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Purpose: Current staging methods for squamous cell carcinomas (SCC) of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Because hematogenous tumor cell dissemination is a key event in tumor progression, we assessed the prognostic significance of disseminated tumor cells (DTC) in bone marrow and circulating tumor cells (CTC) in peripheral blood from patients with OSCC.Experimental Design: From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest, and mononuclear cells (MNC) were enriched by Ficoll density gradient centrifugation. To detect DTCs, MNCs were immunostained with the pan-keratin antibody A45-B/B3. Results were correlated with clinicopathologic parameters and clinical outcome such as recurrence and death during follow-up time (mean 916 days).Results: Ten of 80 patients (12.5%) harbored CTCs in peripheral blood, whereas in 18 of 90 patients (20.0%) DTCs in bone marrow could be detected. Surprisingly, in only 2 patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found for CTCs and tumor size (P = 0.04), nodal status and DTCs (P = 0.02), and distant metastasis with CTCs (P = 0.004) and DTCs (P = 0.005). Univariate and multivariate analyses revealed that CTCs and DTCs were significant and independent predictors of recurrence-free survival (P < 0.001).Conclusions: Both DTCs and CTCs are independent prognostic markers in patients with OSCC, predicting relapse with higher sensitivity at various disease stages than routine staging procedures. Bone marrow might be an interesting target organ for future therapeutic interventions. Clin Cancer Res; 20(2); 425–33. ©2013 AACR.

PDF file 404K, Supplementary Table 1: Detailed information for each CTC-positive patient regarding tumor size (T-stage), lymph node involvement (N-stage) and distant metastasis (M-stage) at diagnosis and number of CTCs/7.5 mL blood. Supplementary Table 2: Detailed information for each DTC-positive patient regarding tumor size (T-stage), lymph node involvement (N-stage) and distant metastasis (M-stage) at diagnosis and number of DTCs/2x106 mononuclear cells. Supplementary Figure 1: Gallery of CTC images generated with the CellSearch system from cases #1-10 equivalent to Patient ID in Supplementary Table 1. Supplementary Figure 2: Time to relapse for CTC-positive patients by adjuvant therapy (none, radiotherapy, radiochemotherapie, A left), A right: Time to relapse for CTC-negative patients by adjuvant therapy (none, radiotherapy, radiochemotherapie); B left: Time to relapse for DTC-positive patients by adjuvant therapy (none, radiotherapy, radiochemotherapie), right: Time to relapse for DTC-negative patients by adjuvant therapy (none, radiotherapy, radiochemotherapie) Supplementary Figure 3: Time to locoregional relapse for CTC-positive patients without metastatic disease at diagnosis (A); Time to locoregional relapse for DTC-positive patients without metastatic disease at diagnosis (B) Supplementary Figure 4: Gallery of detected DTCs from cases #1-18 equivalent to Patient ID in Supplementary Table 2

Summary Purpose The aim of this study was to prove the hypothesis that intraoperative fluorescence-angiography using indocyanine-green (ICGFA) can be used to predict the occurrence of perfusion-associated complications following microvascular reconstruction. Materials and Methods Consecutively perioperative data of patients who received microvascular reconstruction of the head and neck region and underwent ICGFA immediately after anastomosis was established were analyzed. The flow parameters analyzed in the investigation were (1) the baseline (IntMin) and (2) peak intensity (IntMax) of fluorescence, (3) the quotient of the two aforementioned parameters (Fmax/min) as an expression of the relative total increase, (4) the absolute difference in the two parameters (DiffInt) in terms of amplitude, (5) the duration of the intensity increase (TRise) until the peak, and (6) the percent intensity increase per second (Rise/secrel). Within the first 2 weeks postoperatively, every flap complication was documented. Subsequently, statistical analysis of the flap outcome was performed based on the flow parameters obtained intraoperatively. Results Data of 67 patients (male/female: 41/26) with an average age of 64 years (range 29-84 years) were analyzed. In 10 of these patients, postoperative perfusion-associated complications were observed (arterial/venous/microcirculatory: 4/4/3; p=0.12). The analysis of the intraoperatively obtained flow parameters showed a significant difference in the ratio of maximum and minimum intensity in arterial pedicle perfusion (Fmax/min) of patients with and without complications (with vs. without complications: 2.3±1.0 vs. 5.0±4.9; p Conclusion The ratio of maximum and minimum intensity (Fmax/min) is a predictor for postoperative venous stasis, arterial hypoperfusion and impaired microcirculation of a microvascular flap. Anastomoses with Fmax/min

