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The aim of this study was to investigate if bone regeneration can be promoted by homologous transplantation of STRO-1 sorted (STRO-1+) porcine tooth germ mesenchymal stem cells (TGSCs) with the combination of polyethylenglycol (PEG)-based hydrogel and biphasic calcium phosphate (BCP) scaffolds. TGSCs were isolated from impacted third molars of domestic pigs. Nine critical-sized defects were created as (1) untreated defect; filled with (2) autogenous bone; (3) BCP + PEG; (4) BCP + PEG + unsorted TGSCs; (5) BCP + unsorted TGSCs; (6) BCP + PEG + STRO-1-sorted TGSCs; (7) BCP + STRO-1-sorted TGSCs; (8) BCP + PEG + osteogenic induced unsorted TGSCs; and (9) BCP + PEG + osteogenic induced STRO-1-sorted TGSCs in 20 domestic pigs. CM-DiI labelling was used to track cells in vivo. Histomorphometric assessment of new bone formation was achieved by toluidine blue O staining and microradiography after 1, 2, 4 and 12 weeks posttransplantation. Complete healing was achieved in all defects although defects with PEG hydrogel presented better bone formation while STRO-1+ and unsorted TGSCs showed similar ability to form new bone after 12 weeks. Transplanted cells were seen in defects where PEG hydrogel was used as carriers in contrast to defects treated with cells and only bone grafts. PEG hydrogel is an efficient carrier for homologous stem cell transplantation. TGSCs are capable of promoting bone healing in critical-sized defects in combination with bone graft and PEG hydrogel. This study provides information about the importance of the delivery vehicle for future translational stem cell delivery approaches.

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.

Background Various causes for bone defects of the lower jaw have been described. As a result, patients often suffer from compromised aesthetics and a loss of, or reduction in, important physiological functions, such as swallowing, breathing, and speaking. A change in the shape of the lower jaw can impair the natural occlusion and leads to an atypical or modified position of the temporomandibular joint. Titanium reconstruction plates are the standard approach to jaw reconstruction, and are used for temporary bridging of a jaw defect or fixation of a bone graft. Conventionally these plates are intraoperatively adjusted to the mandible by the surgeon. Computer-aided manufacturing, computer-aided design, and rapid prototyping have gained increasing importance in the field of medicine, as they allow the production of individual models of the lower jaw, with the possibility of preoperatively bending the reconstruction plates. In this retrospective study, the accuracy of pre-bent titanium plates and their effect on the temporomandibular joint situation in comparison with intraoperatively curved plates will be discussed. Materials and Methods Patients who attended our department for lower jaw reconstruction between March 2013 and February 2015 were included in this retrospective study. Within that time 20 patients were treated with pre-bent reconstruction plates (group 1). 20 comparable patients were selected with reconstruction and conventional intraoperative bending (group 2). To evaluate the accuracy of the plates and the condylar position, postoperative cone beam computed tomograms and computed tomograms were used to assess the bone–plate distance at 12 defined points and four angles in axial reconstruction. The results were compared, statistically evaluated, and discussed. Results Regarding the maximum bone–plate distances and the sum of distances, there was a significant difference between the accuracy of the pre-bent and the conventionally bent reconstruction plates (p = 0.022, p = 0.048). Regarding the condylar position, there was no significant difference between both methods (p = 0.867). Conclusion The results of this study show that a better fitting accuracy can be achieved using pre-bent plates. Preparation of the plates proves to be advantageous and meaningful, especially in complex bone defects and deformations of the lower jaw. Nevertheless, concerning the position of the temporomandibular joint, no significant difference could be ascertained between the shown methods, contradicting several studies.

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.Endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E‑ and P‑selectin, 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.Endothelial expression of ICAM-1, VCAM-1, E‑ and P‑selectin 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.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.HINTERGRUND: Freie mikrovaskuläre Transplantate stellen heute ein Standardverfahren in der rekonstruktiven Kopf-Hals-Chirurgie dar. Eine vorausgegangene Bestrahlung ist hierbei mit einer höheren Rate an transplantatbezogenen Durchblutungsstörungen und operativen Revisionen assoziiert. Bestrahlte Gefäße weisen charakteristische histomorphologische und strukturelle Änderungen auf. Die Veränderungen der Endothelzellen bestrahlter Gefäße sind bislang unvollständig verstanden. Dies trifft v. a. für die langfristige endotheliale Dysfunktion zu, die mit einem prothrombotischen und -inflammatorischen intraluminalen Milieu einhergeht.Bestrahlte und unbestrahlte Arterien wurden für eine immunhistochemische Untersuchung herangezogen, um die Expression von ICAM-1 („vascular cell adhesion molecule-1“), VCAM-1 („intercellular adhesion molecule-1“), E‑ und P‑Selectin, eNOS („endotheliale NO-Synthase“), Thrombomodulin sowie PAI-1 („plasminogen activator inhibitor-1“) via Remmele-Score zur Graduierung der Färbeintensität und der Endotheloberfläche zu bestimmen. Die durchschnittlich verabreichte Strahlendosis lag bei 58,7 ± 7,0 Gy, der mittlere Zeitraum nach Bestrahlung bis zur Probenentnahme betrug 106,0 ± 86,8 Monate.Die endotheliale Expression von ICAM-1, VCAM-1, E‑ und P‑Selectin sowie PAI-1 war in bestrahlten Arterien signifikant erhöht im Vergleich zu unbestrahlten Kontrollen, wohingegen Thrombomodulin und eNOS keine Veränderungen zeigten. Im Vergleich nichtbestrahlter Transplantatarterien und bestrahlter Arterien aus der Kopf-Hals-Region bei entsprechenden Personen zeigte sich die eNOS-Expression signifikant erniedrigt in bestrahlten Gefäßen, während ICAM-1, VCAM-1, E‑/P-Selectin und PAI-1 signifikant höher exprimiert waren.Noch mehrere Jahre nach einer Bestrahlung zeigt sich eine persistierende endotheliale Dysfunktion im Sinne einer verstärkten Expression prothrombotischer und -inflammatorischer Marker im Lumen bestrahlter Arterien. Die gezielte Behandlung dieser Dysfunktion könnte dazu beitragen, die Komplikationsrate bei mikrovaskulären Rekonstruktionen bestrahlter Patienten in Zukunft zu reduzieren.

