Oral leukoplakia (OL) is a precancerous condition typically assessed through histopathological examination of mucosal lesion biopsies. Identifying histological features of oral lichenoid lesions (OLL) within OL samples is clinically important, as they influence the risk of malignant transformation and may indicate oral lichen planus (OLP). However, interpretation is challenging, with substantial intra- and inter-observer variability. Artificial intelligence (AI) offers the potential to provide reproducible, objective support for histopathological classification. We developed an AI system to (a) segment histological layers and extract characteristics of the keratinization zone, (b) classify keratinization types, and (c) distinguish OL from OLL. A retrospective cohort of 240 histological slides from 192 patients was included. Of these, 175 transversely sectioned slides underwent manual segmentation of subepithelium, epithelium, keratinization zone, and nuclei in the keratinization zone. Measurements of keratin thickness and nuclei density were performed to classify the keratinization zone into (hyper)orthokeratosis, parakeratosis, or hyperparakeratosis. All 240 slides were labeled as OL or OLL and crops were extracted for diagnosis classification. Segmentation was evaluated with Dice–Sørensen coefficient (DSC), and classification was evaluated by accuracy. Segmentation of histological layers was highly effective (DSC > 0.92), with lower performance for nuclei (DSC = 0.68). Keratinization classification reached 0.92 accuracy: (hyper)orthokeratosis 0.98, hyperparakeratosis 0.93, parakeratosis 0.94. Lesion-level OL/OLL classification achieved 0.929 accuracy, with slightly better effectiveness in transverse sections than tangential sections (0.944 vs. 0.925). The AI system demonstrated strong segmentation and classification capabilities, supporting its potential to enhance diagnostic accuracy, reproducibility, and efficiency for the assessment of OL samples.

Introduction:Periodontitis prevalence is elevated in patients with inflammatory bowel diseases (IBD). Biological therapies targeting cytokines such as tumor necrosis factor (TNF) and interleukin-12/23 (IL-12/23) are central to IBD management, yet their impact on periodontal health remains unclear. Methods:In a cross-sectional, hypothesis-generating design, 45 patients with IBD were examined and stratified into three groups according to their biological therapy: anti-TNF therapy (n = 15), anti-IL-12/23 therapy (n = 15), and a control group not receiving these biologics (n = 15). Periodontal status was assessed using the Periodontal Screening Index (PSI; codes 0-4) across all sextants as a standardized screening measure. Medical history, oral hygiene behavior, and prior periodontal diagnoses were documented. To assess local immune activity, interleukin-6 (IL-6) concentrations in gingival crevicular fluid (GCF) were quantified by enzyme-linked immunosorbent assay (ELISA). Results:Overall, 16 patients exhibited either known or previously undiagnosed periodontitis, with interindividual variability in severity. Patients receiving anti-IL-12/23 therapy exhibited lower mean and maximal PSI scores compared with anti-TNF-treated patients, and no sextants with advanced periodontal inflammation (PSI 3-4) were detected in this group. In contrast, active or latent periodontitis was observed in both the anti-TNF and control cohorts. Concordantly, IL-6 levels in GCF were significantly reduced in patients undergoing IL-12/23 blockade compared with controls, indicating attenuated local inflammatory signaling at the periodontal interface. These findings were observed despite no statistically significant differences in clinical or endoscopic disease activity between groups. Conclusions:These exploratory findings suggest that systemic inhibition of the IL-12/23 axis in IBD is associated with reduced periodontal inflammatory burden and decreased local IL-6 activity, supporting a role for IL-23-dependent immune pathways in linking intestinal and oral mucosal inflammation. While causality cannot be inferred from this cross-sectional study, the data provide a mechanistic rationale for further longitudinal investigations into the impact of cytokine-targeted biologic therapy on the oral-gut immune axis.

