Altered bone development with impaired cartilage formation precedes neuromuscular symptoms in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a fatal neurodegenerative disease of newborns and children caused by mutations or deletions of the survival of motoneuron gene 1 resulting in low levels of the SMN protein. While neuromuscular degeneration is the cardinal symptom of the disease, the reduction of the ubiquitously expressed SMN additionally elicits non-motoneuron symptoms. Impaired bone development is a key feature of SMA, but it is yet unknown whether this is an indirect functional consequence of muscle weakness or caused by bone-intrinsic mechanisms. Therefore, we radiologically examined SMA patients in a prospective, non-randomized cohort study characterizing bone size and bone mineral density (BMD) and performed equivalent measurements in pre-symptomatic SMA mice. BMD as well as lumbar vertebral body size were significantly reduced in SMA patients. This growth defect but not BMD reduction was confirmed in SMA mice by µCT before the onset of neuromuscular symptoms indicating that it is at least partially independent of neuromuscular degeneration. Interestingly, the number of chondroblasts in the hypertrophic zone of the growth plate was significantly reduced. This was underlined by RNAseq and expression data from developing SMA mice vertebral bodies, which revealed molecular changes related to cell division and cartilage remodeling. Together, these findings suggest a bone intrinsic defect in SMA. This phenotype may not be rescued by novel drugs that enhance SMN levels in the central nervous system only.

Prelamination of the Radial Forearm Free Flap Using Free Full-Thickness Eyelid Skin Grafts: A New Approach for Intraoral Defect Reconstruction.

ABSTRACT: Free flap transfer for reconstruction of intraoral defects is a common procedure in oral and maxillofacial surgery. For tumor-related defects, the radial forearm flap is widely used for soft tissue restoration. However, transfer of free skin grafts to the donor site region is often required for wound closure after free flap harvesting, resulting in esthetic disturbances due to shrinkage of the grafted skin, attendant scarring, or mismatches in skin texture or color. Furthermore, free flap transfer may result in hair follicle transfer into the oral cavity, causing unfavorable intraoral hair growth in adult men in particular. Free flap prelamination can help reduce the potential disadvantages of free flaps, in terms of both flap design and size and donor site morbidity. For surgical treatment of oral cancer in middle-aged and elderly patients, eyelid dermatochalasis may present as a comorbidity leading to esthetic impairments or, in cases involving the upper eyelid, even a reduced field of view. In these cases, bilateral blepharoplasty can reduce the excess eyelid skin. The present study is the first to attempt to use excised skin after bilateral blepharoplasty as full-thickness skin grafts for radial forearm free flap prelamination. This approach combined surgical therapy of eyelid dermatochalasis with free flap prelamination, thereby avoiding the need to harvest free skin grafts from other anatomically healthy regions to close the donor site defect and preventing the accompanying disadvantages. The reconstruction results and clinical outcomes of patients revealed that radial forearm free flap prelamination using bilateral free full-thickness eyelid skin grafts was an easy and feasible method for intraoral defect reconstruction. In particular, this approach could avoid intraoral hair growth and additional skin grafting from other healthy anatomical regions, yielding good esthetic and functional results at the flap's recipient and donor sites.

Fulfillment of patients' information needs during oral cancer treatment and its association with posttherapeutic quality of life.