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.

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 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.

Purpose Safety checklists in medicine have been shown to be effective in the prevention of complications and adverse events in patients undergoing surgery. Such checklists are not as common in dentistry. The aims of this study were to propose a safety checklist for the ambulatory treatment of patients undergoing oral and implant surgery and to assess its impact on patient safety and staff satisfaction. Materials and Methods After implementation of a surgical safety checklist in the ambulatory treatment of patients undergoing oral and implant surgeries, a questionnaire regarding staff satisfaction and safety-related parameters was randomly administered. Incidents, complications, and adverse events were documented. Outcomes with (n = 40 surgeries) and without (n = 40 surgeries) use of the checklist were analyzed and compared. Results Staff reported high satisfaction with the use of the checklist, which demonstrably improved team communication and lowered stress levels during surgery. There was a statistically significantly higher frequency of reported incidents without the use of the checklist (n = 43) than with the use of the checklist (n = 10; P = .000). Most incidents were reported in the context of pre- and post-procedural processes. Conclusions Safety checklists help to improve work processes, optimize communication, and lower stress levels. Their use in clinical dental practice is recommended.

PURPOSE Soft tissue interactions with ceramic dental implants have previously been shown to have favorable esthetic outcomes. This study aimed to evaluate the papilla-crown proportion around zirconia implants in a 3-year follow-up study and the correlation between the gingival biotype and changes in papillary height. MATERIALS AND METHODS This was a prospective study of 39 patients with 40 single-gap implants (Straumann PURE Ceramic ZLA Implant). The papilla-crown proportion was assessed after 3 months, 1 year, and 3 years. In addition, correlations between the peri-implant biotypes and changes in papillary heights were evaluated. RESULTS The papilla-crown proportion improved from 35.5% after 3 months to 41.7% after 3 years. The gingival biotype was correlated very weakly to papilla height alterations. Significant papillary fill was observed in the interdental space between 3 months and 3 years (p < 0.001). CONCLUSIONS An ideal papilla-crown proportion of 40% around single implants was observed after 3 years. A thin or thick gingival biotype showed a very weak correlation with soft tissue alterations.

Aims: Complete maxillary edentulism and prosthetic rehabilitation with removable full dentures are known to affect speech intelligibility. The aim of this study was to prospectively investigate the long-term effect of time on speech intelligibility in patients being rehabilitated with newly fabricated full maxillary dentures. Materials and Methods: Speech was recorded in a group of 14 patients (male = 9, female = 5; mean age ± standard deviation [SD] = 66.14 ± 7.03 years) five times within a mean period of 4 years (mean ± SD: 47.50 ± 18.16 months; minimum/maximum: 24/68 months) and in a control group of 40 persons with healthy dentition (male = 30, female = 10; mean age ± SD = 59 ± 12 years). All 14 participants had their inadequate removable full maxillary dentures replaced with newly fabricated dentures. Speech intelligibility was measured by means of a polyphone-based speech recognition system that automatically computed the percentage of accurately spoken words (word accuracy [WA]) at five different points in time: 1 week prior to prosthetic maxillary rehabilitation (both with and without inadequate dentures in situ) and at 1 week, 6 months, and a mean of 48 months after the insertion of newly fabricated full maxillary dentures. Results: Speech intelligibility of the patients significantly improved after 6 months of adaptation to the new removable full maxillary dentures (WA = 66.93% ± 9.21%) compared to inadequate dentures in situ (WA = 60.12% ± 10.48%). After this period, no further significant change in speech intelligibility was observed. After 1 week of adaptation, speech intelligibility of the rehabilitated patients aligned with that of the control group (WA = 69.79% ± 10.60%) and remained at this level during the examination period of 48 months. Conclusion: The provision of new removable full maxillary dentures can improve speech intelligibility to the level of a healthy control group on a long-term basis.

Objectives This study aimed to assess the impact of different abutment materials on peri-implant tissue regeneration after surgical treatment of peri-implantitis in a large animal model. Material and Methods Titanium implants ( n = 51) were inserted in the upper and lower jaw of eight beagle dogs and a peri-implant infection was induced. After two months the peri-implant infection was surgically treated and abutments with different surfaces (Ti-2: n = 14; CoCrMb: n = 13; Ag-modified Ti-4: n =14; Ti-4 control: n = 10) were applied. Clinical attachment level (CAL), modified sulcus bleeding index (mBI), bleeding on probing (BoP), and the sulcus fluid flow rate (SFFR) were determined 4, 8, and 12 weeks after surgical treatment to document the peri-implant tissue reaction. Results Superior levels for CAL and mBI were found with the Ti-4 control and the Ag-modified abutments, with the Ag-modified abutments showing the best values after 12 weeks. Lowest SFFR values compared with the other treatment groups underlined the superior soft tissue reaction adjacent to Ag-modified abutments. After 12 weeks inferior CAL, SFFR, BOP and mBI values were documented for the Ti-2 surface. Conclusion Within limitations of the study, Ag-modified abutments lead to superior tissue reactions. Further studies are needed to investigate the properties of abutment materials.

