Bisphosphonate and Medication-Related Osteonecrosis of the Jaw: A Review.

For patients with malignant disease taking bisphosphonates and denosumab, the incidence of medication-related osteonecrosis of the jaw (MRONJ) is up to 15% in contrast to 0.01% in patients with osteoporosis. Clinical presentation of MRONJ extends from asymptomatic exposure of bone in 94% of patients to severe cases of mandibular fractures in a minority of 4.5%. The strongest risk factors for MRONJ are invasive dental procedures and dental infections. Advances in imaging provide more preoperation information compared with panoramic radiograph. Prevention strategies are the elimination of potential risk factors leading to invasive dental procedures and maintenance of good oral hygiene prior to the administration of antiresorptive agents. Management of MRONJ depends on the underlying disease, extent of the necrosis, and the presence of contributing therapy. Conservative therapies include topical anti-infective rinses and systemic antibiotic therapy. The most important part of surgical therapy is to remove the exposed and necrotic bone. Several options for defect closure are possible from local tissue flaps to microvascular free flap procedures. The development of MRONJ in conjunction with dental implants is a severe side effect and should be avoided if potentially harmful medication has already been administered.

Opened end-to-side technique for end-to-side anastomosis and analyses by an elastic true-to-scale silicone rubber model.

The end-to-side anastomosis is frequently used in microvascular free flap transfer, but detailed rheological analyses are not available. The purpose of this study was to introduce a new modified end-to-side (Opened End-to-Side, OES-) technique and compare the resulting flow pattern to a conventional technique. The new technique was based on a bi-triangulated preparation of the branching-vessel end, resulting in a "fish-mouthed" opening. We performed two different types of end-to-side anastomoses in forty pig coronary arteries and produced one elastic, true-to-scale silicone rubber model of each anastomosis. Then we installed the transparent models in a circulatory experimental setup that simulated the physiological human blood flow. Flow velocity was measured with the one-component Laser-Doppler-Anemometer system, recording flow axial and perpendicular to the model at four defined cross-sections for seven heart cycles in each model. Maximal and minimal axial velocities ranged in the conventional model between 0.269 and -0.122 m/s and in the experimental model between 0.313 and -0.153 m/s. A less disturbed flow velocity distribution was seen in the experimental model distal to the anastomosis. The OES-technique showed superior flow profiles distal to the anastomosis with minor tendencies of flow separation and represents a new alternative for end-to-side anastomosis.

Autonomization of free flaps in the oral cavity: A prospective clinical study.

Controversy exists over how long a free flap is dependent on its pedicle and if neovascularization is different between flap types, recipient sites, and irradiated and nonirradiated patients. An understanding of the timing of this process should optimize the safety of secondary procedures involving the flap. In a prospective clinical study, hemoglobin oxygenation and capillary flow were measured in 50 flaps (25 forearm flaps, 15 osteocutaneous fibula flaps, and 10 anterolateral thigh flaps) 4 and 12 weeks postoperatively. The flaps were located at the floor of the mouth, cheek, or tongue (n = 39) or at the hard or soft palate (n = 11). Measurements were carried out using the O2C monitoring system under temporary digital occlusion of the pedicle. After 4 weeks, 17 free flaps were found to be autonomized indicated by the O2C measurements comparing both values before and after digital compression of the vascular pedicle. After 12 weeks, 41 patients had completion of free flap autonomization, as indicated by the HbO(2) and CF before and after pedicle compression. The location of free flap in the lower jaw (P < 0.0001 after 4 weeks, P = 0.013 after 12 weeks), fasciocutaneous radial forearm flaps after 4 weeks (P < 0.0001), and not irradiated recipient site after 4 weeks (P = 0.014) were found to be positive factors significantly influencing autonomization. In conclusion, free flap autonomization depends on several variables which should be considered before further surgery after free flap reconstruction as the transferred tissue can be still dependent on its pedicle.

Free flap reconstruction for patients with bisphosphonate related osteonecrosis of the jaws after mandibulectomy.

