The immunomodulatory ballet of tumour-derived extracellular vesicles and neutrophils orchestrating the dynamic CD73/PD-L1 pathway in cancer.

Head and neck squamous cell carcinoma (HNSCC) is a global cancer burden with a 5-year overall survival rate of around 50%, stagnant for decades. A tumour-induced immunosuppressive microenvironment contributes to HNSCC progression, with the adenosine (ADO) pathway and an upregulated expression of inhibitory immune checkpoint regulators playing a key role in this context. The correlation between high neutrophil-to-lymphocyte ratio (NLR) with advanced tumour staging suggests involvement of neutrophils (NØ) in cancer progression. Interestingly, we associated a high NLR with an increased intracellular PD-L1 localization in primary HNSCC samples, potentially mediating more aggressive tumour characteristics and therefore synergistically favouring tumour progression. Still, further research is needed to harness this knowledge for effective treatments and overcome resistance. Since it is hypothesized that the tumour microenvironment (TME) may be influenced by small extracellular vesicles (sEVs) secreted by tumours (TEX), this study aims to investigate the impact of HNSCC-derived TEX on NØ and blockade of ADO receptors as a potential strategy to reverse the pro-tumour phenotype of NØ. UMSCC47-TEX exhibited CD73 enzymatic activity involved in ADO signalling, as well as the immune checkpoint inhibitor PD-L1. Data revealed that TEX induce chemotaxis of NØ and the sustained interaction promotes a shift into a pro-tumour phenotype, dependent on ADO receptors (P1R), increasing CD170high subpopulation, CD73 and PD-L1 expression, followed by an immunosuppressive secretome. Blocking A3R reduced CD73 and PD-L1 expression. Co-culture experiments with HNSCC cells demonstrated that TEX-modulated NØ increase the CD73/PD-L1 axis, through Cyclin D-CDK4/6 signalling. To support these findings, the CAM model with primary tumour was treated with NØ supernatant. Moreover, these NØ promoted an increase in migration, invasion, and reduced cell death. Targeting P1R on NØ, particularly A3R, exhibited potential therapeutic strategy to counteract immunosuppression in HNSCC. Understanding the TEX-mediated crosstalk between tumours and NØ offers insights into immunomodulation for improving cancer therapies.

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.

Levels of small extracellular vesicles in patients treated with hyperbaric oxygenation.

Introduction: Hyperbaric oxygen (HBO2) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating small extracellular vesicles (sEVs) play important roles in human physiology and pathology. Therefore, the objective of this pilot study was to monitor the impact of HBO2 therapy on the levels of circulating sEVs in the serum of patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) or idiopathic sudden sensory neural hearing loss (ISSNHL). Material and methods: Serum-derived sEVs were isolated and quantified in 80 patients before and after HBO2 therapy applied for NSTI, ISSNHL and ABN patients as well as in normal controls who received neither HBO2 therapy nor steroids. Results: We observed a significant increase of circulating sEVs in patients with ISSNHL after HBO2 therapy (p < 0.05), as well as significantly elevated levels of sEVs after HBO2 therapy compared to patients with NSTI (p < 0.05) and ABN (p < 0.01). Conclusions: The increase in the levels of sEVs in ISSNHL may be evidence for both the intended reduction of inflammation as a result of steroid therapy and the inhibitory effect of oxidative stress induced by HBO2 therapy. Thus, sEVs released during HBO2 therapy might play an important biological role in mediating the response to therapy and might be a promising approach to gain further insights into the therapeutic efficacy of HBO2 therapy.

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.

"Utility of Smartphone-based Three-dimensional Surface Imaging for Digital Facial Anthropometry".