Compared to conventional techniques, Laser surgery procedures provide a number of advantages, but may be associated with an increased risk of iatrogenic damage to important anatomical structures. The type of tissue ablated in the focus spot is unknown. Laser-Induced Breakdown-Spectroscopy (LIBS) has the potential to gain information about the type of material that is being ablated by the laser beam. This may form the basis for tissue selective laser surgery. In the present study, 7 different porcine tissues (cortical and cancellous bone, nerve, mucosa, enamel, dentine and pulp) from 6 animals were analyzed for their qualitative and semiquantitative molecular composition using LIBS. The so gathered data was used to first differentiate between the soft- and hard-tissues using a Calcium-Carbon emission based classifier. The tissues were then further classified using emission-ratio based analysis, principal component analysis (PCA) and linear discriminant analysis (LDA). The relatively higher concentration of Calcium in the hard tissues allows for an accurate first differentiation of soft- and hard tissues (100% sensitivity and specificity). The ratio based statistical differentiation approach yields results in the range from 65% (enamel-dentine pair) to 100% (nerve-pulp, cancellous bone-dentine, cancellous bone-enamel pairs) sensitivity and specificity. Experimental LIBS measuring setup.

The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains unknown, and the development of a reliable experimental model would help to improve our understanding of it. We used 12 domestic pigs of which 6 made up the experimental group and were treated with zoledronate 4mg intravenously weekly for 5 weeks, while the control group (n=6) were given no drugs. On day 60 the right second maxillary and mandibular third molars were extracted. Thirty days later 3 animals in each group were killed; the rest were killed 90 days later. Histopathological specimens from the extraction sites were analysed for bone density, collagen architecture, density of osteons, and the amount of non-mineralised bone. Bone density, amount of non-mineralised bone, and density of osteons differed significantly between the 2 groups (p0.001 in each case), but the chromatic pattern dictated by the collagen architecture did not. Our results correspond to the observations that have been made in patients with BRONJ, which means that the histomorphometric conditions seen in patients can be reproduced in this experimental setting.

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.

Objectives The study aims to establish a peri-implant dehiscence-type bone defect in a diabetic animal model of human bone repair and to quantify the influence of diabetes on peri-implant bone regeneration. Material and methods Experimental diabetes was induced in three domestic pigs by streptozotocin. Three animals served as healthy controls. After 12 months four standardized peri-implant dehiscence bone defects were surgically created in the ramus mandibulae. The animals were sacrificed after 90 days. Samples were histologically analyzed to quantify new bone height (NBH), bone-to-implant-contact (BIC), area of newly formed bone (NFB), bone-density (BD), and bone mineralization (BM) in the prepared defect (-D) and in a local control region (-L). Results After 90 days, diabetic animals revealed a significantly lower BIC ( p = 0.037) and BD ( p = 0.041) in the defect area (-D). NBH and BM-D differences within the groups were not significant ( p > 0.05). Significant more NFB was measured in the healthy control group ( p = 0.046). In the region of local bone BIC-L was significant less in the diabetic group ( p = 0.028). In the local control region BD-L and BM-L was lower in the diabetic group compared to the healthy control animals ( p > 0.05). Conclusion Histological evidence indicates impaired peri-implant defect regeneration in a diabetic animal model.

Hintergrund: In den letzten Jahren werden vermehrt die Beziehungen zwischen operativer Tumortherapie und Inzidenz von Angstlichkeit und Depressionen diskutiert. Diese prospektive Studie ist ein Vergleich zwischen der Einschrankung der Sprachverstandlichkeit nach der Behandlung von Mundhohlentumoren und der Anzeichen von Depressivitat und Angstlichkeit. Material und Methoden: Bei 90 Patienten im Alter von 60±12 Jahren nach Behandlung von Mundhohlenkarzinomen wurde ein Jahr postoperativ der Verstandlichkeitsgrad standardisiert mittels automatischer Spracherkennung bestimmt (Worterkennungsrate, WR). Mogliche Anzeichen von Depressivitat und Angstlichkeit wurden mittels des Fragebogens Hospital-Anxiety-and-Depression-Scale (HADS) erfasst. Die Beziehungen zwischen WR und HADS und der Einflussgrosen wurden statistisch analysiert. Ergebnisse: Der WR-Mittelwert lag bei 53,2±17,2. Der Unterschied in der WR zwischen den Tumorklassen T1 und T4 war signifikant. Frauen zeigten eine hohere WR als Manner. Weitere signifikante Unterschiede gab es bei WR-Vergleichen innerhalb der Gruppen „Tumorlokalisation“, „Transplantatentnahmestelle“, „Transplantatmorphologie“, „Zungenbeweglichkeitsgrade“ und „Tracheostoma“. Fur die Zungenbeweglichkeit bestanden Interaktionen mit der Transplantatmorphologie, Transplantatentnahmeregion und Tumorlokalisation. Die HADS-Werte waren im Mittel erhoht: HADS-Total=43,3%, HADS-A=43,3% und HADS-D=51,1%. Es bestand eine Korrelation fur die WR mit den HADS-D-Scores, aber nicht mit den HADS-A-Scores. Schlussfolgerungen: Kommunikationseinschrankungen nach chirurgischer Tumortherapie im Orofazialbereich konnen von dem Ausmas der Behandlungsmasnahmen abhangen und mit depressiver Beeintrachtigung im Zusammenhang stehen. Dies sollte im Rehabilitationskonzept beachtet werden.