PURPOSE: Surgical therapy for oral cancer can lead to severe physical and psychological disorders that negatively impact patient quality of life (QoL). This study aimed to evaluate the relationship between fulfillment of patients' information needs during oral cancer treatment and patients' perception of posttherapeutic disorders influencing QoL. METHODS: A retrospective analysis of 1359 patients who were surgically treated for oral cancer using questionnaires administered during the multicenter rehabilitation study by the German-Austrian-Swiss Cooperative Group on Tumors of the Maxillofacial Region (DÖSAK). Patients and medical practitioners completed questionnaires following cancer treatment. RESULTS: Approximately 37% of patients felt inadequately informed about possible physical and psychological consequences of surgery. In contrast, only 16% of patients felt they were given inadequate information about the operative procedure and possible complications, and with regard to tumor diagnosis and cancer disease, only 15% of patients. Significant correlations were found between lacking information and increased perception of posttherapeutic disorders, whereas correlations with tumor-specific and operation-related parameters were markedly lower. The patients with superior QoL after treatment stated more frequently, nearly independent of individual patient characteristics, that the information that they were given prior to therapy was adequate. Information concerning possible physical and psychological consequences of an operation, however, was frequently stated to be inadequate, independent of QoL. CONCLUSION: Patients whose information needs concerning the diagnosis and treatment of oral cancer are adequately fulfilled may benefit in terms of their therapeutic outcome, experiencing less perception of posttherapeutic physical and psychological disorders and a superior QoL.

Angiogenic effects of mesenchymal stem cells in combination with different scaffold materials.

Tissue survival in regenerative tissue engineering requires rapid vascularization, which is influenced by scaffold material and seeded cell selection. Poly-l-lactide-co-glycolide (PLGA) and beta-tricalcium phosphate (ß-TCP) are well-established biomaterials with angiogenic effects because of their material properties. Given the importance of the seeded cell type as a co-factor for vascularization, mesenchymal stem cells (MSCs) are known to have high angiogenic potential. We hypothesized that PLGA and ß-TCP scaffolds seeded with MSCs would effectively induce a potent angiogenic response. Therefore, we studied the angiogenic effects after implanting PLGA and ß-TCP scaffolds seeded with isogeneic MSCs in vivo. Fifty-six BALB/c mice were equally divided into seven groups and underwent implantation of the dorsal skinfold chambers. Two MSC groups were seeded on collagen-coated PLGA or ß-TCP scaffolds, whereas groups 3-6 received collagen-coated or uncoated scaffolds without MSCs. No scaffold implantation was performed for group 7, which served as the control. Angiogenesis was assessed in vivo via intravital fluorescence microscopy. Angiogenic responses were noted on all scaffolds, whereupon MSC angiogenic response was significantly enhanced on days 6 and 10. Additionally, a comparison of biomaterials indicated increased angiogenic activity for ß-TCP scaffolds compared with PLGA scaffolds. In conclusion, seeding ß-TCP scaffolds with MSCs can accelerate vitalization and a combination of both significantly improves angiogenesis.

Deglutition in Patients With Hypernasality Associated With Unilateral Cleft Lip and Palate Evaluated With High-Resolution Manometry.

OBJECTIVE: To evaluate pharyngeal pressure profiles during swallowing in patients with unilateral cleft lip and palate (UCLP) and identify compensation mechanisms. DESIGN: Prospective experimental study. SETTING: University Hospital and Medical School. PARTICIPANTS: Ten volunteers and 10 patients with nonsyndromic repaired UCLP with hypernasality (age: 19-27 years, 5 females and 5 males per group) were included. INTERVENTIONS: All participants swallowed 2 and 10 mL of water and underwent high-resolution manometry (HRM). MAIN OUTCOME MEASURES: Pharyngeal and upper esophageal sphincter (UES) parameters were measured using HRM. Student t test was used for statistical intergroup comparisons. Additionally, the Sydney Swallowing Questionnaire (SSQ) was used as a subjective measure. RESULTS: Patients exhibited reduced velopharyngeal closing pressure and velopharyngeal and tongue base (TB) region contraction times, compared to volunteers (P < .05). The UES opening and closing functions did not change. The SSQ revealed nasal regurgitation in some patients. CONCLUSIONS: In patients with UCLP, velopharyngeal region alterations are caused by impaired muscle force and function. The reduced TB contraction time may be a compensation mechanism allowing bolus transportation without nasal regurgitation. However, deglutition is not completely altered since UES function remains normal. Future studies will need to reveal at which point a decrease in velopharyngeal closing pressure will result in velopharyngeal insufficiency.