In 2017, a statement was released by the executive boards of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC) and the German Society of Oral and Maxillofacial Surgery (DGMKG) declaring the equal necessity of both medical disciplines, particularly regarding emergency services. The current consensus paper provides an updated and expanded version of this statement. Owing to the structure of their continuing education programs, the practice of both specialties in conservative and surgical treatment areas, and their economic bases, Oto-Rhino-Laryngology and Oral and Maxillofacial Surgery are independent disciplines. However, due to the anatomic involvement, the fields have various points of contact and interfaces as well as boundaries, which are summarized in this joint statement and consensus paper. These include jointly run center structures, working groups, training and continuing education initiatives, economic issues, health care policy interest groups, and research activities. To facilitate constructive discussions between the executive boards of the two societies, the "board consultations" begun in 2025 are to be continued on a regular basis, and mutual invitations to congresses are to be extended to promote scientific and professional dialogue.

Background:Oral squamous cell carcinoma (OSCC) is the predominant histological subtype of oral cavity cancers, with a 5-year survival rate of approximately 50%. The tumour microenvironment, particularly macrophage infiltration and polarization, plays a critical role in tumour progression and patient prognosis. Models describing macrophages as either M1 (pro-inflammatory) or M2 (anti-inflammatory) are increasingly recognized as oversimplified, given the functional heterogeneity and plasticity of tumour-associated macrophages (TAMs). This study aims to evaluate the expression of macrophage markers CD68, CD163, CD11c, and CD115 in OSCC compared to normal oral mucosa (NOM), to assess their diagnostic and prognostic value. Methods:A cross-sectional study of 179 tissue samples (111 OSCC, 68 controls) analysed macrophage markers (CD68, CD163, CD11c, CD115) via real-time qPCR. Statistical tests included Mann-Whitney U, ROC analysis for diagnostic utility, Spearman's ρ for correlations, and assessments of associations with prognosis and recurrence. Cut-offs for gene overexpression were based on ROC results and evaluated clinically. Results:All four markers showed significantly higher expression in OSCC compared to NOM (p < 0.001 for CD68, CD163, CD11c; p = 0.001 for CD115). ROC analyses demonstrated diagnostic AUCs of 0.69 (CD68), 0.78 (CD163), 0.81 (CD11c), and 0.66 (CD115), indicating poor, fair and good discriminative capacity, respectively. Overexpression of the genes defined by COP was significantly associated with malignancy (p < 0.01). Elevated CD68 and CD163 levels correlated with higher tumour grading (G2/G3), while increased CD11c expression was linked to nodal metastasis (p = 0.04). Strong positive correlations existed between CD115 and the other markers (ρ > 0.61, p < 0.001), supporting a model of macrophage heterogeneity and plasticity. Concurrent upregulation of pro-inflammatory (CD11c) and M2-associated (CD163) markers suggests a complex, dynamic TAM landscape rather than a simple M1/M2 dichotomy. Conclusions:Altered RNA expression of the macrophage cell surface markers CD115, CD68, CD163 and CD11c in OSCC, and their respective association with tumour grading, N-status and perineural sheath infiltration, may serve as a basis for future single-cell sequencing or immunohistological - multiplex immunofluorescence - studies. Further investigation of these markers could lead to promising insights into the modulation of the tumour immune microenvironment.

Background/Objectives: Accurate visualization of peroneal perforator vessels prior to autologous transplantation of osteomyocutaneous fibular flap is essential for surgical success. Our aim was to improve and simplify pre-surgical diagnostics of peroneal perforators using a dedicated dual-energy Computed Tomography Angiography (CTA) protocol and semiautomatic Vessel Unfolding Reconstruction algorithm (VUR). Methods: CTA of both lower legs was performed in 22 patients using dual-energy acquisitions from a third-generation dual-source CT scanner and a high iodine flux (7 mL/s, 350 mg/mL). Low-energy virtual monoenergetic reconstructions (40 keV) were automatically reconstructed from the scanner and used for centerline labeling of the peroneal arteries and their perforators on a post-processing console using a dedicated vascular workflow. Separate segmentation and curved multiplanar reconstructions (MPRs) of each identified peroneal perforator vessel were regarded as the gold standard. Traditional visualization techniques of the entire volume like thin-slice maximum intensity projections (MIPs) or the volume rendering technique (VRT) were compared to a new VUR algorithm that aimed to adjust the visualization plane to the course of the vessels. The identified numbers and lengths of the perforator arteries were compared between curved MPRs, thin-slice MIPs in oblique coronal orientation, posterior-view VRT and coronal VUR of each lower leg. Results: The VUR algorithm was feasible in all patients and the same quantity of peroneal perforator vessels could be detected in comparison to the gold standard. The mean number of perforator vessels per lower leg was 2.6. Mean perforator length in VUR was slightly shorter by 1.6% and did not significantly differ from curved MPRs (p = 0.54), whereas length values from oblique coronal MIP and VRT reconstructions were significantly shorter (both p < 0.001). Conclusions: The combination of virtual monoenergetic reconstructions and the VUR algorithm enables comprehensive and precise depiction of small peroneal perforator vessels prior to autologous fibular flap transplantation, representing a diagnostic tool comparable to traditional visualization methods.

