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.

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.

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.

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.

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.

Diagnostic accuracy of contrast-enhanced computed tomography in assessing cervical lymph node status in patients with oral squamous cell carcinoma.

OBJECTIVE: Accurate preoperative prediction of lymph node (LN) status plays a pivotal role in determining the extension of neck dissection (ND) required for patients with oral squamous cell carcinoma (OSCC). This study aims to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) in detecting LN metastases (LNMs) and to explore clinicopathological factors associated with its reliability. METHODS: Data from 239 patients with primary OSCC who underwent preoperative CT and subsequent radical surgery involving ND were retrospectively reviewed. Suspicious LNs were categorized into three groups: accentuated (< 10 mm), enlarged (≥ 10 mm), and melted. Statistical analysis encompassing correlation and comparative analysis, and determination of sensitivity, specificity, PPV, and NPV were performed. RESULTS: Overall, sensitivity was significantly higher in the accentuated LNs group (83.54%) compared to the melted LNs group (39.24%, p < 0.05, t test). Conversely, specificity was significantly higher in the melted LNs group (98.19%) compared to the accentuated LNs group (55.15%, p < 0.05, t test). Accentuated LNs exhibited a false negative rate of 13.00%. False positive rates were 51.80%, 30.26% and 8.82%, respectively. Diagnostic accuracy for detecting LNMs in level IIa and IIb exceeded that of level III. Patients with solely accentuated LNs were more likely to have a small, well-differentiated tumor. However, no distinctions emerged in terms of the occurrence of T4 tumors among the three groups. CONCLUSION: CT proves sufficient to predict LNMs in patients with OSCC. Looking ahead, the potential integration of artificial intelligence and deep learning holds promise to further enhance the reliability of CT in LNMs detection. However, this prospect necessitates further investigation.

An ex vivo model for education and training of unilateral cleft lip surgery.

BACKGROUND: Unilateral cleft lip surgery is a complex procedure, and the outcome depends highly on the surgeon's experience. Digital simulations and low-fidelity models seem inadequate for effective surgical education and training. There are only few realistic models for haptic simulation of cleft surgery, which are all based on synthetic materials that are costly and complex to produce. Hence, they are not fully available to train and educate surgical trainees. This study aims to develop an inexpensive, widely available, high-fidelity, ex vivo model of a unilateral cleft lip using a porcine snout disc. METHODS: A foil template was manufactured combining anatomical landmarks of the porcine snout disc and the anatomical situation of a child with a unilateral cleft. This template was used to create an ex vivo model of a unilateral cleft lip from the snout disc. Millard II technique was applied on the model to proof its suitability. The individual steps of the surgical cleft closure were photo-documented and three-dimensional scans of the model were analysed digitally. Sixteen surgical trainees were instructed to create a unilateral cleft model and perform a unilateral lip plasty. Their self-assessment was evaluated by means of a questionnaire. RESULTS: The porcine snout disc proved highly suitable to serve as a simulation model for unilateral cleft lip surgery. Millard II technique was successfully performed as we were able to perform all steps of unilateral cleft surgery, including muscle suturing. The developed foil-template is reusable on any porcine snout disc. The creation of the ex vivo model is simple and inexpensive. Self-assessment of the participants showed a strong increase in comprehension and an eagerness to use the model for surgical training. CONCLUSIONS: A porcine snout disc ex vivo model of unilateral cleft lips was developed successfully. It shows many advantages, including a haptic close to human tissue, multiple layers, low cost, and wide and rapid availability. It is therefore very suitable for teaching and training beginners in cleft surgery and subsequently improving surgical skills and knowledge. Further research is needed to finally assess the ex vivo model's value in different stages of the curriculum of surgical residency.

Quantitative analysis of zirconia and titanium implant artefacts in three-dimensional virtual models of multi-slice CT and cone beam CT: does scan protocol matter?