Three-dimensional analysis of the velopharyngeal region in patients with cleft palate and healthy individuals.

PURPOSE: This study aims to attain metric data of the velopharyngeal dimensions of healthy subjects as well as patients with velopharyngeal insufficiency using the example of cleft and lip palate (CLP) in order to determine possible differences in the volumes of both groups. METHODS: Volumes and distances of velopharyngeal areas were analyzed retrospectively using cone beam computed tomography data sets (n = 60). Group 1 included healthy patients receiving dental implants (n = 31). Group 2 was represented by patients with surgically closed cleft lip and palate (n = 29). RESULTS: Biggest differences among mean values of both groups were found for: minimum axial area (p = 0.000), airway area caudal (p = 0.000), distance between posterior nasal spine and posterior pharyngeal wall (PPW) (p = 0.014), mean distance between velum and PPW (p = 0.000), length of PPW (p = 0.000) and length of anterior pharyngeal wall (p = 0.000). CONCLUSION: Differences in the shape and geometry of the velopharyngeal area in subjects with a regular velopharyngeal structure and function and patients with cleft palate do exist. The significant differences found here can be categorized into two groups: one reflects distances between the anterior and posterior pharynx, presenting longer distances for patients with CLP. The second significant difference regards values of length in cranio-caudal direction, which is longer in healthy subjects. With regards to these values, one could conclude, that even though total volumes of both groups did not differ in size, group 1 shows three-dimensional velopharyngeal shapes that are longer and narrower, whereas shapes of patients of group 2 tend to be wider and shorter in general.

CD24+ tumor-initiating cells from oral squamous cell carcinoma induce initial angiogenesis in vivo.

BACKGROUND: In oral squamous cell carcinoma (OSCC), a minor subset of cancer stem cells has been identified using the surface marker CD24. The CD24+ cell population is involved in initiating, maintaining, and expanding tumor growth, but has not been reported to be involved in angiogenesis to date. METHODS: NOD/SCID mice were equipped with dorsal skinfold chambers and gelatin sponges seeded with CD24+, CD24-, and unsorted cancer cells suspended in Matrigel® were implanted. Following intravital fluorescence microscopy, specimens were examined by immunohistology. RESULTS: Sponges seeded with CD24+ cells showed a significantly higher functional capillary density than those seeded with CD24- cells. The presence of endothelial cells was confirmed by immunohistochemistry for CD31. CONCLUSION: For the first time, CD24+ tumorigenic cells with angiogenic potential, which were isolated from OSCC, were characterized. Our findings provide a promising in vivo model to facilitate the development of therapeutic agents against cancer stem cells and their angiogenic pathways.

Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo.

Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation. In this study, the influence of cancer stem cells on initial angiogenesis was evaluated for the metastatic melanoma cell line D10. Following flow cytometry, CD133+ and CD133- cells were isolated using magnetic cell separation and different cell fractions were transferred to porcine gelatin sponges, which were implanted into the dorsal skinfold chamber of immunocompromised mice. Angiogenesis was analyzed based on microvessel density over a 10-day period using in vivo fluorescence microscopy, and the results were verified using immunohistology. CD133+ D10 cells showed a significant induction of early angiogenesis in vivo, contrary to CD133- D10 cells, unsorted D10 cells, and negative control. Neovascularization was confirmed by visualizing endothelial cells by immunohistology using an anti-CD31 antibody. Because CD133+ cells are rare in clinical specimens and hardly amenable to functional assays, the D10 cell line provides a suitable model to study the angiogenic potential of putative cancer stem cells and the leukocyte-endothelial cell interaction in the dorsal skinfold chamber in vivo. This cancer stem cell model might be useful in the development and evaluation of therapeutic agents targeting tumors.

Presentation and Evaluation of a Modified Wax-Bite Dental Splint for Surgical Navigation in Craniomaxillofacial Surgery.

