Kobra Surgery Simulator-A Possibility to Improve Digital Teaching? A Case-Control Study.

Computer-aided simulations have long been of great importance in university teaching; however, to date, there is limited use of such simulations in the dental surgical sector. For this purpose, an oral surgery simulator, "Kobra", was implemented in student training and was evaluated for dental education. Dental students (group 1, third-year and group 2, fourth-year) and dentists of the faculty (control group) were trained to use the simulator. The outcomes for group 1 (apicoectomy of an upper lateral incisor with Kobra), group 2 (removal of an impacted lower wisdom tooth with Kobra) and the control group (both procedures with Kobra) were evaluated. For evaluation purposes, subjective parameters (improvement of practical skills, comparison between conventional training and Kobra simulation, and implementation of simulation-based teaching) and objective parameters (removal of bone, tooth substance and soft tissue measured while performing the Kobra simulation) were assessed using questionnaires with a scale ranging from 1-5. A total of 49 students (third-year n = 29, with 22 women and 7 men; fourth-year n = 20, with 17 women and 3 men) and 10 dentists (women n = 5 and men n = 5) participated. Compared to the Kobra simulation, the conventional training method with plastic models was still favored (the difference was non-significant). Compared to the dentists, the simulation data showed a less precise surgical performance of the students (the difference was not significant). The Kobra simulation may offer an additional method to conventional surgery training using plastic models, with benefits for students and faculty staff.

Lineage-associated connexin 43 expression in bisphosphonate-exposed rat bones.

Expression of signaling proteins in bone cells depends on their embryological mesoderm-derived (e.g. tibia) or cranial neural crest (CNC)-derived (e.g. jaw) origin. Connexin 43 (Cx43) is a gap junction protein that plays an essential role in the mode of action of bisphosphonates (BP). This study aimed to investigate Cx43 expression and the influence of BP application on mesoderm- and CNC-derived bone. Using a rat model, molar extraction and tibia osteotomy with (Group 4) or without (Group 3) previous BP application was performed. Untreated (Group 1) and animals selectively treated with BPs (Group 2) served as controls. Cx43 expression was immunohistochemically determined 12 and 16 weeks postoperatively via a labeling index. Cx43 expression in CNC-derived bone was significantly higher compared with mesodermal bone. BP application decreased Cx43 expression; however, detected expression levels were still higher in jawbone (Group 2 tibia vs jaw: 5.83 ± 5.06 vs 23.52 ± 6.42; p = 0.007). During bone healing after surgical intervention (Group 3) there were no expression differences between tibia and jawbone. BP treatment prior to surgery resulted in significantly lower Cx43 expression in CNC-derived compared with tibia bone (Group 4 tibia vs jaw: 56.84 ± 15.57 vs 16.40 ± 5.66; p < 0.01). Increased Cx43 expression in jaw compared with tibia bone is in line with their embryological origins. A significant Cx43 suppression in jawbone after BP application and surgery might contribute to the selectively altered osseous turnover and development of MRONJ in CNC-derived bone.

Endothelial inflammatory and thrombogenic expression changes in microvascular anastomoses - An immunohistochemical analysis.

The aim of this study was to investigate intraluminal vessel diameters and endothelial expression levels of pro-inflammatory and -thrombotic mediators in patent and non-patent microvascular anastomoses. Endothelial expression of CD31, VCAM-1, E- and P-Selectin, eNOS, iNOS and PAI-1 was evaluated by immunohistochemistry and compared to non-anastomosed arteries as controls. Intraluminal diameters were determined via H.E.-staining. In 20 human anastomoses (8 patent, 12 non-patent) neither the analysis of endoluminal de-endothelialization (p = 0.966) nor luminal narrowing (p = 0.750) revealed any significant differences between patent and non-patent microanastomoses. Expressions of pro-inflammatory mediators were significantly higher in patent anastomoses compared to controls but did not show any difference compared to non-patent anastomoses (p > 0.050). iNOS was higher in non-patent compared to patent anastomoses (p = 0.030) and controls (p = 0.001), whereas eNOS did not reveal any differences between these groups (p = 0.611 and p = 0.130). In non-patent anastomoses PAI-1 was expressed higher compared to patent anastomoses and controls (p = 0.021 and p < 0.001). Irrespective of their patency, anastomoses are characterized by endothelial dysfunction with a pro-inflammatory and pro-thrombotic milieu. Avoiding endothelial trauma during suturing is essential in order not to aggravate existing endothelial dysfunction in microanastomoses. Additionally, the influence of medication-related changes on anastomoses should be investigated as this is still an indistinctive topic.