Purpose We aimed to compare complication rates and functional outcomes in patients with bilateral mandibular fractures treated with different degrees of internal fixation rigidity. Patients and Methods This international, multicenter randomized controlled trial included adults with bilateral mandibular fractures located at either the angle and body, angle and symphysis, or body and symphysis. Patients were treated with either a combination of rigid fixation for the anterior fracture and nonrigid fixation for the posterior fracture (mixed fixation) or nonrigid fixation for both fractures. The primary outcome was complications within 6 weeks after surgery. Secondary outcomes were complications within 3 months, Helkimo dysfunction index, and mandibular mobility at 6 weeks and 3 months after surgery. Results Of the 315 patients enrolled, 158 were randomized to the mixed fixation group and 157 to the nonrigid fixation group. The overall complication rate at 6 weeks in the intention-to-treat population was 9.6% (95% confidence interval [CI], 5.3% to 15.6%) in the mixed fixation group and 7.8% (95% CI, 4.0% to 13.5%) in the nonrigid fixation group. With an unadjusted odds ratio of 1.25 (95% CI, 0.51 to 3.17), there were no statistically significant differences in complication rates between the 2 groups (P = .591). A multivariable model for complication risk at 6 weeks found no significant differences between treatment groups, but patients with moderate or severe displacement had a higher complication rate than those with no or minimal displacement (adjusted odds ratio, 4.58; 95% CI, 1.16 to 18.06; P = .030). There were no significant between-group differences in complication rates at 3 months. Moreover, no significant differences in Helkimo dysfunction index and mandibular mobility index at 6 weeks and 3 months were found between groups according to treatment allocated and treatment received. Conclusions A combination of rigid and nonrigid fixation in patients with bilateral mandibular fracture has similar complication rates and functional outcomes to nonrigid fixation for both fractures.

Studies evaluating plate-related complications in patient-specific versus conventional fixation systems in free flap surgery are lacking. This was a retrospective study of 128 osseous free flaps with a minimum follow-up of 12 months. Wound healing disorders, plate exposure, fixation failure, and subtotal osseous union were recorded and evaluated statistically by univariate and regression analysis. Complication rates were as follows: wound healing disorders 33.6% (computer-aided design and computer-aided manufacturing (CAD/CAM) vs. conventional: 35.1% vs. 33.0%); plate exposure 21.9% (29.7% vs. 18.7%); fixation failure 7.0% (8.1% vs. 6.6%); subtotal osseous union 36.7% (45.9% vs. 33.0%). Radiotherapy (P

Aim The purpose of this study was to survey the current opinions of hospitals and medical practices concerning the perioperative management of patients undergoing direct oral anticoagulant therapy (DOAC) and discuss recommendations for the clinical practice. Materials and methods A questionnaire with 13 topics and multiple ordinal-polytomous subitems was designed and sent to 120 Departments of Oral and Maxillofacial Surgery in Austria, Switzerland and Germany, as well as to 85 oral and maxillofacial/oral surgeons in medical offices in Hamburg, Germany. The data were statistically evaluated by Chi-square, Fisher's exact and Jonckheere-Terpstra tests. Results The rate of response was 42%. Thirty-seven percent of respondents reported treating over 50 patients per year with undergoing DOAC therapy and only 18% assess a high bleeding risk [33% for vitamin K antagonists (VKA)]. In contrast to that, 62% of respondents would interrupt the DOAC therapy for extraction of one tooth, while 94% would continue VKA therapy. Significantly more clinicians apply suture than those in a medical office. The use of additional hemostatic measures varied between clinic and medical practice. There was a clear request for more detailed guidelines. Conclusion The study shows the current opinion for perioperative management of patients undergoing DOAC therapy. Multi-centric studies under controlled conditions are needed for a safer treatment of anticoagulated patients as therapy strategies differ greatly between institutions and therefore a complication analysis is hardly possible.

Certain skeletal defects may develop in neurofibromatosis type 1 (NF1), a common tumor-suppressor syndrome, such as cranial lesions confined to the lambdoid suture region. Here, we report on the repair of osseous defects of occipital bone in a NF1 patient with history of skull trauma and tumorous hemorrhage. Computer-aided design and computer-aided manufacturing (CAD/CAM)-assisted devices were applied to safely close the bone defects. The variable phenotype of NF1 in the occipital skull region is discussed and a brief review is presented on NF1-related therapies for tumors and malformations of the occipitoparietal skull region.

Background/Aim: Osteotomy as the first step in surgery, provides access to the field and its application could influence the outcome. Nowadays, the conventional burr reduction is being challenged by newer sonic and ultrasonic methods. We investigated the bone structural integrity and metal attrition residues both in bone and the irrigation fluid. Materials and Methods: Bovine ribs were cut using three methods. Bone cuts were studied using Environmental Scanning Electron Microscopy (ESEM) for tissue discrepancies and Scanning Electron Microscopy/Energy Dispersion X-Ray Microanalysis (SEM/EDX) for organic and inorganic debris. Results: Better preservation of bone architecture was seen in piezo and sono surgery while metal attrition was not conclusive (p>0.05). Unlike in bone analyses, both bur and ultrasonic osteotomies showed statistically significant higher median inorganic detection per analysis (p=0.021 and p=0.037, respectively). Conclusion: Sono and piezo surgery proved to be less invasive while attrition properties were the same.

Intensity-modulated radiation therapy (IMRT) enables radiation oncologists to optimally spare organs at risk while achieving homogeneous dose distribution in the target volume. Despite great advances in technology, xerostomia is one of the most detrimental long-term side effects after multimodal therapy in patients with locally advanced head and neck cancer (HNC). This prospective observational study examines the effect of parotid sparing on quality of life in long-term survivors. A total of 138 patients were grouped into unilateral (n = 75) and bilateral (n = 63) parotid sparing IMRT and questioned at 3, 24, and 60-month follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. Treatment-related toxicity was scored according to the RTOG/EORTC toxicity criteria. Patients’ QoL 24 and 60 months after IMRT was analyzed by ANCOVA using baseline QoL (3 months after IMRT) as a covariate. Patients with bilateral and unilateral parotid-sparing IMRT surviving 60 months experience similar acute and late side effects and similar changes in QoL. Three months after IMRT, physical and emotional function as well as fatigue, nausea and vomiting, pain, dyspnea, and financial problems are below (function scales) or above (symptom scales) the threshold of clinical importance. In both groups, symptom burden (EORTC H&N35) is high independent of parotid sparing 3 months after IMRT and decreases over time in a similar pattern. Pain and financial function remain burdensome throughout. Long-term HNC survivors show a similar treatment-related toxicity profile independent of unilateral vs. bilateral parotid-sparing IMRT. Sparing one or both parotids had no effect on global QoL nor on the magnitude of changes in function and symptom scales over the observation period of 60 months. The financial impact of the disease and its detrimental effect on long-term QoL pose an additional risk to unmet needs in this special patient population. These results suggest that long-term survivors need and most likely will benefit from early medical intervention and support within survivorship programs.