Background: The utilization of three-dimensional (3D) surface imaging for facial anthropometry is a significant asset for patients undergoing maxillofacial surgery. Notably, there have been recent advancements in smartphone technology that enable 3D surface imaging.In this study, anthropometric assessments of the face were performed using a smartphone and a sophisticated 3D surface imaging system. Methods: 30 healthy volunteers (15 females and 15 males) were included in the study. An iPhone 14 Pro (Apple Inc., USA) using the application 3D Scanner App (Laan Consulting Corp., USA) and the Vectra M5 (Canfield Scientific, USA) were employed to create 3D surface models. For each participant, 19 anthropometric measurements were conducted on the 3D surface models. Subsequently, the anthropometric measurements generated by the two approaches were compared. The statistical techniques employed included the paired t-test, paired Wilcoxon signed-rank test, Bland-Altman analysis, and calculation of the intraclass correlation coefficient (ICC). Results: All measurements showed excellent agreement between smartphone-based and Vectra M5-based measurements (ICC between 0.85 and 0.97). Statistical analysis revealed no statistically significant differences in the central tendencies for 17 of the 19 linear measurements. Despite the excellent agreement found, Bland-Altman analysis revealed that the 95% limits of agreement between the two methods exceeded ±3 mm for the majority of measurements. Conclusion: Digital facial anthropometry using smartphones can serve as a valuable supplementary tool for surgeons, enhancing their communication with patients. However, the proposed data suggest that digital facial anthropometry using smartphones may not yet be suitable for certain diagnostic purposes that require high accuracy.

Correction: Schuderer et al. Risk Factors for Flap Loss: Analysis of Donor and Recipient Vessel Morphology in Patients Undergoing Microvascular Head and Neck Reconstructions. J. Clin. Med. 2023, 12, 5206.

In the original publication by Schuderer et al., there was a mistake in Table 1 as published [...].

Treatment of late-onset temporomandibular joint prosthesis infection by prosthesis revision: a case report.

Late-onset infection of an inserted temporomandibular joint prosthesis is a difficult complication to treat. Most treatment protocols for late prosthetic infections include device replacement. A 40-year-old female patient with an infected and exposed temporomandibular joint prosthesis presented 3 years after implant placement. The patient was treated with prosthesis revision including fistula coverage with a temporalis muscle flap and prolonged antibiotic therapy for 10 weeks. Since completion of treatment, the patient has been infection-free.

Subcellular localization of PD-L1 and cell-cycle-dependent expression of nuclear PD-L1 variants: implications for head and neck cancer cell functions and therapeutic efficacy.

The programmed cell death 1 ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis is primarily associated with immunosuppression in cytotoxic T lymphocytes (CTLs). However, mounting evidence is supporting the thesis that PD-L1 not only functions as a ligand but mediates additional cellular functions in tumor cells. Moreover, it has been demonstrated that PD-L1 is not exclusively localized at the cellular membrane. Subcellular fractionation revealed the presence of PD-L1 in various cellular compartments of six well-characterized head and neck cancer (HNC) cell lines, including the nucleus. Via Western blotting, we detected PD-L1 in its well-known glycosylated/deglycosylated state at 40-55 kDa. In addition, we detected previously unknown PD-L1 variants with a molecular weight at approximately 70 and > 150 kDa exclusively in nuclear protein fractions. These in vitro findings were confirmed with primary tumor samples from head and neck squamous cell carcinoma (HNSCC) patients. Furthermore, we demonstrated that nuclear PD-L1 variant expression is cell-cycle-dependent. Immunofluorescence staining of PD-L1 in different cell cycle phases of synchronized HNC cells supported these observations. Mechanisms of nuclear PD-L1 trafficking remain less understood; however, proximity ligation assays showed a cell-cycle-dependent interaction of the cytoskeletal protein vimentin with PD-L1, whereas vimentin could serve as a potential shuttle for nuclear PD-L1 transportation. Mass spectrometry after PD-L1 co-immunoprecipitation, followed by gene ontology analysis, indicated interaction of nuclear PD-L1 with proteins involved in DNA remodeling and messenger RNA (mRNA) splicing. Our results in HNC cells suggest a highly complex regulation of PD-L1 and multiple tumor cell-intrinsic functions, independent of immune regulation. These observations bear significant implications for the therapeutic efficacy of immune checkpoint inhibition.

Animal Bite Injuries to the Face: A Retrospective Evaluation of 111 Cases.