Background The purpose of this study was to evaluate risk factors that influence overall survival (OS)/disease-free survival (DFS)/locoregional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS) in patients with high-risk primary salivary gland carcinoma who underwent surgery and postoperative (chemo)radiotherapy with curative intention. Methods We reviewed data of 63 patients with high-risk primary salivary gland carcinoma in a retrospective single-center audit. Results At a median follow-up of 31 months (range, 5–145 months), cumulative OS and DFS were 91.7%, 77.6%, and 62.9%, and 82.1%, 65.6%, and 57.7%, respectively, after 1, 2, and 5 years. LRFS and DMFS were 92%, 86%, and 86%, and 83.4%, 70.4%, and 62.3% after 1, 2, and 5 years, respectively. Of all patient-related, tumor-related, and treatment-related factors, high-grade histology (G3) was the only factor in univariate and multivariate analysis that was predictive for a shorter DMFS (low/intermediate vs high-grade: 100%, 100%, and 89.4% vs 72.9%, 54.3%, and 42.8% after 1, 2, and 5 years, respectively) and a shorter DFS (low/intermediate vs high-grade: 100%, 90%, and 84.4% vs 71.2%, 50.1%, and 39.4% after 1, 2, and 5 years, respectively) and OS (low/intermediate vs high-grade: 100%, 100%, and 86.5% vs 86.5%, 63.2%, and 46.5% after 1, 2, and 5 years, respectively). Conclusion High-grade tumor histology is a highly significant predictor of a shorter DMFS, OS, and DFS in salivary gland carcinoma, irrespective of histological subtype. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Summary 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 > 5 mm 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.

Even though increasing knowledge is emerging about synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome its pathogenesis remains enigmatic. Women are preferentially affected by SAPHO syndrome. Here we present the case of a 39-year-old woman suffering from this syndrome whose bone involvement was first interpreted as diffuse sclerosing osteomyelitis of the mandible. As treatment with clindamycin did not improve the symptoms, the decision was made to administer bisphosphonates intravenously. This treatment led to a rapid improvement in symptoms, which could be explained by the apparent tendency of bisphosphonates to exert a positive effect on the jaw. With this case report we attempt to offer an explanation for the influence of this group of medications on patients suffering from SAPHO syndrome with mandibular involvement.

Objectives Three-dimensional radiological imaging data play an increasingly role in planning, simulation, and navigation in oral and maxillofacial surgery. The aim of this study was to establish a new, highly precise, in vitro measurement technology for the evaluation of the geometric accuracy down to the micrometric range of digital imaging data. Material and methods A macerated human mandible was scanned optically with an industrial, non-contact, white light scanner, and a three-dimensional (3D) model was obtained, which served as a master model. The mandible was then scanned 10 times by cone beam computed tomography (CBCT), and the generated 3D surface bone model was virtually compared with the master model. To evaluate the accuracy of the CBCT scans, the standard deviation and the intraclass coefficient were determined. Results A total of 19 measurement points in 10 CBCT scans were investigated, and showed an average value of 0.2676 mm with a standard deviation of 0.0593 mm. The standard error of the mean was 0.0043 mm. The intraclass correlation coefficient (ICC) within the 10 CBCT scans was 0.9416. Conclusions This highly precise measuring technology was demonstrated to be appropriate for the evaluation of the accuracy of digital imaging data, down to the micrometric scale. This method is able to exclude human measurement errors, as the software calculates the superimposition and deviation. Thus inaccuracies caused by measurement errors can be avoided. This method provides a highly precise determination of deviations of different CBCT parameters and 3D models for surgical, navigational, and diagnostic purposes. Thus, surgical procedures and the post-operative outcomes can be precisely simulated to benefit the patient.

This review provides an overview of review and consensus articles of the past 5 years regarding surgical complications in implant dentistry. The focus in this article is on surgical complications occurring after implant insertion and on risk factors that compromise oral implant osseointegration.

The aim of this study is to evaluate the effects of nanoporous anodic aluminum oxide (alumina) with pore diameters from 15 to 40 nm on osteoblasts (hFOB) and fibroblasts (HFF). After 7 days, a significantly higher proliferation of osteoblasts with a regular cell morphology is visible on the 40 nm samples compared to the 15 nm pore diameter (p = 0.003). Fibroblasts, on the other hand, have a significantly higher proliferation rate on the 15 nm pore diameter samples compared to the 40 nm samples (p = 0.000). The pore diameter of AAO affects fibroblasts and osteoblasts in opposite ways and makes it possible to cope in a perfect way with different requirements of cells on the implant surface.

Background. Prospective speech intelligibility assessments lack objectivity in patients undergoing surgery for oral squamous cell carcinoma (OSCC) of the tongue. Methods. Speech intelligibility was measured based on word recognition by means of an automatic and objective speech recognition system preoperatively, and 14 to 20 days, and 3 months, 6 months, and 12 months postoperatively. The study comprised 25 patients with OSCC of the tongue and a healthy control group (n=40). Results. Patients yielded significant speech impairments compared to the healthy control group both before surgery and after 12 months (p

Objectives Porcine collagen matrices are proclaimed being a sufficient alternative to autologous free gingival grafts (FGG) in terms of augmenting the keratinized mucosa. The collagen matrix Mucograft® (CM) already showed a comparable clinical performance in the early healing phase, similar histological appearance, and even a more natural appearance of augmented regions. Predictability for long-term stability does not yet exist due to missing studies reporting of a follow-up >6 months. Material and methods The study included 48 patients with atrophic edentulous or partially edentulous lower jaw situations that had undergone an implant treatment. In the context of implant exposure, a vestibuloplasty was either performed with two FGGs from the palate (n = 21 patients) or with the CM (n = 27 patients). Surgery time was recorded from the first incision to the last suture. Follow-up examinations were performed at the following time points: 10, 30, 90, and 180 days and 1, 2, 3, 4, and 5 years after surgery. The width of keratinized mucosa was measured at the buccal aspect of each implant, and augmented sites were evaluated in terms of their clinical appearances (texture and color). Results The groups showed similar healing with increased peri-implant keratinized mucosa after surgery (FGG: 13.06 mm ± 2.26 mm and CM: 12.96 mm ± 2.86 mm). The maximum follow-up was 5 years (5 patients per group). After 180 days, the width of keratinized mucosa had decreased to 67.08 ± 13.85% in the FGG group and 58.88 ± 14.62% in the CM group with no statistically significant difference. The total loss of the width of keratinized mucosa after 5 years was significant between the FGG (40.65%) and the CM group (52.89%). The CM group had significantly shorter operation times than the FGG group. Augmented soft tissues had a comparable clinical appearance to adjacent native gingiva in the CM group. FGGs could still be defined after 5 years. Conclusions The FGG and the CM are both suitable for the regeneration of the peri-implant keratinized mucosa with a sufficient long-term stability. With the CM, tissue harvesting procedures are invalid, surgery time can be reduced, and regenerated tissues have a more esthetic appearance.

