Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.

BACKGROUND: Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. METHODS: The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. RESULTS: Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. CONCLUSION: Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

Tanshinone IIA Ameliorates Inflammation Response in Osteoarthritis via Inhibition of miR-155/FOXO3 Axis.

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder characterized by degeneration of the articular cartilage and joint destruction with an associated risk of mobility disability in elderly people. Although a lot of achievements have been made, OA is still regarded as an incurable disease. Therefore, the pathological mechanisms and novel therapeutic strategies of OA need more investigation. METHODS: MTT assay was conducted to measure the viability of chondrocytes after LPS treatment. Cell apoptosis was analyzed by annexin V/propidium iodide labeling. ELISA was used to determine the concentrations of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the culture supernatant of chondrocytes. The expression level of miR-155, IL-1ß, FOXO3, TNF-α, IL-6, caspase-3, and caspase-9 in chondrocytes was analyzed by RT-qPCR or Western blot. RESULTS: We found that LPS led to inflammatory responses, cell apoptosis, and increased miR-155 expression in human articular chondrocytes. Tanshinone IIA could inhibit LPS-induced inflammation and cell apoptosis of chondrocytes via regulating the expression of miR-155 and FOXO3. miR-155 directly targeted the 3'-UTR of FOXO3 to regulate its expression. CONCLUSIONS: Taken together, our data suggest tanshinone IIA ameliorates inflammation response in OA via inhibition of the miR-155/FOXO3 axis, and provide some evidences that tanshinone IIA could be designed and developed as a new promising clinical therapeutic drug for OA patients.

Expert Consensus on Procedures and Operations of Navigation-guided Needle Biopsy Techniques for Skull Base Tumours.

Skull base surgery is an interdisciplinary subject. The anatomical structures in the skull base related to oral and maxillofacial surgery include the parapharyngeal space, the pterygopalatine fossa and the infratemporal space. This operative area is one of the most challenging surgical areas in oral and maxillofacial surgery due to its deep site, complex anatomy and high risk. Obtaining pathological information of the tumour preoperatively may help surgeons optimise their treatment plan. Needle biopsy is one of the major minimally invasive techniques that allows preoperative pathological results to be obtained. The navigation technology, which is developing rapidly nowadays, provides a reliable assistance for deep tissue biopsy surgery. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association formulated an expert consensus on the procedures and operations of navigation-guided needle biopsy techniques for skull base tumours, so as to standardise and promote the application and operation of navigation-guided needle biopsy for skull base tumours.

MR imaging as a precise technique to evaluate skull-base tumor volume: Comparison of CT, MR imaging and FDG PET from murine and clinical data.

In spite of the many imaging modalities used in clinics, the one that best reflects the true delineation of skull-base (infratemporal fossa, ITF) malignancies is still unknown. In order to compare the tumor recognition capabilities of different imaging modalities, established murine models and patients with skull-base tumors were evaluated by computer tomography (CT), magnetic resonance (MR) imaging, and fluorine-18 fluorodeoxyglucose (18FDG) positron emission tomography (PET) for delineation of gross tumor volume (GTV). PET, MR imaging, and CT enhanced by iodine staining were all sensitive to, and able to recognize, the skull-base tumor in the murine model. No significant difference (p > 0.9999) was observed between average GTV according to MR imaging (176.67 ± 19.6 mm3) and the histological measurement result (170.23 ± 22.24 mm3) for the murine model. In contrast, the GTVs according to CT (88.77 ± 13.03 mm3, p < 0.0001) and 18FDG PET (35.67 ± 6.56 mm3, p < 0.0001) were much smaller. In nine patients for whom the three modalities were available, tumor volume comparisons tended to be consistent with the murine model data. According to both the established murine model and clinical patient data, MR imaging possessed the optimal ability to recognize tumor contours.

Performance of Robotic Assistance for Skull Base Biopsy: A Phantom Study.

Objectives This study aims to evaluate the feasibility of a custom robot system guided by optical cone beam computed tomography (CBCT)-based navigation for skull base biopsy. Design An accuracy study was conducted. Setting Platform for navigation and robot-aided surgery technology. Participants Phantom skull. Main Outcome Measures The primary outcome measure was to investigate the accuracy of robot-assisted needle biopsy for skull base tumors. A 14-gauge needle was automatically inserted by the five degrees of freedom robot into the intended target, guided by optical navigation. The result was displayed on the graphical user interface after matrix transformation. Postoperative image scanning was performed, and the result was verified with image fusion. Results All 20 interventions were successfully performed. The mean deviation of the needle tip was 0.56 ± 0.22 mm (measured by the navigation system) versus 1.73 ± 0.60 mm (measured by image fusion) ( p < 0.05). The mean insertion depth was 52.3 mm (range: 49.7-55.2 mm). The mean angular deviations off the x-axis, y-axis, and z-axis were 1.51 ± 0.67, 2.33 ± 1.65, and 1.47 ± 1.16 degrees, respectively. Conclusions The experimental results show the robot system is efficient, reliable, and safe. The navigation accuracy is a significant factor in robotic procedures.