INTRODUCTION: Bisphosphonate related osteonecrosis of the jaws (BRONJ) is a recognised unwanted effect of these drugs which affect bone remodelling. Treatment options range from conservative approaches through local bone debridement to free flap reconstruction following segmental resection. This current study aims to evaluate clinical outcomes after microvascular tissue transfer in BRONJ patients. MATERIAL AND METHODS: A total of 212 BRONJ patients were included in this prospective investigation. Those who met defined inclusion criteria and received a surgical intervention were reviewed regularly during a follow-up period of at least 6 months. RESULTS: Twenty-five patients (11.8%) received free flap reconstructions. A mean of 2.12 local debridements were performed before microvascular tissue transfer. A mean of 29.25% showed BRONJ recurrence after minimalist surgical intervention, compared to significantly less in patients after resection and free flap reconstruction. The postoperative fistula rate was significantly higher in patients, who received mucoperiosteal flaps. DISCUSSION: This study underlines the importance and effectiveness radical resection and free flap reconstruction in the complex and challenging surgical treatment of BRONJ patients in a large patient cohort study. Nevertheless, all patients received radical intervention after failure of minimally invasive treatment. An individualized analysis and planning is necessary to identify appropriate patients for free flap reconstructions.

The role of mylohyoid flap in the treatment of bisphosphonate-related osteonecrosis of the jaws.

INTRODUCTION: Surgical treatment of bisphosphonate-related osteonecrosis of the jaws (BRONJ) combines excision of adequate damaged bone and watertight coverage by appropriate vascularized tissue. Local tissues are preferred when possible. This study compares local mucoperiosteal flaps with mylohyoid flaps with special emphasis on their influence on wound healing. MATERIAL AND METHODS: A total of 195 patients with BRONJ in the mandible were included in this prospective study. The control group (n = 169) were treated with a mucoperiosteal flap, whereas patients of the study group (n = 26) received a mylohyoid flap. RESULTS: Recurrence of BRONJ was significantly reduced (p = 0.023) as was extent of necrosis (p = 0.001) in patients with mylohyoid flaps. DISCUSSION: This study demonstrates the importance of a sufficient mucosal coverage in surgical treatment of BRONJ. The mylohyoid flap provides an additional tissue coverage, which seems to account for the significantly reduced rate of disease recurrence. CONCLUSION: The vascularized mylohyoid flap is an important tool in the complex and challenging surgical care of BRONJ.

Do measurements of inflammatory mediators in blood predict recurrence in patients with bisphosphonate-related osteonecrosis of the jaws?

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is well-recognised, difficult to manage, and often recurs. The aim of this study was to examine the value of preoperative measurements of inflammatory mediators in blood in 212 patients with BRONJ who were studied prospectively. Multiple logistic regression analysis was used to assess the importance of the amounts of substances in the blood that are independently associated with the dependent variable "recurrence of BRONJ". The only factor that significantly influenced the development of recurrent BRONJ was reduction in the white cell count (p<0.0001; hazard ratio 5.324; 95% CI 2.373 to 11.945). Neither white cell counts nor C-reactive protein concentrations within or above the reference ranges were significantly associated with recurrent BRONJ. Patients whose white cell counts were lower than the reference range were at increased risk of recurrent BRONJ. This may be a marker of reduced immunocompetence, and additional prophylactic measures or treatment should be considered for these patients.

Prevention of bisphosphonate-related osteonecrosis of the jaws in patients with prostate cancer treated with zoledronic acid - A prospective study over 6 years.

