Virtual tumor mapping and margin control with 3-D planning and navigation.

Computer technology-based treatment approaches like intraoperative navigation and intensity-modulated radiation therapy have become important components of state of the art head and neck cancer treatment. Multidirectional exchange of virtual three-dimensional patient data via an interdisciplinary platform allows all medical specialists involved in the patients treatment to take full advantage of these technologies. This review article gives an overview of current technologies and future directions regarding treatment approaches that are based on a virtual, three-dimensional patient specific dataset: storage and exchange of spatial information acquired via intraoperative navigation allow for a highly precise frozen section procedure. In the postoperative setting, virtual reconstruction of the tumor resection surface provides the basis for improved radiation therapy planning and virtual reconstruction of the tumor with integration of molecular findings creates a valuable tool for postoperative treatment and follow-up. These refinements of established treatment components and novel approaches have the potential to make a major contribution to improving the outcome in head and neck cancer patients.

Donor site morbidity after computer assisted surgical reconstruction of the mandible using deep circumflex iliac artery grafts: a cross sectional study.

BACKGROUND: Computer Assisted Design and Computer Assisted Manufacturing (CAD/CAM) have revolutionized oncologic surgery of the head and neck. A multitude of benefits of this technique has been described, but there are only few reports of donor site comorbidity following CAD/CAM surgery. METHODS: This study investigated comorbidity of the hip following deep circumflex iliac artery (DCIA) graft raising using CAD/CAM techniques. A cross-sectional examination was performed to determine range of motion, muscle strength and nerve disturbances. Furthermore, correlations between graft volume and skin incision length with postoperative donor site morbidity were assessed using Spearman's rank correlation, linear regression and analysis of variance (ANOVA). RESULTS: Fifteen patients with a mean graft volume of 21.2 ± 5.7 cm3 and a mean incision length of 228.0 ± 30.0 mm were included. Patients reported of noticeable physical limitations in daily life activities (12.3 ± 11.9 weeks) and athletic activities (38.4 ± 40.0 weeks in mean) following surgery. Graft volume significantly correlated with the duration of the use of walking aids (R = 0.57; p = 0.033) and impairment in daily life activities (R = 0.65; p = 0.012). The length of the scar of the donor-site showed a statistically significant association with postoperative iliohypogastric nerve deficits (F = 4.4, p = 0.037). Patients with anaesthaesia of a peripheral cutaneous nerve had a larger mean scar length (280 ± 30.0 mm) than subjects with hypaesthesia (245 ± 10.1 mm) or no complaints (216 ± 27.7 mm). CONCLUSIONS: Despite sophisticated planning options in modern CAD/CAM surgery, comorbidity of the donor site following  iliac graft harvesting is still a problem. This study is the first to investigate comorbidity after DCIA graft raising in a patient group treated exclusively with CAD/CAM techniques. The results indicate that a minimal invasive approach in terms of small graft volumes and small skin incisions could help to reduce postoperative symptomatology. Trial registration Retrospectively registered at the German Clinical Trials Register (DRKS-ID: DRKS00029066); registration date: 23/05/2022.

Analysis of the accuracy of computer-assisted DCIA flap mandibular reconstruction applying a novel approach based on geometric morphometrics.

BACKGROUND: This study evaluated the accuracy of computer-assisted surgery (CAS)-driven DCIA (deep circumflex iliac artery) flap mandibular reconstruction by traditional morphometric methods and geometric morphometric methods (GMM). METHODS: Reconstruction accuracy was evaluated by measuring distances and angles between bilateral anatomical landmarks. Additionally, the average length of displacements vectors between landmarks was computed to evaluate factors assumed to influence reconstruction accuracy. Principal component analysis (PCA) was applied to unveil main modes of dislocation. RESULTS: High reconstruction accuracy could be demonstrated for a sample consisting of 26 patients. The effect of the number of segments and length of defect on reconstruction accuracy were close to the commonly used significance threshold (p = 0.062/0.060). PCA demonstrated displacement to result mainly from sagittal and transversal shifts. CONCLUSIONS: CAS is a viable approach to achieve high accuracy in mandibular reconstruction and GMM can facilitate the evaluation of factors influencing reconstruction accuracy and unveil main modes of dislocation in this context.