Prospects of Robot-Assisted Mandibular Reconstruction with Fibula Flap: Comparison with a Computer-Assisted Navigation System and Freehand Technique.

Background Function and aesthetics have a significant impact on the quality of life in patients undergoing mandibular reconstructive surgery, but achieving satisfactory results remain challenging. The aim of the study is to investigate the feasibility and accuracy of robot-assisted mandibular reconstruction with fibula flap in comparison to that with a computer-assisted navigation system and the freehand technique. Methods Experimental procedures (15 phantom studies and 6 animal experiments) were performed with a custom three-arm robotic system automatically, under the guidance of a computer-assisted navigation system, and by the freehand technique, respectively. The accuracy of the reconstruction was assessed by comparison between the preoperative and postoperative three-dimensional surface virtual models. Results All procedures were successfully performed. In the phantom study, the mean deviation of the fibula implant was 1.221, 1.581, and 2.313 mm, respectively, with the robotic system, the navigation system, and the freehand technique; in the animal experiment the corresponding figures were 1.7697, 1.7847, and 2.0815 mm, respectively. The mean deviation of the proximal mandibular ramus was 1.0420, 1.0532, 1.8800 mm with the robotic system, computer-assisted navigation system, and freehand technique, respectively, and the mean deviation of the distal mandibular segment was 1.1645, 2.7198, and 2.8445 mm, respectively. Conclusions The robotic system is feasible, efficient, and reliable for mandibular reconstruction. The accuracy of the fibula implant orientation with the robotic system was comparable to that with navigation system and superior to that with the freehand technique.

[Clinical features of osteonecrosis of jaws after bisphosphonates therapy for bone metastasis of breast cancer].

OBJECTIVE: To understand the clinical features of osteonecrosis of the jaw after bisphosphonates use for therapy of breast cancer patients with bone metastasis. METHODS: The cases diagnosed as bisphosphonates-related osteonecrosis of the jaws (BRONJ) were retrospectively analyzed from January 2011 to August 2015 in the Peking University School and Hospital of Stomatology, and those breast cancer patients with bone metastasis were selected. The clinical symptoms, imaging characteristics and treatment results were summarized. RESULTS: A total of 14 cases of breast cancer patients with bone metastasis were selected, with an average age of 60.21 years. The average time of suffering from breast cancer was 9.77 years, and the average time of bone metastasis and bisphosphonates drugs use was 5.67 and 3.29 years individually. There was no patient with systemic application history of hormone therapy, and no history of diabetes. There were 9 patients with tooth extractions history, and the mean time of bone necrosis symptoms was 8.58 months. There were 10 cases with bone necrosis occurring on mandible, 3 cases on maxilla, and one case with both upper and lower jaws involved. Among the 10 patients with surgical treatment, there were 3 cases cured, and 6 cases improved. However, the clinical symptoms of 2 cases with conservative treatment were significantly aggravated. CONCLUSION: The medication time between the bisphosphonates use beginning and the occurrence of BRONJ is relatively long. The history of diabetes and long-time hormone use did not exist in this group. Tooth extraction itself does not determine the severity of BRONJ. Mandible is the most common site involved by BRONJ. Surgical treatment can alleviate the clinical symptoms of BRONJ with breast cancer to some extent.

Application of a computer-aided navigation technique in surgery for recurrent malignant infratemporal fossa tumors.