Backround This study was designed to analyse the value of preoperative Cone Beam CTs (CBCT) prior to the surgical removal of complex lower third molars. Furthermore, the aim was to assess injuries to the inferior alveolar nerve (IAN) bundle and postoperative neurological disorders depending on the position of the lower third molar and the inferior alveolar nerve bundle. Methods In this retrospective examination preoperative Cone Beam CTs and Orthopantomographs (OPT) of 324 patients were analysed concerning the location of the lower third molars in relation to the mandible and the inferior alveolar nerve bundle. Surgery protocols of all patients who underwent the surgical removal of at least one complex lower third molar were analysed concerning patient data, length of surgery, intraoperative haemorrhage, intraoperative exposure of the inferior alveolar nerve bundle, postoperative swelling and postoperative neurological disorders. The data was then compared to data from international studies. Results In all 324 patients a permanent neurological damage was not found. Temporary neurological damage was recorded in 13 cases (2.6%). A caudal nerve position with no measurable distance to the root of the lower third molar was associated with the highest risk of a temporal neurological damage. A vestibular touching nerve route also correlated with postoperative sensitivity impairment. If a mesioangulation (Winter) or a Pell and Gregory Type IIIC appears in the OPT, risk of neurological damage is at its highest. Conclusions Three-dimensional radiographic imaging, in our patient group, does not significantly affect the risk for complications during the surgical removal of complex lower third molars. Therefore, it should only be utilized for risk assessment, especially in cases of symptom-free lower third molars. A preoperative orthopantomogram still can be accepted as standard for radiographic imaging. An intraoperative exposure of the IAN bundle does not necessarily predict simultaneous neurological damage. Exposure of the IAN bundle is no indication for a discontinuation of the surgery.

PURPOSE To evaluate the frequency of deep lingual concavities in the lower jaw, which can cause surgical complications while inserting dental implants. METHODS Cross-sections of the mandible alveolar ridge at the edentulous sockets were obtained via cone-beam computed tomography. Measurements were carried out using the freeware 'IC Measure' and based on the basic definitions of a previous study. RESULTS Most (767/826 = 93%) sockets had concavities of various degrees (30-90°), while 59 (7%) sockets had no concavity. However, the majority of the concavities (71%) were mild, with angles > 60°. The other 220 (26%) sockets had deeper concavities of

Background/aim The purpose of this study was to evaluate a potential widening of the periodontal space as an initial measurable imaging criterium on panoramic radiographs in patients with the diagnosis of antiresorptive drug related osteonecrosis of the jaw (ARONJ). Patients and methods A retrospective analysis of panoramic radiographs of 16 patients (12 females and 4 males; mean age is 70.5 years, standard deviation is 14 years) was performed, over a period of 12 months with the diagnosis of ARONJ. Panoramic radiographs of 16 healthy patients (12 females and 4 males; mean age was 70.6 years, standard deviation was 13.8 years) without diagnosis of ARONJ served as controls. All images were taken with the same device and were evaluated by two experienced maxillofacial surgeons and one dentist. Results Compared to the control group, a mean widening of the periodontal space of 0.06 mm (confidence interval (CI)=0.05-0.17 mm) was found in the study group. However, this difference was not statistically significant. Conclusion Although a very extensive and sophisticated interindividual comparison was performed to evaluate for slight changes of the periodontal space in patients with antiresorptive drug therapy, our results demonstrate that PDS widening is not a predictive parameter for ARONJ. Therefore, our results indicate that panoramic radiographs are not sufficient enough to allow assessment of stages and disease progress in ARONJ patients regarding to periodontal space widening.

Purpose Free flap surgery can be associated with donor-site morbidity. The purpose of this study was to analyze long-term functional outcomes at the donor site after deep circumflex iliac artery (DCIA) bone flap harvesting. Methods Fourteen patients (8 men and 6 women, mean age 53.9 years; range 22-87 years) with mandible resection (8 carcinomas, 4 ameloblastomas, 1 osteonecrosis, and 1 myxofibroma) and DCIA flap reconstruction were included in an observational study. Ranges of motion in the hip and lumbar spine, Harris hip score (HHS), jumping mechanography, chair rising, and balance testing were performed on a ground force reaction plate (Leonardo Mechanograph, Novotec Medical GmbH, Germany). The primary outcome was the Esslinger fitness index (EFI, maximum peak power in W/kg normalized to age and gender). Results Functional assessment was performed preoperatively and 29.0 months postoperatively (range 12-51 months). Mean DCIA flap length was 6.3 cm (range 3.3-10.1 cm). Jaw reconstruction was successful in all cases. HHS (99.2 vs. 97.7 points, P = .004) and all ranges of motion in the lumbar spine and hip joint except for dorsal extension were significantly reduced postoperatively (range -4° to -11.0°). There was no significant difference between pre- and postoperative EFI (77.9% vs. 74.28%, P = .591) and body sway (1.25 cm2 vs. 2.01 cm2 , P = .806). Sensory deficits (n = 5), load dependent pain (n = 3), and limitations of daily activities (n = 3) were subjective complaints. Conclusion Functional donor site morbidity after DCIA harvesting can be expected to be low in the long-term.