As immunotherapy (IT) with checkpoint inhibitors continues to make rapid progress in the treatment of oral squamous cell carcinoma (OSCC), response rates still necessitate substantial improvement. Current concepts to improve therapy response mainly consider identification of further immunological targets eligible for extension of IT. One auspicious immune checkpoint is CD137 and its ligand CD137L, but expression rates and relevance for progression of OSCC are still unknown. Tissue and peripheral blood from 159 OSCC patients and 55 healthy oral mucosa (HOM) controls was collected and subsequently analyzed for expression of CD137 and CD137L by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Furthermore, OSCC and HOM tissue samples from both groups were evaluated for CD137 protein expression by immunohistochemistry (IHC). Expression rates were analyzed and subsequently correlated with histomorphological characteristics. CD137 exhibited highly significant upregulation in OSCC tissue on mRNA and protein level, as evidenced by both RT-qPCR (p < 0.001) and IHC (p < 0.001) analysis. Regarding the CD137L expression in the examined tissue specimens, there was no significant difference detectable on mRNA level (p = 0.53). Comparative analysis of RT-qPCR blood data showed no statistically significance in expression rates of CD137 (p = 0.653) and CD137L (p = 0.351). Correlation analysis revealed no highly significant results with reference to the histopathological parameters. CD137 showed a highly significant upregulation in OSCC tissue compared to the HOM control group. Consequently, it may be a relevant checkpoint involved into formation and progression of OSCC. Further investigations are needed to evaluate, if CD137 represents a suitable target for a novel IT approach in OSCC treatment.

Objectives: Post-extraction remodelling of hard and soft tissues results in volume reduction, leading to aesthetic challenges in planning prosthetic restorations, particularly in the anterior maxilla. This study assessed whether atraumatic vertical extraction, versus conventional extraction, could reduce postoperative volume loss and aesthetic compromises at the extraction site and adjacent teeth. Methods: Following randomized tooth extraction with unassisted healing in the test (Benex® extraction, n = 10) and control group (conventional extraction, n = 10), postoperative scans were conducted at 30 days (t1), 60 days (t2), 90 days (t3) and 12 months (t4). Each scan was aligned with the baseline scan (t0), and surface comparison was performed with five regions of interest (ROIs: central, mesial, distal, papilla mesial and papilla distal). Aesthetic parameters, including recession and Pink Esthetic Score (PES) of adjacent teeth, were clinically evaluated at each follow-up appointment. Statistical analysis used a mixed linear model accounting for confounding factors such as smoking, buccal bone integrity, gingival phenotype, and provisional use. Results: Both groups showed significant volume reduction from baseline to t3 and t4. The largest volume loss occurred in the central ROI in both test (t4: −65.34 ± 36.89 mm3) and control group (t4: −70.85 ± 30.96 mm3), with no significant difference between groups. A decline in PES and recession at the adjacent teeth was noted in both groups at 12 months. Conclusions: Both groups showed significant volume reduction with aesthetic impairment at the adjacent teeth’s soft tissue.