Correction to: Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis.

Correction to: Strahlenther Onkol 2018 https://doi.org/10.1007/s00066-018-1382-3 The original version of this article unfortunately contained a mistake. The correct version of the Acknowledgements is given ….

Fluorescence-guided bone resection: A histological analysis in medication-related osteonecrosis of the jaw.

PURPOSE: Surgical treatment of medication-related osteonecrosis of the jaw (MRONJ) consists of necrotic bone removal followed by dense mucosal closure. Fluorescence-guided surgery has become a promising tool to intraoperatively distinguish between healthy and necrotic bone. Until now, there has been a lack of histopathological studies correlating the intraoperative fluorescence situation to histopathological analyses of the respective bone areas in order to further validate this method. MATERIALS AND METHODS: Histopathological sections from intraoperatively detected fluorescence- and non-fluorescence-labeled bone were analyzed detecting osteocyte and collagen content, RANK(L) and TRAP expression as well as proportion of immature bone regeneration. Samples were compared with viable-looking bone areas according to the intraoperative clinical situation. RESULTS: Staining revealed a significant decrease of osteocytes and collagen type-I fibers in necrotic, non-fluorescing areas compared to fluorescing bone (R/RGB [%]: 0.56 ± 0.38 (fluorescence positive) vs. 3.18 ± 2.22 (fluorescence negative), p = 0.041). Furthermore, the number of osteocytes was higher in fluorescing, clinically viable bone samples (cell/mm2: 151.26 ± 95.77 (fluorescence positive) vs. 0.56 ± 0.38 (fluorescence negative), p = 0.028). Additionally, the amount of immature bone was substantially increased in luminescent jaw bone (proportion of red [%]: 6.78 ± 7.00 (fluorescence positive) vs. 2.24 ± 1.36 (fluorescence negative), p = 0.442). RANK(L) and TRAP expression did not differ between the investigated areas, resembling a generalized decrease in osteocyte-osteoclast function all over the jaw (RANK(L) -positive cells per mm2: 8.97 ± 7.85 (fluorescence positive) vs. 7.76 ± 6.41 (fluorescence negative), p = 0.793; TRAP-positive cells per mm2: 0.36 ± 0.38 (fluorescence positive) vs. 0.33 ± 0.41 (fluorescence negative), p = 0.887). CONCLUSION: Intraoperative fluorescence-guided surgery might be more precise in identifying and resecting the necrotic bone compared to previous indicators like bone bleeding, which could be useful to further improve surgical therapy in MRONJ patients.

Collagen Matrix Vascularization in a Peri-Implant Vestibuloplasty Situation Proceeds Within the First Postoperative Week.

PURPOSE: Vestibuloplasty is a frequently performed surgical procedure to create or increase soft tissue mucosal sealing around dental restorations. Collagen matrices have exhibited comparable clinical results as free gingival grafts in the context of intraoral tissue augmentation. However, the process of matrix vascularization, the basic requirement for local healing, is incompletely understood. Therefore, this study investigated collagen matrix perfusion in a clinical intraoral setting. MATERIALS AND METHODS: In a prospective cohort study, vestibuloplasty was performed during implant exposure using prefabricated collagen matrices. Matric perfusion was determined intraoperatively and at days 2, 5, 7, 14, 30, and 90 using a laser Doppler spectrophotometer measuring oxygen saturation, relative amount of hemoglobin, blood flow, and blood velocity as primary outcome variables. These parameters were compared with perfusion of the oral mucosa surrounding the matrices. Statistical analysis was performed by applying variance and regression models. RESULTS: In 10 patients (average age, 60.9 yr), vestibuloplasty was performed exclusively in the anterior mandible. Blood flow and tissue oxygen saturation in the augmented zones markedly increased until postoperative day 5 and approximated perfusion values of the adjacent mucosa at the following 2 time points. Likewise, matrix oxygen saturation markedly increased until day 7 and subsequently converged to perfusion parameters of the surrounding mucosa at the following time points. CONCLUSION: Flow signals in incorporated collagen matrices occurred on day 2 after vestibuloplasty and further increased until days 5 to 7. Therefore, matrix perfusion mainly occurs within the first postoperative week, converging to perfusion levels of the surrounding mucosa with minimal alterations during the following course.

Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis.

BACKGROUND: Microvascular free flap reconstruction has become a standard technique in head and neck reconstructive surgery. Pre-operative radiotherapy is associated with a higher incidence of free flap malperfusion and the need for operative revision. Irradiated vessels present characteristic histomorphological and structural changes. Alterations in endothelial cells of irradiated arteries remain incompletely investigated especially with regard to long-term changes in endothelial dysfunction supporting an intraluminal pro-thrombotic and pro-inflammatory milieu. METHODS: Endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E­ and P­selectin, endothelial NO-synthase (eNOS), thrombomodulin and plasminogen activator inhibitor-1 (PAI-1) in irradiated and non-irradiated arteries was analysed using immunohistochemistry and Remmele scale grading. The average radiation dose was 58.7 ± 7.0 Gy; the time interval between end of radiation and tissue sampling was 106.0 ± 86.8 months. RESULTS: Endothelial expression of ICAM-1, VCAM-1, E­ and P­selectin as well as PAI-1 was significantly increased in previously irradiated arteries compared with non-irradiated controls, whereas thrombomodulin and eNOS expression did not show any differences. However, when comparing non-irradiated free flap arteries with irradiated arteries from the head and neck area in respective individuals, eNOS expression was significantly lower in irradiated vessels whereas ICAM-1, VCAM-1, E­/p-Selectin and PAI-1 showed significantly higher expression levels. CONCLUSION: There is ongoing endothelial dysfunction in terms of increased expression of pro-thrombotic and pro-inflammatory markers in irradiated arteries even years after radiotherapy. Treating this endothelial dysfunction might reduce the complication rates associated with microvascular free flap reconstructions in irradiated patients.

Galectin 3 expression in regional lymph nodes and lymph node metastases of oral squamous cell carcinomas.

BACKGROUND: Neck dissection is standard in surgical management of oral squamous cell carcinomas (oscc). However, the immunologic link between primary tumor and lymph nodes is insufficiently understood. Galectin 3 (Gal3) promotes M2 polarization of macrophages and contributes to immunosuppression. The current study analyzes the association between Gal3 expression in regional lymph nodes of oscc with histomorphologic parameters (T-, N-, L- Pn-stage, grading) of the primary tumor. Additionally, Gal3 expression is correlated with markers of macrophage polarization (M1 vs. M2). METHODS: Preoperative diagnostic biopsies (n = 26), tumor resection specimens (n = 34), tumor-free lymph nodes (n = 28) and lymph node metastases (n = 10) of T1/T2 oscc patients were immunohistochemically analyzed for Gal3 and macrophage marker (CD68, CD11c, CD163 and MRC1) expression. The number of positive cells and the expression ratios were quantitatively assessed. RESULTS: High Gal3 expression in tumor-free regional lymph nodes was significantly (p < 0.05) associated with increased tumor size. The epithelial compartment of lymph node metastases showed a significantly (p < 0.05) increased Gal3 expression compared to biopsies and tumor resection specimens. Cell density of M2 macrophages was significantly (p < 0.05) and positively correlated with the number of Gal3 expressing cells in lymph nodes and tumor specimens. CONCLUSION: Gal3 expression in regional lymph nodes might be associated with oscc progression. The increased Gal3 expression in regional lymph nodes of larger tumors underlines the need of immunomodulatory treatment concepts in early-stage oscc. Blocking of Gal3 might be a therapeutic option in oral cancer.

Correlation between pain and MRI findings in TMD patients.

