The Immune Checkpoint BTLA in Oral Cancer: Expression Analysis and Its Correlation to Other Immune Modulators.

In oral squamous cell carcinoma (OSCC) tissues, an immunotolerant situation triggered by immune checkpoints (ICPs) can be observed. Immune checkpoint inhibitors (ICIs) against the PD1/PD-L axis are used with impressive success. However, the response rate is low and the development of acquired resistance to ICI treatment can be observed. Therefore, new treatment strategies especially involving immunological combination therapies need to be developed. The novel negative immune checkpoint BTLA has been suggested as a potential biomarker and target for antibody-based immunotherapy. Moreover, improved response rates could be displayed for tumor patients when antibodies directed against BTLA were used in combination with anti-PD1/PD-L1 therapies. The aim of the study was to check whether the immune checkpoint BTLA is overexpressed in OSCC tissues compared to healthy oral mucosa (NOM) and could be a potential diagnostic biomarker and immunological target in OSCC. In addition, correlation analyses with the expression of other checkpoints should clarify more precisely whether combination therapies are potentially useful for the treatment of OSCC. A total of 207 tissue samples divided into 2 groups were included in the study. The test group comprised 102 tissue samples of OSCC. Oral mucosal tissue from 105 healthy volunteers (NOM) served as the control group. The expression of two isoforms of BTLA (BTLA-1/2), as well as PD1, PD-L1/2 and CD96 was analyzed by RT-qPCR. Additionally, BTLA and CD96 proteins were detected by IHC. Expression levels were compared between the two groups, the relative differences were calculated, and statistical relevance was determined. Furthermore, the expression rates of the immune checkpoints were correlated to each other. BTLA expression was significantly increased in OSCC compared to NOM (pBTLA_1 = 0.003; pBTLA_2 = 0.0001, pIHC = 0.003). The expression of PD1, its ligands PD-L1 and PD-L2, as well as CD96, were also significantly increased in OSCC (p ≤ 0.001). There was a strong positive correlation between BTLA expression and that of the other checkpoints (p < 0.001; ρ ≥ 0.5). BTLA is overexpressed in OSCC and appears to be a relevant local immune checkpoint in OSCC. Thus, antibodies directed against BTLA could be potential candidates for immunotherapies, especially in combination with ICI against the PD1/PD-L axis and CD96.

Development of a porcine training model for microvascular fasciocutaneous free flap reconstruction.

BACKGROUND: In reconstructive surgery, improvements are needed in the effective teaching of free flap surgery. There is a need for easily accessible and widely available training without high financial costs or ethical concerns while still providing a realistic experience. Our aim was to develop an appropriate training model for microvascular flaps. METHODS: We identified pig head halves as most appropriate regarding availability, cost, and realism. These accrue largely by the food industry, so no animals need to be sacrificed, making it more ethical from an animal welfare perspective. We evaluated the suitability as flap donor site and analyzed the vascular anatomy of 51 specimens. RESULTS: Anatomical evaluation revealed a reliable and constant vascular anatomy, allowing the design of a flap model that can effectively illustrate the entire process of microvascular flap surgery. The process was divided into 6 key steps. The flap can be harvested after marking the vascular pedicle 5.3 cm from the lateral corner of the mouth. Skin island design and subsequent tissue dissection follow until a fasciocutaneous flap is raised, similar to a radial flap. Upon completion of flap harvesting, it can be freely transferred for defect reconstruction. Microvascular anastomosis can be performed on recipient vessels in the cervical region, and the difficulty can be individually adjusted. CONCLUSIONS: The developed training model is a reasonable compromise in terms of surgical realism, availability, didactic value, and cost/time effectiveness. We believe it is a powerful and effective tool with high potential for improving surgical education and training.

Advancements in diagnosing oral potentially malignant disorders: leveraging Vision transformers for multi-class detection.