Aspirin, heparin and ischemia time in microvascular free flap surgery - their influence and an optimal anticoagulation protocol.

BACKGROUND: Microvascular surgery has become a standardized technique for reconstruction of large tissue defects in Head and Neck Reconstructive Surgery. However, the main dreaded complications are thrombosis of blood vessels or major bleeding after surgery. Several different anticoagulation protocols have been established in the last decades to overcome these problems with varying degrees of success. METHODS: Over a period of six years, a standardized anticoagulation protocol including acetylsalicylic acid (ASA) and unfractionated heparin (UFH) for direct intraoperative and postoperative administration was established, optimized and compared to a previously used non-standardized protocol. A total of 178 flap surgeries were included in the development and optimization process of the protocol. RESULTS: ASA significantly increased the risk of complications when used for longer than 72 h (OR = 2.52; p = 0.002; 95% CI 1.39-4.59). Administration of UFH reduced flap loss (bolus: OR 0.68; p = 0.47; 95% CI 0.24-1.93; continuous UFH administration: OR = 0.61; p = 0.33; 95% CI 0.22-1.66), however doses greater than 500 IU/ h of UFH as continuous infusion increased the risk of complications. Reduction in ischemia time had no effect on the occurrence of complications. CONCLUSION: Anticoagulation regimes in microvascular surgery can influence the postoperative complication rate. The optimal protocol should consist of a combination of ASA and UFH for the intraoperative and direct postoperative phase. Prolonged administration of ASA as well as doses >500 IU/ h of UFH are to be avoided due to the increased complication rate.

Evaluation of computed tomography settings in the context of visualization and discrimination of low dose injections of a novel liquid soft tissue fiducial marker in head and neck imaging.

BACKGROUND: Intraoperative incorporation of radiopaque fiducial markers at the tumor resection surface can provide useful assistance in identifying the tumor bed in postoperative imaging for RT planning and radiological follow-up. Besides titanium clips, iodine containing injectable liquid fiducial markers represent an option that has emerged more recently for this purpose. In this study, marking oral soft tissue resection surfaces, applying low dose injections of a novel Conformité Européenne (CE)-marked liquid fiducial marker based on sucrose acetoisobutyrate (SAIB) and iodinated SAIB (x-SAIB) was investigated. METHODS: Visibility and discriminability of low dose injections of SAIB/x-SAIB (10 µl, 20 µl, 30 µl) were systematically studied at different kV settings used in clinical routine in an ex-vivo porcine mandible model. Transferability of the preclinical results into the clinical setting and applicability of DE-CT were investigated in initial patients. RESULTS: Markers created by injection volumes as low as 10 µl were visible in CT imaging at all kV settings applied in clinical routine (70-120 kV). An injection volume of 30 µl allowed differentiation from an injection volume of 10 µl. In a total of 118 injections performed in two head and neck cancer patients, markers were clearly visible in 83% and 86% of injections. DE-CT allowed for differentiation between SAIB/x-SAIB markers and other hyperdense structures. CONCLUSIONS: Injection of low doses of SAIB/x-SAIB was found to be a feasible approach to mark oral soft tissue resection surfaces, with injection volumes as low as 10 µl found to be visible at all kV settings applied in clinical routine. With the application of SAIB/x-SAIB reported for tumors of different organs already, mostly applying relatively large volumes for IGRT, this study adds information on the applicability of low dose injections to facilitate identification of the tumor bed in postoperative CT and on performance of the marker at different kV settings used in clinical routine.

Effects of Red Blood Cell Transfusions on Distant Metastases of Oral Squamous Cell Carcinomas.

