Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie

BACKGROUND: Aluminum is regularly taken up with the daily diet. It is also used in antiperspirants, as an adjuvant for vaccination, and in desensitization procedures. In this review, we present the scientifically documented harmful effects of aluminum on health and the threshold values associated with them. METHODS: This review is based on publications retrieved by a selective search of the PubMed and SCOPUS databases on the topic of aluminum in connection with neurotoxicity, Alzheimer's disease, and breast cancer, as well as on the authors' personal experience in occupational and environmental medicine. RESULTS: The reference values for the internal aluminum load (<15 μg/L in urine, <5 μg/L in serum) are especially likely to be exceeded in persons with occupational exposure. The biological tolerance value for occupational exposure is 50 μg of aluminum per gram of creatinine in the urine. For aluminum welders and workers in the aluminum industry, declining performance in neuropsychological tests (attention, learning, memory) has been found only with aluminum concentrations exceeding 100 μg/g creatinine in the urine; manifest encephalopathy with dementia was not found. Elevated aluminum content has been found in the brains of persons with Alzheimer's disease. It remains unclear whether this is a cause or an effect of the disease. There is conflicting evidence on carcinogenicity. The contention that the use of aluminum-containing antiperspirants promotes breast cancer is not supported by consistent scientific data. CONCLUSION: The internal aluminum load is measured in terms of the concentration of aluminum in urine and blood. Keeping these concentrations below the tolerance values prevents the development of manifest and subclinical signs of aluminum toxicity. Large-scale epidemiologic studies of the relationship between aluminum-containing antiperspirants and the risk of breast cancer would be desirable.

The LeFort I osteotomy has become a routine procedure in elective orthognathic surgery. The authors report the occurrence of intra- or perioperative complications in a series of 1000 consecutive LeFort I osteotomies performed within a 20-year period. In total, 64 (6.4%) patients experienced complications. Anatomical complications affected 26 (2.6%), patients, including 16 (1.6%) with a deviation of the nasal septum and 10 (1.0%) with non-union of the osteotomy gap. Extensive bleeding that required blood transfusion occurred in 11 (1.1%) patients exclusively after bimaxillary corrections; in 1 patient a ligation of the external carotid artery became necessary. Significant infections such as abscesses or maxillary sinusitis occurred in 11 (1.1%) patients. No patient experienced an osteomyelitis. Ischemic complications affected 10 (1.0%) patients, including 2 (0.2%) who experienced an aseptic necrosis of the alveolar process and 8 (0.8%) who, under critical revision, were affected by retractions of the gingiva. Five (0.5%) patients experienced an insufficient fixation of the osteosynthesis material. The risk and the extent of complications was enhanced in patients with anatomical irregularities (eg, in patients with craniofacial dysplasias, orofacial clefts, or vascular anomalies). The risk of ischemic complications was enhanced in extensive dislocations or transversal segmentation of the maxilla. The authors conclude that patients with major anatomical irregularities should be informed about an enhanced risk of Le-Fort I osteotomies. Preoperative planning avoiding transversal segmentation or extensive dislocations of the maxilla should reduce the occurrence of complications. For healthy individuals, the risk of complications with the LeFort I osteotomy is considered low.

Abstract Two important rapid‐prototyping technologies (3D Printing and 3D Bioplotting) were compared with respect to the computer‐aided design and free‐form fabrication of biodegradable polyurethane scaffolds meeting the demands of tissue‐engineering applications. Aliphatic polyurethanes were based on lysine ethyl ester diisocyanate and isophorone diisocyanate. Layer‐by‐layer construction of the scaffolds was performed by 3D Printing, that is, bonding together starch particles followed by infiltration and partial crosslinking of starch with lysine ethyl ester diisocyanate. Alternatively, the 3D Bioplotting process permitted three‐dimensional dispensing and reactive processing of oligoetherurethanes derived from isophorone diisocyanate, oligoethylene oxide, and glycerol. The scaffolds were characterized with X‐ray microtomography, scanning electron microscopy, and mechanical testing. Osteoblast‐like cells were seeded on such scaffolds to demonstrate their potential in tissue engineering. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 624–638, 2004

Dental implant surgery has developed to a widely used procedure for dental rehabilitation and is a secure and predictable procedure. Local and systemic risk factors can result in higher failure rates. Diabetes mellitus is a chronic disease that goes in with hyperglycemia and causes multifarious side effects. Diabetes as a relative contraindication for implant surgery is controversially discussed. Because the number of patients suffering from diabetes increases, there are more diabetic patients demanding implant procedures. We aimed to answer the PICO question "Do diabetic patients with dental implants have a higher complication rate in comparison to healthy controls?" by a systematic literature search based on the PRISMA statement. We identified 22 clinical studies and 20 publications of aggregated literature, which were quite heterogeneous concerning methods and results. We conclude that patients with poorly controlled diabetes suffer from impaired osseointegration, elevated risk of peri-implantitis, and higher level of implant failure. The influence of duration of the disease is not fully clear. The supportive administration of antibiotics and chlorhexidine seems to improve implant success. When diabetes is under well control, implant procedures are safe and predictable with a complication rate similar to that of healthy patients.