Abstract Introduction The prevalence of periodontitis is elevated in patients with inflammatory bowel disease (IBD). The neutralisation of antibodies against the cytokines TNF and interleukin-12/23 (IL-12/23) is a fundamental component of the clinical management of IBD. However, the extent to which such cytokine blockade in IBD influences the clinical picture of periodontitis remains to be elucidated. Methods In this exploratory study, 45 patients suffering from IBD who were undergoing biological therapy with cytokine blockers were examined for the presence of periodontitis. The prospective study identified three distinct groups: anti-TNF therapy (n = 15), anti-IL-12/IL-23 therapy (n = 15), no anti-TNF or anti-IL-23 therapy (control group; n = 15). The depth of the gum pockets in all sextants was determined using the Periodontal Screening Index (PSI). Furthermore, a comprehensive medical history pertaining to IBD and oral hygiene was obtained. IL-6 levels were determined by ELISA in gingival crevicular fluid (GCF). Results Of the 45 patients with IBD, 14 had known or evidence of previously unknown periodontitis. The investigation revealed that the mean PSI index in the anti-IL-12/IL-23 group was significantly lower than in the other groups. Within the anti-IL-12/IL-23 group, two individuals with a history of periodontitis exhibited a PSI index of 0, while no subjects demonstrated indications of latent periodontitis. In contrast, three individuals in the anti-TNF group and six individuals in the control group had previously been diagnosed with periodontitis, and two and three additional individuals from these groups exhibited signs of previously unknown periodontitis. IL-6 levels in GCF were significantly lower in the anti-IL-12/IL-23 group as compared to the control group. Conclusion This exploratory study suggested that anti-IL-12/IL-23 therapy in IBD may have protective effects against periodontitis. Possible links between biologic therapy and periodontitis should be investigated prospectively in larger cohorts. Funding Source N/A Topic Categories Immune Mechanisms of Human Disease (HUM)

Objectives Complex horizontal and vertical alveolar ridge defects remain challenging in implant dentistry due to limited graft stability and unpredictable contour maintenance. This case series presents the TESS (Tensioned Engineered Shell System) technique, a resorbable shell-based augmentation approach utilizing a polydioxanone (PDS) shell stabilized with fixation screws to establish a biologically favorable three-dimensional regenerative compartment. Materials and methods Three patients presenting with combined horizontal and vertical alveolar ridge deficiencies underwent reconstruction using a 0.5 mm resorbable PDS shell fixed orally and vestibularly using a titanium fixation system. The created compartment was filled with autologous particulate bone alone or combined with xenograft material. In one maxillary case, bilateral sinus floor elevation was performed simultaneously. Cone beam computed tomography (CBCT) measurements were obtained preoperatively and postoperatively at standardized levels using implant-axis–based measurements. Results All cases demonstrated successful ridge contour reconstruction with substantial crestal bone gain. In the bilateral maxillary reconstruction case, discontinuous crestal defects were successfully bridged. The most pronounced augmentation was consistently observed at the crestal level, while basal ridge dimensions remained comparatively stable. Implant placement with adequate primary stability was achieved in two cases. No postoperative infections, graft failures, or wound dehiscence occurred. Conclusions The TESS technique appears to provide predictable three-dimensional contour stabilization and effective space maintenance for complex alveolar ridge reconstruction. The use of a resorbable PDS shell may represent a biologically favorable alternative to non-resorbable rigid barrier systems by supporting the fundamental surgical principles of stability, trophic integration, and protected healing.