There is no consensus on the effect of red blood cell (RBC) transfusions on patients with oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between RBC administration and the occurrence of distant metastases (M+) after surgical treatment of OSCC. All medical records of patients who underwent primary surgery for OSCC in our department (2003-2019) were analyzed retrospectively (n = 609). Chi and Cox regression models were used to analyze the influence of transfusion on the development of M+, and survival rates. Kaplan-Meier curves were used for graphical presentation. A multitude of patient-specific factors showed a statistical impact in univariate analysis (transfusion, age, gender, diabetes, pT, pN, L, V, Pn, G, UICC, adjuvant therapy, free microvascular transplant, preoperative hemoglobin level). Transfusion status and pN stage were the only variables that showed a significant correlation to M+ in the multivariate Cox model. The hazard ratios for the occurrence of M+ were 2.42 for RBC transfusions and 2.99 for pN+. Administration of RBC transfusions was identified as a significant prognostic parameter for the occurrence of distant metastases after surgical treatment of OSCC. Hence, the administration of RBC transfusions should be considered carefully in the perioperative management.

Intraoperative marking of the tumour resection surface for improved radiation therapy planning in head and neck cancer: preclinical evaluation of a novel liquid fiducial marker.

OBJECTIVE: To evaluate a novel liquid fiducial marker for intraoperative marking of the tumour resection surface in oral cancer patients to facilitate precise postoperative delineation of the interface between the tumour resection border and reconstructed tissue for intensity-modulated radiation therapy. METHODS: A total of 200 markers were created by injecting the volumes of 10 µl, 20 µl, 30 µl, 40 µl and 50 µl of a liquid marker composed of sucrose acetoisobutyrate (SAIB) and iodinated sucrose acetoisobutyrate (x-SAIB) into the soft tissue of porcine mandible segments. Visibility of the resulting markers was quantified by threshold-based segmentation of the marker volume in CT- and CBCT imaging and by a comparison of signal intensities in MRI. RESULTS: Even the lowest volume of SAIB-/x-SAIB investigated (10 µl) resulted in a higher visibility (CTSoft tissue: 88.18 ± 13.23 µl; CTBone: 49.55 ± 7.62 µl; CBCT: 54.65 ± 12.58 µl) than observed with the incorporation of titanium ligature clips (CTSoft tissue: 50.15 ± 7.50 mm3; CTBone: 23.90 ± 3.39 mm3; CBCT: 33.80 ± 9.20 mm3). Markers created by the injection of 10 µl and 20 µl could reliably be delineated from markers created by the injection of higher volumes. CONCLUSION: SAIB/x-SAIB, which has recently become available as a Conformité Européenne (CE)-marked fiducial marker, provides an option for fast and reliable production of markers with excellent visibility in imaging modalities used in oral cancer radiation therapy (RT) planning routine.

Tooth extractions in patients under antiresorptive therapy for osteoporosis: Primary closure of the extraction socket with a mucoperiosteal flap versus application of platelet-rich fibrin for the prevention of antiresorptive agent-related osteonecrosis of the jaw.

PURPOSE: The aim of this study was to compare primary closure of the extraction socket to application of platelet-rich fibrin (PRF) without subsequent primary closure for the prevention of osteonecrosis of the jaw (ONJ) in patients administered antiresorptive therapy for osteoporosis. MATERIALS AND METHODS: Primary closure of the extraction socket was performed with a mucoperiosteal flap and two-layer suturing or PRF was inserted into the extraction socket without subsequent primary closure. In all patients, intra- and postoperative complications as well as the overall treatment outcome were recorded. RESULTS: The patient sample consisted of 77 patients; primary closure with a mucoperiosteal flap was performed in 39 patients (group A), and application of PRF without subsequent primary closure was performed in 38 patients (group B). There were no statistically significant differences (p > 0.05) between the two groups in terms of age and gender, duration and type of antiresorptive therapy, teeth to be extracted (number, location and type) as well as comorbidities. No intraoperative complications occurred in either of the groups. Postoperative complications were found in 6 patients in group A and in one patient in group B. Analyzing risk factors for these complications, the highest OR (6.72 with p = 0.085 in univariate analysis; 12.81 with p = 0.052 in multivariate analysis) was found for the type of procedure (group A/group B). All patients had complete mucosal coverage without any signs of antiresorptive agent-related osteonecrosis of the jaw at the final control examination 90 days postoperatively. CONCLUSION: Based on the results of this study, the use of PRF can be recommended as a preventive measure in patients requiring tooth extractions while being under antiresorptive therapy for osteoporosis.