INTRODUCTION: To explore the preventive effect of a prophylactic oral and maxillofacial treatment to reduce bisphosphonate associated necrosis of the jaws (BRONJ) in metastatic prostate cancer (PC) patients treated with zoledronic acid (4.0 mg i.v./months). MATERIALS AND METHOD: 253 PC patients with bone metastases were prospectively randomized. All patients received baseline assessments including a dental panoramic tomogram. Group A was monitored and treated where deemed necessary by the patient's dentist and were re-evaluated once a year. In group B patients were monitored and treated where necessary by the authors at 12 week intervals. We compared the incidence rate per year (IR) and incidence proportion (IP) in both cohorts and assessed independent risk factors for BRONJ. RESULTS: Patients in group A were evaluated 3.2 (range 2-4) vs. 6.8 times (range 4-24) in group B. A significantly higher proportion of dental extractions was performed in group B vs. A (26.7% vs. 22.7%, p = 0.006). A BRONJ was detected with an IP of 23.3% vs. 2.2% in group A vs. B, revealing a 2.59 fold higher relative risk for group A (p = 0.01, 95% CI 0.01-0.56). The IR in group A was 0.073 cases/year while the IR in group B was significantly decreased by 82% to 0.0131 (p < 0.001). Extraction therapy was the only independent risk factor for BRONJ (p < 0.0001; 95% CI 21.22-189.06). CONCLUSIONS: Preventive oral and maxillofacial treatment before bisphosphonate application combined with 3-monthly dental follow-ups significantly reduces the occurrence and risk of BRONJ in PC patients. Therefore this approach should be implemented in the specific treatment algorithms.

Special training in maxillofacial surgery for medical students--economic burden or investment in the future?

We measured the motivation and interest of medical students in oral and maxillofacial surgery at a German university. After a detailed cost-benefit analysis of a course that used an ex-vivo animal model and active participation in the operating theatre, we measured changes in the students' interest in taking up a surgical specialty in the future. We found that practical experience could lower the expenses of the course by almost 70%. Twenty per cent of students chose oral and maxillofacial surgery as an elective in their final year. These students could be residents one day.

Risk of Thromboembolus after Application of Different Tissue Glues during Microvascular Anastomosis.

BACKGROUND: Tissue glues are a useful tool for hemostasis and a potential tool for microvascular anastomosis. The hemostatic power and thrombotic risk of these surgical aids have been the subject of debate, but studies regarding thromboembolic risks of tissue glues are lacking. METHODS: The authors compared the thromboembolic risk of three different tissue glues (six interrupted sutures complemented with fibrin, FloSeal, or TachoSil) against a control group (12 interrupted sutures) in the aorta-filter model in the rat. Each group consisted of 10 rats, examined 4 hours and 14 days postoperatively (total n = 80) using a structured protocol to assess the patency and condition of the filter, amount of thromboembolic material, and histologic appearance of the vessel wall. RESULTS: In total, 160 anastomoses were performed in 80 rats. The overall patency rate for the groups was 90 percent (control), 35 percent (fibrin glue), 25 percent (FloSeal), and 10 percent (TachoSil). All experimental groups had significantly faster mean anastomotic times and less blood loss compared with the control group. Patency rates were reduced and thromboembolic material was significantly increased in all experimental groups. Histologically, the use of tissue glue reduced the incidence of irritation of the internal elastic lamina and was associated with an increased incidence of fibrocyte infiltration of the media, hypercellularity of the adventitia, and adventitial neovascularization and lymphangiogenesis. CONCLUSION: The application of tissue glues in microvascular anastomosis reduces the time needed for anastomosis but was associated with a statistically significant increase in thromboembolism.

The value of early intraoral incisions in patients with perimandibular odontogenic maxillofacial abscesses.