OBJECTIVES: Diagnosing oral potentially malignant disorders (OPMD) is critical to prevent oral cancer. This study aims to automatically detect and classify the most common pre-malignant oral lesions, such as leukoplakia and oral lichen planus (OLP), and distinguish them from oral squamous cell carcinomas (OSCC) and healthy oral mucosa on clinical photographs using vision transformers. METHODS: 4,161 photographs of healthy mucosa, leukoplakia, OLP, and OSCC were included. Findings were annotated pixel-wise and reviewed by three clinicians. The photographs were divided into 3,337 for training and validation and 824 for testing. The training and validation images were further divided into five folds with stratification. A Mask R-CNN with a Swin Transformer was trained five times with cross-validation, and the held-out test split was used to evaluate the model performance. The precision, F1-score, sensitivity, specificity, and accuracy were calculated. The area under the receiver operating characteristics curve (AUC) and the confusion matrix of the most effective model were presented. RESULTS: The detection of OSCC with the employed model yielded an F1 of 0.852 and AUC of 0.974. The detection of OLP had an F1 of 0.825 and AUC of 0.948. For leukoplakia the F1 was 0.796 and the AUC was 0.938. CONCLUSIONS: OSCC were effectively detected with the employed model, whereas the detection of OLP and leukoplakia was moderately effective. CLINICAL RELEVANCE: Oral cancer is often detected in advanced stages. The demonstrated technology may support the detection and observation of OPMD to lower the disease burden and identify malignant oral cavity lesions earlier.

Treatment with (chemo)-radiation in old patients (≥76 years of age) with newly diagnosed non-metastatic squamous cell cancer of the head and neck region: real-world data from a tertiary referral center.

Purpose: Treatment of patients with cancer of the head and neck region is in focus in a multitude of studies. Of these patients, one patient group, those aged 76 and more, is mostly underrepresented despite requiring thorough and well-reasoned treatment decisions to offer curative treatment. This study investigates real-world data on curative treatment of old (≥76 years) patients with newly diagnosed squamous cell carcinoma of the head and neck region (HNSCC). Patients and methods: Between January 2010 and December 2021, we identified 71 patients older than 76 years with newly diagnosed HNSCC and cM0 at the Department of Radiation Oncology of the University Hospital of Erlangen-Nuremberg. Using electronic medical records, we analyzed treatment patterns and outcomes in terms of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rate. Additionally, we performed univariate risk analysis and Cox regression in order to identify predictive factors associated with the abovementioned treatment outcomes. Results: The median follow-up was 18 months. OS was 83%, 79%, and 72% after 1 year, 2 years, and 3 years, respectively. PFS was 69%, 54%, and 46% after 1 year, 2 years, and 3 years, respectively. A total of 34 (48%) patients were treated with standard therapy according to current guidelines. The reasons for deviation from standard therapy before or during treatment were as follows: unfitness for cisplatin-based chemotherapy (n = 37), reduction of chemotherapy (n = 3), and dose reduction/interruption of radiotherapy (n = 8). Carboplatin-based systemic therapy showed improved PFS compared to cisplatin or cetuximab (60 vs. 28 vs. 15 months, p = 0.037) but without impact on OS (83 vs. 52 vs. 38 months, p = 0.807). Oropharyngeal tumor localization (p = 0.026) and combined treatment (surgery and postoperative treatment) (p = 0.008) were significant predictors for a better OS. In multivariate analysis, oropharyngeal tumor localization (p = 0.011) and combined treatment (p = 0.041) showed significantly increased PFS. After 1 year, 2 years, and 3 years, the cumulative incidence of locoregional recurrences (LRRs) was 13%, 24%, and 27%, respectively, and was significantly decreased in patients with oropharyngeal tumor localization (p = 0.037). Conclusions: Adherence to treatment protocols for radiotherapy alone in old patients with HNSCC is good, whereas the application of concurrent chemotherapy often deviates from guidelines in terms of de-escalation. An important risk factor for decreased OS, PFS, and a higher rate of LRR appears to be non-oropharyngeal tumor location in old patients.

Diagnostic accuracy of contrast-enhanced computed tomography in assessing bone invasion in patients with oral squamous cell carcinoma.

OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) in detecting bone invasion in oral squamous cell carcinoma (OSCC) patients and to explore clinicopathological factors associated with its reliability. MATERIALS AND METHODS: 417 patients underwent preoperative contrast-enhanced CT followed by radical surgery. The presence or absence of bone invasion served as the outcome variable, with histopathologic examination of the resection specimen considered the gold standard. Statistical analyses, comprising correlation analyses and the determination of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were conducted. RESULTS: CT exhibited 76.85% sensitivity, 82.20% specificity, 47.14% PPV, and 89.67% NPV. False-positive and false-negative rates were 11.27% and 5.99%, respectively. Artifacts affected assessment in 44 patients, but not in those with bone invasion. Tumor size, depth of invasion (DOI), tumor localization at the upper jaw, lymphatic invasion, and perineural invasion correlated with incorrect identification of bone invasion (Chi-square, p < 0.05). CONCLUSIONS: Despite utilizing thin-section CT, notable false-positive and false-negative results persisted. Patients with T3 tumors, DOI ≥ 10 mm, or upper jaw tumors are at higher risk for misidentification of bone invasion. Combining multiple methods may enhance diagnostic accuracy, and the integration of artificial intelligence or tracking electrolyte disturbances by tumor depth profiling shows promise for further assessment of bone invasion before histopathology. CLINICAL RELEVANCE: Surgeons should consider these insights when planning tumor resection. Supplementary imaging may be warranted in cases with high risk factors for misidentification. Further methodological advancements are crucial for enhancing diagnostic precision.

Three-dimensional assessment of upper airway changes associated with mandibular positional deviations following fibula free flap reconstruction.

OBJECTIVES: Fibula free flaps (FFF) are the standard approach to mandibular reconstruction after partial resection, with the goal of restoring aesthetics and masticatory function. The graft position affects both and must be carefully selected. Correlations between sagittal positioning and upper airway anatomy are known from orthognathic surgery. This study aims to evaluate changes in mandibular position and upper airway anatomy after reconstructive surgery with FFF and corresponding correlations. MATERIALS AND METHODS: Mandibular position after reconstruction was evaluated using three-dimensional datasets of pre- and postoperative computed tomography scans of patients treated between 2020 and 2022. Three-dimensional measurements were performed on both condyles and the symphyseal region. Changes in upper airway volume and minimum cross-sectional area (minCSA) were analysed. Intra-rater reliability was assessed. Correlations between changes in upper airway anatomy and sagittal mandibular position were tested. RESULTS: The analysis included 35 patients. Intra-rater reliability was good to excellent. Condylar deviations and rotations were mostly rated as small. Changes in symphyseal position were considerably greater. Median airway volume decreased in the oropharynx and hypopharynx. Posterior deviation of the symphysis was associated with a decreasing minCSA in the hypopharynx and vice versa. CONCLUSIONS: The overall accuracy of mandibular reconstructions with FFF is high, but there is room for optimization. The focus of research should be extended from masticatory to respiratory rehabilitation. CLINICAL RELEVANCE: Effects on respiratory function should be considered prior to graft positioning. The clinical relevance of upper airway changes within the complex rehabilitation of reconstructive surgery patients needs to be further investigated.

Improved recurrence rates and progression-free survival in primarily surgically treated oral squamous cell carcinoma - results from a German tertiary medical center.

OBJECTIVES: This study aimed to explore survival and recurrence patterns in patients undergoing primarily surgical treatment for oral squamous cell carcinoma (OSCC) at a high-volume tertiary medical center in Germany. MATERIALS AND METHODS: The study included 421 patients with primary OSCC who underwent radical tumor resection, neck dissection, and reconstruction with a free flap. Prognostic relevance of clinicopathological characteristics was assessed using Cox proportional-hazards models. Kaplan-Meier method estimated local recurrence-free survival, progression-free survival (PFS), and overall survival (OS), while the log-rank test compared survival outcomes between groups. RESULTS: Recurrence manifested in 16.63% of the patients (70 patients), encompassing local recurrence in 54 patients (77.14%) and distant metastasis in 24 patients (34.28%). Neck recurrence occurred in only 1 patient (0.24%) on the contralateral side. The majority of recurrences occurred within the initial twelve months following primary tumor surgery (64.29%). Overall, the 5-year OS stood at 58.29%, while the 5-year PFS reached 72.53%. Patients with early recurrence within ≤ 12 months showed the least favorable prognosis (log-rank, all p < 0.001). CONCLUSIONS: Our findings show a significant decrease in recurrence rates and enhanced PFS at a high-volume tertiary medical center in Germany compared to previous studies. Local recurrence was the primary form observed, with most recurrences happening within the initial twelve months post-surgery. Opting for treatment at a high-volume center and devising therapy plans in interdisciplinary tumor boards may not only enhance OS but also contribute to improved PFS. CLINICAL RELEVANCE: These findings offer valuable insights for physicians regarding the post-treatment care of patients with OSCC. The results underscore the importance of frequent follow-up appointments, particularly during the initial year, and highlight the critical need for vigilance in monitoring for local recurrence.