Primary wound closure and perioperative antibiotic therapy for prevention of bisphosphonate-related osteonecrosis of the jaw after tooth extraction.

OBJECTIVES: Tooth extractions are suspected to be a major trigger for the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Preventive measures like perioperative antibiotic therapy and primary wound closure have been found to be effective in preventing the development of BRONJ following tooth extraction. The aim of this study was to present long-term results of a treatment protocol for patients under bisphosphonate therapy requiring tooth extraction. METHOD AND MATERIALS: Between January 2008 and December 2012, 232 tooth extractions were performed in 84 patients under current or previous bisphosphonate treatment. Extractions were performed applying an atraumatic technique under prolonged intravenous antibiotic therapy. The bony edges were rounded off meticulously and the extraction sockets were covered with a mucoperiosteal flap. RESULTS: Out of 84 patients, two developed osteonecrosis of the jaw (ONJ), resulting in an incidence-rate of 2.4%. Both ONJ patients had received radiation therapy to the head and neck region following tooth extraction. The remaining 82 patients had uneventful healing and did not present any signs or symptoms of BRONJ during the follow-up period of 41.5 months. CONCLUSION: Tooth extractions, if performed under certain circumstances, would not seem to constitute a major risk factor for the development of BRONJ. The treatment protocol presented in this article seems to be highly effective in preventing development of ONJ after tooth extraction in patients under current or previous bisphosphonate therapy.

Vascularized scapula and latissimus dorsi flap for CAD/CAM assisted reconstruction of mandibular defects including the mandibular condyle: technical report and clinical results.

BACKGROUND: Reconstruction of mandibular continuity and function after tumor resection is challenging, particularly in cases including the mandibular condyle. Various approaches for reconstruction after disarticulation resection have been reported. However, the scapula flap has received little attention as a treatment option in these cases. PATIENTS AND METHODS: Three cases of computer aided design and computer aided manufacturing (CAD/CAM) assisted reconstruction after disarticulation resection using a vascularized scapula and latissimus dorsi flap are reported. All cases required reconstruction of the mandibular ramus and condyle in combination with the reconstruction of large and complex soft tissue defects. RESULTS: The surgical procedure was deemed successful in all cases. The scapula flap could be placed as preoperatively planned and patients regained their preoperative occlusion pattern and satisfying mouth opening-ranges. The large soft tissue defects could reliably be reconstructed using a latissimus dorsi flap. CONCLUSIONS: The scapula and latissimus dorsi flap can be considered a suitable option for the reconstruction of mandibular disarticulation resection defects in combination with large soft tissue defects.

Analysis of the accuracy of a novel preformed osteosynthesis plate for the reduction and fixation of zygomaticomaxillary complex fractures.

INTRODUCTION: There has been a shift toward surgical treatment of ZMC (zygomaticomaxillary complex) fractures with open reduction and subsequent fixation in the past decades. Anatomically preformed osteosynthesis plates, already used in the field of craniomaxillofacial surgery for the treatment of fractures of the mandible and the orbit, might be a suitable option for ZMC fractures as well. MATERIAL AND METHODS: A statistical shape model was created from 179 cranial CT scans. Based on this surface model, an anatomically preformed plate for the reduction and fixation of ZMC fractures was developed in 3 sizes (S, M, L). Virtual analysis of the accuracy of the plate was performed on a dataset consisting of 120 CT scans. RESULTS: Within a determined tolerance range of 0-1.5 mm, analysis revealed a high accuracy of the plate in 70-87 % of the CT scans. The S-sized plate has the highest overall accuracy, whereas the L-sized plate has highest accuracy at the "base" region which is essential for the placement of the plate. DISCUSSION: The newly developed plate can be placed via an intraoral approach and analysis of the plate has confirmed its accuracy to be sufficient to ensure an adequate fracture reduction and fixation. It thus might allow for a less extensive approach and less approaches/incisions necessary overall to reduce and fixate ZMC fractures.

Catching condyle - Endoscopic-assisted transoral open reduction and rigid fixation of condylar process fractures using an auto reposition and fixation osteosynthesis plate.