PURPOSE: The purpose of the present study was to introduce and evaluate the use of a modified "wax-bite dental splint" for surgical navigation in craniomaxillofacial surgery. MATERIALS AND METHODS: A 2-layer wax bite dental splint was fabricated with an anterior extension, and 8 gutta percha markers were incorporated in each splint for marker-based pair-point registration. To evaluate the accuracy, the occlusal registration of the wax bite dental splint was performed on 10 artificial skulls. Consecutively, all the skulls were scanned using a standardized cone-beam computed tomography scanning protocol with the 2-layer wax bite dental splint in place. Automatic rigid marker-based pair-point registration was performed using the iPlan CMF software, version 3.0 (Brainlab AG, Feldkirchen, Germany) using 8 gutta percha markers incorporated into the wax bite dental splint. Additionally, the registration accuracy of 6 anatomic skeletal landmarks was measured on each skull. RESULTS: The mean registration error for each wax bite dental splint ranged from 0.78 to 1.01 mm. The overall mean registration error for the wax-bite dental splint-based registration was 0.89 ± 0.08 mm. The mean registration error for the 6 anatomic landmarks ranged from 1.23 to 2.3 mm. The overall mean registration error was 1.68 ± 0.28 mm. CONCLUSION: The results of the present study show the potential for a wax-bite dental splint as an alternative rigid registration method for surgical navigation in craniomaxillofacial surgery. Moreover, from a clinical viewpoint, the method is accurate, user-friendly, inexpensive, and not time-consuming.

Differences in velopharyngeal pressures during speech sound production in patients with unilateral cleft lip and palate (UCLP) and healthy individuals.

Background: During articulation the velopharynx needs to be opened and closed rapidly and a tight closure is needed. Based on the hypothesis that patients with cleft lip and palate (CLP) produce lower pressures in the velopharynx than healthy individuals, this study compared pressure profiles of the velopharyngeal closure during articulation of different sounds between healthy participants and patients with surgically closed unilateral CLP (UCLP) using high resolution manometry (HRM). Materials and methods: Ten healthy adult volunteers (group 1: 20-25.5 years) and ten patients with a non-syndromic surgically reconstructed UCLP (group 2: 19.1-26.9 years) were included in this study. Pressure profiles during the articulation of four sounds (/i:/, /s/, /ʃ/ and /n/) were measured by HRM. Maximum, minimum and average pressures, time intervals as well as detection of a previously described 3-phase-model were compared. Results: Both groups presented with similar pressure curves for each phoneme with regards to the phases described and pressure peaks, but differed in total pressures. An exception was noted for the sound /i:/, where a 3-phase-model could not be seen for most patients with UCLP. Differences in velopharynx pressures of 50% and more were found between the two groups. Maximum and average pressures in the production of the alveolar fricative reached statistical significance. Conclusions: It can be concluded that velopharyngeal pressures of patients with UCLP are not sufficient to eliminate nasal resonance or turbulence during articulation, especially for more complex sounds. These results support a general understanding of hypernasality during speech implying a (relative) velopharyngeal insufficiency.

Dental rehabilitation in irradiated oral cancer patients using patient-specific dental implants - Clinical outcome and oral health-related quality of life.