Oral mucosa - an examination map for confocal laser endomicroscopy within the oral cavity: an experimental clinical study.

OBJECTIVES: Confocal laser endomicroscopy (CLE) is an optical method that enables microscopic visualization of oral mucosa. Previous studies have shown that it is possible to differentiate between physiological and malignant oral mucosa. However, differences in mucosal architecture were not taken into account. The objective was to map the different oral mucosal morphologies and to establish a "CLE map" of physiological mucosa as baseline for further application of this powerful technology. MATERIALS AND METHODS: The CLE database consisted of 27 patients. The following spots were examined: (1) upper lip (intraoral) (2) alveolar ridge (3) lateral tongue (4) floor of the mouth (5) hard palate (6) intercalary line. All sequences were examined by two CLE experts for morphological differences and video quality. RESULTS: Analysis revealed clear differences in image quality and possibility of depicting tissue morphologies between the various localizations of oral mucosa: imaging of the alveolar ridge and hard palate showed visually most discriminative tissue morphology. Labial mucosa was also visualized well using CLE. Here, typical morphological features such as uniform cells with regular intercellular gaps and vessels could be clearly depicted. Image generation and evaluation was particularly difficult in the area of the buccal mucosa, the lateral tongue and the floor of the mouth. CONCLUSION: A physiological "CLE map" for the entire oral cavity could be created for the first time. CLINICAL RELEVANCE: This will make it possible to take into account the existing physiological morphological features when differentiating between normal mucosa and oral squamous cell carcinoma in future work.

Prevalence and implications of bilateral and solely contralateral lymph node metastases in oral squamous cell carcinoma.

OBJECTIVES: Effective management of neck in oral squamous cell carcinoma (OSCC) is pivotal for oncological outcomes. Although consensus exists for ipsilateral neck dissection (ND), the necessity for contralateral ND remains controversial. This study aimed to assess the prevalence and implications of bilateral/solely contralateral (B/SC) lymph node metastases (LNMs) to determine the need for contralateral elective ND. Additionally, it examined the prevalence and implications of occult B/SC metastases. MATERIALS AND METHODS: In a retrospective cohort study, 420 OSCC patients underwent primary surgical treatment following German guidelines at a tertiary center. Preoperative contrast-enhanced computed tomography was conducted, and ND adhered to a standardized approach. RESULTS: Solely contralateral metastases occurred in 0.95% of patients, with bilateral metastases observed in 7.13%. Occult B/SC metastases occurred in 3.81% of the cases. Correlation analysis revealed a statistically significant association between B/SC metastases and higher tumor stages, tumor localization at the upper jaw or floor of the mouth, proximity to the midline, ipsilateral LNMs, and lymphatic invasion (all p < 0.05). Patients with B/SC metastases showed poorer disease-free survival, with statistical significance reached in the bilateral LNMs group (p = 0.010). Similarly, a significant difference was noted in overall survival between patients with bilateral and solely ipsilateral metastases (p = 0.044). CONCLUSIONS: B/SC LNMs are rare in patients with OSCC, especially in those who present with clinico-radiologically negative ipsilateral necks. Higher rates of B/SC metastases occur in case of advanced tumors and those localized at the upper jaw or floor of the mouth. Ipsilateral LNMs significantly elevate the risk of contralateral LNMs, tripling the associated risk. CLINICAL RELEVANCE: These findings provide valuable insights for surgeons considering contralateral ND or extended adjuvant treatment for OSCC patients. However, the absence of high-level evidence from randomized controlled trials impedes the establishment of a definitive standard of care.

Clinical insights into traumatic injury of the inferior alveolar and lingual nerves: a comprehensive approach from diagnosis to therapeutic interventions.