INTRODUCTION: Fractures of the mandibular condyle are reported to account for 9 %-45 % of all mandibular fractures. There has been a long lasting controversy on the superiority of different treatment options with endoscopic-assisted transoral approaches gaining increasing attention in recent years. In this article, we report the application of a newly developed osteosynthesis plate for an auto reposition, reconstruction and rigid fixation of condylar process fractures. MATERIAL AND METHODS: We present 6 cases of uni- or bilateral fractures of the condylar process treated with a transoral open reduction and rigid fixation using an auto reposition plate. Via a transoral endoscopic assisted approach the proximal condyle fragment is captured using an anatomical defined clinch of the cranial part of the plate. The reposition of the condyle is facilitated with the distal bridge of the plate ranging around the posterior part of the ascending ramus. RESULTS: The results show a sufficient reposition, rigid fixation and no facial nerve palsy or postoperative long-term occlusal disturbances. The mean operating time was 86 min. CONCLUSION: Transoral endoscopic-assisted surgery with application of an auto reposition, reconstruction and fixation plate offers a quick and convenient way for open reconstruction and rigid fixation of condylar process fractures.

Correction to: Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells.

In the Original publication of the article, the co-author has been misspelled as Fabian Duttenhöfer in the article "Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells" published in October 2017, Volume 105, Issue 4 of Odontology. The correct name is "Fabian Duttenhoefer".

Sexual activity and quality of life in patients after treatment for breast and ovarian cancer.

OBJECTIVE: Sexual activity (SA) and functioning (SF) are important factors influencing quality of life (QoL). Anticancer treatment can cause or promote sexual dysfunctions. In this study we analyzed the SA, SF and QoL in patients after completion of treatment for breast cancer (BC) and ovarian cancer (OC). METHODS: In this retrospective multicenter study 396 BC patients and 93 OC patients aged between 18 and 70 years were surveyed at least 24 months after cancer diagnosis and compared to 60 healthy women. Data were collected through validated questionnaires (Sexual Activity Questionnaire, Female Sexual Function Index-d, EORTC Quality of Life Questionnaire-C30). RESULTS: 45.9% of BC patients and 56.5% of OC patients reported SA. SF and well-being of sexually active BC patients were not influenced by the type and radicality of surgery or the administration of chemotherapy. Patients who received antihormonal therapy at the time of evaluation showed a lower frequency of SA (p = 0.007), less satisfaction (p = 0.003) and more discomfort during SA (p = < 0.001) compared to healthy controls but no differences in experiencing orgasms, health status, QoL and global health status. In contrast, BC patients without antihormonal therapy showed only a higher discomfort score (p = 0.028) than healthy controls and estimated their health status and QoL significantly better than patients who received antihormonal therapy (p = 0006). In general, SA was associated with a better health status (p = 0.007), a better QoL (p = 0.004) and a better global health status (p = 0.004) in BC patients. Sexually active OC patients showed no significant differences in SF, QoL and health status compared to healthy controls. CONCLUSIONS: Compared to healthy controls BC patients showed limitations in SF with a lower SA rate and more discomfort. Antihormonal therapy was an important factor influencing SF and well-being. Breast and OC survivors reported good physical and psychical health without differences in QoL and health status compared to controls. This might be explained by a change of perspective on life difficulties and altered priorities through a life threatening disease.

Necrotizing fasciitis as a complication of osteonecrosis of the jaw related to oral bisphosphonate application in a patient with osteoporosis: a case report.

