Osteonecrosis of the jaw in patients transitioning from bisphosphonates to denosumab treatment for osteoporosis.

Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but severe side effect of antiresorptive treatment with bisphosphonates or RANKL-antibody denosumab in patients with malignant diseases or osteoporosis. Whilst osteonecrosis of the jaw (ONJ) related to the administration of bisphosphonates (BPs) has been investigated for more than 1 decade now, only few data are available on denosumab-related ONJ, especially in patients with osteoporosis. From 2008 to 2016, 52 osteoporosis patients were treated with ARONJ in the Department of Oral and Maxillofacial Surgery, University Medical Center Freiburg, Germany. In all patients, a surgical regimen consisting of complete removal of necrotic bone, primary wound closure and perioperative i.v. antibiotic therapy was applied. Of the 52 patients, 38 developed ARONJ after BP monotherapy; in 11 patients, antiresorptive therapy had been transitioned from BPs to denosumab and 3 patients had received denosumab monotherapy. From July 2013, when the first patient with ONJ and transitioning therapy from BPs to denosumab presented to our department, to October 2016, we found recurrences in 17.6% of the patients with BP monotherapy and in 45.5% of the patients with transitioning therapy from BPs to denosumab. Transitioning antiresorptive therapy from BPs to denosumab may be an additional risk factor for developing ARONJ. In these patients, treatment of ARONJ-lesions seems to provoke more complications. An additional dental screening before transitioning should be initiated. Further studies are needed to evaluate if a first-line treatment with denosumab decreases the incidence of ARONJ in patients with osteoporosis and simplifies its treatment.

[Intraoperative quality management modalities in head and neck surgery]. / Intraoperative Modalitäten zur Qualitätssicherung in der Kopf­Hals­Chirurgie.

Immediate intraoperative control via suitable imaging techniques is necessary to achieve the best possible surgical outcome. Intraoperative imaging increases patient safety, offers the surgeon direct support in challenging anatomic regions, and affords the possibility of direct correction with a reduced rate of corrective surgery. The procedures are based on cone beam computed tomography (CBCT), endoscopy, or navigation-assisted surgery. This article describes available intraoperative quality management modalities for fracture management and tumor treatment in the field of head and neck surgery.

[Sensibility changes of the infraorbital nerve after primary surgery on patients with unilateral cleft lip according to J. Delaire]. / Évaluation à long terme de la sensibilité du nerf infraorbitaire chez les patients porteurs de fente labiale unilatérale complète après traitement primaire selon la technique de J. Delaire.

OBJECTIVE: The aim was to determine the overall sensibility changes in the area of the infraorbital nerve on patients with unilateral clefts lips and unilateral clefts lips and palate who had undergone primary surgical correction according to the principles of Delaire. PATIENTS AND METHOD: Twenty patients (7-20years) with unilateral cleft lips (and palate) who had undergone surgery in infancy according to Delaire were included. Cutaneous sensibilities of the nasolabial fold and of the upper lip were tested using four cutaneous modalities. A tactil superficial sensibility light touch test, a two-point discrimination test (McKinnon-Dellon Disk-Criminator), and the determination of cold and warm detection thresholds (Quantitative Sensory Testing, Medoc Thermal Sensory Analyser). The possible difference of the sensibility between operated and controlateral sides of the face were compared. Results were finally compared to a control group of twenty healthy volunteers. RESULTS: No significant difference could be found between the operated and non-operated side of the cleft group. There was also no difference between the cleft and the control group. Specific difference of perception between nasolabial fold and lip encountered in the literature were confirmed by the experiments. CONCLUSION: The large subperiostal approach according to Delaire during the primary surgical procedure have not affected long term infraorbital sensibility of patients with unilateral complete cleft lip.

Osteopenia in the maxillofacial area: a study in sheep.

