Marco Blessmann

Current trends and future perspectives of bone substitute materials - from space holders to innovative biomaterials.

An autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacement materials as an alternative have a long history of success. With increasing technological advances the spectrum of grafting materials has broadened to allografts, xenografts, and synthetic materials, providing material specific advantages. A large number of bone-graft substitutes are available including allograft bone preparations such as demineralized bone matrix and calcium-based materials. More and more replacement materials consist of one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; and osteoinductive proteins, which sustain mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment. All substitutes can either replace autologous bone or expand an existing amount of autologous bone graft. Because an understanding of the properties of each material enables individual treatment concepts this review presents an overview of the principles of bone replacement, the types of graft materials available, and considers future perspectives. Bone substitutes are undergoing a change from a simple replacement material to an individually created composite biomaterial with osteoinductive properties to enable enhanced defect bridging.

Outcome and complications of 540 microvascular free flaps: the Hamburg experience.

The aim of this study was to retrospectively analyze surgical outcome and complications of 540 free flap procedures performed at the Department of Oral and Maxillofacial Surgery of the University Medical Center Hamburg-Eppendorf during 1987–2005. A total of 532 patients were reconstructed with 540 flaps: 32% were latissimus dorsi flaps, 23% were radial forearm flaps, 21% were iliac crest flaps, 10% were fibula flaps, 6% were jejunal flaps, and 8% were other flaps. Thrombosis of one of the vessels and hematoma were the most frequent causes of failure in microvascular free tissue transfer. A total free flap failure occurred in 34 (6.2%) and a partial flap failure in 42 (7.7%) patients. The most reliable flap in regard to survival was the radial forearm flap. The present study confirms that free flaps are extremely reliable in achieving successful reconstruction of the head and neck.

Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of Patients with Squamous Cell Carcinoma of the Oral Cavity

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.

Intraoperative Cone-Beam Computed Tomography in Oral and Maxillofacial Surgery Using a C-Arm Prototype : First Clinical Experiences After Treatment of Zygomaticomaxillary Complex Fractures

PURPOSE To describe the first clinical applications of intraoperative cone-beam computed tomography with an integrated flat-panel detector in oral and maxillofacial surgery after surgical treatment of zygomaticomaxillary complex fractures PATIENTS AND METHODS Nine cone-beam computed tomography datasets of patients with zygomaticomaxillary complex fractures were intraoperatively acquired using a mobile isocentric C-arm (PowerMobil; Siemens Medical Solutions, Erlangen, Germany), including a flat-panel detector. Datasets based on 400, 200, and 100 fluoroscopic images were performed with different tube currents (4.6 mA, 3.3 mA, 2.3 mA, 1.2 mA, and 0.5 mA) and a current tube voltage of 100 kV. Postprocessing resulted in 15 different datasets available for comparison with corresponding preoperative computed tomography datasets. Four oral and maxillofacial surgeons and 2 experienced radiologists evaluated each dataset regarding noise, transition, and the delimitation of landmarks. RESULTS All examinations were successfully performed. Reconstructed datasets showed high-resolution images of all midfacial osseous structures in near-computed tomography quality. Regarding high-contrast structures, detailed analyses of datasets acquired in this study suggest that the parameters 400 projections, 1.2 mA, and 100 kV are sufficient. In terms of soft-tissue visualization, a higher level of mA seems preferable. CONCLUSIONS The tested prototype predicts a new era in cone-beam computed tomography imaging. The integration of a flat-panel detector will overcome the limitations of current available systems. The size of the field of view is increased allowing regularly the visualization of the whole facial skeleton. Particularly in cases of open reduction of unilateral fractures, the assessment of symmetry is of clinical value.

The detection of oral pre- malignant lesions with an autofluorescence based imaging system (VELscopeTM) – a single blinded clinical evaluation

The online version of the original article can be found at

Clinical follow-up examination of surgically treated fractures of the condylar process using the transparotid approach.

PURPOSE The surgical approaches for the open treatment of condylar process fractures have been controversial. In our study, we evaluated the morbidity of the transparotid approach during 2 years of follow-up. PATIENTS AND METHODS A total of 48 patients with condylar process Class II and IV fractures according to classification of Spiessl and Schroll, were included in the present study. Of the 48 patients, 16 were female and 32 male. The patient age range was 16 to 79 years (average 36.52). All patients were treated using the transparotid approach, with rigid internal fixation using miniplates. Follow-up examinations were performed for a minimum of 6.5 months and a maximum of 25 months (average 12.16) after surgical treatment. At the follow-up examination, the patients completed the Mandibular Function Impairment Questionnaire, and the examiner completed the Helkimo index. X-rays taken before, directly after, and 6 months after surgery were compared. RESULTS None of our patients had problems with wound healing; 2 patients developed a fistula of the parotid gland; and 4 patients developed palsy of the facial nerve that was completely reversible after 6 weeks. The results of the Mandibular Function Impairment Questionnaire and the Helkimo index revealed only a few subjective and objective problems after 6 months. CONCLUSIONS The transparotid approach to condylar process fractures is most appropriate for strongly displaced Class II fractures. Especially for very old patients with dementia, for whom maxillomandibular fixation is contraindicated, this approach is very appropriate. Another benefit to this type of patient is the short operating time, with an average of 45 minutes.