BACKGROUND: Necrotizing fasciitis has been reported as a complication secondary to bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a low number of patients. The only report of such a case in an osteoporosis patient found in current literature was related to short-term bisphosphonate but long time corticosteroid and methotrexate treatment. CASE PRESENTATION: In this article, we report a case of necrotizing fasciitis secondary to osteonecrosis of the jaw related to long-term oral bisphosphonate treatment in an osteoporosis patient additionally suffering from poorly controlled type 2 diabetes. Diabetes mellitus not only has been reported to be a systemic risk factor regarding BRONJ but also to be the most common comorbidity in patients presenting with necrotizing fasciitis and to increase mortality of this condition. Necrotizing fasciitis and BRONJ in the patient could eventually be resolved by a surgical approach and intravenous antibiotic therapy. CONCLUSIONS: The case presented suggests diabetes mellitus potentially having been an important factor in the particularly unfavorable course of therapy. It emphasizes the importance of an adequate therapy and surveillance of modifiable systemic risk factors like diabetes mellitus in patients being at risk for development of BRONJ. If necrotizing fasciitis is suspected, early diagnosis and aggressive surgical and medical management are essential to minimize morbidity and mortality.

Numb Chin as Signal for Malignancy-Primary Intraosseous Diffuse Large B-Cell Lymphoma of the Mandible.

Malignant lymphomas are about 5% of all malignant tumors. Extranodal non-Hodgkin's lymphomas (NHLs) are found in 26% of these cases. Lymphomas of the head-and-neck area occur in 2%-3% of all malignancies, with 28% with an extranodal manifestation. Extranodal NHLs in the oral cavity are usually found in the maxilla, and rarely in the mandible. Their symptoms and clinical manifestation have no pathognomonic features; therefore, the expression of this uncommon entity can be diagnosed with an odontogenic inflammatory process, leading to a misdiagnosis. Delay in the decision for a biopsy, and adequate treatment for the patient directly impairs the prognosis of this neoplasm. This study reports a case of a patient with discomfort in the right mandible and paresthesia of the right lower lip and chin without any dental focus. After performing further diagnostic examinations including a subsequent biopsy, the final diagnosis was a diffuse large B-cell lymphoma (DLBCL). Intraosseous DLBCLs are uncommon in the daily clinical routine, but emphasize the need for careful examination by the clinicians also considering the differential diagnosis of sensory neuropathy. Neurological symptoms with no apparent cause should raise the suspicion of malignancy until the opposite is proven.

Protocol based evaluation for feasibility of extubation compared to clinical scoring systems after major oral cancer surgery safely reduces the need for tracheostomy: a retrospective cohort study.

BACKGROUND: Despite risks, complications and negative impact to quality of life, tracheostomy is widely used to bypass upper airway obstruction after major oral cancer surgery (MOCS). Decision to tracheostomy is frequently based on clinical scoring systems which mainly have not been validated by different cohorts. Delayed extubation in the Intensive Care Unit (ICU) may be a suitable alternative in selected cases. We hypothesize that delayed routine ICU extubation after MOCS instead of scoring system based tracheostomy is safe, feasible and leads to lower tracheostomy rates. METHODS: We retrospectively analyzed our clinical protocol which provides routine extubation of patients after MOCS in the ICU. The primary outcome measure was a composite of early reintubation within 24 h or secondary tracheostomy. Secondary outcome measures included airway obstruction related morbidity and mortality. Predictor variables included tumor localisation, surgical procedure and reconstruction method, length of operation and pre-existing morbidity. Furthermore we assessed the ability of four clinical scoring systems to identify patients requiring secondary tracheostomy. Statistical processing includes basic descriptive statistics, Chi-squared test and multivariate logistic regression analysis. RESULTS: Two hundred thirty four cases were enclosed to this retrospective study. Fourteen patients (6%) required secondary tracheostomy, Ten patients (4%) required reintubation within 24 h after extubation. No airway obstruction associated mortality, morbidity and cannot intubate cannot ventilate situation was observed. Seventy five percent of the patients were extubated within 17 h after ICU admission. All evaluated scores showed a poor positive predictive value (0.08 to 0.18) with a sensitivity ranged from 0.13 to 0.63 and specificity ranged from 0.5 to 0.93. CONCLUSIONS: Our data demonstrate that common clinical scoring systems fail to prevent tracheostomy in patients after MOCS. Application of scoring systems may lead to a higher number of unnecessary tracheostomies. Delayed routine extubation in the ICU after MOCS seems an appropriate and safe approach to avoid tracheostomy and the related morbidity.