Microvascular free tissue transfer is a standard method in head and neck reconstructive surgery. However, previous radiotherapy of the operative region is associated with an increased incidence in postoperative flap-related complications and complete flap loss. As transforming growth factor beta (TGF-β) 1 and galectin-3 are well known markers in the context of fibrosis and lectin-like oxidized low-density lipoprotein 1 (LOX-1) supports vascular atherosclerosis, the aim of this study was to evaluate the expression of TGF-β1 and related markers as well as LOX-1 in irradiated vessels.To evaluate the expression of galectin-3, Smad 2/3, TGF-β1, and LOX-1, 20 irradiated and 20 nonirradiated arterial vessels were used for immunohistochemical staining. We semiquantitatively assessed the ratio of stained cells/total number of cells (labeling index).Expression of galectin-3, Smad 2/3, and TGF-β1 was significantly increased in previously irradiated vessels compared with nonirradiated controls. Furthermore, LOX-1 was expressed significantly higher in irradiated compared with nonirradiated vessels.Fibrosis-related proteins like galectin-3, Smad 2/3, and TGF-β1 are upregulated after radiotherapy and support histopathological changes leading to vasculopathy of the irradiated vessels. Furthermore, postoperative complications in irradiated patients can be explained by increased endothelial dysfunction caused by LOX-1 in previously irradiated patients. Consequently, not only TGF-β1 but also galectin-3 inhibitors may decrease complications after microsurgical tissue transfer.

Introduction Among numerous techniques that have been described for lip repair, the Tennison–Randall method has gained popularity over time and is preferred by many surgeons due to the predictability of the outcome. This study aims to evaluate the esthetic outcome reached in the nasolabial region following primary lip repair with the use of this method. Materials and methods Forty-four patients with unilateral cleft lip (with or without alveolar cleft) were assessed retrospectively through a photographic evaluation by two clinicians with regard to the aesthetics of the lip and nose separately as anatomical subunits as well as of the nasolabial region as an anatomical complex. The collected data were statistically analyzed with regard to the cleft subtype and the performance of corrective surgeries for the lip and/or the nose. Results The method was associated with good results, especially when it comes to the appearance of the nose as an anatomical subunit, as well as of the nasolabial region as a complex, regarding cleft lip patients without an alveolar cleft. Conclusion The Tennison–Randall technique proved to be a very satisfying method in terms of the esthetic long-term outcome in our patient collective.

In solid malignancies the influence of immunological parameters - especially of macrophages - on invasiveness, metastatic potential and prognosis has been shown. There are no studies quantitatively analysing the macrophage polarization in oral squamous cell carcinoma (oscc). The aim of this study was to correlate macrophage polarization in the epithelial and stromal compartment of oscc with histopathologic parameters.T1 and T2 oscc samples (n = 34) were used. Automated immunohistochemical staining detected CD68, CD11c, CD163 and MRC1 positive cells. All samples were completely digitalized using whole slide imaging and the number of stained cells per area was assessed quantitatively.Primary tumours with lymphogenic metastasis (N+) showed a significantly (p0.05) increased count of CD68, CD11c, CD163 and MRC1 positive cells in the epithelial fraction compared to N0 tumours. The ratio of CD163 positive cells (M2 macrophages) to CD68 positive cells (M1 and M2 macrophages) was significantly (p0.05) increased in N+ tumours.An increased macrophage infiltration and an increased M2 polarization in primary oral squamous cell carcinomas with lymphogenic metastasis was shown. Macrophages that migrated into the epithelial tumour fraction seem to be of special biological importance. The results indicate a central role of macrophages in the progression of oscc.

This study aimed to identify anatomical areas where resections of oral squamous cell carcinomas (OSCC) are significantly associated with close or positive margins. This retrospective study included 330 patients with a primary OSCC from 2010 to 2015. Patient and tumour data were categorised into three groups by R-status (R0 [clear], ≥ 5 mm, 185 patients [56.06%]; R1 [positive]

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.

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 Y‑box 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. 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. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. 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.

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. 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. 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. 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. 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.

Objectives The long-term outcome after sinus augmentation with autogenous bone or a bovine xenograft (Bio-Oss®) was assessed in 47 patients. Inclusion criterion was a vertical dimension of the maxilla of 0.05); both treatments are equivalent (confidence interval 90%) for the equivalence interval [−0.1; 0.1]. 43.5% of the cases showed no reduction in the augmentation height 5 years after implant insertion, when augmentation was performed with autogenous bone, while in the Bio-Oss® group, no resorption was found in 50% of the augmented areas. Up to 25% reduction in augmentation height was found in 47.8% in the autogenous and in 45.8% in the Bio-Oss® group. In 8.7% of all cases in the autogenous bone group and in 4.2 % in the Bio-Oss® group, up to 50% of the augmented height was resorbed. Conclusion After a 5 years evaluation period, Bio-Oss® as material for the indication maxillary sinus augmentation shows to be equivalent to autogenous bone grafting.