INTRODUCTION: Magnetic resonance imaging has been established as the gold standard for assessment of the temporomandibular joint. Apart from an excellent assessment of the soft tissues it has the advantage not to expose the patient to ionizing radiation. There is a lack of literature concerning the correlation between pain intensity and radiological findings of the temporomandibular joint. Moreover there is the question of whether a progressive degeneration of the cartilaginous components is accompanied by an increasing degeneration of the osseous parts of the mandibular joint and vice versa. Therefore, this study aims at analyzing correlations between pain and radiological findings. Furthermore, the link between osseous and cartilaginous degeneration is studied. MATERIALS AND METHODS: 91 patients who attend our outpatient clinic for temporomandibular disorders are included in this prospective study. Apart from a detailed anamnesis and clinical examination - adapted to the Research Diagnostic Criteria for Temporomandibular Disorders -magnetic resonance imaging of both mandibular joints is performed. Pain intensity is measured using the visual analog scale. To assess and grade the radiological findings a classification system is established. The evaluation of the osseous components is based on the classification of osteoarthritis by Kellgren and Lawrence whereas the rating of the cartilaginous components is adapted to the Research Diagnostic Criteria for Temporomandibular Disorders. Correlations are verified by Spearman-Rho. RESULTS: 83,5% of all patients are female. Most of the time, both sides are affected (47.25%). Women state an average pain of 5.7 (±2.4), men 3.5 (±2.5). 182 discs are examined and assessed with our classification system. Most discs (n = 71) show no pathological changes. The majority of patients show no dislocation (n = 104). The most common forms of dislocation are anterior dislocations (n = 51). The majority of patients show no changes in the osseous component (n = 115). Weak to moderate correlations are found between disc and bone degeneration. Moderate to strong correlations are found between left and right TMJ. CONCLUSIONS: The classification system which is designed and applied during the study proves to be a reliable and practical Instrument. A standardized evaluation of pathologies concerning the temporomandibular joint is possible by using this system. Numerous patients attending our outpatient clinic do not show any signs of degenerative dysfunctions in the mandibular joints. Degenerations of the osseous components tend to be connected with degenerations of the cartilaginous components and vice versa. The question remains if in the future new procedures in imaging will be able to record pathologies not yet detected.

Treatment of enucleated odontogenic jaw cysts: a systematic review.

OBJECTIVES: In this systematic review, we aimed to assess the impact of filling or not filling enucleated odontogenic jaw cysts on bony defect consolidation. In terms of filling, we aimed to assess which is the best filling material based on current evidence. STUDY DESIGN: An electronic search was performed using PubMed, Embase, and MEDLINE databases with the logical operators: "odontogenic cysts" AND "jaw cysts" AND "treatment AND therapy." RESULTS: Thirteen studies with primary enucleation (6 with filling and 7 without filling) were included. In terms of filling, either synthetic bone substitutes or autologous bone were used. The primary outcome was bony regeneration judged by radiographic follow-up measurements. Two-dimensional (2-D) radiographic follow-up measurements (densitometry) revealed a bone density increase and comparable bone regeneration in both groups. CONCLUSIONS: Because of the low number of studies and the heterogeneity of the included data, evidence-based treatment recommendations cannot be given at this time. Also, outcomes based on 2-D measurements should be interpreted with caution. However, the following factors are suggested as having an impact on bony defect consolidation: defect size, defect configuration, the preservation of the periosteum, and localization (upper or lower jaw). Prospective comparable clinical studies with a 3-dimensional follow-up are needed.

Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts.

OBJECTIVES: Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts. MATERIALS AND METHODS: Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed. RESULTS: Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions. CONCLUSIONS: The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin. CLINICAL RELEVANCE: As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.

Galectin 3 expression in primary oral squamous cell carcinomas.