Purpose The purpose of this clinical study was to evaluate the sensitivity and specificity of cervical sentinel lymph node biopsy after mapping with indocyanine green fluorescence (ICG) for imaging early-stage oral cancer. Patients and methods A sentinel lymph node biopsy (SLNB) was performed during a selective neck dissection (SND) in 20 patients with oral squamous cell carcinoma (OSCC, cT1 or cT2, N0 status). The sentinel lymph nodes (SLN) were identified using an infrared video camera after ICG injection. Lymph nodes were examined histologically. The endpoint of this study was to investigate the rate of false-negative results in SLNB. Results Sentinel lymph nodes could be detected after 8.1 min (range 1–22 min). In eight out of 20 cases, lymph node metastases were found during histopathological evaluation of the neck dissection specimen. In four cases a metastasis could be found in the detected SLN (sensitivity 50%). In the other four cases metastases were found in different lymph nodes. Specificity was 100%, positive predictive value 100%, and negative predictive value 75%. Conclusion In this study, reliability of sentinel lymph node biopsy after ICG imaging could not be verified, as there were false-negative results in 50% of the cases. Therefore, SND can still be recommended as for patients with cT1 or cT2 OSCC, and a N0 neck status.

Strong expression of survivin is associated with worse survival in many different tumours, and in cell culture, a correlation between radiation resistance and survivin expression can be seen. The potential of survivin expression as a prognostic/predictive marker or therapeutic target has not been examined in head and neck squamous cell carcinomas (HNSCC) yet. Retrospective study of 452 tissue samples and clinical data from patients with squamous cell carcinomas of the larynx/hypopharynx (LSCC), oral cavity (OSCC) and oropharynx (OPSCC) treated in the University Medical Centre Hamburg-Eppendorf between 2002 and 2006. The expression patterns were detected by tissue microarray technique and correlated with clinical parameters (sex, age, tumour location, TNM 7th edition, grading, recurrence-free and overall survival). 222 OSCC, 126 OPSCC and 105 LSCC tumours of 118 females and 335 males with a mean follow-up of 41.3 months were examined. Survivin expression correlates with pN, cM, pT and overall survival. The potential of survivin as a prognostic/predictive marker is very high. The findings have to be confirmed in a larger cohort of HNSCC esp. in those tumours treated primarily with radio/radiochemotherapy.

Purpose To test the antimicrobial properties, surface topography, reaction of surrounding tissue (biocompatibility), and osseointegration of ultrathin implant surfaces containing polysiloxane and nanoscaled silver particles. Materials and methods Implants with polysiloxane coating and nanoscaled silver particles (Ag/SiOxCy; HyProtect, Bio-Gate) were compared with implants with polysiloxane coating alone and with noncoated (grit-blasted and acid-etched) implants. A total of 72 implants were inserted into the calvaria of eight domestic pigs (nine implants each, three of each type). After 3 months, histologic sections were evaluated for inflammatory cell infiltration and bone implant contact. Results Roughness parameters did not differ between all three implant types. The Ag/SiOxCy coating exhibited a good antimicrobial effect in vitro and no sign of inflammatory cell infiltration in vivo. The noncoated implants demonstrated 10.85% and 14.48% more bone contact than the polysiloxane-coated implants (P = .003) and the Ag/SiOxCy‑coated implants (P ≤ .001), respectively. Osseointegration was not significantly different between the Ag/SiOxCy‑coated and polysiloxane-coated implants (P = .72). Conclusion The osseointegration capability of the Ag/SiOxCy-coated implants was equal to that of the polysiloxane-coated implants but less than that of the grit-blasted and acid-etched implants. Because of the biocompatibility of the polysiloxane coating, further studies should be conducted in load-bearing models and in the oral cavity to investigate the antimicrobial effect of the embedded silver clusters.

Magnesium is a highly promising candidate with respect to its future use as a material for resorbable implants. When magnesium degrades, hydrogen gas is released. High doses of gas emergence are reported to impair osseointegration and may therefore lead to fixation failure. The successful delay and reduction of the degradation rate by applying plasma electrolytic oxidation (PEO) as a post processing surface modification method for magnesium alloy has recently been demonstrated. The aim of this study was thus to compare the degradation behavior of a WE43-based plate system with and without respective PEO surface modification and to further investigate osseointegration, as well as the resulting effects on the surrounding bony tissue of both variants in a miniature pig model. WE43 magnesium screws and plates without (WE43) and with PEO surface modification (WE43-PEO) were implanted in long bones of Gottingen Miniature Pigs. At six and twelve months after surgery, micro-CT and histomorphometric analysis was performed. Residual screw volume (SV/TV; WE43: 28.8 ± 21.1%; WE43-PEO: 62.9 ± 31.0%; p = 0.027) and bone implant contact area (BIC; WE43: 18.1 ± 21.7%; WE43-PEO: 51.6 ± 27.7%; p = 0.015) were increased after six months among the PEO-modified implants. Also, surrounding bone density within the cortical bone was not affected by surface modification (BVTV; WE43: 76.7 ± 13.1%; WE43-PEO: 73.1 ± 16.2%; p = 0.732). Intramedullar (BV/TV; WE43: 33.2 ± 16.7%; WE43-PEO 18.4 ± 9.0%; p = 0.047) and subperiosteal (bone area; WE43: 2.6 ± 3.4 mm2; WE43-PEO: 6,9 ± 5.2 mm2; p = 0.049) new bone formation was found for both, surface-modified and non-surface-modified groups. After twelve months, no significant differences of SV/TV and BV/TV were found between the two groups. PEO surface modification of WE43 plate systems improved osseointegration and significantly reduced the degradation rate within the first six months in vivo. Osteoconductive and osteogenic stimulation by WE43 magnesium implants led to overall increased bone growth, when prior PEO surface modification was conducted.