OBJECTIVES: This scoping review explores the risk and management of traumatic injuries to the inferior alveolar and lingual nerves during mandibular dental procedures. Emphasizing the significance of diagnostic tools, the review amalgamates existing knowledge to offer a comprehensive overview. MATERIALS AND METHODS: A literature search across PubMed, Embase, and Cochrane Library informed the analysis. RESULTS: Traumatic injuries often lead to hypo-/anesthesia and neuropathic pain, impacting individuals psychologically and socially. Diagnosis involves thorough anamnesis, clinical-neurological evaluations, and radiographic imaging. Severity varies, allowing for conservative or surgical interventions. Immediate action is recommended for reversible causes, while surgical therapies like decompression, readaptation, or reconstruction yield favorable outcomes. Conservative management, utilizing topical anesthesia, capsaicin, and systemic medications (tricyclic antidepressants, antipsychotics, and serotonin-norepinephrine-reuptake-inhibitors), proves effective for neuropathic pain. CONCLUSIONS: Traumatic nerve injuries, though common in dental surgery, often go unrecorded. Despite lacking a definitive diagnostic gold standard, a meticulous examination of the injury and subsequent impairments is crucial. CLINICAL RELEVANCE: Tailoring treatment to each case's characteristics is essential, recognizing the absence of a universal solution. This approach aims to optimize outcomes, restore functionality, and improve the quality of life for affected individuals.

Expression of Inflammatory Mediators in Biofilm Samples and Clinical Association in Multiple Sclerosis Patients in Remission-A Pilot Study.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of unknown etiology that affects the central nervous system and can lead to neurological impairment. Our aim was to determine whether MS patients also show inflammatory changes in the oral cavity more frequently than healthy individuals. For this purpose, we examined plaque samples for various mediators and their correlation with clinical findings. A study group (MS) and a control group were examined and compared. The plaque samples were analyzed for the expression of interleukins (IL-2, -6, -10), matrix metalloproteinases (MMP-7, MMP-9), and a surface antigen CD90 by quantitative real-time PCR. The clinical parameters examined were the Mombelli plaque index; bleeding on probing (BOP) index; periodontal pocket depth; and decayed, missing, and filled tooth (DMFT) index. The expression of MMP9 was significantly (p = 0.035) higher in the control group. The expression of IL-2 was increased four-fold in the MS group; however, this difference was not statistically significant. The mean PD (p < 0.001) and BOP index (p = 0.029) values were increased in the study group. The clinical parameters of the BOP index and PD were significantly amplified in the MS patients. However, no causal relationship between the investigated inflammatory mediators and the clinical findings could be established in this case series.

Comparison of the prognostic value of lymph node yield, lymph node ratio, and number of lymph node metastases in patients with oral squamous cell carcinoma.

BACKGROUND: The aim of this study was to assess the prognostic significance of lymph node yield (LNY), lymph node ratio (LNR), and the number of lymph node metastases (LNMs) in patients affected by oral squamous cell carcinoma (OSCC). METHODS: The study included patients who underwent surgical treatment for primary OSCC. Receiver operating characteristic curves were generated to determine the optimal threshold values. Kaplan-Meier curves were employed, along with the log-rank test, for the analysis of survival. To compare the performance in terms of model fit, we computed Akaike's information criterion (AIC). RESULTS: This study enrolled 429 patients. Prognostic thresholds were determined at 22 for LNY, 6.6% for LNR, and 3 for the number of LNMs. The log-rank test revealed a significant improvement in both overall survival and progression-free survival for patients with a LNR of ≤6.6% or a number of LNMs of ≤3 (p < 0.05). Interestingly, LNY did not demonstrate prognostic significance. The AIC analyses indicated that the number of LNMs is a superior prognostic indicator compared to LNY and LNR. CONCLUSIONS: Incorporating LNR or the number of LNMs into the TNM classification has the potential to improve the prognostic value, as in other types of cancers. Particularly, the inclusion of the number of LNMs should be contemplated for future N staging.

Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer-Analyses of CD68, CD163, TGF-ß1, GLUT-1 and HIF-1α Expressions.