Obstructive sleep apnea is the most common sleep-related breathing disorder, with a surprisingly high prevalence. The treatment of choice is nasal continuous positive airway pressure (CPAP) ventilation during sleep, which has to be applied throughout the patient's whole life. Because of various underlying pathomechanisms in patients with certain craniofacial disorders--narrow posterior airway space and maxillary-mandibular deficiency--surgical therapy by craniofacial osteotomies seems possible. A series of 38 consecutive patients were treated by 10-mm maxillomandibular advancement by retromolar sagittal split osteotomy and Le Fort I osteotomy, respectively. Obstructive sleep apnea syndrome was improved considerably in all patients; there was no significant difference compared to the results under nasal CPAP. In 37 of 38 patients, the postoperative apnea-hypopnea index was reduced clearly to under 10 per hour, oxygen saturation rose, and sleep quality improved. This was achieved by maxillomandibular advancement of 10 mm without secondary refinements in all but 2 patients. In one patient, the apnea-hypopnea index could only be reduced to 20 per hour, probably because of insufficient maxillary advancement. These results indicate that successful surgical treatment is possible in a high percentage of selected patients with certain craniofacial characteristics. In addition to cardiorespiratory polysomnography, there should be routine cephalometric evaluation of all patients. Maxillomandibular advancement should be offered as an alternative therapy to all patients with maxillary and/or mandibular deficiency or dolichofacial type in combination with narrow posterior airway space.

In recent years obstructive sleep apnea syndrome has gained increasing interest. Treatment of choice is nasal continuous positive airway pressure ventilation during sleep for upper airway patency, which does not cure sleep apnea and has to be applied throughout a patient's lifetime. In respect to various underlying pathomechanisms, in certain cases with craniofacial disorders, causal therapy by craniofacial osteotomies seems possible. A series of 21 consecutive patients with maxillary and mandibular deficiency were treated primarily with a 10-mm maxillomandibular advancement by retromolar sagittal split osteotomy and Le Fort-I osteotomy, respectively. Obstructive sleep apnea syndrome was considerably improved in all patients. In 20 of 21 patients, the postoperative respiratory disturbance index (RDI) was reduced clearly to under 10, oxygen saturation rose and sleep quality improved. This was achieved by a maxillomandibular advancement of 10 mm without secondary refinements. In one patient the RDI could only be reduced to 20, probably due to insufficient maxillary advancement; oxygen desaturations still existed despite secondary corrections. These results indicate that successful surgical treatment is possible in a high percentage of selected patients with certain craniofacial characteristics. In addition to cardiorespiratory polysomnography there should be routine cephalometric evaluation of all patients. Maxillomandibular advancement should be offered as an alternative therapy to all patients with maxillary and/or mandibular deficiency or dolichofacial type in combination with narrow posterior airway space.

Obstructive sleep apnoea (OSA) is a common disorder with potentially serious consequences. If maxillary and mandibular deficiency, often in combination with a narrow posterior airway space is present, therapy of OSA by maxillomandibular osteotomy is possible. However, long-term follow-up of patients undergoing these procedures is lacking. We present the results of 15 OSA patients (1 female and 14 males), who underwent maxillomandibular advancement surgery with a follow-up of at least 2 yrs. Polysomnography was performed before surgery, after 6-12 weeks, and 1 and 2 yrs postoperatively. Mean apnoea/hypopnoea index (AHI) decreased from 51.4 events.h-1 before therapy to 5.0 events.h-1 6 weeks postoperatively, and was 8.5 events.h-1 after 2 yrs. Oxygen saturation significantly increased following surgery. After 2 yrs, the AHI was < 10 events.h-1 in 12 out of 15 subjects. No significant changes were found comparing the 6-12 weeks versus the 2 year follow-up data. The significant increase in stage 3/4 non-rapid eye movement (NREM) sleep and decrease in stage 1 NREM sleep, indicative of the restoration of normal physiological sleep structure, persisted in 14 of the 15 subjects 2 yrs postoperatively. Three patients, however, did not show satisfactory improvement 2 yrs postoperatively; two showed obstructive and one central respiratory events. This study demonstrates that maxillomandibular advancement is successful in a high percentage of patients carefully selected by cephalometric and polysomnographic investigation. Postoperative success has proved to be stable over a period of 2 yrs. Further preoperative evaluation seems necessary in patients with predominantly mixed or central apnoeas.