Introduction Salivary gland carcinomas (SGC) are rare tumours. The term SGC is not more than an umbrella for a variety of histogenetically, morphologically and biologically distinct entities. Accordingly, SGCs have not been sufficiently investigated to date. Their rarity makes it difficult to reach high patient numbers for individual entities in clinical studies, leading to pooling patients with different histological subtypes to attain sufficient participants. The different histological subtypes of SGC differ significantly in their clinicopathological features, such as their grading, their occurrence and their outcome. SGCs are usually stratified into low-grade, intermediate-grade or high-grade tumours. In most kinds of SGC, specific targetable molecular markers are lacking. The inclusion of immunotherapy (IT), however, might improve the outcome of patients suffering from high-grade SGCs. In order to integrate IT as a therapeutic option for SGC and to facilitate therapeutic decisions based on tumour (immune) biology, predictive and prognostic immunological biomarkers are indispensable.Methods and analysis In this prospective study, 500 patients will be enrolled, who are distributed in three arms. The observational cohort includes patients with malignant salivary gland tumours, whereas patients with benign tumours of a salivary gland are grouped in the control group 1. In the control cohort, 2 patients do not have a salivary gland tumour but have a planned functional surgery of the nose or ear or a maxillofacial surgery. The local immune status from the tumour tissue and the microbiome will be sampled before treatment. In addition, the systemic immune status from peripheral blood will be analysed before and after surgery and after the adjuvant and definitive chemoradiotherapy, if applicable. Clinical baseline characteristics and outcome parameters will additionally be collected. Data mining and modelling approaches will finally be applied to identify interactions of local and systemic immune parameters and to define predictive and prognostic immune signatures based on the evaluated immune markers.Ethics and dissemination Approval from the institutional review board of the Friedrich-Alexander-Universität Erlangen-Nürnberg was granted in September 2023 (application number 23-292-B). The results will be disseminated to the scientific audience and the general public via presentations at conferences and publication in peer-reviewed journals.Trial registration number NCT06047236.

The yearly incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) continues to rise in the ongoing skin cancer epidemic. Mousa and colleagues have previously highlighted the crucial role of the immune system in the development and progression of both tumor types. Therefore, immune cells in close proximity to, or even infiltrating, the tumor should be of particular interest. Previously, we demonstrated differential expression of immune checkpoint markers, including both activating and inhibitory markers, between BCC and cSCC. The present study aims to further investigate the tumor microenvironment, with a focus on T cells, macrophages, and dendritic cells, among others. Furthermore, we analyzed possible associations between cSCC marker expression and clinicopathological data. In order to evaluate the expression levels and topographic distribution profiles of CD4, CD8, Foxp3, CD68, CD163, and CD11c, tissue microarrays of the invasive front as well as the tumor core of BCC and cSCC samples were analyzed. Chromogenic immunohistochemistry was performed, and the labeling index was determined using QuPath. Stroma cell labeling indices of CD4**, CD8*, Foxp3*, CD68*, CD163**, and CD11c* were significantly higher in both the tumor core and the invasive front of cSCC samples as compared to BCC (*p < 0.001; **p < 0.050). In cSCC, the ratios of CD163/CD68 (p < 0.001) and CD163/CD11c (p = 0.001) were markedly elevated. The invasive front of both tumor entities showed higher expression levels of all immune markers compared to the tumor core, when significant levels were reached. Lastly, an association between cSCC sLI CD4 and T status (p = 0.011), CD11c and N status (p = 0.041), CD68 and infiltrations depth (p = 0.018), as well as CD8 and CD11c and previous tumor (p = 0.006; p = 0.029, respectively) was observed. This study provides a comprehensive analysis of the tumor microenvironment (TME) of BCC and cSCC, emphasizing the distinct expression patterns of the TME with regard to T cell and macrophage-associated markers. The cSCC TME exhibited higher expression levels of all investigated markers, predominantly at the invasive front rather than the tumor core. Further, more comprehensive analysis of these TMEs is required to understand their impact on clinicopathological data, response to immunotherapy and predictive ability.