UNLABELLED: Osteoporosis is a major public health problem worldwide. Its significance in the fields of traumatology and implantology of the maxillofacial area requires investigation. A large animal model was used to assess bone loss in the lumbar spine and mandible. INTRODUCTION: Osteoporosis is a prevalent disease characterized by low bone mass and microarchitectural deterioration of bone tissue. Osteoporosis-related fractures represent a major public health burden. The presence and relevance of osteoporosis in the maxillofacial area remain controversial. Research in humans is limited by difficulties in finding large homogenous study groups and, due to ethical considerations, numerous animal models have been used in osteoporosis research. The aim of this study was to assess a sheep model of generalized osteopenia for changes in the maxillofacial area. METHODS: Bone loss was induced in ten Merino sheep by ovariectomy, intramuscular administration of glucocorticoids, and a calcium-reduced diet. Five untreated animals served as controls. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry at the lumbar spine at baseline and after 1, 3, 6, 9, and 12 months. Lumbar and mandibular bone biopsies were obtained and analyzed with microcomputed tomography. RESULTS: Lumbar BMD decreased progressively in the intervention group and was most significantly low after 6 months (p < 0.001). Lumbar trabecular bone showed a significant decrease in bone volume (BV)/tissue volume (TV; p < 0.05) in the inducted group. Significant changes were found in both analyzed mandibular regions for BV/TV (p < 0.05). Regional variations were found for other parameters in the mandible. The cortical width was substantially reduced in the intervention group (p < 0.001). CONCLUSIONS: Microstructural changes occurring in sheep as a result of induction seem to have a generalized nature. This sheep model meets the criteria for further investigation in the maxillofacial area.

Medication-related osteonecrosis of the mandible: an unusual presentation and treatment.

A 71-year-old woman was referred to the clinic with extensive medication-related osteonecrosis of the jaw (MRONJ) involving the mandible. She had received 7 years of zoledronate therapy. On cone beam computed tomography, the MRONJ presented as a large sequestrum spanning from the left to the right condylar process, surrounded by thick sub-periosteal bone. The sequestrum was excised via an intraoral approach, leaving the newly formed sub-periosteal bone as a neo-mandible. The patient recovered well from the operation and was discharged 5 days after surgery. She healed completely without complications. This case report presents an alternative surgical treatment that may be considered if there is clinically stable sub-periosteal bone surrounding extensive MRONJ.

Interdisciplinary management of skull base surgery.

Skull base surgery remains one of the challenging areas in the field of cranio-maxillofacial surgery, otolaryngology and neurosurgery. Subsequent reconstruction of bone and soft tissue are an essential component to restore function and appearance after ablative surgery. Establishment of interdisciplinary tumor boards with presentation of the individual patient cases have become standard. Multiplanar reconstruction using MRI or CT imaging techniques combined with virtual 3D planning allow precise planning of the procedures. Intraoperative navigation helps for complete resection of malignant findings with safety margins; surgical approaches provide a good overview of the surgical site. Reconstruction using local flaps have a low complication rate with equally reliable results in reconstruction of small tissue defects. Free flap surgery makes reconstruction of large tissue defects possible. Alloplastic materials are alternatively used for reconstruction of bone defects. Based on selected patients, treatment algorithms and standard surgical procedures in extracerebral skull base surgery will be illustrated. Current techniques and new approaches will be discussed with emphasize on hard and soft tissue reconstruction.

Combined androgen deprivation therapy in recurrent androgen-receptor-positive salivary duct carcinoma - a case report and review of the literature.

Salivary duct carcinoma (SDC) is a rare and highly aggressive neoplasm of the salivary glands associated with high rates of local and distant recurrence and poor overall survival. We present a patient with SDC, who relapsed despite extensive multimodal therapy including surgery, postoperative radiochemotherapy, and heavy ion therapy. In the recurrent setting, immunohistochemical analysis confirmed androgen receptor positivity, prompting initiation of combined androgen deprivation therapy (ADT), which resulted in a fast and durable remission of the local tumor now lasting for 26 months. Analyzing the histopathologic specimens of all SDC patients treated at our department since 2009, we found significant AR expression in all patients. This is in line with other reports found in current literature and indicates AR positivity as a consistent feature of SDC, supporting ADT as a viable therapeutic option for SDC.