Untreated complex regional pain syndrome (CRPS) may progress from acute stages with increased hair and nail growth in the affected limb to chronic stages with atrophy of the skin, muscles and bones. The aim of this study was to investigate whether tissue hypoxia could be one mechanism responsible for this late CRPS symptoms. Nineteen patients with CRPS and two control groups (healthy control subjects, surgery patients with edema) participated in this study. Skin capillary hemoglobin oxygenation (HbO(2)) was measured non-invasively employing micro-lightguide spectrophotometry (EMPHO). The EMPHO probe was mounted force-controlled onto the skin of the affected and unaffected hand. HbO(2) was measured at rest and during postischemic reactive hyperemia. HbO(2) did not differ between the right (58.20%+/-1.12) and left (57.79%+/-1.31, ns) hand in control subjects. However, in patients, HbO(2) of the affected side (36.63%+/-2.16) was significantly decreased as compared to the clinically unaffected side (46.35%+/-2.97, P<0.01). As compared to controls, HbO(2) in CRPS was reduced on both sides (P<0.001). Postischemic hyperoxygenation was impaired on the affected side in CRPS (60.81%+/-2.90)--as compared to the unaffected side (67.73%+/-1.50, P<0.04) and to controls (68.63%+/-0.87, P<0.005). The unaffected limb in CRPS did not differ from controls. Despite skin edema, pre- (49.06%+/-2.02) and postsurgery HbO(2) (53.15%+/-4.44, ns) were not different in the second control group. Our results indicate skin hypoxia in CRPS. Impairment of nutritive blood flow in the affected limb may be one factor contributing to atrophy and ulceration in chronic CRPS. The investigation of patients after surgery revealed that edema could not be the only reason for hypoxia.

Osseous craniofacial defects are commonly seen problems after operative treatment of craniosynostoses. This case report describes a calvarial reconstruction by means of computer-aided fabrication of a customised implant. Three-dimensional imaging is followed by computer-aided design and fabrication of a medical grade PCL-TCP biodegradable scaffold using the rapid prototyping technology fused deposition modelling (CAD/CAM). After six months the implant was well integrated, no defect area could be palpated any more and a beginning bony consolidation could be detected via CT.

BACKGROUND: Although helmet therapy is widely accepted in the treatment of severe positional plagiocephaly, treatment regimens, especially regarding starting age, are controversial. This study investigated the importance of starting age to optimize the management of helmet therapy. METHODS: Sixty-two infants with severe positional plagiocephaly were enrolled in this prospective longitudinal study. Twenty-four started helmet therapy before 6 months of age (group 1) and 38 were older than 6 months (group 2). Cranial diagonal measurements were taken. Resulting differences and Cranial Vault Asymmetry Index values were compared and categorized by age at initiation of therapy. The Mann-Whitney U test was used for statistical analysis. RESULTS: Duration of therapy was significantly shorter in group 1 (14 weeks) compared with group 2 (18 weeks) (p = 0.013), with significantly better outcomes. The Cranial Vault Asymmetry Index in group 1 was reduced to a normal mean value less than 3.5 percent. Infants in group 2 did not achieve normal values (index value, 4.5 percent) (p = 0.021). The relative improvement in asymmetry was significantly better in group 1 (75.3 percent) compared with group 2 (60.6 percent) (p = 0.001). After 4 to 11 weeks of treatment, group 1 already showed a better absolute reduction (p < 0.001) and a better relative reduction (p = 0.002). CONCLUSIONS: Optimal starting age for helmet therapy is months 5 to 6 of life, and early recognition of infants in need is essential. Delaying the onset of treatment significantly deteriorates the outcome. The still often-practiced regimen of starting helmet therapy after physiotherapy should be replaced by a combined therapy in severe cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Because of its high requirements on dexterity and microsurgical skills and the need of complete understanding of flap anatomy, microvascular free flap transfer belongs to the most demanding surgical procedures. Therefore, courses for flap raising and microvascular exercise are considered a prerequisite to prepare for clinical practise. To achieve teaching conditions as realistic as possible we used a novel cadaver embalming method enabling tissue dissection comparable to the living body. Thirty cadavers which were offered to us by the Institute of Anatomy for the purpose of running flap raising courses were embalmed in the technique described by Thiel. On each cadaver, nine free flaps were dissected according to a structured protocol by each course participant and afterwards used for microvascular exercise. The conservation of fine vascular structures and the suitability of the embalmed tissue for microvascular suturing were observed and photographically documented. The Thiel embalming technique provided flap raising procedures to be performed under realistic conditions similar to the living body. Vessels and nerves could be exposed and dissected up to a diameter of 1 mm and allowed for microvascular suturing even after weeks like fresh specimens. The Thiel embalming method is a unique technique and ideally suited to teach flap raising and microvascular suturing on human material.