BACKGROUND:Orofacial malformations, especially when associated with syndromes, may complicate airway management in children. However, only a few studies have addressed the airway management in children undergoing cleft lip and/or palate surgery. AIMS:To report on perioperative airway management and complications in children undergoing cleft lip or palate surgery over an 8-year retrospective period. METHODS:We performed a retrospective analysis of patients younger than 2 years of age who underwent surgery for cleft lip or palate at the Department of Oral and Cranio-Maxillofacial Surgery of a German university hospital between 2016 and 2023. The study assessed patient demographics, airway management techniques, airway management difficulties, and adverse events. RESULTS:During the observation period, 274 cases were included. Difficult laryngoscopy occurred in 16 cases (6%). Direct laryngoscopy failed in five cases (1.9%), leading to successful video-laryngoscopic intubation. There was a noticeable higher incidence of difficult laryngoscopy (16.7% vs. 5.3%) and failed direct laryngoscopy (11.1% vs. 1.2%) in cleft patients with a syndrome association. In eight cases (2.9%) with an expected difficult airway, a primary hybrid technique was used for intubation due to a proven syndromic disorder. Airway complications were significantly more common in patients associated with a syndromic disorder (40.7% vs. 23.5%; p = 0.049, φ = 0.12). CONCLUSION:Airway management in children undergoing cleft lip or palate surgery presents unique challenges, with an increased incidence of difficult and failed direct laryngoscopy and a significantly higher rate of complications in patients with a syndromic disorder. Video laryngoscopy and, if a difficult airway is anticipated, a hybrid technique for intubation is a safe and effective approach to airway management in these patients. However, the postextubation period can be very challenging, particularly in patients with associated syndromes. Epinephrine inhalation may prevent reintubation and ventilated admission to the intensive care unit. CLINICAL IMPLICATIONS:Cleft lip and palate significantly complicate airway management, especially in infants with syndromic conditions. It was already known that these children are at higher risk for difficult intubation and respiratory complications. The new findings of this study, analyzing 274 procedures in children under 2 years, found that the hybrid technique (video laryngoscopy combined with flexible bronchoscopy) is highly effective for anticipated difficult airways and highlights the importance of an individualized, stepwise approach to ensure safe anesthesia in cleft surgery. Additionally, the study identified a higher incidence of postextubation stridor, particularly in syndromic patients, pointing to the need for tailored postoperative care.

This study aims to analyze facial trauma management, practice patterns, and patient care in Oral and Maxillofacial Surgery (OMFS) in Germany by using a dynamic online questionnaire with up to 54 questions. The survey, comprising single/multiple-choice and open-ended questions, was implemented via SurveyMonkey® and distributed to OMFS departments and surgeons in Germany. Data was analyzed anonymously and descriptively. Eighty-four OMFS departments and surgeons participated, revealing diverse facial trauma management. Monthly facial trauma patient volumes ranged from 0 to 10 (37.8 %) to more than 75 (4.88 %). Computed tomography (CT) was the primary imaging modality (82.05 %), supplemented by cone-beam CT and panoramic radiographs (56.41 % each). Orbital floor reconstruction primarily involved transconjunctival access (42.86 %) and prefabricated titanium meshes (69.01 %). Champy mini-plate osteosynthesis mainly managed mandibular angle fractures (51.47 %). Variability persists in the management of mandibular condylar process fractures in Germany. While a significant number of participants favor conservative treatment for condylar process fractures overall (26.87 %), the rate of surgical intervention for condylar head fractures is notably higher than international standards (59.42 %). Endoscopic techniques were rare (18.84 %). The management of standard thrombosis prophylaxis and perioperative antibiotic administration varied. Differences in specific facial trauma management were identified and assumed to be based on internal experiences and structural and personnel resources.