Perimandibular abscesses require drainage and removal of the underlying cause of infection. Traditionally drainage was established extraorally, but this can be associated with delay to treatment, because this is done under general anaesthesia. Between July 2008 and June 2013, 205 patients were initially either treated by immediate intraoral incision under local anaesthesia or extraoral incisions under general anaesthesia and prospectively evaluated. Predictors of treatment outcomes and complications were analysed. Fewer secondary procedures were needed for patients with primary treatment under general anaesthesia (p < 0.0001), but the overall stay in hospital was shorter after initial treatment under local anaesthesia (p < 0.0001, Odds Ratio (OR) 0.72, 95% CI 0.62-0.85). Postoperative complications occurred significantly more often under general anaesthesia (p < 0.0001, OR = 16.63, 95% CI 5.59-49.5). Significant prognostic variable was the administration of amoxicillin combined with clavulanic acid (p = 0.016, OR = 1.24, 95% CI 1.09-1.41) and adverse prognostic factors were infections with Human Immunodeficiency Virus (HIV) (p = 0.048, OR 17.45, 95% CI 1.02-298) or diabetes mellitus (p = 0.003, OR 10.39, 95% CI 2.23-48.41). Amoxicillin combined with clavulanic acid showed a significant impact on the treatment course of patients with perimandibular abscesses.

Quality of life after different oncologic interventions in head and neck cancer patients.

Patient reported outcomes following head and neck cancer are of great importance, given the functional, psychological, and social impacts of the disease and its treatment. In addition, not only is the number of publications on health-related quality of life (HRQOL) increasing in a variety of specialties, but there is also a growing awareness of the potential role of HRQOL in practice. Therefore, we aimed to investigate the HRQOL of head and neck cancer patients following different oncologic interventions, using an internationally established test. In this cross-sectional study, we included three different groups of 32 patients each. Participants had histologically confirmed invasive oral squamous cell carcinoma (OSCC) in the anterior floor of the mouth. Group allocation was based on treatment modality, as follows: only surgery (group 1), operation and adjuvant radiotherapy (XRT) (group 2), and the additional presence of osteoradionecrosis (ORN) (group 3). All patients were questioned about their HRQOL, using the standardized University of Washington Quality of Life Questionnaire (UW-QOL). Surveys for groups 1 and 2 were conducted at least 24 months after the end of tumor-related treatment, in cases of ORN (group 3) 12 months after completion of disease-related treatment. A total of 96 patients were included into this study. The mean age was 62.79 ± 8.93 years. The patients in groups 1 and 2 revealed a reduced quality of life, of a greater magnitude after radiation therapy. Patients felt that radiotherapy was much worse than surgery; however, half of the patients stated that they would repeat radiation therapy if necessary. The subjective evaluation of the HRQOL after surgery and radiotherapy was a valuable instrument for assessing the rehabilitation of patients in the context of their function and quality of life. Radiation therapy can be considered a trigger of functional limitations and emotional distress that contributes to decreased HRQOL in patients with head and neck cancer.

The buccal fat pad in the closure of oro-antral communications: an illustrated guide.

This article is intended as an illustrated, step-by-step guide in the use of the pedicled buccal fat pad in the closure of oro-antral communications. The advantages and disadvantages of its use are discussed, along with its basic anatomy.

Focused review of investigation, management and outcomes of salivary gland disease in specialty-specific journals.

We review papers on diseases of the salivary glands published in journals relating to the head and neck, which are commonly read by members of our specialty. Most of the papers focus on the investigation and treatment of diseases of the parotid gland, which reflects the relative prevalence of parotid lesions among salivary gland diseases. Minimally invasive surgery is increasingly of interest. There is a lack of clinical trials that address the many controversies concerning salivary gland surgery, and much of the evidence for treatment is based on small case series and expert opinion, partly because of the relative rarity of salivary disease and the disparate groups that treat it. This problem could be addressed if regional and national oral and maxillofacial surgery (OMFS) units, and possibly other specialties, could collaborate more closely and combine data.

Functional outcome after different oncological interventions in head and neck cancer patients.