BACKGROUND: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in phase 2 trials. In this context, the addition of radio- and chemotherapy is being reconsidered. Therefore, a better understanding of the tumor-biologic effects of neoadjuvant RCT would be beneficial. The current study was conducted on a retrospective cohort of patients who received neoadjuvant RCT for the treatment of oral cancer. The aim of the study was to evaluate the influence of neoadjuvant RCT on the immunological tumor microenvironment (TME) and hypoxic and glucose metabolisms. METHODS: A cohort of 45 OSSC tissue samples from patients were analyzed before and after RCT (total 50.4 Gy; 1.8 Gy 5× weekly; Cisplatin + 5-Fluorouracil). Immunohistochemistry for CD68, CD163, TGF-ß, GLUT-1 and HIF-1α was performed using tissue microarrays and automated cell counting. Differences in expression before and after RCT and associations with histomorphological parameters (T-status, N-status) were assessed using the Mann-Whitney U test. RESULTS: Tumor resection specimens after neoadjuvant RCT showed a significant decrease in CD68 infiltration and a significant increase in CD163 cell density. The CD68/CD163 ratio was significantly lower after RCT, indicating a shift toward M2 polarization. The GLUT-1 and HIF-1α expressions were significantly lower after RCT. Larger tumors (T3/T4) showed a lower GLUT-1 expression. Other biomarkers were not associated with the T- and N-status. CONCLUSIONS: Neoadjuvant RCT with 50.4 Gy induced a shift toward the M2 polarization of macrophages in the TME. This change in immune composition is not favorable and may be prognostically negative and counteract immunotherapeutic approaches. In addition, the decreased expressions in GLUT-1 and HIF-1α indicate reductions in the glucose metabolism and hypoxic energy metabolism in response to "high dose" neoadjuvant RCT, which may be therapeutically desirable.

Airway management in a two-year-old child with a tongue tumor using video laryngoscope-assisted flexible bronchoscopic nasotracheal intubation (hybrid technique).

Airway management in children can be challenging. A hybrid technique using a video laryngoscope-assisted flexible bronchoscopic nasotracheal intubation allowed a successful airway management in a two-year-old child with a large tongue tumor.

Occult metastasis is no burden factor in oral squamous cell carcinoma patients when adhering to a standardized approach in neck dissection.

OBJECTIVES: Management of the neck in patients with oral squamous cell carcinoma (OSCC) is pivotal to oncologic control and survival. However, there is controversy regarding necessity of neck dissection (ND) in patients with clinically node-negative neck. We aimed to assess risk factors for occult metastasis and to explore whether the presence of occult lymph node metastases (LNMs) has an impact on recurrence and survival. MATERIAL AND METHODS: A retrospective cohort study was performed including patients with primary OSCC who underwent radical tumor resection and ND in a high-volume center adhering to the prevailing German guideline. The ND was performed according to a standardized approach. RESULTS: Four hundred twenty-one patients with primary surgically treated OSCC were included. The incidence of occult metastasis was 14.49%. A pathological T stage > 1 (multivariate analysis, odds ratio (OR) 3.958, p = 0.042) and the presence of extranodal extension in LNMs (multivariate analysis, OR 0.287, p = 0.020) were identified as independent risk factors for occult metastasis. When comparing patients with and without occult metastasis, there were no significant differences in terms of progression-free survival (log-rank, p = 0.297) and overall survival (log-rank, p = 0.320). There were no cases of ipsilateral neck recurrence. One patient developed contralateral neck metastasis; however, he initially presented with a unilateral pT1 pN0 tumor. CONCLUSIONS: Overall, our findings suggest that conducting a standardized approach in ND should be applied in terms of management of the neck in order to maintain survival rates and to prevent neck recurrence in OSCC patients. CLINICAL RELEVANCE: None of the risk factors for occult metastasis can be reliably assessed preoperatively. Although elective ND does not guarantee the complete prevention of neck recurrence, it increases the likelihood of either timely removal of micrometastases or strengthens the justification for adjuvant therapy. Consequently, this approach leads to improvements in clinical outcomes.

Comparison of the 7th and revised 8th UICC editions (2020) for oral squamous cell carcinoma: How does the reclassification impact staging and survival?