OBJECTIVES: Artefacts from dental implants in three-dimensional (3D) imaging may lead to incorrect representation of anatomical dimensions and impede virtual planning in navigated implantology. The aim of this study was quantitative assessment of artefacts in 3D STL models from cone beam CT (CBCT) and multislice CT (MSCT) using different scanning protocols and titanium-zirconium (Ti-Zr) and zirconium (ZrO2) implant materials. METHODS: Three ZrO2 and three Ti-Zr implants were respectively placed in the mandibles of two fresh human specimens. Before (baseline) and after implant placement, 3D digital imaging scans were performed (10 repetitions per timepoint: voxel size 0.2 mm³ and 0.3 mm³ for CBCT; 80 and 140 kV in MSCT). DICOM data were converted into 3D STL models and evaluated in computer-aided design software. After precise merging of the baseline and post-op models, the surface deviation was calculated, representing the extent of artefacts in the 3D models. RESULTS: Compared with baseline, ZrO2 emitted 36.5-37.3% (±0.6-0.8) artefacts in the CBCT and 39.2-50.2% (±0.5-1.2) in the MSCT models. Ti-Zr implants produced 4.1-7.1% (±0.3-3.0) artefacts in CBCT and 5.4-15.7% (±0.5-1.3) in MSCT. Significantly more artefacts were found in the MSCT vs CBCT models for both implant materials (p < 0.05). Significantly fewer artefacts were visible in the 3D models from scans with higher kilovolts in MSCT and smaller voxel size in CBCT. CONCLUSIONS: Among the four applied protocols, the lowest artefact proportion of ZrO2 and Ti-Zr implants in STL models was observed with CBCT and the 0.3 mm³ voxel size.

An ex vivo model for education and training of bilateral cleft lip surgery.

BACKGROUND: Bilateral cleft lip surgery is very challenging and requires a high level of skill, knowledge and experience. Existing high-fidelity simulation models that can be used by novice cleft surgeons to gain experience and expand their knowledge are rare and expensive. In this study, we developed a bilateral cleft lip model using porcine snout discs, which are available anywhere and inexpensive. METHODS: Anatomic reference points of a patient with a bilateral cleft lip were superimposed with landmarks of the porcine snout disc on a foil template. The template was used to construct an ex vivo bilateral cleft lip model. Surgery was performed on the model according to Millard and the surgical steps were photodocumented analogous to two clinical cases of bilateral cleft lip surgery. The suitability of the model was further tested by twelve participants and evaluated using self-assessment questionnaires. RESULTS: The bilateral cleft lip ex vivo model made of a porcine snout disc proved to be a suitable model with very low cost and ease of fabrication, as the template is reusable on any snout disc. The Millard procedure was successfully performed and the surgical steps of the lip plasty were simulated close to the clinical situation. Regarding the nasal reconstruction, the model lacks three-dimensionality. As a training model, it enhanced the participants comprehension of cleft surgery as well as their surgical skills. All participants rated the model as valuable for teaching and training. CONCLUSIONS: The porcine snout discs can be used as a useful ex vivo model for bilateral cleft lip surgery with limitations in the construction of the nose, which cannot be realistically performed with the model due to anatomical differences with humans. Benefits include a realistic tissue feel, the simulation of a multi-layered lip construction, a wide and rapid availability and low cost. This allows the model to be used by novice surgeons also in low-income countries. It is therefore useful as a training model for gaining experience, but also as a model for refining, testing and evaluating surgical techniques for bilateral lip plasty.

Postoperative Changes in Systemic Immune Tolerance Following Major Oncologic versus Minor Maxillofacial Surgery.

BACKGROUND: There is increasing evidence of the benefits of adjuvant and neoadjuvant immunotherapy in the treatment of solid malignancies like oral squamous cell carcinoma (OSCC). To optimize (neo-)adjuvant treatment, the systemic immunomodulatory effects of tumor surgery itself need to be considered. Currently, there is little evidence on the immunological effects of major surgery, such as free microvascular flap reconstruction. The current study aims to analyze how and to what extent maxillofacial surgery affects systemic parameters of immune tolerance. METHODS: A total of 50 peripheral whole blood samples from patients (Group 1 (G1) = extensive OSCC surgery; Group 2 (G2) = free flap reconstruction without persistent malignant disease; Group 3 (G3) = minor maxillofacial surgery) undergoing surgery were included for real-time quantitative polymerase chain reaction (RT-qPCR) to examine changes in mRNA expression of the biomarkers IL-6, IL-10, FOXP3, and PD-L1. Blood samples were taken immediately before and after surgery as well as on the second, fourth, and tenth postoperative days. Differences in mRNA expression between groups and time points were calculated using statistical tests, including Mann-Whitney U-test and Pearson correlation analysis. RESULTS: Comparing postoperative expression of G1 and G3, there was a significantly higher PD-L1 expression (p = 0.015) in G1 compared to G3 and a significantly lower IL-6 (p = 0.001) and FOXP3 (p = 0.016) expression. Interestingly, IL-10 expression was higher pre- (0.05) and postoperative (p < 0.001) in G1 compared to G3. Additionally, in G1, there was a significant overexpression of IL-10 post-surgery compared to the preoperative value (p = 0.03) and a downregulated expression of FOXP3 between pre- and 2 d post-surgery (p = 0.04). Furthermore, there was a significant correlation between the duration of surgery and the perioperative expression changes of the analyzed biomarkers. As the duration of surgery increased, the expression of IL-10 and PD-L1 increased, and the expression of IL-6 and FOXP3 decreased. CONCLUSION: Extensive surgery in OSCC patients is associated with a transient shift toward postoperative systemic immune tolerance compared with patients undergoing minor surgery. However, even extensive surgery causes no signs of long-lasting systemic immunosuppression. The degree of immune tolerance that occurred was associated with the duration of surgery. This supports efforts to minimize the duration of surgery.