BACKGROUND: Mesenchymal stem cells (MSC) are multipotent cells which can differentiate along osteogenic, chondrogenic, and adipogenic lineages. The present study was designed to investigate the influence of mechanical force as a specific physiological stress on the differentiation of (MSC) to osteoblast-like cells. METHODS: Human MSC were cultured in osteoinductive medium with or without cyclic uniaxial mechanical stimulation (2000 mustrain, 200 cycles per day, 1 Hz). Cultured cells were analysed for expression of collagen type I, osteocalcin, osteonectin, and CD90. To evaluate the biomineral formation the content of bound calcium in the cultures was determined. RESULTS: After 14 days in culture immunfluorescence staining revealed enhancement of collagen type I and osteonectin expression in response to mechanical stimulation. In contrast, mechanically stimulated cultures stained negative for CD90. In stimulated and unstimulated cultures an increase in the calcium content over time was observed. After 21 days in culture the calcium content in mechanical stimulated cultures was significantly higher compared to unstimulated control cultures. CONCLUSION: These results demonstrate the influence of mechanical force on the differentiation of human MSC into osteoblast-like cells in vitro. While significant enhancement of the biomineral formation by mechanical stimulation is not detected before 21 days, effects on the extracellular matrix became already obvious after 14 days. The decrease of CD90 expression in mechanically stimulated cultures compared to unstimulated control cultures suggests that CD90 is only transiently expressed expression during the differentiation of MSC to osteoblast-like cells in culture.

Aspergillus fumigatus is a ubiquitous mold that can cause severe infections in immunocompromised patients, typically manifesting as invasive pulmonary aspergillosis (IPA). Adaptive and innate immune cells that respond to A. fumigatus are present in the endogenous repertoire of patients with IPA but are infrequent and cannot be consistently isolated and expanded for adoptive immunotherapy. Therefore, we gene-engineered A. fumigatus –specific chimeric antigen receptor (Af-CAR) T cells and demonstrate their ability to confer antifungal reactivity in preclinical models in vitro and in vivo. We generated a CAR targeting domain AB90-E8 that recognizes a conserved protein antigen in the cell wall of A. fumigatus hyphae. T cells expressing the Af-CAR recognized A. fumigatus strains and clinical isolates and exerted a direct antifungal effect against A. fumigatus hyphae. In particular, CD8 + Af-CAR T cells released perforin and granzyme B and damaged A. fumigatus hyphae. CD8 + and CD4 + Af-CAR T cells produced cytokines that activated macrophages to potentiate the antifungal effect. In an in vivo model of IPA in immunodeficient mice, CD8 + Af-CAR T cells localized to the site of infection, engaged innate immune cells, and reduced fungal burden in the lung. Adoptive transfer of CD8 + Af-CAR T cells conferred greater antifungal efficacy compared to CD4 + Af-CAR T cells and an improvement in overall survival. Together, our study illustrates the potential of gene-engineered T cells to treat aggressive infectious diseases that are difficult to control with conventional antimicrobial therapy and support the clinical development of Af-CAR T cell therapy to treat IPA.