INTRODUCTION: Dental rehabilitation in oral cancer patients is essential for good oral health-related quality of life (OHRQoL). Patient-specific dental implants are suitable for treating tumor-related bony defects, resulting in satisfactory OHRQoL. However, knowledge concerning the clinical outcome and OHRQoL following tumor irradiation is lacking. MATERIAL AND METHODS: A retrospective analysis was carried out to evaluate clinical outcomes and OHRQoL in eight patients who received patient-specific dental implants and implant-supported dentures after surgical treatment for oral cancer with additional irradiation. OHRQoL assessment was performed using the German long version of the oral health impact profile (OHIP) questionnaire (OHIP-G53). RESULTS: Clinical examination revealed successful dental rehabilitation in all the patients with only minor impairments. Restricted stability and function of implants were not observed. OHIP sum-scores of all the patients indicated acceptable OHRQoL, but this varied between patients treated in the upper or lower jaw. Single-item sum-scores concerning the adverse events "difficulty in chewing," "food catching," "sore jaw," "sore spots," and "unclear speech" were detected to be the worst, and pain-related OHIP dimensions demonstrated the highest scores (followed by functional limitation, physical disability, and psychosocial impact) with a worse OHRQoL following lower jaw treatment. Other dimension sum-scores were overall lower and nearly equally distributed in patients. CONCLUSIONS: Dental rehabilitation of irradiated oral cancer patients using patient-specific dental implants may be suitable, leading to acceptable OHRQoL. However, implant insertion in the upper jaw seems to be more favorable. Further studies on patient-specific dental implants are warranted to validate the current results.

Additive effect of mesenchymal stem cells and VEGF to vascularization of PLGA scaffolds.

Bone marrow derived mesenchymal stem cells (bmMSCs) are widely used for the generation of tissue engineering constructs, since they can differentiate into different cell types occurring in bone tissues. Until now their use for the generation of tissue engineering constructs is limited. All cells inside a tissue engineering construct die within a short period of time after implantation of the construct because vascularization and establishment of connections to the recipient circulatory system is a time consuming process. We therefore compared the influences of bmMSC, VEGF and a combination of both on the early processes of vascularization, utilizing the mice skinfold chamber model and intravital fluorescence microscopy. Tissue engineering constructs based on collagen coated Poly d,l-lactide-co-glycolide (PLGA) scaffolds, were either functionalized by coating with vascular endothelial growth factor (VEGF) or vitalized with bmMSC. PLGA without cells and growth factor was used as the control group. Functionalized and vitalized tissue engineering constructs showed an accelerated growth of microvessels compared to controls. Only marginal differences in vascular growth were detected between VEGF containing and bmMSC containing constructs. Constructs containing VEGF and bmMSC showed a further enhanced microvascular growth at day 14. We conclude that bmMSCs are well suited for bone tissue engineering applications, since they are a valuable source of angiogenic growth factors and are able to differentiate into the tissue specific cell types of interest. The dynamic process of vascularization triggered by growth factor producing cells can be amplified and stabilized with the addition of accessory growth factors, leading to a persisting angiogenesis, but strategies are needed that enhance the resistance of bmMSC to hypoxia and increase survival of these cells until the tissue engineering construct has build up a functional vascular system.

Functional features of cancer stem cells in melanoma cell lines.

BACKGROUND: Recent evidence suggests a subset of cells within a tumor with "stem-like" characteristics. These cells are able to transplant tumors in immunodeficient hosts. Distinct from non-malignant stem cells, cancer stem cells (CSC) show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumor cells, and resistance to chemotherapy or radiation. They are often characterized by elevated expression of stem cell surface markers, in particular CD133, and sets of differentially expressed stem cell-associated genes. CSC are usually rare in clinical specimens and hardly amenable to functional studies and gene expression profiling. In this study, a panel of heterogenous melanoma cell lines was screened for typical CSC features. METHODS: Nine heterogeneous metastatic melanoma cell lines including D10 and WM115 were studied. Cell lines were phenotyped using flow cytometry and clonogenic assays were performed by limiting dilution analysis on magnetically sorted cells. Spheroidal growth was investigated in pretreated flasks. Gene expression profiles were assessed by using real-time rt-PCR and DNA microarrays. Magnetically sorted tumor cells were subcutaneously injected into the flanks of immunodeficient mice. Comparative immunohistochemistry was performed on xenografts and primary human melanoma sections. RESULTS: D10 cells expressed CD133 with a significantly higher clonogenic capacity as compared to CD133- cells. Na8, D10, and HBL cells formed spheroids on poly-HEMA-coated flasks. D10, Me39, RE, and WM115 cells expressed at least 2 of the 3 regulatory core transcription factors SOX2, NANOG, and OCT4 involved in the maintenance of stemness in mesenchymal stem cells. Gene expression profiling on CD133+ and CD133- D10 cells revealed 68 up- and 47 downregulated genes (+/-1.3 fold). Two genes, MGP and PROM1 (CD133), were outstandingly upregulated. CD133+ D10 cells formed tumors in NSG mice contrary to CD133- cells and CD133 expression was detected in xenografts and primary human melanoma sections using immunohistochemistry. CONCLUSIONS: Established melanoma cell lines exhibit, to variable extents, the typical features of CSCs. The tumorigenic cell line D10, expressing CD133 and growing in spheroids and might qualify as a potential model of melanoma CSCs.