3D assessment of the nasolabial region in cleft models comparing an intraoral and a facial scanner to a validated baseline.

We aimed to validate the metric accuracy of a 3-dimensional (3D) facial scanner (FS) and an intraoral scanner (IOS) in capturing the nasolabial region in ex vivo unilateral cleft lip and palate (UCLP) models. The nasolabial region of 10 UCLP models was scanned using a 3D FS as well as an IOS and a previously validated stationary 3D scanner as a reference. Intraoral scan was performed directly on the UCLP models. In order to apply the FS on the models, they were embedded in a 3D printed sample face. Both test groups were aligned to the reference by applying a section-based best-fit algorithm. Subsequent analysis of the metric deviation from the reference was performed with a 3D analysis tool. Mean distance and integrated distance served as main parameters for surface and volume comparison. Point comparison served as an additional parameter. Statistical analysis was carried out using t-test for unconnected samples. Considering mean distance and integrated distance as main parameters for 3D evaluation of the scanner's accuracy, FS and IOS differ significantly in their metric precision in scanning the cleft model compared to the reference. The IOS proved to be significantly more accurate than the FS compared to the previously described stationary 3D scanner as reference and validated baseline. Further validation of the tested IOS and FS for 3D assessment of the nasolabial region is presented by adding the previously validated ATOS III Triple Scan blue light scanner as a reference. The IOS shows, compared to a validated baseline scan, significantly higher metric precision in experimental cleft model scanning. The collected data provides a basis for clinical application of the IOS for 3D assessment of the nasolabial region.

Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions - an in vivo experiment.

Purpose: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis. The aim of the present study was to compare the macrophage populations between the craniofacial and extracranial skeleton and to investigate the changes induced by zoledronate (Zol) application and surgical interventions. Materials and methods: An in vivo experiment was performed. 120 wistar rats were randomized to 4 groups (G1, G2, G3, G4). G1 served as an untreated control group. G2 and G4 received Zol injections for 8 weeks. Afterwards, the right lower molar of the animals from G3 and G4 was extracted and the right tibia osteotomized followed by osteosynthesis. Tissue samples were taken from the extraction socket and the tibia fracture at fixed time points. Immunohistochemistry was conducted to determine the labeling indexes of CD68+ and CD163+ macrophages. Results: Comparing the mandible and the tibia, we observed a significantly higher number of macrophages and a heightened pro-inflammatory environment in the mandible compared to the tibia. Tooth extraction caused an increase of the overall number of macrophages and a shift toward a more pro-inflammatory microenvironment in the mandible. Zol application amplified this effect. Conclusion: Our results indicate fundamental immunological differences between the jaw bone and the tibia, which might be a reason for the unique predisposition for MRONJ in the jaw bones. The more pro-inflammatory environment after Zol application and tooth extraction might contribute to the pathogenesis of MRONJ. Targeting macrophages might represent an attractive strategy to prevent MRONJ and improve therapy. In addition, our results support the hypothesis of an anti-tumoral and anti-metastatic effect induced by BPs. However, further studies are needed to delineate the mechanisms and specify the contributions of the various macrophage phenotypes.

A Treatment Approach for Carotid Blowout Syndrome and Soft Tissue Reconstruction after Radiotherapy in Patients with Oral Cancer: A Report of 2 Cases.

BACKGROUND: This retrospective case series study aims to demonstrate a salvage technique for the treatment of carotid blow-out syndrome (CBS) in irradiated head and neck cancer patients with a vessel-depleted neck. METHODS: Between October 2017 and October 2021, two patients (N = 2) with CBS were treated at our institution in a multidisciplinary approach together with the Department of Vascular Surgery. Patients were characterized based on diagnoses, treatment procedures, and the subsequent postoperative course. RESULTS: Surgical emergency intervention was performed in both cases. The transition zone from the common carotid artery (CCA) to the internal carotid artery (ICA) was resected and reconstructed with a xenogic (case 1) or autogenic (case 2) interposition (end-to-end anastomosis). To allow reconstruction of the vascular defect, an additional autologous vein graft was anastomosed to the interposition graft in an end-to-side technique, allowing arterial anastomosis for a free microvascular flap without re-clamping of the ICA. Because of the intraoperative ICA reconstruction, none of the patients suffered a neurological deficit. CONCLUSIONS: The techniques presented in the form of two case reports allow for acute bleeding control, cerebral perfusion, and the creation of a vascular anastomosis option in the vessel-depleted neck.