Gene copy number aberrations are involved in oral squamous cell carcinoma (OSCC) development. To delineate candidate genes inside critical chromosomal regions, array-CGH was applied to 40 OSCC specimens using a microarray covering the whole human genome with an average resolution of 1 Mb. Gene copy number gains were predominantly found at 1q23 (9 cases), 3q26 (11), 5p15 (13), 7p11 (7), 8q24 (17), 11q13 (15), 14q32 (8), 19p13 (8), 19q12 (7), 19q13 (8), and 20q13 (9), whereas gene copy number losses were detected at 3p21-3p12 (15), 8p32 (11), 10p12 (8), and 18q21-q23 (10). Subsequent mRNA expression analyses by quantitative real time polymerase chain reaction found high mRNA expression of candidate genes SOX2 in 3q26.33, FSLT3 in 19p13.3, and CCNE1 in 19q12. Tissue microarray (TMA) analyses in a representative OSCC collection found gene copy number gain for SOX2 in 52% (115/223) and for CCNE1 in 31% (72/233) of the tumors. Immunohistochemical analyses on TMA sections of the corresponding proteins detected high expression of SOX2 in 18.1% (49/271) and of CyclinE1 in 23.3% (64/275) of tumors analyzed. These findings indicate that SOX2 and CCNE1 might be activated via gene copy number gain and participate in oral carcinogenesis. The combination of array-CGH with TMA analyses allows rapid pinpointing of novel promising candidate genes, which might be used as therapeutic stratification markers or target molecules for therapeutic interference.

In this in vivo and in vitro study on resorbable (Monocryl and nonresorbable (Deknalon) monofilament sutures used in intraoral dentoalveolar surgery the bacterial colonization was compared. For the in vivo study the sutures were applied in 11 patients during dental surgery. Eight days postoperative the sutures were removed and the adhered bacteria were isolated and identified by biochemistry, morphology, antibiotic susceptibility, and gas chromatography. The colonization was studied by scanning electron microscopy. Aerobic and anaerobic bacteria were isolated in nearly equal colony-forming units (cfu) on each suture. In comparison with Monocryl about 15% more aerobic and anaerobic strains were isolated on Deknalon. Regarding the pathogens only, about three times more anaerobic strains were isolated on both sutures in total. Additionally, more pathogens were found on Deknalon than on Monocryl (aerobic >40%, anaerobic >25%). The variety of bacteria correspond with purulent infections, not with normal oral flora. Intraindividual comparisons of cfu showed differences in dependence of the patient as described for subgingivale plaques. For the in vitro study the sutures were incubated with Streptococcus intermedius and Prevotella intermedia for 0.5 h. Scanning electron microscopy was performed to examine qualitatively the level of bacterial adherence. After 0.5 h the bacteria adhered very well. The colonization rate of Streptococcus intermedius on both sutures was similar. Coccoid bacteria within biofilms were seen. The growth of Prevotella intermedia was much better on Deknalon than on Monocryl. The risk of bacteremia at the time of suture removal is discussed.

BACKGROUND: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%. SUMMARY: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.

BACKGROUND: Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) is an adverse effect of bisphosphonate treatment with varying reported incidence rates. METHODS: In two neighboring German cities, prevalence and additional factors of the development of BP-ONJ in multiple myeloma patients with bisphosphonates therapy were recorded using a retrospective (RS) and cross-sectional study (CSS) design. For the RS, all patients treated from Jan. 2000--Feb. 2006 were contacted by letter. In the CSS, all patients treated from Oct. 2006--Mar. 2008 had a physical and dental examination. Additionally, a literature review was conducted to evaluate all articles reporting on BP-ONJ prevalence. PubMed search terms were: bisphosphonat, diphosphonate, osteonecrosis, prevalence and incidence. RESULTS: In the RS, data from 81 of 161 patients could be obtained; four patients (4.9%) developed BP-ONJ. In the CSS, 16 of 78 patients (20.5%) developed BP-ONJ. All patients with BP-ONJ had received zoledronate; 12 of these had had additional bisphosphonates. All except one had an additional trigger factor (tooth extraction [n = 14], dental surgical procedure [n = 2], sharp mylohyoid ridge [n = 3]). CONCLUSION: The prevalence of BP-ONJ may have been underestimated to date. The oral examination of all patients in this CSS might explain the higher prevalence, since even early asymptomatic stages of BP-ONJ and previously unnoticed symptomatic BP-ONJ were recorded. Since nearly all patients with BP-ONJ had an additional trigger factor, oral hygiene and dental care might help to reduce BP-ONJ incidence.