While the oral health-related quality of life (OHRQoL) is known to be reduced in patients with cleft lip and palate (CLP), its inter-dependency with the soft tissue characteristics of the CLP area remains unclear. This study aimed to evaluate the soft tissue characteristics in the treated cleft area in order to investigate whether gingival esthetics correlate with OHRQoL. Thirty-six patients with unilateral or bilateral CLP (46 cleft areas) were investigated after secondary/tertiary alveolar bone grafting and orthodontic/prosthetic implant treatment using an adapted score to rate gingival esthetics (clinical esthetic score, CES). The patient's OHRQoL was determined using the German short version of the Oral Health Impact Profile questionnaire (OHIP-G14). The results showed a significantly better rating in patients with their own teeth in situ (12.05±1.10) than in patients with implants (6.95±4.78) or prosthetics (4.00±3.58). The best OHRQoL values were achieved by patients with their own teeth integrated into the cleft area (1.32±2.31), followed by patients with implants (2.33±2.33) and prosthetics (3.75±5.87). A significant (P=0.017) correlation was found between OHIP-G14 and CES scores, suggesting an increased OHRQoL in cases with higher oral esthetics in the cleft area. The therapeutic strategy contributes to both gingival esthetics and OHRQoL. The patient's subjective perception of OHRQoL can be attributed to objective gingival esthetic ratings.

The present study evaluated the relevance of EGFR overexpression in prediction of malignant transformation of oral leukoplakia (OLP). The retrospective study comprised paraffin-embedded tissue samples of OLP that transformed into oral squamous cell carcinoma (OSCC) (n=53) and tissue samples of OLP that did not transform into OSCC (n=45) during a follow-up period of 5 years. EGFR overexpression was assessed immunohistochemically. A significantly different expression rate of EGFR was determined between transformed and non-transformed OLP (p=0.017). A statistically significant increase of EGFR expression for low dysplasia lesions in group I compared to group II was proven (D0, p=0.013; D1, p=0.049). By calculation of ROC curve and determination of highest Youden index the optimal threshold value [cut-off point (COP) = 44.96] for distinguishing the transformed from non-transformed lesions was estimated (critical expression rate of EGFR). Using the determined COP the correlation between high-risk lesions and the detection of increased expression rates were significant (p=0.001). In the future, the assessment of EGFR overexpression in OLP may allow identifying OLP lesions with an increased risk of malignant transformation that may have been regarded harmless when only the grade of dysplasia had been taken into account.

In the present paper we report the oral findings of a patient who was diagnosed with hyperoxaluria. Hyperoxalurias can basically be classified as primary and secondary, with the first being inborn errors of metabolism and the second a result of excessive oxalate intake. Primary hyperoxalurias form a rare group of metabolic diseases that are inherited in the autosomal recessive fashion. The affected genes code for specific hepatic enzymes that are involved in glyoxylate metabolism and their deficiency results in overproduction of oxalate. Two different types are described: Primary hyperoxaluria type I results from a deficiency of peroxisomal enzyme alanine-glyoxylate aminotransferase and the more rare type II from a deficiency of cytosolic enzyme D-glycerate dehydrogenase. Since oxalate is primarily excreted through the kidneys, abnormally high concentration of oxalate in the urine occurs. This can in turn result in recurrent kidney stones and parenchymal renal damage and end-stage renal disease (ESRD). Inability to further excrete oxalate through the kidneys leads to its deposition in various organs (oxalosis). Several oral findings have been described in patients with oxalosis, most important of whose are bone resorption in the jaws, external root resorption and rapidly progressive dental mobility, as well as dental pain associated with deposition of oxalate in the dentine and the pulp.

Regional odontodysplasia is a rare and unique dental anomaly involving both dentitions, but mostly the teeth of 1 quadrant. This report describes the combined surgical and orthodontic treatment of a boy with regional odontodysplasia. The mandibular right central and lateral incisors and the canine (as well as the deciduous predecessors) were affected. In a 2-step procedure, the maxillary right and left second premolars were autotransplanted to the affected area. The extraction sites in the maxilla were closed, and a good functional occlusion was established.

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.

Purpose Postoperative pain management is important for improved patient care. Our primary objective was to investigate the effect of analgesic treatment adaptation by the pain clinic on postoperative pain relief at an oral and maxillofacial surgery department. Additionally, we aimed to present patients' pain characteristics and the administered analgesic treatment. Materials and methods A total of 128 patients treated at our clinic in the period 2012–2015 who required analgesic treatment adaptation by our pain clinic were included. They were further divided into 10 groups: tumor, temporomandibular joint disorder, tooth extraction, osteomyelitis, bisphosphonate-related osteonecrosis of the jaw, submandibular abscess, orthognathic surgery, cyst, sinusitis, and fracture. Pain characteristics evaluated were intensity on a numerical rating scale (NRS) before and after intervention of the pain clinic, quality, genesis, and type. Results Post treatment pain intensity values at rest 1.8 (SD: 1.4) and on exercise (walking and physical therapy) 4 (SD: 2) were statistically significant better compared to pretreatment values (4.2, SD: 2.5, and 6.8 SD: 2, respectively). The highest pain intensities were reported after tooth extractions, orthognathic surgery, cystectomies, and fracture reposition. Pain was mainly continuous and related to a combination of a somatic and a neuropathic pathophysiological mechanism. Conclusions Intervention by a specialized pain clinic leads to reduction of postoperative pain.

Background Chronic recurrent multifocal osteomyelitis (CRMO) is a rare acquired inflammatory skeletal disorder of unknown origin. CRMO was first described by Gideon in 1972 and mainly affects children and young adults of female gender. The CRMO is part of the clinical picture of non-bacterial Osteomyelitis (NBO) and typically presents a relapsing recurring course with both remission and spontaneous exacerbation. CRMO is typically encountered in the limbs and the metaphysis of long bones in particular. Usually the clinical symptoms include painful swellings of the affected regions. This case report describes the rare case of a CRMO of the mandible in association with pyoderma gangraenosum. Case presentation A 14-year old female caucasian patient, residing in the south of Germany, presented in the oncological outpatient clinic of our Department of Paediatrics and Adolescent Medicine in June 2014 complaining of increasing neck pain and progressive swelling at her left cheek ongoing for about 6 weeks. These symptoms had been occurring quarterly for 4 years, but had never been as pronounced. Blood biochemistry showed a moderately elevated CRP (35 mg/l) and a significantly increased blood sedimentation rate (BSR 48/120 mm). The panoramic radiograph, however, revealed a bone alteration in the left mandibular region. Further investigations confirmed the diagnosis of CRMO. Conclusion The present case underlines the fact that rare diseases might occasionally present with even more rare symptoms. These occasions can obviously be considered to present a considerable diagnostic challenge.