Alendronate reduces periosteal microperfusion in vivo.

Objectives: Bisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of bisphosphonates on microperfusion; therefore, this study aimed to investigate alendronate-induced microcirculatory reactions in the calvarial periosteum of rats. Study design: Bone chambers were implanted into 48 Lewis rats. Microhemodynamics, inflammatory parameters, functional capillary density and defect healing were examined after alendronate treatment for two and six weeks using repetitive intravital fluorescence microscopy for two weeks. Results: Microhemodynamics remained unchanged. In alendronate-treated rats, inflammation was slightly increased, functional capillary density was significantly reduced (day 10: controls 100.45 ± 5.38 cm/cm2, two weeks alendronate treatment 44.77 ± 3.55 cm/cm2, six weeks alendronate treatment 27.54 ± 2.23 cm/cm2) and defect healing was decelerated. The changes in functional capillary density and defect healing were dose-dependent. Conclusion: The bisphosphonate alendronate has a significant negative impact on periosteal microperfusion in vivo. This could be a promising target for the treatment of MRONJ.

Dentin as a suitable bone substitute comparable to ß-TCP--an experimental study in mice.

Microvascular supply is of fundamental importance to the survival and integration of grafting. Since the autogenous bone is still the gold standard for osseous augmentation, the aim of this study was to analyze the initial osseous, angiogenic and inflammatory response and subsequent osseointegration after implantation of dentin and beta-tricalcium phosphate (ß-TCP) scaffolds into the calvaria chamber of balb/c mice comparing with bone. The vascularisation of perforated implants of dentin (n=8), ß-TCP (n=8) and isogenic calvarial bone (n=8) displaying pores similar in size and structure was analyzed in vivo using intravital fluorescence microscopy. In additional animals (n=24) the osseointegration of dentin, ß-TCP and bone implants was assessed by fluorochrome sequential labelling of growing bone for up to 12 weeks. Animals without implants served as controls. Intravital fluorescence microscopy revealed that implantation of bone substitutes caused an only mild inflammatory response. Comparable to isogenic bone both dentin and ß-TCP scaffolds were found nearly completely vascularized by day 22 and osseointegrated within 12 weeks. In conclusion, dentin and ß-TCP scaffolds are similar to isogenic bone in terms of inflammatory and neovascularization response, highlighting their potential utility in regeneration of bone defects.

A quantitative approach to orbital decompression in Graves' disease using computer-assisted surgery: a compilation of different techniques and introduction of the "temporal cage".