BACKGROUND: Because of the complexity of the local anatomy, tumors in the infratemporal fossa present a great challenge to oral and maxillofacial surgeons. Recurrent malignant tumors in this area are particularly difficult and precarious to resect because scars from previous operations may dislocate some important structures. METHODS: From August 2010 to December 2013, all recurrent cases of malignant infratemporal fossa tumors at Peking University Stomatological Hospital were enrolled in this study. The patients were divided into 2 groups: the navigation group and the nonnavigation group, with different managements. The following factors were evaluated: operation time, bleeding volume, tumor size, surgical approach and complications, follow-up survey, and outcomes.In addition, survival analyses were performed for all patients. RESULTS: In total, 42 patients were investigated. The mean operation time for the navigation group was not significantly longer than that of the nonnavigation group (283.64 versus 252.10 min, respectively; P = 0.393); the group's mean intraoperative bleeding volumes were similar (536.36 versus 503.87 mL, respectively; P = 0.814). The surgical approach was determined and categorized as an inferior approach (transmandibular approach, with or without splitting of the mandible), anterior approach (transmaxillary approach), lateral approach (subtemporal-preauricular approach), or combined approach. The inferior approach was most frequently used in both groups (ie, 63.6% for the navigation group and 80.6% for the nonnavigation group). The tumors were completely resected in 4 patients from the navigation group and 24 patients from the nonnavigation group. Regarding complications in the navigation and nonnavigation groups, the incidence was not significantly different (27.2% versus 41.9%, respectively; P = 0.485). The 3-year survival for patients in the navigation group was 71.6% compared with 52.9% in the nonnavigation group, with no significant difference. In the survival analysis, no significant factor was determined. CONCLUSIONS: A computer-aided navigation technique has been successfully introduced to resect infratemporal fossa tumors and was successfully applied to the resection of recurrent malignant tumors. This new technique alone does not determine the outcome of patients with recurrent malignant infratemporal fossa tumors. Although some improvements are necessary, the visible navigation during surgery could increase the accuracy and safety of the operations and enhance surgeon confidence.

Primary cN0 lip squamous cell carcinoma and elective neck dissection: Systematic review and meta-analysis.

BACKGROUND: Management of clinically negative lymph nodes (cN0) in primary lip squamous cell carcinoma (SCC) has always been a controversial topic. METHODS: A systematic review of English-language electronic databases using Medline, Embase, Cochrane library, Google Scholar, SCI, and specific journals on the subject matter was done. Only the studies mentioning primary nonmetastatic lip SCC with cN0 neck treated by surgery only and having at least 2 years of follow-up data were selected. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analysis was followed. RESULTS: The pooled estimate of occult metastasis in neck dissected specimen was 0.17 (95% confidence interval [CI], 0.10-0.28) and that of delayed nodal metastasis in patients without neck dissection was 0.08 (95% CI, 0.01-0.18). CONCLUSION: The results do not prove sufficient to justify elective treatment of the neck in primary cN0 lip SCC and close observation would be a viable option in such cases. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1392-1400, 2015.

[Application of computer-aided design and navigation technology in skull base and infratemporal fossa tumor surgery].

OBJECTIVE: To evaluate the application of computer-aided design and navigation technology in skull base and infratemporal fossa tumor surgery and to analyze its advantages and disadvantages. METHODS: Twenty-nine cases with tumor of skull base and infratemporal fossa were treated with computer-aided design and navigation surgery. The Parameters of age, gender, primary or recurrent tumor, tumor nature and surgical approach were recorded. RESULTS: En bloc resection was performed in 20 cases and subtotal resection in 9 cases. The margin status was negative margin in 8 cases, near-tumor margin in 17 cases and positive resection margin in 4 cases. Postoperative complication rate was 14% (4/29). During the follow-up period, 2 benign cases recurred.In the malignant group, there were 7 cases of recurrence, 2 cases of metastasis and 3 deaths. The 5-year overall survival and progression-free survival rate were 69% and 40% respectively. CONCLUSIONS: Navigation technology can enhance the confidence of the surgeons and operation safety in handling malignant tumors in skull base and infratemporal fossa.

Relation between a first branchial cleft anomaly and the facial nerve.

Relations between first branchial cleft anomalies and the facial nerve vary. We reviewed 41 patients' medical records and pathological sections to clarify the relation, and found that those on the right side in young patients, which were Work type II and situated low down, were likely to be deep to the facial nerve.

[Application of three-dimensional reconstruction of the enhanced CT in infratemporal fossa and parapharygeal space tumors].

OBJECTIVE: To reconstruct three-dimensional CT image of the skull, the blood vessels and the infratemporal fossa and parapharyngeal space tumors using Mimics software, and to discuss the clinical significance of the three-dimensional CT in diagnosis and preoperative surgical design. METHODS: Four infratemporal fossa and parapharyngeal space tumors were studied using spiral CT Siemens 16 scanning technology, based on 2 mm thickness, and Mimics software was used to directly read the original image, and surface shaded technology was applied for reconstructing the spatial relationship of the vascular, skull and tumor structures. RESULTS: The three-dimensional reconstruction images can clearly demonstrate the extent of the tumor size, location, and its relation to blood vessels and the skull. CONCLUSION: The three-dimensional reconstruction of enhanced CT image is conducive to operation plan designed to avoid damaging important anatomical structures.