Lymph node abscess caused by Francisella tularensis - a rare differential diagnosis for cervical lymph node swelling: a case report.

BACKGROUND: Cervical lymph node swelling is quite a common symptom mainly caused by infections in the face or as metastasis of a malignant tumor. In infection cases in particular, rare diseases should never be overlooked. With an incidence of 120 cases in the United States of America (USA) and approximately 25 cases in Germany per year, infection with the pathogen Francisella tularensis is one of these rare diseases that can cause massive lymph node swellings and might even be fatal. CASE PRESENTATION: The example of a healthy 67-year-old German woman who was treated at our university hospital presents a typical progression of a localized form of tularemia. The pathogen could be identified in a universal 16S ribosomal deoxyribonucleic acid (DNA) polymerase chain reaction. Pathogen-specific treatment with lymph node abscess incision, daily rinsing of the abscess cavity, and orally administered antibiotic therapy with doxycycline could cure our patient completely without any remaining complications. CONCLUSION: In patients with cervical lymph node swelling caused by infection it is indispensable to perform specific identification of the pathogen for further local and specific antibiotic treatment. Possible infections with atypical bacteria like Francisella tularensis should never be ignored. Universal polymerase chain reactions are a suitable method for early detection of such rare pathogens.

Retrospective evaluation of diagnostic accuracy of free flap monitoring with the Cook-Swartz-Doppler probe in head and neck reconstruction.

The Cook-Swartz-Doppler probe is an easy to handle and reliable tool for free flap monitoring. In the head and neck region different confounders can affect the read out. We therefore analyzed the use of the Doppler probe regarding these potential difficulties and to compare the diagnostic accuracy in arterial or venous monitoring of free flaps in the head and neck region. A retrospective study was performed in which all patients were included who underwent free flap surgery in the head and neck region in the Department of Plastic Surgery and the Department of Maxillofacial Surgery of our institution between 2010 and 2018 and were monitored with an implanted Doppler probe. 147 free tissue transfers were included. No significance was found for arterial and venous placement of the Doppler probe for sensitivity (artery 83.3%; vein 84.6%; p = 0.87), specificity (artery 89.2%; vein 96.1%; p = 0.17) and negative predictive value (artery 96.7%; vein 94.2%; p = 0.55). A better positive predictive value for placing the Doppler probe around the artery (82.7%) than the vein (61.1%) was found in our study (p = 0.056). The better positive predictive value in arterial monitoring suggests that this is the more reliable measuring method to assess flap perfusion in the head and neck region.

Preliminary functional results of endoscope-assisted transoral treatment of displaced bilateral condylar mandible fractures.

Temporomandibular joint (TMJ) function was evaluated following endoscope-assisted transoral open reduction and miniplate fixation of displaced bilateral condylar mandibular fractures. The transoral treatment of bilateral condylar fractures was performed in 13 patients from May 2000 to December 2004. Eleven of the 13 patients had additional mandibular fractures. Out of 26 fractures of the condylar process, 11 were located at the condylar neck and 15 were subcondylar. One, 6 and 12 months after surgery TMJ function was evaluated. Anatomic reduction was achieved using an endoscope-assisted transoral approach even when the condylar fragment was displaced medially and in fractures with comminution. Good TMJ function was noted 6 and 12 months after surgery. Mouth opening was measured to be more than 40 mm without deviation. Postoperative range of motion with a satisfying lateral excursion was found. Early rehabilitation and pre-injury TMJ function was achieved following minimally invasive anatomic fracture reduction.

Comparative in vitro study of the proliferation and growth of human osteoblast-like cells on various biomaterials.