BACKGROUND: Immunologic factors can promote the progression of oral squamous cell carcinomas (oscc). The phylogenetic highly conserved protein Galectin 3 (Gal3) contributes to cell differentiation and immune homeostasis. There is evidence that Gal3 is involved in the progression of oscc and influences the regulation of macrophage polarization. Macrophage polarization (M1 vs. M2) in solid malignancies like oscc contributes to tumor immune-escape. However, the relationship between macrophage polarization and Gal3 expression in oscc is not yet understood. The current study analyzes the association between histomorphologic parameters (T-, N-, L- Pn-status, grading) and Gal3 expression resp. the ratio between Gal3 expressing cells and CD68 positive macrophages in oscc specimens. METHODS: Preoperative diagnostic biopsies (n = 26) and tumor resection specimens (n = 34) of T1/T2 oscc patients were immunohistochemically analyzed for Gal3 and CD68 expression. The number of Gal3 expressing cells and the ratio between CD68 and Gal3 expressing cells was quantitatively assessed. RESULTS: In biopsy and tumor resection specimens, the number of Gal3 positive cells as well as the Gal3/CD68 ratio were significantly (p < 0.05) higher in T2 oscc compared to T1 cases. In biopsy specimens, a significantly (p < 0.05) increased Gal3 expression and Gal3/CD68 ratio was associated with the progression marker lymph vessel infiltration (L1). Tumor resection specimens of cases with lymph node metastases (N+) had a significantly (p < 0.05) increased Gal3 expression. Additionally, a high Gal3/CD68 ratio correlated significantly (p < 0.05) with higher grading (G3) in tumor resection specimens. CONCLUSION: High Gal3 expression in oscc is associated with tumor size (T-status) and parameters of malignancy (N-, L-status, grading). Gal3 might contribute to M2 macrophage mediated local immune tolerance. Gal3 expression shows association with prognosis in oscc and represent a potential therapeutic target.

Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

PURPOSE: Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y­box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. MATERIALS AND METHODS: DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. RESULTS: DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. CONCLUSION: Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

Prognostic significance of altered miRNA expression in whole blood of OSCC patients.

Currently, there is a lack of blood markers for the detection of recurrent oral squamous cell carcinoma (OSCC). The present study aimed to investigate whether the aberrant expression of single microRNAs (miRNAs) in whole blood of patients could serve as a biomarker for persistent or recurrent OSCC. Whole blood of 2 groups of formerly treated OSCC patients was investigated by RT-qPCR for their circulating miRNA profiles. The R-OC group included patients with recurrence of OSCC (n=21) and the NR-OC group included patients without recurrence (n=21). Fold-changes and significance of the differences in miRNA expression levels between the groups were determined. A cut-off point (COP) for the discrimination between the R-OC and NR-OC groups was calculated and the significance between over/under expression of the miRNAs and the recurrence of malignancy was determined. Significant differences in the miRNA expression in whole blood of the R-OC and NR-OC groups were found. The levels of miR-3651 and miR-494 were significantly increased and the level of miR-186 was significantly decreased in whole blood of the R-OC patients (pmiR-3651=0.001, pmiR-494=0.003 and pmiR-186=0.001). By the determination of the COP, increased or decreased expression of the markers was significantly correlated to the recurrence of the disease. Altered expression of miR-494, miR-3651 and miR-186 appears to be associated with the recurrence of OSCC. The present study may form the basis for establishing a blood test as a minimally invasive method for the detection of the recurrence of OSCC.

Macrophage and osteoclast polarization in bisphosphonate associated necrosis and osteoradionecrosis.

PURPOSE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of antiresorptive therapy with nitrogen-containing bisphosphonates (BP). With various suggestions as to pathogenesis, the etiology of BRONJ is not sufficiently understood. Osteoclasts and their precursors, that is, macrophages, are the main target cells of BP. BP can repolarize regeneration- and healing-associated M2 macrophages towards the tissue destructive M1-type. The current study aims to elucidate differences in macrophage and osteoclast polarization in BRONJ, osteoradionecrosis (ORN) and healthy control specimens. MATERIALS AND METHODS: A total of 39 jaw bone samples (18 BRONJ, 8 ORN and 13 healthy controls) were processed for immunohistochemistry to detect CD68-, CD11c- and CD163-positive cells. Macrophages and osteoclasts were distinguished on the basis of morphological differences. Samples were digitized, and the macrophage and osteoclast cell counts were quantitatively analyzed. RESULTS: In jaw bone affected by BRONJ, a significantly increased macrophage infiltration and M1 polarization of macrophages can be seen. The density of CD68-expressing osteoclasts is significantly increased in BRONJ specimens compared to ORN and to healthy controls. CONCLUSIONS: A bisphosphonate-derived shift of macrophage polarization towards M1-polarized macrophages might impair bone tissue homeostasis and thus contribute to the pathogenesis of BRONJ. The observed increase in osteoclast density might be caused by BP-induced prolonged osteoclast survival.