BackgroundImmune cells play a major role in the development and progression of inflammatory and malignant diseases of the oral mucosa. There is growing evidence that immune cells contribute to oral cancer progression and metastases. Inflammatory carcinogenesis is believed to be relevant for oral Lichen Planus as well as for oral Leukoplakia. In addition, there is growing evidence that periodontitis might also be linked to oral cancer development. Yet there is no analysis available comparing the immune cell composition in these different inflammatory and malignant neoplastic diseases. A better understanding of similarities and differences of the diseases could eventually also pave the way for the use of immunotherapy in non-malignant diseases.MethodsIn the current pilot study, a tissue microarray (TMA) was created of a total of 29 patients with periodontitis (PD, n=4), oral Leukoplakia (OL, n=4), oral Lichen Planus (OLP, n=4), oral squamous cell cancer without lymphatic metastases (OSCC N0, n=5), or with lymphatic metastases (OSCC N+, n=4), OSCC biopsies prior to and resection specimens after anti-PD1 immunotherapy (IT) (each n=3) as well as healthy control gingiva (n=5). In each patient two tissue samples were analyzed. The TMA was stained with a 4X multiplex immunofluorescent staining for IL-23R, CD68, CD11c, and CD163. Samples were digitalized and an AI-based cell counting was performed. Statistical analysis was performed using the Mann-Whitney U test.ResultsIL-23R expression, macrophage infiltration as well as M2 polarization in OL and OLP were significantly higher compared to controls. OLP showed a significantly higher M2 infiltration and polarization than OL. PD showed a trend for increased macrophage infiltration compared to controls without significance. N+ OSCC showed a significantly increased macrophage infiltration compared to N0 cases. In response to anti-PD1 IT, CD11c and CD163 infiltration was significantly increased. Most IL-23R positive cells co-expressed macrophage markers.ConclusionA TMA in combination with 4-plex immunofluorescence is suitable for immune cell characterization in different oral diseases. Macrophage infiltration and polarization in precursor lesions seems to be associated with OSCC development as well as metastatic spread. IL-23 pathway inhibition might be a potential target for oral Lichen and Leukoplakia.

BackgroundA link between chronic inflammation and malignant transformation is evident in various cancer types. Periodontitis is the most common chronic inflammatory condition in oral medicine with a proven association with systemic diseases like diabetes. Although there is scant evidence of a potential link between periodontitis and oral cancer there is no proof for a correlation yet. We hypothesize that radiographic bone loss (RABL) as indicator of chronic periodontitis is associated with the occurrence of oral squamous cell carcinomas (OSCC).Methods206 orthopantomograms (OPTs) from a cohort of OSCC cases and controls without OSCC, both between the age of 40 and 70, were analyzed in this retrospective study. Radiographic oral health parameters like radiographic alveolar bone loss (RABL), remaining teeth as well as implants were analyzed and compared between the two groups. The analyses of the study were controlled for the impact of confounders such as diabetes, smoking of tobacco and age. Welch-test, Chi-Square-Test and a two-way Analysis of Covariance (ANCOVA) followed by a Bonferroni post-hoc test for multiple pairwise comparison were performed.ResultsSeveral statistically significant differences were identified between the two groups, with a greater than twofold prevalence of nicotine consumption among the OSCC group. Additionally, the OSCC cohort exhibited a mean age approximately 3.5 years higher and a lower number of remaining teeth compared to the control group. After eliminating the effect of these confounders, a significantly greater loss of bone mass was observed in the OSCC cohort in comparison to the control cohort.ConclusionIn consideration of the confounders, patients with OSCC had more bone loss, compared to controls. These data indicate an association between periodontitis derived chronical inflammation and the malignant transformation of oral epithelium.

Treatment for a cleft lip can result in significant functional and aesthetic changes to the nasolabial region. Although three-dimensional (3D) measurements are the gold standard for evaluating cleft surgery, most short- and long-term evaluations still rely on subjective assessment or the measurement of patient photographs. To our knowledge, this work establishes the first baseline and reference group for the nasolabial region in children aged 3 to 9 months without cleft lip or palate. This group can be used for future evaluations, such as those of surgical outcomes or NAM therapy, via 3D anthropometric measurement. Data was collected cross-sectionally from 25 children aged 3 to 9 months using a validated intraoral scanner (Trios 4, 3Shape). Scans were analysed according to 3D anthropometric criteria by metrically accurate measurements of distances, surface curves and angles using 3D inspection software (GOM Inspect, Co. Zeiss, Jena, Germany). Results are presented as reference database combined with a step-by-step guide on the measurement methodology. For easy application all data are additionally presented in the form of formulae in which clinical data can be inserted. Based on the data from healthy children, we propose a new classification of alar base types ranging from 1 to 3. Unlike conventional assessment methods, surface curves and other 3D anthropometric tools provide a highly accurate and objective quantification of the anatomy of the nasolabial region and thus serve as a foundation for future clinical research on cleft lip surgery. Alar base type classification may influence future surgical approaches to cleft lip surgery.