In vitro studies about the growth behavior of osteoblasts onto biomaterials is a basic knowledge and a screening method for the development and application of scaffolds in vivo. In this in vitro study human osteoblast-like (HOB) cells were cultured on seven different biomaterials used in dental and craniomaxillofacial surgery, respectively. The tested biomaterials were synthetic biodegradable (MacroPore, Ethisorb, PDS, Beriplast P) and nonbiodegradable polymers (Palacos) as well as calcium phosphate cement (BoneSource) and titanium. The cell proliferation and cell colonization were analyzed by scanning electron microscopy and EZ4U-test. Statistical analysis were performed. HOB-like cells cultivated on Ethisorb showed the highest proliferation rate. The proliferation rate was statistically significant compared with Palacos, MacroPore, and BoneSource. Whereas, Beriplast, PDS, and titanium yielded lower proliferation rates. However, there was no statistically significant difference compared with Palacos, MacroPore, and BoneSource. SEM analysis showed no significant difference in individual cell features and cell colonization. But an infiltration and a growth of HOB-like cells throughout the porous structure of Ethisorb, which is formed by crossing fibers, is a striking different feature (macrotopography). This feature can explain the highest proliferation rate of Ethisorb. The results showed that HOB-like cells appear to be sensitive to substrate composition and topography. Moreover, the basis for further studies with such biomaterial/osteoblast constructs in vivo are provided. Further focusing points are developing techniques to fabricate three-dimensional porous biomaterial/cell constructs, studying the tissue reaction and the bone regeneration of such constructs compared with the use of autologous bone.

Comparative in vitro study of the cell proliferation of ovine and human osteoblast-like cells on conventionally and rapid prototyping produced scaffolds tailored for application as potential bone replacement material.

Reconstruction of bone defects in the field of craniomaxillofacial surgery is a relevant problem. In regenerative medicine, autologous bone is not available sufficiently. The full replacement of autologous bone grafts is required. A promising research field is the bone engineering. Especially the application of rapid prototyping (RP) enables new perspectives concerning the scaffold design. The aim of the study was to compare scaffolds produced by RP-technology (native and plasma-coated PLGA-scaffolds) with conventionally produced scaffolds (agar plates with hydroxyapatite and hyaluronic acid coated agar plates with hydroxyapatite) relating to proliferation, adhesion, and morphology of osteoblasts to get knowledge about the application potential of such 3D-manufactured matrices for bone engineering. TissueFoil E served as reference. To compare the scaffolds, 12 ovine and 12 human osteoblast-like cell cultures of the skull were used. Results were obtained by EZ4U, scanning electron microscopy, and light microscopy. The highest cell proliferation rate of human osteoblast-like cells was measured on TissueFoil E followed by plasma-coated PLGA-scaffolds and uncoated PLGA-scaffolds, whereas of ovine osteoblast-like cells on plasma-coated PLGA-scaffolds followed by TissueFoil E and uncoated PLGA-scaffolds. Human and ovine osteoblast-like cells on coated and uncoated agar plates had significant lower proliferation rates compared with TissueFoil E and PLGA-scaffolds. These results showed the potential of RP in the field of bone engineering. Mechanical properties of such scaffolds and in vivo studies should be investigated to examine if the scaffolds hold up the pressure it will undergo long enough to allow regrowth of bone and to examine the revascularization.

Topographical CT-data analysis of the human orbital floor.

The aim of this study was to evaluate the topographical anatomy of the human orbital floor for the production of prefabricated implants on the basis of computer tomography data. A database of 279 CT scans of Caucasian patients without traumatic deformation of the midface was analysed. 3D-image segmentation of the midfacial skeleton was performed using a computer-assisted protocol. A virtual plane (50 x 50 mm (2)) was constructed using defined landmarks above the orbital floor. An automated procedure was used to measure the distance between the orbital floor and the constructed plane at 400 distinct points. A mathematical algorithm was used to analyse the data, and to calculate a map of the orbital floor. Statistical analysis of the data revealed that orbital floor topography could be classified as distinct clusters. There were 12 variations of orbital floor anatomy: three unique patterns of the orbital floor for the right orbit and three corresponding patterns for the left side, all of which varied between the sexes. The 12 patterns were constructed with a statistical confidence interval of 1.36+/-0.6mm.