PD-L1 expression in tumor tissue and peripheral blood of patients with oral squamous cell carcinoma.

BACKGROUND: Immune checkpoints like programmed cell death-1 (PD-1) and its ligand PD-L1 are involved in immune escape mechanisms of solid tumors including oral squamous cell carcinoma (OSCC). Inhibitors of the pathway are successfully used for treating especially advanced disease. However, the physiological relevance of PD-1/PD-L1-signaling in OSCC is insufficiently understood. The aim of the study was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples of OSCC patients is associated with histomorphological tumor parameters and if PD-L1 expression in patients is different from controls. RESULTS: OSCC tumor specimens showed a significantly higher PD-L1 expression than oral mucosa controls (p < 0.001; upregulation more than 3-fold). Cross-tabulation revealed an association of increased expression of PD-L1 mRNA in tissue specimens with malignancy (p < 0.001).OSCC cases with higher tumor grade and cases with lymph node metastases (N+) were significantly (p < 0.05) associated with increased PD-L1 expression in peripheral blood. Cross-tabulation revealed an significant association with lymph node metastases (N+) (p ≤ 0.002). MATERIALS AND METHODS: PD-L1 mRNA expression was analyzed in tumor specimens and corresponding samples of healthy oral mucosa and peripheral blood of 45 OSCC patients and 36 healthy control persons using RT-qPCR analysis. A Mann-Whitney U-test, a cut-off point analysis and a Chi-square test were carried out. CONCLUSIONS: PD-L1 expression in OSCC could contribute to the immunosuppressive local tumor microenvironment. Increased malignant behavior (higher tumor grade, positive nodal status) might be associated with PD-L1 mediated systemic immune tolerance. Thus, PD-L1 expression in peripheral blood might be an indicator of the existence of metastatic disease (N+) in OSCC.

The impact of different cone beam computed tomography and multi-slice computed tomography scan parameters on virtual three-dimensional model accuracy using a highly precise ex vivo evaluation method.

OBJECTIVES: Multi-slice computed tomography (MSCT) and cone beam computed tomography (CBCT) are indispensable imaging techniques in advanced medicine. The possibility of creating virtual and corporal three-dimensional (3D) models enables detailed planning in craniofacial and oral surgery. The objective of this study was to evaluate the impact of different scan protocols for CBCT and MSCT on virtual 3D model accuracy using a software-based evaluation method that excludes human measurement errors. MATERIAL AND METHODS: MSCT and CBCT scans with different manufacturers' predefined scan protocols were obtained from a human lower jaw and were superimposed with a master model generated by an optical scan of an industrial noncontact scanner. To determine the accuracy, the mean and standard deviations were calculated, and t-tests were used for comparisons between the different settings. RESULTS: Averaged over 10 repeated X-ray scans per method and 19 measurement points per scan (n = 190), it was found that the MSCT scan protocol 140 kV delivered the most accurate virtual 3D model, with a mean deviation of 0.106 mm compared to the master model. Only the CBCT scans with 0.2-voxel resolution delivered a similar accurate 3D model (mean deviation 0.119 mm). CONCLUSION: Within the limitations of this study, it was demonstrated that the accuracy of a 3D model of the lower jaw depends on the protocol used for MSCT and CBCT scans.

Soft tissue volume alterations after connective tissue grafting at teeth: the subepithelial autologous connective tissue graft versus a porcine collagen matrix - a pre-clinical volumetric analysis.