Major Mandibular Surgical Procedures as an Indication for Intraoperative Imaging

PURPOSE This study investigated 3-dimensional (3D) imaging with intraoperative cone beam computed tomography (CBCT) in major mandibular reconstruction procedures. PATIENTS AND METHODS The study group was comprised of 125 patients (83 males, 42 females) admitted for surgical treatment of the mandible. The patients ranged in age from 3 months to 91 years (average age, 40.72 +/- 22.843 years). Surgical procedures of the mandible were subdivided into repair of body fractures (17 patients), angle fractures (21 patients), condylar fractures (14 patients), and multiple fractures (30 patient). In addition, the study group included 21 patients undergoing orthognatic surgery and 22 undergoing reconstructive surgery on the mandible. Intraoperatively, 3D images were generated with a mobile CBCT scanner (Arcadis Orbic 3D; Siemens Medical Solutions, Erlangen, Germany). RESULTS During open reduction of mandibular fractures, not all fracture sites can be readily exposed for direct visual control. For example, the lingual cortical bone of the mandible is difficult to assess intraoperatively. This structure and others can be effectively visualized using the 3D mode of CBCT. Furthermore, screw placement can be evaluated, specifically in insertions near the alveolar nerve. The intraoperative acquisition of the data sets is uncomplicated, and the image quality is sufficient to allow evaluation of the postoperative result in all cases. CONCLUSION Intraoperative CBCT has proven to be a reliable imaging technique for providing visual control during major mandibular procedures.

Intraoral osteotomies using piezosurgery for distraction in an infant with Pierre–Robin sequence

Airway management in infants with Pierre Robin sequence (PRS) is often challenging. Advancement of the tongue base using mandibular distraction in neonates can avoid tracheotomy and is increasingly propagated. The osteotomies can be performed via intra- and extraoral approaches. Nowadays, for precise bone cutting, piezosurgical devices have been introduced in maxillofacial surgery, which we used for osteotomies via the intraoral approach in the 7-week-old patient presented in this study. Instead of a preoperative CT scan, a 3D data set was generated preoperatively in the operating theatre using a 3D C-arm system. After bilateral transcutaneous pin placement and osteotomies, a second 3D data set was acquired. Primary and secondary reconstructions clearly visualized the patient’s bone despite the low level of ossification in newborns and the presence of a large amount of metal implants. In view of the low level of radiation exposure going along with the 3D C-arm imaging, a follow-up examination after removal of the distractors was performed. With this report of a 7-week-old female infant with the diagnosis of PRS, we want to extend the surgical and diagnostic armamentarium for the treatment of infants with PRS.

Immunohistochemical and FISH analysis of EGFR and its prognostic value in patients with oral squamous cell carcinoma

OBJECTIVES To study immunohistochemical expression of the epithelial growth factor receptor (EGFR) in oral carcinomas and the head and neck region to examine possible associations with various features of the tumors and survival of the patients. MATERIALS AND METHODS Sections were made from two tissue arrays composed of 206 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, and examined for EGFR expression and Ki-67 labeling index by means of immunohistochemistry, and for EGFR gene amplification by means of fluorescence in situ hybridization. Correlation between resulting parameters and with clinical features was evaluated using chi-square test and Kaplan-Meyer analysis. RESULTS A statistically significant association was observed for strong EGFR immunohistochemical (IHC) expression with advanced lymph node involvement (P = 0.02). EGFR immunohistochemical expression did not significantly correlate with patient disease specific (DS) or overall survival (OS). EGFR gene amplification was not correlated with any of the tumor features nor to survival of the patients (DS and OS). DISCUSSION Epithelial growth factor receptor IHC expression and gene amplification might be suitable to predict locoregional control in oral squamous cell carcinoma patients but an inappropriate predictor for patients survival.

L1 is Highly Expressed in Tumors of the Nervous System: A Study of Over 8000 Human Tissues

BACKGROUND L1 cell adhesion molecule (CD171) has been detected in different malignant tumors and is associated with unfavorable outcome. It thus represents a target for tumor diagnosis and therapy. In this study, we assessed L1 expression in more than 8000 normal human tissues and different types of tumors, both malignant and non-malignant, and neural and non-neural. MATERIALS AND METHODS Tissue micro-arrays, including a multi-tumor-array of 128 different tumor types, up to 50 samples of each type (approximately 5500 different samples), arrays with approximately 3000 different prostate and 600 mesenchymal tumor samples, and a normal human tissue-array were analyzed by immunohistochemistry with a monoclonal antibody using immunoperoxidase staining. RESULTS L1 expression was detected in tumors of neural and neural crest origin and other types of non-neural tumors, but not in those of epithelial origin. In normal human tissues, L1 was detected in skin basal cells and small blood vessels, most notably in the mature placenta and peripheral nerves. CONCLUSION This first comprehensive study of the importance of L1 expression in human demonstrates strong L1 overexpression in tumors of neuroectodermal and neural crest origin and an expression in only very few normal human tissues. L1 thus is a potentially important therapeutic target, particularly with respect to malignant melanoma, gastrointestinal stromal tumor, neuroblastoma, and certain subtypes of non-neural tumors.