FGFR1 is a receptor tyrosine kinases involved in tumor growth signaling, survival, and differentiation in many solid cancer types. There is growing evidence that FGFR1 amplification might predict therapy response to FGFR1 inhibitors in squamous cell lung cancers. To estimate the potential applicability of anti FGFR1 therapies in squamous cell carcinomas of the head and neck, we studied patterns of FGFR1 amplification using fluorescence in situ hybridization (FISH). A tissue microarray was constructed from 453 primary treatment-naive squamous cell carcinomas of the head and neck regions with histopathological and clinical follow-up data [including oral cavity (n = 222), oropharynx (n = 126), and larynx (n = 105)]. FGFR1 and centromere 8 copy numbers were assessed by dual-color FISH. FGFR1 amplification was defined as a copy number ratio FGFR1: centromere 8 ≥ 2.0. HPV sequencing and p16 immunohistochemistry (IHC) were applied to FGFR1-amplified cancers. FISH analysis was successful in 297 (66%) of the 453 cancers. FGFR1 amplification was found in 6% of analyzable tumors, and was more frequent in tumors of the oral cavity (13/133 amplified, 10%), than cancers of other localizations (1/79 oropharynx, 4/85 larynx; p = 0.007 and 0.159, respectively). One out of 18 FGFR1 amplified cancers was HPV positive. No associations were found between FGFR1 amplification and tumor phenotype or p16 IHC. Head and neck cancers are recurrently affected by FGFR1 amplification, with a predominance in cancers of the oral cavity. Finding only one HPV positive and FGFR1 amplified cancer argues against a causal relationship between HPV and FGFR1 amplifications.

Aufgrund der persistierend hohen Inzidenz von Tumoren im Kopf-Hals-Bereich besteht diesbezuglich ein hoher Bedarf an Therapieoptionen. Trotz Fortschritten in der onkologischen Tumortherapie ist eine ausgedehnte operative Resektion bei diesen Tumoren weiterhin in vielen Fallen unumganglich. Anhand eines klinischen Beispiels mochten wir in diesem Artikel die Fortschritte der operativen Therapie, insbesondere der CAD-/CAM-basierten (CAD/CAM: Computer Aided Design/Manufacturing) plastischen Rekonstruktion, erlautern.

BioMed research international 2017, 1-9 (2017). doi:10.1155/2017/3848207, Published by Hindawi, New York [u.a.]

Patients with oropharyngeal carcinoma (OPC) often have difficulty swallowing, which may affect quality of life (QoL). Radiation dose to constrictor muscles plays an important role. 54 patients with locally advanced OPC were evaluated after intensity-modulated radiotherapy. Data were collected at standardized intervals using the EORTC questionnaires QLQ-C30 and QLQ-HN35 within two years. The pharyngeal constrictors (superior, middle, and inferior) were each contoured as an organ at risk. Influence of dose to the constrictors (≥55 Gy vs.

Frakturen des Gesichtsschadels sind eine sehr haufige Verletzungsart. Gewaltdelikte zahlen neben Sturzen, Sportverletzungen und Verkehrsunfallen zu den fuhrenden Ursachen. Die Therapie der Wahl ist heute in den meisten Fallen die Reposition und Osteosynthese mittels Miniplatten aus Titan. Das Management von eingebrachtem Osteosynthesematerial (OSM) im Gesichtsbereich wird haufig durch die Hauspolitik der jeweiligen Klinik bestimmt. Dieser Ubersichtsartikel beschreibt die aktuelle Datenlage zur Entfernung von in situ befindlichem OSM in der kraniomaxillofazialen Chirurgie.

This study assesses the biocompatibility of novel silk protein membranes with and without modification, and evaluates their effect on facilitating bone formation and defect repair in guided bone regeneration. Two calvarian bone defects 12 mm in diameter were created in each of a total of 38 rabbits. Four different types of membranes, (silk-, hydroxyapatite-modified silk-, β-TCP-modified silk- and commonly clinically used collagen-membranes) were implanted to cover one of the two defects in each animal. Histologic analysis did not show any adverse tissue reactions in any of the defect sites indicating good biocompatibility of all silk protein membranes. Histomorphometric and histologic evaluation revealed that collagen and β-TCP modified silk membranes supported bone formation (collagen: bone area fraction p = 0.025; significant; β-TCP modified silk membranes bone area fraction: p = 0.24, not significant), guided bone regeneration and defect bridging. The bone, which had formed in defects covered by β-TCP modified silk membranes, displayed a more advanced stage of bone tissue maturation with restoration of the original calvarial bone microarchitecture when compared to the bone which had formed in defects, for which any of the other test membranes were used. Micro-CT analysis did not reveal any differences in the amount of bone formation between defects with and without membranes. In contrast to the collagen membranes, β-TCP modified silk membranes were visible in all cases and may therefore be advantageous for further supporting bone formation beyond 10 weeks and preventing soft tissue ingrowth from the periphery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