PURPOSE: Since 1911, when Dollinger first described surgical orbital decompression, many different techniques and approaches have been described, including 1-, 2-, and 3-wall decompressions with orbital fat removal. The indications for surgical treatment have been widened and include additional to optic neuropathy severe proptosis causing exposure keratopathy and disfigurement. Popular techniques for surgical decompression are the transantral or transpalpebral approach to the medial wall and orbital floor. Sometimes theses approaches are combined with lateral canthotomy incisions for access to the lateral wall ("3-wall decompression"). This report shows a compilation of different techniques using computer-assisted surgery for a 3-wall decompression with the introduction of the "temporal cage" in patients suffering from Graves' disease and the combination with zygomatic bone osteotomy. PATIENTS AND METHODS: Twelve patients suffering from Graves' disease presented for surgical treatment in our clinic. For surgical planning, a computed tomographic scan with navigation markers was carried out. The navigation was planned with voxel-based navigation software (VoXim or BrainLab). RESULTS: Of the patients, 1 had unilateral and 11 had bilateral decompressions. Of the 11 patients with bilateral procedures, 1 patient underwent simultaneous and 10 underwent sequential procedures. The 3-wall decompression in all cases was performed by transconjunctival approach. Temporary double vision could be observed in all cases. There was a significant reduction in proptosis. CONCLUSION: It was concluded that this approach and the computer-assisted surgery would be the operation of first choice when there is an indication for orbital decompression.

Endoscope-assisted transoral reduction and internal fixation versus closed treatment of mandibular condylar process fractures--a prospective double-center study.

PURPOSE: The aim of this international AO-study was to compare the functional outcome after open versus closed treatment of mandibular condylar neck fractures. PATIENTS AND METHODS: A prospective comparative study with two follow-ups (FU) at 8-12 weeks and 1 year was undertaken in two clinics, which exclusively privileged either surgical or conservative treatment due to different therapeutic agendas. Patients from clinic 1 (ENDO group) received endoscope-assisted transoral open reduction and internal fixation, whereas patients from clinic 2 (CONS group) were treated conservatively without surgery. Patients with unilateral condylar neck fractures showing one or more of the following conditions were included: displacement of the condyle with an inclination >30° and/or severe functional impairment such as malocclusion or open bite, with or without dislocation of the condylar fragment; severe pain upon palpation or movement, and/or vertical shortening of the ascending ramus. High or intracapsular condylar neck fractures were excluded. RESULTS: 75 patients (44 CONS and 31 ENDO patients) with condylar neck fractures were included in this study. The Asymmetric Helkimo Dysfunction Score (A-HDS) was slightly lower in the CONS group than in the ENDO group at the 8-12-week FU, corresponding to better function on the short-term. At the 1-year FU, however, there were slightly better values in the ENDO group. For the Clinical Dysfunction Index (Di) and the Anamnestic Dysfunction Index (Ai), CONS patients had a better outcome than ENDO patients at the 8-12 week FU, ie, a higher proportion of ENDO patients had severe symptoms due to the operative trauma. Yet these symptoms improved by one year, finishing with a significant higher proportion of symptom-free patients in the ENDO group. In addition, these patients had better values for the Index for Occlusion and Articulation Disturbance (Oi) at both FU examinations, ie, the proportion of patients without any occlusal disturbances was significantly higher in the ENDO group. On average, the duration of postoperative maxillo-mandibular fixation (MMF) was 3 times longer for the CONS group than for the ENDO group (33 vs. 11 days). CONCLUSION: Both treatment options may yield acceptable results for displaced condylar neck fractures. Especially in patients with severe malocclusion directly after trauma, however, endoscope-assisted transoral open reduction and fixation seems to be the appropriate treatment for prevention of occlusal disturbances during FU.

Bisphosphonate-associated osteonecrosis of the mandible: reliable soft tissue reconstruction using a local myofascial flap.

For the treatment of bisphosphonate-associated osteonecrosis of the jaw (BP-associated ONJ), poor cure rates are reported. In many cases, repeated osseous exposition and infection may occur. The currently recommended management of affected patients is antibiotic treatment and bony decortication, which is often complicated by soft tissue deficits due to chronic infection. In severe cases osteonecrosis can be managed often only by continuity resections of the mandible. For this purpose, we developed a new surgical procedure, which allows an effective closure of difficult jaw wounds in the lateral mandible. In the last 3 years, 20 patients with BP-associated osteonecrosis of the lower jaw were treated successfully with a modified defect-covering method using a myofascial flap. A mylohyoid muscle flap was detached from mylohyoid line and used to cover the bony defect. During 19 months mean follow-up, 90% of patients were asymptomatic, the oral mucosa was intact, and no exposed bone was observed. In consequence, we are able to demonstrate that a mylohyoid muscle flap provides a reliable wound closure in the lower jaw in patients treated with BPs. Although there are still no consensual therapy guidelines for patients affected by BP-associated ONJ, the results of the presented study provide evidence for an effective surgical therapy with long-term success. Covering compromised bone with well-vascularized tissue, a muscle flap, increased healing chances by enabling and supporting the necessary nutrition and defense against opportunistic infections. This therapy concept showed a good clinical outcome.