The Prevention of Medication-related Osteonecrosis of the Jaw.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a preventable complication of antiresorptive treatment. It arises in 1-20% of patients with bone metastases of solid tumors and hematologic malignancies and in 0.1-2% of patients being treated for osteoporosis with bisphosphonates. Depending on the underlying disease and medication dosage, the risk of MRONJ can be elevated even in the first year of antiresorptive treatment. The treatment of MRONJ is difficult and often involves surgery of the jaw. METHODS: We systematically reviewed publications retrieved by a selective search for literature on the prevention of MRONJ in the PubMed and Cochrane Library databases and with the aid of the Google Scholar search engine. RESULTS: 15 of 559 retrieved publications were included in the analysis. The quality of the evidence in the studies was generally moderate to low, with most of them being case series. In one case series of over 1200 patients with multiple myeloma, the incidence of MRONJ was lowered from 4.6% to 0.8% through regular dental checkups and improved oral hygiene. Tooth extraction, in particular, is associated with a high risk of MRONJ. In a retrospective study, 57% of patients who underwent tooth extraction without antibiotic prophylaxis developed MRONJ, compared to 0% with antibiotic prophylaxis. CONCLUSION: Before antiresorptive medication is begun, oral hygiene should be improved. Moreover, it seems that perioperative antibiotic prophylaxis and adequate plastic wound closure can often prevent MRONJ. In view of the fact that bisphosphonates can persist in bone for more than 15 years, patients should be thoroughly informed of the risk that antiresorptive treatment can cause MRONJ, and the measures discussed should be initiated.

Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells.

Treatment strategies for medication-related osteonecrosis of the jaw (MRONJ) remain controversial. Although the AAOMS suggests a conservative approach, a surgical management with necrosectomy is often required when conservative management has failed. Moreover, recent studies have shown promising results using an early stage surgical treatment. Over the past decade, cell-based bone regeneration utilizing bone marrow mesenchymal stem cells (MSCs) received increased attention. MSCs are known to promote wound healing and induce new bone formation in compromised tissue. Accordingly, the aim of this study was to assess the role of MSCs in the management of MRONJ. This study included 6 patients referred to our department with the diagnosis of MRONJ. Upon informed consent, the patients underwent surgical resection of necrotic bone followed by MSCs grafting. The MSCs were separated from bone marrow cells aspirated from the iliac crest using a bone marrow aspirate concentrate system. The MSCs were grafted into the defect with autologous thrombin and the defect was covered with a collagen membrane. In all cases, bony edges were rounded and the wound was closed using a three-layered technique. In the follow-up from 12 to 54 months, all patients including those who had impaired conditions, sepsis, or pathological fracture, showed satisfactory healing with no signs of wound infection. This pilot study indicated that surgical management in combination with MSCs transplantation seems to be a promising treatment modality in the therapy of MRONJ.

Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab.

OBJECTIVES: Some recent reports have indicated that local infection causes osteonecrosis of the jaw and described that tooth extraction may not be a direct cause of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive medications. Tooth extraction and elimination of the source of infection are expected to reduce the risk of developing MRONJ. However, there is no data regarding prevention for developing osteonecrosis of the jaw in patients receiving denosumab. Therefore, the aim of this study was to investigate the outcome of tooth extractions with proper wound closure in patients receiving denosumab. PATIENTS AND METHODS: Forty teeth in 19 patients treated with denosumab therapy were extracted under preoperative intravenous antibiotics. Patients who had already developed MRONJ in the extraction sites or who had a history of radiation therapy were excluded. During surgery, bone edges were smoothed and all wounds were closed using the double-layered technique. RESULTS: Thirty-seven extraction sites (92.5 %) in 17 out of 19 patients (89.5 %) were healed. However, three extraction sites in two patients had complications; one patient had exposed bone and developed MRONJ (stage 1) and the other developed a mucosa fistula. Additional surgical procedures were performed and all wounds were completely healed. CONCLUSIONS: Tooth extractions in patients receiving denosumab can be performed in an appropriate manner and result in good outcomes. CLINICAL RELEVANCE: This study indicated that tooth extraction with proper wound closure to avoid secondary infection may be effective for the prevention of MRONJ even in high-risk patients.