Since its introduction in 1968, the TNM (tumor, node, metastasis) classification established by the International Union Against Cancer has provided a consistent framework for staging of oral squamous cell carcinoma (OSCC). The introduction of the 8th edition in 2017 brought about significant modifications, encompassing the integration of depth of invasion (DOI) and extranodal extension (ENE) into the T and N classifications. Further, the UICC the criteria for the T3 and T4a categories were amended in 2020. This study aimed to evaluate the impact of reclassification on staging and, subsequently, the survival of patients with OSCC. Primary OSCCs from 391 patients were classified according to the 7th and revised 8th UICC editions (2020). Stage migration was assessed, and stage-specific progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The log-rank test was used to compare the different stages. Cox-proportional hazard modeling was used to compare the two editions. Incorporating the DOI into the T classification resulted in an upstaging of 77 patients, constituting 19.69% of the cohort. In addition, 49 (12.53%) patients experienced an upstaging when considering ENE in the N classification. Consequently, 103 patients underwent upstaging in UICC staging, accounting for 21.74% of cases. Upstaging mainly occurred from stage III to IVA (26.92%) and from stage IVA to IVB (31.78%). Upon comparing the categories in survival analysis, significant differences in OS and PFS were especially observed between stage IVB and lower stages. When examining the hazard ratios, it became evident that UICC 8 stage IVB is burdened by a 5.59-fold greater risk of disease progression than stage I. Furthermore, UICC 8 stage IVB exhibits a 3.83 times higher likelihood of death than stage I disease. We demonstrated significant stage migration from the 7th to the revised 8th UICC edition. Overall, incorporating DOI and ENE into the T and N classifications represents a substantial clinical advancement, leading to a more accurate staging of OSCC patients. Both staging systems exhibited statistically significant discrimination between stages; however, the 8th UICC edition allowed for a more precise categorization of patients based on their prognosis and led to enhanced hazard discrimination, particularly within higher stages.

Introducing a novel educational training programme in dental implantology for pregraduate dental students.

INTRODUCTION: This study aimed to determine whether implant surgery procedures can be implemented in the dental curriculum by designing novel courses for students. Additionally, this study assesses the perception of these courses and how they can be established in the future. MATERIALS AND METHODS: Students from the third to fifth years participated in a programme consisting of 4 modules according to their academic year. The modules taught theoretical and practical content as well as clinical references. After participating, the students completed two questionnaires with research questions (RQ1 = evaluation of the relevance and effects; RQ2 = impact of modules 3 and 4) to evaluate the programme. The questionnaires consisted of 52 statements, each rated on a 6-point scale (1 'totally disagree' to 6 'totally agree'). Cronbach's alpha analysis was used, and median values, interquartile ranges and Pearson correlations (p-value) were statistically calculated. RESULTS: In total, 94 students completed the questionnaires. Cronbach's alpha exceeded 0.7 for all constructs except for one (skills training). The highest evaluated median was 6, and the lowest was 4.75. Pearson correlations were significant (<0.05) for perceived importance/lectures, perceived importance/tutor performance, lectures/skills training, skills training/tutor performance and tutor performance/lectures. Seventeen analysed free comments expressed strong interest in implantology courses for the curriculum. 88% of the students wished for more practical exercises in dental implantology during the curriculum or suggested expanding the programme in the future. CONCLUSION: The programme was highly accepted among dental students. The students wished for more practice in the future to perform supervised procedures on patients.

MRI of Temporomandibular Joint Disorders: A Comparative Study of 0.55 T and 1.5 T MRI.

OBJECTIVES: Temporomandibular disorders (TMDs) are common and may cause persistent functional limitations and pain. Magnetic resonance imaging (MRI) at 1.5 and 3 T is commonly applied for the evaluation of the temporomandibular joint (TMJ). No evidence is available regarding the feasibility of modern low-field MRI for the assessment of TMDs. The objective of this prospective study was to evaluate the image quality (IQ) of 0.55 T MRI in direct comparison with 1.5 T MRI. MATERIALS AND METHODS: Seventeen patients (34 TMJs) with suspected intraarticular TMDs were enrolled, and both 0.55 and 1.5 T MRI were performed on the same day. Two senior readers independently evaluated the IQ focusing on the conspicuity of disc morphology (DM), disc position (DP), and osseous joint morphology (OJM) for each joint. We analyzed the IQ and degree of artifacts using a 4-point Likert scale (LS) at both field strengths. A fully sufficient IQ was defined as an LS score of ≥3. Nonparametric Wilcoxon test for related samples was used for statistical comparison. RESULTS: The median IQ for the DM and OJM at 0.55 T was inferior to that at 1.5 T (DM: 3 [interquartile range {IQR}, 3-4] vs 4 [IQR, 4-4]; OJM: 3 [IQR, 3-4] vs 4 [IQR 4-4]; each P < 0.001). For DP, the IQ was comparable (4 [IQR 3-4] vs 4 [IQR 4-4]; P > 0.05). A sufficient diagnostic IQ was maintained for the DM, DP, and OJM in 92% of the cases at 0.55 T and 100% at 1.5 T. Minor image artifacts (LS score of ≥3) were more prevalent at 0.55 T (29%) than at 1.5 T (12%). CONCLUSIONS: Magnetic resonance imaging of the TMJ at 0.55 T yields a lower IQ than does MRI at 1.5 T but maintains sufficient diagnostic confidence in the majority of patients. Further improvements are needed for reliable clinical application.

