: A Radiological Retrospective Cohort Study Based on Panoramic Radiographs.

Background: The aim of this study was to evaluate the impact of irradiation and time of irradiation on the ossification of jaws reconstructed with free bone grafts. Methods: In total, 100 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs (immediate postOP, approximately 6, 12 and 24 months follow-up). Three subgroups were divided according to the time of irradiation: preoperative radiation therapy (n = 41), postoperative radiation therapy (n = 26) and patients without any radiation therapy (n = 33) as the control group. Ossification time and influencing factors were documented. Results: The fastest ossification with a median of 304 ± 37 days was observed (p < 0.001) in the nonirradiated control group. No significant difference (p = 0.087) in ossification was found between the pre- (447 ± 136 days) and postoperative (510 ± 112 days) radiation groups. Ossification between two graft segments (336 ± 38 days) showed significantly (p < 0.001) faster ossification than between the original and grafted bone (448 ± 85 days). Moreover, closer initial contact between the segments resulted in faster ossification (p < 0.001). When analyzing cofactors, tobacco consumption was the only negative factor aggravating ossification (p = 0.006). Conclusion: Head and neck radiation corresponded with the impaired and prolonged ossification of jaw reconstructions with free bone grafts. There was no difference in ossification if radiotherapy was performed before or after reconstructive surgery. A close bony contact was particularly important for ossification between the original and grafted bone.

Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma.

Invasion of the mandibular bone is frequent in oral squamous cell carcinoma (OSCC), which often results in extensive ablative and reconstructive procedures for the patient. The purpose of this single-center, retrospective study was to identify and evaluate potential biomarkers and risk factors for bone invasion in OSCC. Initially, in silico gene expression analysis was performed for different HNSCC tumor T-stages to find factors associated with invasive (T4a) tumor growth. Afterwards, the protein expression of bone-metabolizing MMP-27, TNFRSF11B (Osteoprotegerin, OPG), and TNFSF11 (RANKL) was investigated via Tissue Microarrays (TMAs) for their impact on mandibular bone invasion. TMAs were assembled from the bone-tumor interface of primary OSCCs of the floor of the mouth and gingiva from 119 patients. Sixty-four carcinomas with patho-histological jaw invasion (pT4a) were compared to 55 carcinomas growing along the mandible without invasion (pT2, pT3). Tissue samples were additionally evaluated for patterns of invasion using the WPOI grading system. Statistical analysis of in silico data revealed decreased MMP-27 mRNA expression to be strongly associated with the pT4a-stage in OSCC, indicating invasive tumor growth with infiltration of adjacent anatomical structures. Our own clinico-pathological data on OSCCs presented a significant decrease of MMP-27 in tumors invading the nearby mandible (pT4a), compared to pT2 and pT3 tumors without bone invasion. Loss of MMP27 evolved as the strongest predictor of mandibular bone invasion in binary logistic regression analysis. To our knowledge, this is the first study investigating the role of MMP-27 expression in OSCC and demonstrating the importance of the loss of MMP-27 in mandibular bone invasion.