Aim: In order to provide adequate treatment to a patient with a subtype of Oromandibular Limb Hypogenesis Syndromes (OLHS), this study aimed to review and to analyze the current literature and treatment options of OLHS. Methods: Literature review in PubMed and Sciencedirect. Due to the small number of results, all available references were analyzed precisely. Results: Cases of OLHS are formerly rare and often incomplete. There are various classifications available, which, however, often seem confusing and are of little practical relevance. Furthermore, we present a complete case report of a patient with Charlie M syndrome, a type IV (Chicarilli)/ V (Hall) OLHS malformation. We also describe embryologic pathogenesis and differential diagnoses. Conclusion: As a result of our literature review, we recommend an adjusted classification for OLHS.

To compare multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) regarding radiation, resolution, image noise, and image quality. CBCT and 256-MDCT were compared based on three scan protocols: Standard-dose (≈24 mGy), reduced-dose (≈9 mGy), and low-dose (≈4 mGy). MDCT images were acquired in standard- and high-resolution mode (HR-MDCT) and reconstructed using filtered back projection (FBP) and iterative reconstruction (IR). Spatial resolution in linepairs (lp) and objective image noise (OIN) were assessed using dedicated phantoms. Image quality was assessed in scans of 25 cadaver heads using a Likert scale. OIN was markedly higher in FBP-MDCT when compared to CBCT. IR lowered the OIN to comparable values in standard-mode MDCT only. CBCT provided a resolution of 13 lp/cm at standard-dose and 11 lp/cm at reduced-dose vs. 11 lp/cm and 10 lp/cm in HR-MDCT. Resolution of 10 lp/cm was observed for both devices using low-dose settings. Quality scores of MDCT and CBCT did not differ at standard-dose (CBCT, 3.4; MDCT, 3.3-3.5; p > 0.05). Using reduced- and low-dose protocols, CBCT was superior (reduced-dose, 3.2 vs. 2.8; low dose, 3.0 vs. 2.3; p

Aim Treatment-associated lymphedema is a common side effect after multimodal therapy for locally advanced head and neck cancer (LAHNC). This study aims to evaluate potential prognostic factors for head and neck lymphedema (HNL) and its potential impact on clinical outcome. Methods This is a prospective data registry analysis on 280 patients treated for locally advanced head and neck cancer (LAHNC). All patients received surgery and risk-adapted platinum-based adjuvant intensity modulated radio(chemo)therapy (R(C)T, IMRT). Treatment- related toxicity was prospectively registered in a data base in regular intervals (baseline 3 months after R(C)T, every 3 months for 3 years, and every 6 months thereafter) and documented according to RTOG/EORTC toxicity criteria. Results Predictive for any grade HNL 3 months after R(C)T were age, BMI, number of removed nodes and RT modality. Multivariable logistic regression analysis showed that in the acute toxicity phase (3 months after R(C)T) higher body mass index (BMI), extracapsular spread (ECE), linac-based IMRT, bilateral treatment to the neck (surgery and RT), and the addition of chemotherapy increase the risk for grade 2 HNL. For chronic HNL, higher BMI, linac-based IMRT and ECE were predictive for grade 2 HNL. Higher BMI is associated with better local control rates. Advanced age and ECE had a negative impact on OS. Conclusion HNL is a common acute and late side effect after multimodal therapy for LAHNC. Knowing risk factors for HNL prior to therapy enables caregivers and patients to take measures prior to treatment to prevent or limit the effects of HNL.

In an effort to generate titanium surfaces for implants with improved osseointegration, we used direct laser interference patterning (DLIP) to modify the surface of pure titanium grade 4 of four different structures. We assessed in vitro cytoxicity and cell attachment, as well as the viability and proliferation of cells cultured directly on the surfaces. Attachment of the cells to the modified surfaces was comparably good compared to that of cells on grit-blasted and acid-etched reference titanium surfaces. In concordance with this, viability and proliferation of the cells directly cultured on the specimens were similar on all the titanium surfaces, regardless of the laser modification, indicating good cytocompatibility.

Increasingly, aging societies pose a challenge, particularly in the most developed countries. This trend leads to an increasing group of old and very old patients presenting unique requirements and challenges. One of these challenges consists in reassessment and adaption of established treatment strategies for the elderly patients. There is an ongoing discussion taking place among cranio-maxillo-facial surgeons about the appropriate extent of reconstructive flap surgery for old patients. This monocentric retrospective cohort study investigated 281 reconstructions with microvascular flaps by comparing the risk for a negative outcome, which was defined as revision, flap loss, and patient death, between three subgroups of elderly patients and younger patients. The three subgroups of elderly patients were defined as—1: young old (65–74 years), 2: old (75–84 years), and 3: oldest old (≥ 85 years). The group of the younger patients was defined by age between 50 and 64 years. Data were obtained within a defined period of 42 months. Significant correlations with a negative outcome were found for the variables stay on IMC/ICU, multiple flaps, and radiotherapy prior surgery. Our data showed no significant correlation between age and a higher risk for a negative outcome. Defect reconstruction with microvascular flaps in old patients is not related with a higher risk for a negative outcome. Independently of age, treatment with microvascular flaps is an option for all operable patients, with an indication for oncologic surgery. For optimal therapy planning, individual patient resources and preferences should be considered instead of chronologic age.