The treatment of bite wounds to the face is discussed controversially in relation to surgery and antibiotics. The aim of this study is a retrospective evaluation of 111 cases of animal bite injuries to the face that presented to our unit of oral and maxillofacial surgery over a 13-year period. Children under 10 years of age were predominantly involved. A total of 94.5% of the assessed injuries were caused by dogs. Wound infections occurred in 8.1%. Lackmann type II was the most common type of injury (36.9%). The perioral area was affected most frequently (40.5%). Primary wound closure was carried out in 74.8% of the cases. In 91.9% of the cases, antibiotic prophylaxis was prescribed. The most often administered type of antibiotic was amoxicillin with clavulanic acid (62.1%). Patients without antibiotics showed an increased infection rate without significance. Wound infections occurred significantly more frequently in wounds to the cheeks (p = 0.003) and when local flap reconstruction was necessary (p = 0.048). Compared to the other surgical treatment options, primary closure showed the lowest infection rates (4.8%, p = 0.029). We recommend antibiotic prophylaxis using amoxicillin with clavulanic acid and wound drains for wounds of Lackmann class II or higher. Primary closure seems to be the treatment of choice whenever possible.

BMSC-HNC Interaction: Exploring Effects on Bone Integrity and Head and Neck Cancer Progression.

In recent research, the tumor microenvironment has been shown to attract mesenchymal stromal cells (MSCs), which is of particular interest due to its implications for cancer progression. The study focused on understanding the interaction between bone marrow-derived MSCs (BMSCs) and head and neck cancer (HNC) cells. This interaction was found to activate specific markers, notably the osteogenic marker alkaline phosphatase and the oncogene Runx2. These activations corresponded with the release of collagenase enzymes, MMP9 and MMP2. To gain insights into bone resorption related to this interaction, bovine bone slices were used, supporting the growth of "heterogeneous spheroids" that contained both BMSCs and HNC cells. Through scanning electron microscopy and energy-dispersive X-ray (EDX) analysis, it was observed that these mixed spheroids were linked to a notable increase in bone degradation and collagen fiber exposure, more so than spheroids of just BMSCs or HNC cells. Furthermore, the EDX results highlighted increased nitrogen content on bone surfaces with these mixed clusters. Overall, the findings underscore the significant role of BMSCs in tumor growth, emphasizing the need for further exploration in potential cancer treatment strategies.

Immunohistochemical Assessment of Microvessel Density in OSCC: Spatial Heterogeneity of Angiogenesis and Its Impact on Survival.

(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a hallmark of cancer, is known to contribute to cancer progression and metastasis. High microvessel density (MVD) has been linked to poor clinical outcomes in various types of cancer. (2) Methods: In this study, we aimed to investigate the spatial heterogeneity of blood vessels by comparing the tumor center and invasion front and to evaluate its prognostic value in OSCC. A total of 71 OSCC patient specimens were collected. The tissue was immunohistochemically stained using CD31 antibody to assess the MVD in the tumor center and the invasion front. Furthermore, the associations between the histopathological parameters, including MVD, disease-free survival (DFS), and overall survival (OS) were computed. (3) Results: In our study, we found a significantly higher presence of blood vessels at the invasion front of OSCCs compared to the tumor center. However, we did not observe any significant differences in MVD between different tumor stages. High intratumoral MVD was shown to be a positive prognostic factor for DFS (p = 0.047). (4) Conclusions: To the best of our knowledge, we were the first to analyze MVD as a prognostic factor by considering its spatial heterogeneity in OSCC. However, further studies are warranted to further elucidate the complexity of microvascular spatial heterogeneity and its influence on prognosis.

Evaluation of Current Studies to Elucidate Processes in Dental Follicle Cells Driving Osteogenic Differentiation.