PURPOSE: Patient-reported outcomes following head and neck cancer are of great importance given the functional, psychological, and social impacts of the disease and its treatment. With an increasing number of publications on HRQOL following head and neck cancer and a growing awareness of the potential role of HRQOL in practice, it was our aim to investigate head and neck functional mobility that is often not taking into account in HRQOL scores. METHODS: In this prospective study, three different groups of 32 patients each were included. Any patient who had histologically confirmed invasive OSCC in the anterior floor of the mouth was eligible. All patients were examined by a standardized test assessing function, including the distance of mouth opening, extension, flexion, and rotation of the head. RESULTS: A total of 96 patients were included in this study. The mean age was 62.79 ± 8.93 years. Head and neck mobility measured in patients is presented and analyzed. Compared to the baseline, a significant reduction of mouth opening and head and neck mobility was noted in all groups. CONCLUSIONS: Although both treatment options (surgery and surgery with radiotherapy) were performed according to the tumor stage of patients, there are significant differences in the functional outcome of these patients as observed in this study. There is a lack of a measuring instrument that will be the "gold standard" in the assessment of head and neck functional mobility. This study will allow the reflection of our current practice and may stimulate further well-designed prospective studies.

Maxillary reconstruction using microvascular free flaps.

OBJECTIVE: Loss of all or part of the maxilla as a result of tumor ablation has both functional and aesthetic consequences. Reconstruction of the maxilla remains a challenge despite the availability of several flaps and the skills of the prosthodontist. We have analyzed a series of maxillary resections that underwent flap reconstruction to guide planning of the rehabilitation of patients with such defects. STUDY DESIGN: The authors present 83 patients with various types of maxillary defects that were reconstructed with different microvascular free flaps. All clinical data, including data on the functional and aesthetic outcome, are analyzed. RESULTS: Flap transfer was successful in 80 of 83 patients who underwent maxillary reconstruction. Separation of the oral and nasal cavities was achieved in all cases. Flap compromise occurred in 6 cases, which made revision necessary. Three of these flaps were salvaged and 3 flaps failed. In 10 of 28 patients with transferred bone, osseointegrated implants were inserted and dentally rehabilitated with excellent functional and aesthetic results. CONCLUSION: Various types of maxillary defects can be reconstructed successfully using different microvascular free flaps. This procedure is challenging because of the anatomical site of reconstruction creating a steep learning curve. If the reconstruction is successful, both facial appearance and oral function can be improved. Microvascular flaps containing bone of the fibula, scapula, or iliac crest facilitate complete dental rehabilitation.

Outcome of treatment and parameters influencing recurrence in patients with bisphosphonate-related osteonecrosis of the jaws.

PURPOSE: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is now a well-recognised entity which is difficult to manage and often recurs. The aim of this study was to examine the success of resection of the necrotic bone and identify risk factors for recurrence in these patients. METHODS: One hundred and eight patients were evaluated prospectively and investigated at least twice. Multiple logistic regression analysis was used to determine factors independently associated with the dependent variable of recurrence of BRONJ. RESULTS: Factors influencing the development of recurrence of BRONJ were the presence of bacterial bone infection of the necrotic area (P = 0.011), type of treatment (either conservative or surgical, P = 0.001) with a lower recurrence rate for surgically treated patients, extent of surgical treatment with better outcome in larger resections (P < 0.0001), number of debridements performed (P < 0.0001), and the extent of radiographic appearance of osteolysis assessed by dental panoramic tomogram (P = 0.028). CONCLUSIONS: An increased risk for recurrence can be found in cases with bacterial bone infection of the necrotic area, type of conservative or surgical treatment, extent of surgical treatment with better outcome in larger resections, and the number of debridements performed. Microvascular tissue transfer should be considered in selected cases if other options have been exhausted.

Production of polyhydroxyalkanoates (PHAs) from waste materials and by-products by submerged and solid-state fermentation.

Polyhydroxyalkanoates are biodegradable polymers produced by prokaryotic organisms from renewable resources. The production of PHAs by submerged fermentation processes has been intensively studied over the last 30 years. In recent years, alternative strategies have been proposed, such as the use of solid-state fermentation or the production of PHAs in transgenic plants. This paper gives an overview of submerged and solid-state fermentation processes used to produce PHAs from waste materials and by-products. The use of these low-cost raw materials has the potential to reduce PHA production costs, because the raw material costs contribute a significant part of production costs in traditional PHA production processes.