Update MRONJ and perspectives of its treatment.

Antiresorptive agents are widely used in catabolic bone diseases. Not only bisphosphonates but also new drugs like Denosumab may induce osteonecrosis of the jaw as a side effect. The present review describes the current effect mechanisms of commonly used antiresorptives, pathogenetic theories for the development of antiresorptive-related osteonecrosis of the jaw (ARONJ), and potential risk factors. Furthermore, diagnostic modalities and treatment options as well as new and innovative strategies are discussed. The major key factor to avoid the occurrence of ARONJ still remains the implementation of throughout preventive measures.

Individually preformed titanium mesh implants for a true-to-original repair of orbital fractures.

The purpose of this investigation is to present the results using preoperatively-formed titanium mesh implants for a true-to-original primary repair of extensive orbital floor and medial wall fractures. Individually preformed implants were used to repair extensive orbital floor injuries in 19 patients at the University Hospital, Freiburg. The form of the orbital floor and walls was analysed by preoperative diagnostic CT scan data. The form of the virtual reconstructed orbit was transformed into a model of the orbital cavity by a template machine. Postoperative imaging by or CT scan verified the exact 3D reconstruction of the orbital cavity 'true to original'. None of the patients demonstrated diplopia or enophthalmos postoperatively. Using individually preformed titanium mesh implants, the accuracy of the 3D orbital reconstruction was within a range of 1mm. The reconstruction using preformed implants proved to be less time consuming, more precise and less invasive, compared to 'free hand' efforts, for the repair of orbital injuries using titanium mesh and calvarial grafts.

Inferior alveolar nerve transposition--an in vitro comparison between piezosurgery and conventional bur use.

An in vitro comparison between a new ultrasound-based piezoelectric device and a conventional bur was performed for lateralization or transposition of the inferior alveolar nerve to evaluate the effects on soft and hard tissue. Transposition of the inferior alveolar nerve was performed in the cadaver mandibles of 10 sheep: the left nerve was uncovered with a saline-cooled diamond-coated spherical bur (2000 rpm), and the right nerve was uncovered with the piezoelectric device mounted with a spherical diamond tip. The surface, the zone of bone defect, and the nerve were examined by light microscopy and laser microscopy. Bone treated with the rotary bur showed significantly smoother surfaces and shallower defect zones (50 microm) in comparison with the piezoelectric device (150 microm). Lesions of the epineurium and an increased amount of bone particles were found in the lesions prepared with the piezoelectric device. In vitro preparation with the piezoelectric device was more invasive to the bone than was a conventional diamond bur. Touching the inferior alveolar nerve resulted in roughening of the epineurium without affecting deeper structures. The degree of injury was lower than when using the conventional rotary bur.

Pathological mandibular fractures following third molar removal.

Seventeen patients, who presented mandibular fractures following third molar removal, were treated in the Department of Oral and Maxillofacial Surgery at the University Hospital Freiburg between 2000 and 2004. Clinical and radiological data were analysed to evaluate the possible risk of fracture following third molar removal. Our data show an increased rate of pathological mandibular fractures in males over 40 years of age, following removal of a difficult lower wisdom tooth with a high retention grade that necessitated bone removal. Fourteen out of 17 fractures occurred postoperatively. In six cases, no fracture was visible in radiographs during the primary investigation. Pathological mandibular fractures were typically located anterior to the mandibular angle (n=15). We recommend informing patients about possible risks and, in selective cases, a soft diet for up to 4 weeks after the operation. A cracking noise reported by the patient is the most important indication of a fracture. If, initially, the fracture is radiologically undetectable, we recommend the use of radiological controls.