Background Confocal laser endomicroscopy (CLE) is an optical biopsy method allowing in vivo microscopic imaging at 1000-fold magnification. It was the aim to evaluate CLE in the human oral cavity for the differentiation of physiological/carcinomatous mucosa and to establish and validate, for the first time, a scoring system to facilitate CLE assessment. Methods The study consisted of 4 phases: (1) CLE-imaging (in vivo) was performed after the intravenous injection of fluorescein in patients with histologically confirmed carcinomatous oral mucosa; (2) CLE-experts (n = 3) verified the applicability of CLE in the oral cavity for the differentiation between physiological and cancerous tissue compared to the gold standard of histopathological assessment; (3) based on specific patterns of tissue changes, CLE-experts (n = 3) developed a classification and scoring system (DOC-Score) to simplify the diagnosis of oral squamous cell carcinomas; (4) validation of the newly developed DOC-Score by non-CLE-experts (n = 3); final statistical evaluation of their classification performance (comparison to the results of CLE-experts and the histopathological analyses). Results Experts acquired and edited 45 sequences (260 s) of physiological and 50 sequences (518 s) of carcinomatous mucosa (total: 95 sequences/778 s). All sequences were evaluated independently by experts and non-experts (based on the newly proposed classification system). Sensitivity (0.953) and specificity (0.889) of the diagnoses by experts as well as sensitivity (0.973) and specificity (0.881) of the non-expert ratings correlated well with the results of the present gold standard of tissue histopathology. Experts had a positive predictive value (PPV) of 0.905 and a negative predictive value (NPV) of 0.945. Non-experts reached a PPV of 0.901 and a NPV of 0.967 with the help of the DOC-Score. Inter-rater reliability (Fleiss` kappa) was 0.73 for experts and 0.814 for non-experts. The intra-rater reliability (Cronbach’s alpha) of the experts was 0.989 and 0.884 for non-experts. Conclusions CLE is a suitable and valid method for experts to diagnose oral cancer. Using the DOC-Score system, an accurate chair-side diagnosis of oral cancer is feasible with comparable results to the gold standard of histopathology—even in daily clinical practice for non-experienced raters.

The risk of the malignant transformation of oral leukoplakia (OLP) is difficult to predict by histopathology. Melanoma-associated antigen-A (MAGE-A) expression is restricted to malignant cells and may be useful for the more accurate estimation of the potential malignant transformation of pre-malignant lesions. The aim of the present study was to investigate whether the expression of MAGE-A can be used to predict the malignant transformation of OLP. Paraffin-embedded tissue samples of OLP from 74 patients followed-up for at least 5 years were included. A total of 24 progressing and 50 non-progressing OLP, 18 corresponding tumor and 30 healthy mucosa specimens were analysed for MAGE-A 1, 3, 4, 6 10 and 12 expression by nested real‑time RT-PCR and graded for dysplasia. In total, 46% of the progressing lesions expressed at least 1 out of the examined MAGE-A antigens, whereas no expression was detected in any of the non-progressing OLP and normal specimens. The correlation between malignant transformation and MAGE-A expression was statistically significant (p=0.00001). Furthermore, 42% of the progressing OLPs without dysplasia (D0) expressed at least 1 antigen. The correlation between the grade of dysplasia and MAGE-A staining in the malignant transformation group was not significant (p=0.08). The detection of at least 1 MAGE-A antigen may allow the identification of high-risk lesions that may progress into carcinoma with time. Therefore, the investigation of MAGE-A expression should be assessed in order to obtain a more accurate evaluation of the potential cancer risk of OLP.

The purpose of this study was to evaluate risk factors that influence overall survival (OS)/disease-free survival (DFS)/locoregional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS) in patients with high-risk primary salivary gland carcinoma who underwent surgery and postoperative (chemo)radiotherapy with curative intention.We reviewed data of 63 patients with high-risk primary salivary gland carcinoma in a retrospective single-center audit.At a median follow-up of 31 months (range, 5-145 months), cumulative OS and DFS were 91.7%, 77.6%, and 62.9%, and 82.1%, 65.6%, and 57.7%, respectively, after 1, 2, and 5 years. LRFS and DMFS were 92%, 86%, and 86%, and 83.4%, 70.4%, and 62.3% after 1, 2, and 5 years, respectively. Of all patient-related, tumor-related, and treatment-related factors, high-grade histology (G3) was the only factor in univariate and multivariate analysis that was predictive for a shorter DMFS (low/intermediate vs high-grade: 100%, 100%, and 89.4% vs 72.9%, 54.3%, and 42.8% after 1, 2, and 5 years, respectively) and a shorter DFS (low/intermediate vs high-grade: 100%, 90%, and 84.4% vs 71.2%, 50.1%, and 39.4% after 1, 2, and 5 years, respectively) and OS (low/intermediate vs high-grade: 100%, 100%, and 86.5% vs 86.5%, 63.2%, and 46.5% after 1, 2, and 5 years, respectively).High-grade tumor histology is a highly significant predictor of a shorter DMFS, OS, and DFS in salivary gland carcinoma, irrespective of histological subtype. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2041-E2048, 2016.