Positive effects of irradiation with ultraviolet (UV) light or treatment with non-thermal plasma on titanium and zirconia surfaces have been described in various studies. The aim of this study was to assess and compare the changes in the physicochemical surface conditions of titanium and zirconia surfaces after a short treatment with UV light or with non-thermal plasmas of argon or oxygen. Titanium and zirconia samples with moderately rough surfaces were treated for 12 min either in a UV-light oven or in a non-thermal plasma reactor that generates non-thermal plasmas of oxygen or argon. Changes in surface conditions were assessed by confocal microscopy, dynamic contact angle measurement, and X-ray photoelectron spectroscopy (XPS). No changes in roughness occurred. Ultraviolet irradiation and non-thermal plasma significantly increased the wettability of the titanium and zirconia surfaces. X-ray photoelectron spectroscopy showed an increase of oxygen and a significant decrease of carbon after treatment with either method. Thus, ultraviolet light and non-thermal plasma were found to be able to improve the chemical surface conditions of titanium and zirconia following a short exposure time. However, further in vitro and in vivo studies are needed to determine the relevance of the results.

Purpose The preservation of peri-implant bone is one requirement for long-term success of dental implants. The purpose of this study was to evaluate the impact of subcrestal placement on the crestal bone level of immediate versus delayed placed implants after loading. Materials and methods In this retrospective study, data of 159 patients who received 330 implants was analyzed. Implants were placed subcrestally, crestally or supracrestally into fresh sockets or healed sites. Vertical bone level height was assessed radiographically and implants were followed up annually. The influence of patient and implant related risk factors for peri-implant bone loss was evaluated using a linear mixed model. Results Depth of implant placement was significantly correlated with peri-implant bone loss (P = 0.001, 95% CI). Least effective loss of crestal bone was determined when implants were placed between 1 mm and 1.99 mm subcrestally. Smoking significantly enhanced the risk of peri-implant bone loss (P = 0.04, 95% CI). Immediate implant placement was not positively correlated with peri-implant bone loss (P = 0.51, 95% CI). Conclusion Within the limits of this study, implant placement 1.08 mm subcrestally may be recommendable in order to avoid supracrestal expositions of platform-switched titanium implants over time.

Background Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2, plays an important role in tumor development and progression by interacting with histone and non-histone proteins. EZH2 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. Material and methods This study investigates the prognostic relevance of immunohistochemical EZH2 expression in head and neck squamous cell carcinoma. Tissue microarray sections with 667 cancers of oral cavity, oro- and hypopharynx and larynx were analyzed for EZH2 expression. Results Nuclear EZH2 staining was recorded in 322 (81.8%) of 394 cases. Staining was weak in 33 (10.2%), moderate in 128 (39.6%), and strong in 103 (32.0%) cancers. The prevalence of EZH2 expression in tumors of the oral cavity and the orohypopharynx was higher as compared to cancers of the larynx (P = .0023). EZH2 expression was correlated to presence of lymph node metastasis (P = .0089) but was unrelated to histological grade, tumor stage, surgical margin, or distant metastasis. EZH2 expression had no impact on patient survival. Conclusion The high prevalence of EZH2 expression in head and neck squamous cell carcinoma stresses its capability as a therapeutic target.

Socioeconomic aspects play an important role in health care. Patients with locally advanced head and neck cancer (LAHNC) experience detrimental effects on their quality of life (QoL). This prospective study examines QoL differences between patients with different socioeconomic status (SES) after intensity-modulated radiation therapy (IMRT). In all, 161 patients were questioned at the end of IMRT and at 12 and 24 months follow-up using the questionnaires of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-30 and QLQ-HN35. Patients’ QoL 2 years after IMRT was compared to a population reference sample and QoL of patients from lower, middle, and higher social class 2 years after IMRT was analyzed by ANCOVA using baseline QoL (end of radiation treatment) as a covariate. Patients with high SES report worse QoL at the end of IMRT in the domains global health status (−15.2; p = 0.005), role function (−23.8; p = 0.002), and social function (−19.4; p = 0.023) compared to patients with middle and low SES. QoL improved during the first 12 and 24 months. However, 2 years after IMRT, middle and low SES patients report lower QoL in the domains global health status, physical function, and role function, and report a higher general (fatigue, pain, dyspnea) and head and neck cancer-specific symptom burden (pain, swallowing, senses, speech, social eating, opening mouth, and felt ill) than patients with high SES. After IMRT for LAHNC, patients with high SES report worse QoL compared to patients with middle or low SES. There is a marked improvement within the first 24 months in many domains. However, the magnitude of improvement in patients with middle or low SES is significantly smaller compared to patients with high SES.