AIM: This study evaluates a porcine collagen matrix (CM) for soft tissue thickening in comparison to the subepithelial connective tissue graft (SCTG). MATERIAL AND METHODS: In eight beagle dogs, soft tissue thickening was performed at the buccal aspects of the upper canines (SCTG and CM). Impressions were taken before augmentation (i1), after surgery (i2), after one (i3), three (i4) and ten month (i5). Casts were optically scanned with a 3D scanner and each augmented region (unit of analysis) evaluated (primary outcome variable: volume increase in mm(3) ; secondary outcome variables: volume increase in percent, mean and maximum thickness increases in mm). RESULTS: 3D tissue measurements after surgery revealed a significant higher volume increase in the CM (86.37 mm(3)  ± 35.16 mm(3) ) than in the SCTG group (47.65 mm(3)  ± 17.90 mm(3) ). After 10 months, volume increase was non-significant between groups (SCTG:11.36 mm(3)  ± 9.26 mm(3) ; CM: 8.67 mm(3)  ± 13.67 mm(3) ). Maximum soft tissue thickness increase (i1-i5) was 0.66 mm ± 0.29 mm (SCTG) and 0.79 mm ± 0.37 mm (CM) with no significant difference. CONCLUSIONS: Ten months after soft tissue thickening, the CM is statistically non-inferior to the SCTG in terms of soft tissue volume and thickness increase. Further 3D studies are needed to confirm the data.

Prognostic significance of macrophage polarization in early stage oral squamous cell carcinomas.

BACKGROUND: Polarization of tumor infiltrating macrophages is associated with the prognosis of solid malignancies and correlates with the occurrence of lymph node metastases in oral squamous cell carcinomas (oscc). Early stage (T1/T2, N0) oscc are characterized by a good prognosis and can be cured by surgery. The postoperative regime usually contains no adjuvant radio-/chemotherapy. The current pilot study was conducted to elucidate whether macrophage polarization in tumor resection specimens and diagnostic biopsies of early stage oscc is associated with tumor outcome. METHODS: Patients with T1/T2, N0, and R0>5mm oscc without adjuvant therapy and 3-year follow-up after tumor resection were retrospectively selected. Tissue microarrays (TMA) containing diagnostic biopsies (n=17) and tumor resection specimens (n=17) were processed for immunohistochemistry in this pilot study to detect CD68-, CD11c-, CD163- and MRC1-positive macrophages. Samples were digitized, and the expression of macrophage markers was quantitatively analyzed. RESULTS: High infiltration of M2 polarized macrophages correlated with poor tumor outcome in early stage (T1/T2, N0) oscc. This correlation was observed in tumor resection specimens, but was also observed in diagnostic biopsies. M2 macrophage polarization in biopsies - but not in tumor resection samples - correlated with high scores in tumor grading. CONCLUSION: Macrophage polarization in early stage oscc is a potential prognostic marker for tumor outcome. The correlation of M2 polarized macrophages with tumor outcome can already be detected in the initial biopsies. Furthermore, M2 polarization of macrophages in biopsies is associated with an increased dedifferentiation.

Investigation of the interplay between plasma lipids and macrophage polarization in small oral squamous cell carcinomas with different outcome: A pilot study of 17 cases.

INTRODUCTION: Growing evidence suggests a correlation of alternative polarization of macrophages (M2) with a bad outcome of oral cancer. Macrophage polarization plays a significant role in the progression of hyperlipidemia and atherosclerosis, being influenced from plasma cholesterol. On the other hand plasma lipids have been studied epidemiologically as risk factors in carcinogenesis. Goal of our pilot study was the investigation of a possible association of plasma lipids with tumor outcome through their potential influence on macrophage polarization. MATERIALS AND METHODS: 17 patients with small pN0 OSCC with different clinical outcome, treated operatively without postoperative R(C)T constituted our patient collective. Plasma lipids (total cholesterol and triglycerides) were studied in relation to macrophage polarization (determined through the expression of CD68, CD11c, CD163 and MRC1 antibodies) and tumor outcome. RESULTS: Patients with pathological chronic course of either plasma cholesterol or triglycerides demonstrated an increased infiltration with alternatively polarized macrophages in their specimens. Patients with pathological chronic course of plasma cholesterol showed moreover a bad tumor outcome. CONCLUSION: A role of plasma lipids in the tumor outcome via alternative macrophage polarization could be assumed. A larger prospective study is needed to confirm our preliminary results.