Objectives This prospective clinical comparative study aimed to analyze the postoperative bleeding risk of patients continuing their anticoagulation therapy (AT) and undergoing implant surgery and bone grafting procedures. Materials and methods The treatments ranged from the insertion of single or multiple dental implants over implant exposures to sinus floor augmentation and vertical and/or lateral bone grafting with autologous bone grafts. The patients of the test groups (AT groups) were treated with platelet aggregation inhibitors (PAIs), Vitamin-K inhibitors, Vitamin-K inhibitor withdrawal bridged with heparin (LMWH), or new/direct oral anticoagulants (NOACs/DOACs). Patients of the control group were non-anticoagulated (non-AT group). Surgical procedures were performed in the same manner in all groups. Pre, intra, and postoperative data concerning the treatment, extent of the surgery and bleedings was recorded and statistically evaluated. Results There were seven postoperative bleedings in 564 patients (1.2%), four in the AT groups (3.4%), and three in the non-AT group (0.6%). No thromboembolic complication occurred in the whole observation period. The invasiveness of the surgical procedure had no statistically significant effect on bleeding frequencies. Patients taking Vitamin-K inhibitors had a significantly higher risk of a postoperative bleeding compared to patients without any AT (P = 0.038). Two patients were hospitalized due to the severity of the bleeding as a precautionary measure (one in the non-AT and one in the PAI group). All bleedings were easily controllable with local hemostatic measures. There was no postoperative bleeding recorded for patients taking DOACs. Conclusions Anticoagulation therapy should be continued in patients undergoing implant surgery and bone grafting procedures avoiding thromboembolic complications. Surgeons should always apply the most minimally invasive approach to reduce postoperative risks and be able to apply local hemostatic measures in terms of a bleeding complication.

von Wilmowsky C, Stockmann P, Harsch I, Amann K, Metzler P, Lutz R, Moest T, Neukam FW, Schlegel KA: Diabetes mellitus negatively affects peri-implant bone formation in the diabetic domestic pig. J Clin Periodontol 2011; 38: 771–779. doi: 10.1111/j.1600-051X.2011.01746.x. Abstract Aim: Diabetes mellitus is classified as a relative contraindication for implant treatment, and higher failure rates have been seen in diabetic patients. The aim of the present study was to investigate the effect of diabetes on peri-implant bone formation in an animal model of human bone repair. Materials and Methods: Diabetes was induced by an intra-venous application of streptozotocin (90 mg/kg) in 15 domestic pigs. Implants were placed after significant histopathological changes in the hard and soft tissues were verified. The bone–implant contact (BIC), peri-implant bone mineral density (BMD), and expression of collagen type-I and osteocalcin proteins were qualitatively evaluated 4 and 12 weeks after implantation. Fifteen animals served as healthy controls. Results: Diabetes caused pathological changes in the soft and hard tissues. The BIC and BMD were significantly reduced in the diabetic group after 4 and 12 weeks. Collagen type-I was increased in the diabetic group at both time points, whereas osteocalcin was reduced in the diabetic group. Conclusions: Poorly controlled diabetes negatively affects peri-implant bone formation and bone mineralization. These findings have to be taken into consideration for diabetic patients with an indication for implant therapy.

Treatment of oral carcinomas often causes reduced speech intelligibility. It was the aim of this study to objectively evaluate the speech intelligibility of patients after multimodal therapy for oral squamous cell carcinoma (OSCC) with a computer-based, automatic speech recognition system.The speech intelligibility of 59 patients after multimodal tumor treatment for OSCC, located at the lateral tongue, floor of the mouth, or the alveolar crest of the lower jaw, was objectively analyzed by a computer-based speech recognition system that calculates the percentage of correct word recognition (WR).The patients' WR was significantly reduced compared with a healthy control group without speech impairment (P ≤ .001). Higher T-classification was associated with a reduced WR (P.01). Tumors located at the tongue showed a significantly higher WR than tumors at the floor of the mouth or the alveolar crest (P ≤ .001). Surgical resection and reconstruction of the lower jaw bone significantly reduced the WR (P ≤ .001) compared with cases without osseous tumor infiltration.Speech intelligibility after treatment for OSCC, objectively quantified by a standardized automatic speech recognition system, is reduced for increasing tumor size, increasing resection volume, and tumor localization near the lower jaw. Surgical reconstruction techniques seem to have an impact on speech intelligibility.

Introduction: Recently, it has been demonstrated that the nanoscale environment is a critical factor for cellular behaviour. It has been shown that the diameter of TiO2 nanotube layers controls the cellular behaviour of cells involved in the bone-forming process in vitro. Therefore, the aim of the present study was to investigate the effects of the diameter of TiO2 nanotubes on peri-implant bone formation and the expression of bone matrix proteins in vivo. Materials and methods: Ninety experimental implants with a nanotube diameter ranging from 15 up to 100 nm were placed in the frontal skulls of six domestic pigs, whereas untreated implants served as controls. The bone–implant contact (BIC) as well as the expression of bone morphogenetic protein (BMP)-2, collagen type-I and osteocalcin were histomorphometrically and immunohistochemically analysed after 30 days. Results: Evaluating the BIC, a significant higher value, could be found for the 50, 70 and 100 nm groups compared with the controls, whereas a correlation with the BMP-2 expression was present. The BMP-2 expression within the 50, 70 and 100 nm groups was statistically different compared with the control group. Significant difference was found for the osteocalcin expression in the 70 nm group. No statistical difference was found evaluating collagen type-I. SEM evaluation of the specimen surfaces revealed that the nanotube coatings do resist shearing forces evoked by implant insertion. Conclusion: The nanotube diameter can be designed to support cellular functions of osteoblasts and osteoclasts in vivo, including differentiation and protein expression and therefore offer a powerful tool for the controlled formation of peri-implant bone around medical implant devices. To cite this article: von Wilmowsky C, Bauer S, Roedl S, Neukam FW, Schmuki P, Schlegel KA. The diameter of anodic TiO2 nanotubes affects bone formation and correlates with the bone morphogenetic protein-2 expression in vivo. Clin. Oral Impl. Res. 23, 2012; 359–366. doi: 10.1111/j.1600-0501.2010.02139.x