Application of fuzzy inference to European patients to predict cervical lymph node metastasis in carcinoma of the tongue.

In head and neck cancers, the presence of cervical lymph node metastasis is an important determinant of outcome. Many attempts have been made to predict cervical lymph node metastasis, but the accuracy of currently available techniques remains inadequate. We used fuzzy inference to predict cervical lymph node metastasis retrospectively in 75 patients with squamous cell carcinoma of the tongue and prospectively in 23 patients. Our model was based on three variables: tumor size, keratinization, and mode of invasion. The accuracy of fuzzy inference for the prediction of cervical lymph node metastasis in the 75 patients studied retrospectively was 86.7%, the sensitivity was 70.8%, and the specificity was 94.1%. In the 23 patients studied prospectively, the accuracy was 91.3%, the sensitivity was 50.0%, and the specificity was 95.2%. The accuracy obtained in this European series of patients was similar to that previously obtained in Japanese patients. We conclude that fuzzy inference may be a useful method for predicting cervical lymph node metastasis. Its high specificity is likely to reduce the number of unnecessary neck dissections. However, the current level sensitivity is inadequate for routine clinical use. Therefore, other predictors of lymph node metastasis should be identified to refine the current model.

Eagle's syndrome-A non-perceived differential diagnosis of temporomandibular disorder.

INTRODUCTION: This article unveils a case of the classic styloid syndrome and states that panoramic imaging and ultrasound can be an alternative to computed tomography. In addition, the endoscope-assisted extraoral approach using CT-based navigation is useful. Eagle's Syndrome is an aggregate of symptoms described by Eagle in 1937. He described different forms: the classic styloid syndrome consisting of elongation of the styloid process which causes pain. Second, the stylo-carotid-artery syndrome which is responsible for transient ischemic attack or stroke. PRESENTATION OF CASE: Using the example of a 66 years old male patient suffering from long term pain, we explain our diagnostic and surgical approach. After dissecting the styloid process of the right side using an extraoral approach, the pain ceased and the patient could be discharged without any recurrence of the pain up to this point. DISCUSSION: Eagle's syndrome, with its similar symptoms, is rather difficult to differentiate from temporomandibular joint disorders (TMD), but can be easily excluded from possible differential diagnoses of TMD using panoramic radiographs and ultrasound. CONCLUSION: Making use of low cost and easily accessible diagnostic workup techniques can reveal this particular cause for chronic pain restricting quality of life. Thereby differentiation from the TMD symptomatic complex is possible.

Comparison of virtual and titanium clip marking of tumour resection margins for improved radiation planning in head and neck cancer surgery.

Communication between the surgeon and the radiation oncologist is improved with the use of virtual models of the final tumour resection, combining three-dimensional imaging and conventional clip marking with computer-aided navigation. This investigation was designed to determine the deviation of virtual marking procedures compared to conventional marking by titanium ligature clips in oral cancer with different localizations. Seventeen patients with surgically placed clips and virtual landmarks on the resection margin after complete tumour ablation were evaluated. To determine whether the virtual landmarks remain predictive of the resection margin, the deviation of the virtual points from their corresponding clips was analyzed by measuring the distance between their centres of gravity. In total, 189 clips were evaluated. Metric analyses of the deviation between the virtual points and clips showed a deviation of 2.3 ± 0.6mm for tumours with a maxilla localization, 7.2 ± 2.5mm for tumours with a mandible localization, and 12.6 ± 3.8mm for tumours with a tongue localization. A significant statistical relationship was demonstrated in the virtual point-clip deviation as a function of tumour localization. Virtual marking of maxillary tumour resection margins allows accurate definition of the former tumour bed and could lead to novel adjuvant treatment strategies.