When research on osteogenic differentiation in dental follicle cells (DFCs) began, projects focused on bone morphogenetic protein (BMP) signaling. The BMP pathway induces the transcription factor DLX3, whichh in turn induces the BMP signaling pathway via a positive feedback mechanism. However, this BMP2/DLX3 signaling pathway only seems to support the early phase of osteogenic differentiation, since simultaneous induction of BMP2 or DLX3 does not further promote differentiation. Recent data showed that inhibition of classical protein kinase C (PKCs) supports the mineralization of DFCs and that osteogenic differentiation is sensitive to changes in signaling pathways, such as protein kinase B (PKB), also known as AKT. Small changes in the lipidome seem to confirm the participation of AKT and PKC in osteogenic differentiation. In addition, metabolic processes, such as fatty acid biosynthesis, oxidative phosphorylation, or glycolysis, are essential for the osteogenic differentiation of DFCs. This review article attempts not only to bring the various factors into a coherent picture of osteogenic differentiation in DFCs, but also to relate them to recent developments in other types of osteogenic progenitor cells.

Editorial: Special Issue on "The Role of Exosomes in Cancer Diagnosis and Therapy".

As a result of extensive research in recent years, small extracellular vesicles (sEVs), also known as exosomes, are now considered major contributors to intercellular communication in health and disease [...].

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.

Thin PDS Foils Represent an Equally Favorable Restorative Material for Orbital Floor Fractures Compared to Titanium Meshes.

Orbital floor fractures (OFFs) are common injuries of the midface and may result in long-term complications. The aim of this study was to compare two restoration materials, PDS foils and titanium meshes, with regards to (1) clinical outcome and (2) reduction in orbital volume. The monocentric discovery cohort was analyzed retrospectively and included 476 patients with OFFs treated between 2010 and 2020. A subcohort of 104 patients (study cohort) with isolated OFFs and available high-resolution imaging material was used for volume measurements. Postoperative complications were not significantly different between patients treated with different restoration materials. Prevalence of revision surgery was significantly higher in patients treated with thick PDS foils (25 mm). OFFs treated with PDS foils and titanium meshes showed a significant reduction in orbital volume (p = 0.0422 and p = 0.0056, respectively), however, this volume decrease was significantly less pronounced in patients treated with PDS foils alone (p = 0.0134). Restoration using PDS foil in an isolated OFF reduces the orbital volume to a lesser extent than titanium mesh. Class III patients according to the classification of Jaquiéry with a missing bony ledge medial to the infraorbital fissure particularly benefit from restoration with PDS foils due to a lower reduction in the orbital volume. Regarding short- and long-term postoperative complications, a PDS foil thickness of 0.15 mm appears equivalent to titanium mesh in the treatment of OFFs.

Risk Factors for Flap Loss: Analysis of Donor and Recipient Vessel Morphology in Patients Undergoing Microvascular Head and Neck Reconstructions.

In microvascular head and neck reconstruction, various factors such as diabetes, alcohol consumption, and preoperative radiation hold a risk for flap loss. The primary objective of this study was to examine the vessel morphology of both recipient and donor vessels and to identify predictors for changes in the diameters of H.E.-stained specimens associated with flap loss in a prospective setting. Artery and vein samples (N = 191) were collected from patients (N = 100), with sampling from the recipient vessels in the neck area and the donor vessels prior to anastomosis. External vessel diameter transverse (ED), inner vessel diameter transverse (ID), thickness vessel intima (TI), thickness vessel media (TM), thickness vessel wall (TVW), and intima-media ratio (IMR) for the recipient (R) and transplant site (T) in arteries (A) and veins (V) were evaluated using H.E. staining. Flap loss (3%) was associated with increased ARED (p = 0.004) and ARID (p = 0.004). Preoperative radiotherapy led to a significant reduction in the outer diameter of the recipient vein in the neck (p = 0.018). Alcohol consumption (p = 0.05), previous thrombosis (p = 0.007), and diabetes (p = 0.002) were associated with an increase in the total thickness of venous recipient veins in the neck. Diabetes was also found to be associated with dilation of the venous media in the neck vessels (p = 0.007). The presence of cardiovascular disease (CVD) was associated with reduced intimal thickness (p = 0.016) and increased total venous vessel wall thickness (p = 0.017) at the transplant site. Revision surgeries were linked to increased internal and external diameters of the graft artery (p = 0.04 and p = 0.003, respectively), while patients with flap loss showed significantly increased artery diameters (p = 0.004). At the transplant site, alcohol influenced the enlargement of arm artery diameters (p = 0.03) and the intima-media ratio in the radial forearm flap (p = 0.013). In the anterolateral thigh, CVD significantly increased the intimal thickness and the intima-media ratio of the graft artery (p = 0.01 and p = 0.02, respectively). Patients with myocardial infarction displayed increased thickness in the A. thyroidea and artery media (p = 0.003). Facial arteries exhibited larger total vessel diameters in patients with CVD (p = 0.03), while facial arteries in patients with previous thrombosis had larger diameters and thicker media (p = 0.01). The presence of diabetes was associated with a reduced intima-media ratio (p < 0.001). Although the presence of diabetes, irradiation, and cardiovascular disease causes changes in vessel thickness in connecting vessels, these alterations did not adversely affect the overall success of the flap.