Advances and innovations in computer-assisted head and neck oncologic surgery.

Over the past years, computer-assisted surgery has gained more importance in craniomaxillofacial surgery, especially in primary and secondary treatment of head and neck malignancies. The basis for oncologic treatment of the head and neck region requires detailed planning using computed tomography, cone-beam computed tomography, or magnetic resonance imaging in combination with computer-assisted, infrared-based navigation system. These techniques allow a preplanned image-guided path to the tumor region for taking biopsies, resection, or reconstruction. The aim of this work was to show the advances and technical benefits for tumor surgery in a daily clinical routine from the view of the craniomaxillofacial surgeon. The target of our working group was to develop and clinically evaluate a novel three-dimensional planning and navigation software solution for treatment of craniofacial tumors. This work was carried out on 5 categories for oncologic surgical procedures in which computer-assisted surgery was applied from 2005 to 2011: preplanned trajectorial-guided tumor biopsy, intraoperative image-controlled tumor resection, tumor mapping, reconstruction after tumor surgery (true to original), and oral rehabilitation (backward planning). Successful preoperative planning, import of image data suitable for navigation, and intraoperative precise infrared-based navigation were obtained for all 5 categories without any complications. Image-guided navigation technique for head and neck oncologic surgery provides a precise, safe surgical method with real-time excellent anatomic orientation. Regarding the advantages of computer-assisted surgery, this technique will play a major part in craniofacial reconstructive surgery and will address widespread general methodologic solutions that are of great interest in multidisciplinary oncologic treatment.

Moderately Hypofractionated Radiotherapy Without Chemotherapy in Elderly or Frail Patients With Head and Neck Cancer.

BACKGROUND: Comorbidity and frailty are relevant limitations of normofractionated combined radiochemotherapy for squamous cell head and neck cancer (HNSCC), especially in elderly patients. This retrospective study aimed to evaluate the efficacy and toxicity of moderately hypofractionated radiotherapy (HRT) without chemotherapy in patients ineligible for concurrent radiochemotherapy. PATIENTS AND METHODS: Between 2011 and 2018, 51 elderly/frail patients with HNSCC were treated with either definitive (n=23) or adjuvant (n=28) moderate HRT. A dose of 45 Gy was given to the primary tumour region and cervical nodes with a sequential boost up to 50 in the adjuvant and 55 Gy in the definitive cure setting (2.5 Gy/fraction). Patient outcomes of locoregional control, overall survival, and acute and late toxicity were analysed. RESULTS: After a median follow-up of 6 months for the definitive HRT group and 28.5 months for the adjuvant HRT group, we found a median overall survival of 6 vs. 55 months (log-rank test: p<0.001) and a median locoregional control of 9 months vs. not reached (log-rank test: p=0.008), respectively. The 2-year rates of locoregional control were 28.5% for the definitive HRT group vs. 75.2% for the adjuvant HRT group. No acute or late grade 4-5 toxicity occurred; grade 3 toxicity was rarely documented. CONCLUSION: HRT in elderly/frail patients with HNSCC who are unfit for chemotherapy leads to acceptable local control with moderate toxicity in a short overall treatment time. Especially in the postoperative situation, HRT can be considered an appropriate alternative to normofractionated radio(chemo)therapy. Definitive HRT can be a treatment alternative, especially for multimorbid patients.