The aim of our study was to review the outcome of patients with oral squamous cell carcinoma (OSCC) treated according to the current diagnostic and treatment protocols [“Tumor Board Group” (TBG)] compared to patients diagnosed before the introduction of standardized and certified guidelines [“Conventional Group” (CG)]. We also analyzed the influence of prognostic factors on overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) rates. A total of 321 patients (TBG 95 patients and CG 226 patients) with histologically confirmed OSCC were included in our study. RFS, DFS and OS rates were analyzed by Kaplan–Meier estimates. Cox regression was performed for multivariate analysis of prognostic factors. Results were statistically significant with a p value of

Magnesium (Mg) is a promising biomaterial for degradable implant applications that has been extensively studied in vitro and in vivo in recent years. In this study, we developed a procedure that allows an optimized and uniform in vitro assessment of the cytocompatibility of Mg-based materials while respecting the standard protocol DIN EN ISO 10993-5:2009. The mouse fibroblast line L-929 was chosen as the preferred assay cell line and MEM supplemented with 10% FCS, penicillin/streptomycin and 4mM l-glutamine as the favored assay medium. The procedure consists of (1) an indirect assessment of effects of soluble Mg corrosion products in material extracts and (2) a direct assessment of the surface compatibility in terms of cell attachment and cytotoxicity originating from active corrosion processes. The indirect assessment allows the quantification of cell-proliferation (BrdU-assay), viability (XTT-assay) as well as cytotoxicity (LDH-assay) of the mouse fibroblasts incubated with material extracts. Direct assessment visualizes cells attached to the test materials by means of live-dead staining. The colorimetric assays and the visual evaluation complement each other and the combination of both provides an optimized and simple procedure for assessing the cytocompatibility of Mg-based biomaterials in vitro.

Background and Objective In an attempt to develop a new therapeutic approach for highly localized thermal destruction of tissue targets that lack natural pigmentation, the potential of in-vivo dye-enhanced photothermal therapy (PTT) was investigated. PTT involves the application of an exogenous absorber, which accumulates in metabolically active tissues, followed by non-invasive light irradiation, using appropriate wavelengths, exposure durations, and irradiances. The chromophore used, palladium(II) octabutoxynaphthalocyanine (PdNc(OBu)8), strongly absorbs in the near infrared wavelength range which thus permits good penetration depth of the exciting light. The predominant de-excitation routes of the chromophore are radiationless thermal processes. Materials and Methods Using a BALB/c mouse model with a subcutaneously implanted syngeneic EMT6 adenocarcinoma, 96–100 hours after intraperitoneal application of PdNc(OBu)8, tumor, and surrounding tissue were irradiated with a 830 nm continuous wave diode laser applying 30 Wcm−2 for 10–20 seconds. Treatment parameters were based on theoretical calculations. Results Histological evaluation of thermal effects on tumor and normal tissue showed that after PdNc(OBu)8-enhanced photothermal treatment, highly localized and selective thermal damage of the tumors was achieved. The necrotic tumor area was invaded by inflammatory cells, including neutrophils, macrophages, mast cells, and lymphocytes, thus reflecting a prominent host immune response. In tumors treated with PTT for 15 or 20 seconds, respectively, only few surviving tumor cells were detected underneath the epidermis. Adjacent peripheral normal tissue including skin and muscle remained completely unaffected. Conclusion This study highlights the potential of achieving irreversible thermal tissue damage closely localized to the target tissue when PdNc(OBu)8 is used in combination with continuous-wave light. Lasers Surg. Med. 47:452–461, 2015. © 2015 Wiley Periodicals, Inc.

To discriminate clinically relevant aberrance, the accuracy of linear measurements in three-dimensional (3D) reconstructed datasets was investigated.Three partly edentulous human skulls were examined. Landmarks were defined prior to acquisition. Two CBCT-scanners and a Quad-slice CT-scanner were used. Actual distances were physically measured with calipers and defined as a reference. Subsequently, from digital DICOM datasets, 3D virtual models were generated using maximum intensity projections (MIPs). Linear measurements were performed by semi-automated image analysis. Virtual and analogue linear measurements were compared using repeated measurements in a mixed model (p ≤ 0.05).No significant difference was found among all of the digital measurements when compared to one another, whereas a significant difference was found in matched-pairs analysis between CBCT and calipers (p = 0.032). All digitally acquired data resulted in lower mean values compared to the measurements via calipers. A high level of inter-observer reliability was obtained in the digital measurements (inter-rater correlation = 0.988-0.993).The reconstructed datasets led to highly consistent values among linear measurements. Yielding sub-millimeter precision, these modalities are assumed to reflect reality in a clinically irrelevant altered manner. During data acquisition and evaluation, a maximum of precision must be achieved.

Purpose. The purpose of the study was to evaluate the influence of a continued antiplatelet therapy with clopidogrel on postoperative bleeding risk in patients undergoing skin tumor resection and reconstruction with local flaps or skin grafts under outpatient conditions.Patients and Methods. The authors designed and implemented a retrospective clinical cohort study at the General Hospital Balingen. The primary endpoint was the bleeding ratio in patients with clopidogrel treatment in comparison to patients without any anticoagulant or antiplatelet therapy. Wound healing was evaluated on days 1, 3, 5, 7, 10, and 14.Results. 650 procedures were performed, 123 of them under continued clopidogrel therapy. There were significantly more postoperative bleeding complications among patients with continued antiplatelet therapy. Regarding the whole study population, malignant lesions, a larger defect size, and skin grafts were accompanied by a higher rate of bleeding incidents. However, there were no significant findings in the univariate analysis of the clopidogrel group. All bleeding incidents were easily manageable.Conclusion. Despite an increased bleeding ratio among patients under continued clopidogrel therapy, the performance of simple surgical procedures can be recommended. However, cautious preparation and careful hemostasis are indispensable.