Although existing microsurgical models provide a high degree of realism in tissue properties, they often neglect the complex and constrained spatial-anatomical conditions typical of head and neck surgery. This study aims to evaluate the effectiveness of the Head and Neck Realistic Anatomical Condition Experience (RACE) model in enhancing microsurgical education. Using a microsurgical competency assessment tool and self-assessment questionnaires, the head and neck RACE model was evaluated through application in two student courses (10 participants) and one resident course (5 participants). In both groups, first the conventional chicken thigh model and then the RACE model were applied. Data were analyzed using a two-way repeated measures ANOVA with Welch’s statistics to assess differences between the groups. In pregraduate courses, the transition from the conventional chicken thigh model to the RACE model initially led to a decline across all eight microsurgical performance parameters (Q1.1-Q4.2). However, after an additional day of training with the RACE model, all parameters—except tissue-preserving technique (Q1.2) — returned to or significantly exceeded baseline levels (Q1.2 p = 0.373, Q1.3 p = 0.003, Q2.1 p < 0.001, Q2.2 p = 0.022, Q2.3 p = 0.008, Q3.1 = 0.014, Q4.1 p = 0.036, Q4.2 p = 0.002). Conversely, residents showed immediate improvement in all parameters, except for suture distance to the vessel’s margin, upon switching to the RACE model. Head and neck RACE models provide a challenging and practical addition to microsurgery teaching. The positive impact on learning outcomes in this area supports the development of RACE models in other areas of microsurgical and general medical training, and therefore the education of students and clinical practitioners.

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models.

The establishment of immunotherapy applying immune checkpoint inhibitors (ICI) has provided an important new option for the treatment of solid malignant diseases. However, different tumor entities show dramatically different responses to this therapy. BCC responds worse to anti-PD-1 ICIs as compared to cSCC. Differential immune checkpoint expression could explain this discrepancy and, therefore, the aim of this study was to analyze activating and inhibitory immune checkpoints in cSCC and BCC tissues. Tissue microarrays of the invasive front as well as the tumor core of BCC and cSCC samples were used to evaluate PD-1, PD-L1, CD28, and CD86 expression and their topographic distribution profiles by chromogenic immunohistochemistry. QuPath was used to determine the labeling index. The expression of PD-1, PD-L1, and CD28 was significantly higher in both the tumor core and the invasive front of cSCC samples as compared to BCC (p < 0.001). In addition, the ratios of PD-L1/CD86 (p < 0.001) and CD28/CD86 (p < 0.001) were significantly higher in cSCC. The invasive front of both tumor entities showed higher expression levels of all immune markers compared to the tumor core in both tumor entities. The significantly higher expression of PD-1, PD-L1, and CD28 in cSCC, along with the predominance of the inhibitory ligand PD-L1 as compared to the activating CD86 in cSCC, provide a potential explanation for the better objective response rates to anti-PD-1 immunotherapy as compared to BCC. Furthermore, the predominant site of interaction between the immune system and the tumor was within the invasive front in both tumor types.

Chronic inflammatory processes in the oral mucosa and periodontitis are common disorders caused by microflora and microbial biofilms. These factors activate both the innate and adaptive immune systems, leading to the production of pro-inflammatory cytokines. Cytokines are known to play a crucial role in the pathogenesis of gingivitis and periodontitis and have been proposed as biomarkers for diagnosis and follow-up of these diseases. They can activate immune and stromal cells, leading to local inflammation and tissue damage. This damage can include destruction of the periodontal ligaments, gingiva, and alveolar bone. Studies have reported increased local levels of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumor necrosis factor (TNF), IL-6, IL-17, and IL-23, in patients with periodontitis. In experimental models of periodontitis, TNF and the IL-23/IL-17 axis play a pivotal role in disease pathogenesis. Inactivation of these pro-inflammatory pathways through neutralizing antibodies, genetic engineering or IL-10 function has been demonstrated to reduce disease activity. This review discusses the role of cytokines in gingivitis and periodontitis, with particular emphasis on their role in mediating inflammation and tissue destruction. It also explores new therapeutic interventions that offer potential for research and clinical therapy in these chronic inflammatory diseases.