Prevalence of carotid artery calcification detected by different dental imaging techniques and their relationship with cardiovascular risk factors, age and gender.

BACKGROUND: Atherosclerosis and its secondary diseases display a major threat to patient's health. Sequelae, like carotid artery calcification (CAC), usually develop over decades and remain asymptomatic for a long time, making preventive measures to reduce mortality and morbidity extremely important. Through panoramic radiography (PR) and cone beam computed tomography (CBCT), dentists may have helpful tools in aiding the holistic care of patients. In this context, the correlation of atherosclerotic risk factors and CAC development have not yet been sufficiently investigated. Thus, the aim of this observational radiological study was to evaluate the diagnostic value of PR compared with CBCT for the detection of CAC in patients older than 60 years. The radiological findings were correlated with gender, age, and cardiac risk factors. METHODS: PRs and CBCTs of N = 607 patients were used for the qualitative analysis and compared. Basic patient information such as age, gender, body mass index (BMI), smoking history as well as patient's detailed medical history, including heart disease and cardiovascular risk factors such as hypercholesterolemia, arterial hypertension and diabetes mellitus type II were documented and their relation to CAC provided by radiological data was estimated in the form of odds ratios (OR), which were calculated using logistic regression models. Proportions of CAC in different risk groups were compared using Fisher's exact test, the significance level was set to α ≤ 0.05. The interrater reliability of two physicians was estimated using Cohen's kappa. RESULTS: With an accuracy of 90.6%, a sensitivity of 67.5% and a specificity of 99.5% compared to CBCT, PR was a reliable method for the diagnosis of CAC. The overall detection rate for CAC was 27.8% across all age groups. Age (OR: 1.351; p = 0.021), the male sex (OR: 1.645; p = 0.006), arterial hypertension (OR: 2.217; p = < 0.001), heart disease (OR: 1.675; p = 0.006), hypercholesterolemia (OR: 1.904; p = 0.003) and chronic obstructive pulmonary disease (OR: 2.016; p = 0.036) were statistically significant risk factors. When correlated, neither history of stroke nor nicotine abuse showed any statistical significance. CONCLUSIONS: Due to the capabilities of PR in the diagnosis of CAC, dentists can play a vital role in the early diagnosis of vascular disease. Awareness should therefore be raised among dentists regarding the detection of CAC in patients over 60 years of age, with a particular focus on those with arterial hypertension and hypercholesterolaemia.

A novel approach to microsurgical teaching in head and neck surgery leveraging modern 3D technologies.

The anatomically complex and often spatially restricted conditions of anastomosis in the head and neck region cannot be adequately reproduced by training exercises on current ex vivo or small animal models. With the development of a Realistic Anatomical Condition Experience (RACE) model, complex spatial-anatomical surgical areas and the associated intraoperative complexities could be transferred into a realistic training situation in head and neck surgery. The RACE model is based on a stereolithography file generated by intraoperative use of a three-dimensional surface scanner after neck dissection and before microvascular anastomosis. Modelling of the acquired STL file using three-dimensional processing software led to the model's final design. As a result, we have successfully created an economical, sustainable and realistic model for microsurgical education and provide a step-by-step workflow that can be used in surgical and general medical education to replicate and establish comparable models. We provide an open source stereolithography file of the head-and-neck RACE model for printing for educational purposes. Once implemented in other fields of surgery and general medicine, RACE models could mark a shift in medical education as a whole, away from traditional teaching principles and towards the use of realistic and individualised simulators.