BACKGROUND: Bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) is a relatively new disease. The aim of this study was to evaluate the prevalence of BP-ONJ in breast cancer patients with osseous metastasis and bisphosphonate therapy. METHODS: A retrospective study was conducted in a EUSOMA accredited breast unit in Germany. All patients treated from January of 2000 to March of 2006 with metastatic breast cancer and bisphosphonate therapy were reviewed. All patients were contacted, and missing data were completed through structured interviews with their dentists and physicians (n = 75). Primary outcome was the development of BP-ONJ and the detection of possible additional trigger factors for the development of BP-ONJ. RESULTS: A total of 117 patients with breast cancer fulfilled the inclusion criteria, and data for 75 still living patients were included. Of these 75, 4 patients developed a BP-ONJ, resulting in a prevalence of 5.3%: 3 patients received zoledronate only; 1 patient had first pamidronate followed by zoledronate and ibandronate. A tooth extraction could be identified as an additional trigger factor for 2 patients. CONCLUSIONS: With a prevalence of 5.3%, BP-ONJ in breast cancer patients has become a relevant disease that should be discussed with patients for whom bisphosphonates have been recommended. Appropriate dental care before bisphosphonate therapy commences has been advised to reduce the occurrence of BP-ONJ.

In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), gene expression profiling was performed using a whole-transcriptome chip that contains 35,035 gene-specific 70 mere oligonucleotides (Human OligoSet 4.0; Operon, Cologne, Germany) to a set of 35 primary OSCCs. Altogether, 7390 genes were found differentially expressed between OSCC tumor samples and oral mucosa. To characterize the major biologic processes in this tumor collection, MAPPFinder, a component of GenMAPP version 2.1, was applied to this data set to generate a statistically ranked list of molecular signaling pathways. Among others, cancer-related pathways, such as mitogen-activated protein (MAP) kinase signaling (z score = 4.6, P < .001), transforming growth factor-beta signaling (z score = 3.0, P = .015), and signaling pathways involved in apoptosis (z score = 2.1, P = .037), were found deregulated in the OSCC collection analyzed. Focusing on the MAP kinase signaling pathway, subsequent tissue microarray analyses by immunohistochemistry revealed an increase in protein expression of MAP kinase-related proteins ERK1 in 22.8% (48 of 209) and ERK5 in 27.4% (76 of 277), respectively. An association of high ERK5 but not of high ERK1 expression with advanced tumor stage and the presence of lymph node metastases was found (P = .008 and P = .016, respectively). Our analysis demonstrates the reliability of the combined approach of gene expression profiling, signaling pathway analyses, and tissue microarray analysis to detect novel distinct molecular aberrations in OSCC.

BACKGROUND: Within the domain of craniomaxillofacial surgery, orthognathic surgery is a special field dedicated to the correction of dentofacial anomalies resulting from skeletal malocclusion. Generally, in such cases, an interdisciplinary orthodontic and surgical treatment approach is required. After initial orthodontic alignment of the dental arches, skeletal discrepancies of the jaws can be corrected by distinct surgical strategies and procedures in order to achieve correct occlusal relations, as well as facial balance and harmony within individualized treatment concepts. To transfer the preoperative surgical planning and reposition the mobilized dental arches with optimal occlusal relations, surgical splints are typically used. For this purpose, different strategies have been described which use one or more splints. Traditionally, these splints are manufactured by a dental technician based on patient-specific dental casts; however, computer-assisted technologies have gained increasing importance with respect to preoperative planning and its subsequent surgical transfer. METHODS: In a pilot study of 10 patients undergoing orthognathic corrections by a one-splint strategy, two final occlusal splints were produced for each patient and compared with respect to their clinical usability. One splint was manufactured in the traditional way by a dental technician according to the preoperative surgical planning. After performing a CBCT scan of the patient's dental casts, a second splint was designed virtually by an engineer and surgeon working together, according to the desired final occlusion. For this purpose, RapidSplint, a custom-made software platform, was used. After post-processing and conversion of the datasets into .stl files, the splints were fabricated by the PolyJet procedure using photo polymerization. During surgery, both splints were inserted after mobilization of the dental arches then compared with respect to their clinical usability according to the occlusal fitting. RESULTS: Using the workflow described above, virtual splints could be designed and manufactured for all patients in this pilot study. Eight of 10 virtual splints could be used clinically to achieve and maintain final occlusion after orthognathic surgery. In two cases virtual splints were not usable due to insufficient occlusal fitting, and even two of the traditional splints were not clinically usable. In five patients where both types of splints were available, their occlusal fitting was assessed as being equivalent, and in one case the virtual splint showed even better occlusal fitting than the traditional splint. In one case where no traditional splint was available, the virtual splint proved to be helpful in achieving the final occlusion. CONCLUSIONS: In this pilot study it was demonstrated that clinically usable splints for orthognathic surgery can be produced by computer-assisted technology. Virtual splint design was realized by RapidSplint®, an in-house software platform which might contribute in future to shorten preoperative workflows for the production of orthognathic surgical splints.