Systematic review of craniofacial osteosarcoma regarding different clinical, therapeutic and prognostic parameters.

Background: Osteosarcomas are the most common primary bone tumor while occurrence in the craniofacial skeleton is relatively rare. There are clinical differences of osteosarcomas regarding their location. In this regard craniofacial osteosarcomas (COS) have special characteristics. Extracranial osteosarcomas (EOS) occur mainly in the long bones of the extremities (tibia, humerus and femur). These tumors metastasize hematogenically at a very early stage. In comparison, COS are mainly localized in the mandible and maxilla, occur later in life and show significantly less and later metastasis and respond differently to adjuvant therapy. In the literature, clinical characteristics of COS and EOS are rarely compared directly. The aim of this systematic review is to answer the question whether COS and EOS exhibit fundamentally different clinical behavior and how they differ in terms of survival rates and response to different therapies. Methods: A systemic review was performed. Pubmed, Cochrane and Google Scholar were used as search engines. The literature research was done by using clearly defined terms and their links. 124 full texts were selected and evaluated for this review. The inclusion criteria were determined using the PICO model. Results: COS have significantly better survival rates, especially if they are located in the jawbone. Surgical R0 resection is crucial for therapeutic success. The study situation regarding the benefit of neoadjuvant chemotherapy in COS is very inhomogeneous. There is also no evidence for the benefit of adjuvant radio- or chemotherapy in COS. The large heterogeneity of the studies in terms of therapeutic concept, initial situation of the patients and outcome considered, as well as the small number of patients with craniofacial osteosarcoma were limiting factors. Conclusion: The results of this study show the clear therapeutic and prognostic differences between COS and EOS and underline the necessity to consider both types of osteosarcoma as independent tumor entities in future studies. Furthermore, the study highlights the importance of surgical R0 resection for the prognosis of COS patients. There is no evidence for therapeutic benefit of adjuvant/neoadjuvant radio-/chemotherapy in R0 resected COS cases.

The Immune Checkpoint Receptor CD96: A Local and Systemic Immune Modulator in Oral Cancer?

Background: As immunotherapy of oral squamous cell carcinomas (OSCCs), using PD1 inhibitors, is only efficient in a small proportion of patients, additional immune checkpoints need to be identified as potential therapeutic targets. There is evidence that a blockade of CD96 might positively affect the anti-tumor immune response. The aim of this study was to analyze the gene and protein expression of CD96 in the tissue and peripheral blood of OSCC patients compared to healthy controls, while also checking for potential associations with a differential expression to the histomorphological parameters. In addition, possible correlations with the expression of PD1 and PD-L1 as well as the macrophage markers CD68 and CD163 should be tested to obtain further insights into the potential effectiveness of combined checkpoint blockage. Material and Methods: For real-time quantitative polymerase chain reaction (RT-qPCR), a total of 183 blood and tissue samples, divided into a patient and a control group, were included. Additionally, 141 tissue samples were examined by immunohistochemistry (IHC). The relative expression differences between the groups were calculated using statistical tests including the Mann-Whitney U test and AUC method. The Chi-square test was used to determine whether CD96 overexpression in individual samples is associated with malignancy. Correlation analysis was performed using the Spearman correlation test. Results: There was a significant CD96 mRNA and protein overexpression in the OSCC group compared to the controls (p = 0.001). In contrast, CD96 mRNA expression in the peripheral blood of the OSCC patients was significantly lower compared to the control group (p = 0.007). In the Chi-square test, the OSCC tissue samples showed a highly significant upregulation of CD96 mRNA expression (p < 0.001) and protein expression (p = 0.005) compared to the healthy mucosa. CD96 mRNA and protein expression correlated significantly (p = 0.005). In addition, there was a significant positive correlation of CD96 expression with PD1 (p ≤ 0.001), PD-L1 (p ≤ 0.001), and CD163 (p = 0.006) at the mRNA level. Conclusions: CD96 expression in the tumor tissue and peripheral blood of OSCC patients is differentially regulated and appears to be a relevant immune checkpoint.

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

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