Expression and Regulatory Mechanisms of MicroRNA in Cholesteatoma: A Systematic Review.

Cholesteatoma is a temporal bone disease characterized by dysfunctions of keratinocytes. MicroRNAs (miRNAs) are evolutionary conserved noncoding RNAs that regulate mRNA expression. They can be packaged into exosomes and transported to target cells that can be used in the future therapy of cholesteatoma. This study aimed to collect knowledge on the role of miRNAs and exosomal miRNAs in cholesteatoma and was conducted according to the PRISMA guidelines for systematic reviews. Four databases were screened: Pubmed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. The last search was run on the 6th of June 2023. We included full-text original studies written in English, which examined miRNAs in cholesteatoma. The risk of bias was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool, modified for the needs of this review. We identified 118 records and included 18 articles. Analyses revealed the downregulation of exosomal miR-17 as well as miR-10a-5p, miR-125b, miR-142-5p, miR34a, miR-203a, and miR-152-5p and the overexpression of exosomal miR-106b-5p as well as miR-1297, miR-26a-5p, miR-199a, miR-508-3p, miR-21-3p, miR-584-5p, and miR-16-1-3p in cholesteatoma. The role of differentially expressed miRNAs in cholesteatoma, including cell proliferation, apoptosis, the cell cycle, differentiation, bone resorption, and the remodeling process, was confirmed, making them a potential therapeutic target in this disease.

Head and neck oncology management in the time of COVID-19: results of a head and neck cancer center.

PURPOSE: Given the concerns about the effects of the COVID-19 pandemic on cancer care, we analyzed the treatment quality of the head and neck cancer center Regensburg before and throughout 2 years of the pandemic. We included data of 3 years to reflect the extended pandemic period as new developments continued to influence its course. METHODS: This retrospective review included all patients diagnosed with head and neck cancer in 2019, 2020, and 2021 who had not started treatment elsewhere prior to being referred to the head and neck cancer center. We compared tumor characteristics and times to therapy of patients diagnosed before COVID-19 in 2019 (n = 253), during COVID-19 in 2020 (n = 206), and in a phase of partial normalization in a persistent pandemic situation in 2021 (n = 247). RESULTS: Our data revealed no decrease in diagnoses or drift in stages toward more advanced stages. There was an increased percentage of diagnoses confirmed at the head and neck cancer center from 2019 (57.3%) to 2020 (68.0%) and to 2021 (65.6%) compared to confirmation at other institutions (2019, 42.7%; 2020, 32.0%; 2021, 34.4%; P = 0.041). Surgery and radiotherapy were performed with the same frequency. The median days between diagnosis and surgery were decreased in 2020 (19.5 days; P = 0.049) and 2021 (20.0 days; P = 0.026) in comparison to 2019 (23 days). The days to radiotherapy were not affected. CONCLUSION: The data indicate a consistent oncological performance for head and neck cancer patients in all waves of the pandemic and thereafter without a decrease in diagnoses or shift in stages.

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.

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.