Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach.

BACKGROUND: Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing functional, aesthetic, and psychological impairments. The BRAF V600E mutation is present in approximately 80% of mandible ameloblastomas, and BRAF inhibitors have demonstrated sustained responses in unresectable cases. METHODS: We identified ameloblastoma patients planned for ablative surgery and screened them for BRAF V600E mutation. Neoadjuvant BRAF inhibitors were offered to facilitate jaw preservation surgery. Retrospective data collection encompassed treatment regimens, tolerability, tumor response, and conversion to mandible preservation surgery. RESULTS: Between 2017 and 2022, a total of 11 patients received dabrafenib (n = 6) or dabrafenib with trametinib (n = 5). The median age was 19 (range = 10-83) years. Median treatment duration was 10 (range = 3-20) months. All (100%) patients achieved a radiological response. Ten (91%) patients successfully converted to mandible preservation surgery with residual tumor enucleation. One patient attained complete radiological response, and surgery was not performed. Among the 10 surgically treated patients, all exhibited a pathological response, with 4 achieving near complete response and 6 partial response. At a median follow-up of 14 (range = 7-37) months after surgery, 1 case of recurrence was observed. Grade 1-2 adverse effects were reported in 8 (73%) patients, with a single case of grade 3 (hepatitis). Dose modification was necessary for 3 patients, and 4 experienced treatment interruptions, while 1 patient permanently discontinued therapy. CONCLUSIONS: Neoadjuvant BRAF inhibition may offer a safe and effective strategy for organ preservation in mandible ameloblastoma treatment.

Translation, Transcultural Adaptation, and Validation of the Hebrew Language Version of the Orthognathic Quality of Life Questionnaire for the Assessment of Quality of Life in Orthognathic Patients.

INTRODUCTION: Dentofacial deformities impose a negative impact on quality of life (QOL). Orthognathic surgery is the main pillar of treatment for these conditions and has proven its impact on the improvement of the functional and psychosocial aspects of QOL. The Orthognathic Quality of Life Questionnaire (OQLQ), developed by Cunningham and colleagues, is a well-established instrument for assessing QOL in patients with dentofacial deformities. OBJECTIVE: The aim of this study was to perform a translation, transcultural adaptation, and validation of a Hebrew version of the OQLQ. METHODS: Transcultural adaptation was done following guidelines proposed by Beaton and colleagues resulting in a pilot study conducted on 20 patients undergoing orthognathic surgery. Internal consistency, reliability, and sensitivity were evaluated by means of Cronbach alpha, intraclass correlation coefficient (test-retest), and Wilcoxon test, respectively. Validity was assessed by comparing the OQLQ with the Hebrew version of the Oral Health Impact Scale-14 (Oral Health Impact Profile Scale-14) using the Spearman correlation test. RESULTS: Internal consistency showed a good correlation between domains and excellent test-retest reliability. Sensitivity to change was statistically significant in all but 3 questions. The Hebrew version of the OQLQ exhibited a strong correlation with Oral Health Impact Profile Scale-14 in total score and moderate to high correlations among domains. CONCLUSION: The Hebrew version of the OQLQ is a valid and reliable and specific instrument to measure QOL for Hebrew-speaking patients undergoing orthognathic surgery.

Upfront rational therapy in BRAF V600E mutated pediatric ameloblastoma promotes ad integrum mandibular regeneration.

Ameloblastoma is a neoplasm arising in the craniofacial skeleton. Proliferating odontogenic epithelial cells comprise this benign, yet locally invasive tumor, often causing severe disfiguration. High recurrence rate entails ablative surgical resection, which is the current standard of care, resulting in subsequent critical size osteocutaneous defects. The high incidence of BRAF mutations in ameloblastoma, most notably the BRAF V600E mutation, enabled the use of BRAF inhibiting agent in a neoadjuvant setting. In this investigator-initiated, open-label study, three consecutive pediatric patients, with confirmed BRAF V600E ameloblastoma deemed marginally resectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The use of upfront BRAF inhibitor treatment resulted in substantial tumor regression, allowing for non-mutilating complete surgical removal, ad integrum bone regeneration and organ preservation. All patients showed a marked radiologic and clinical response to medical treatment, enabling successful conservative surgery. Microscopically, all patients showed evidence of minimal residual tumor with extensive tumor necrosis, fibrosis and generation of new bone. At a median follow-up of 31 months, all patients remained free of disease. Face preservation therapy was achieved in pediatric patients presenting with BRAF V600E mutated ameloblastoma. Our study demonstrates the translational potential of targeted therapy as a neoadjuvant agent. Patient-specific organ preservation therapy should be considered as the new standard of care in ameloblastoma, mainly for children and adolescents.

18F-FDG PET-CT postoperative changes after maxillectomy: Findings and pitfalls in interpretation.

OBJECTIVE: We investigated the findings and pitfalls of FDG-PET/CT scanning after maxillectomy with reconstruction/rehabilitation procedures, in patients with head and neck malignancies treated during nine years at one tertiary medical centre. METHODS: Fourteen patients (10 males), aged 22-84 years, underwent 17 reconstruction/rehabilitation maxillectomy surgeries and 35 PET/CT scans. Postoperative PET/CT findings were correlated with clinical and imaging follow-up. RESULTS: Increased FDG uptake, mean SUVmax 2.4 ± 1.4 (range 0.3-4.3), was observed at the postoperative bed following 12 of 17 surgeries (71%; 10 obturators, two mesh reconstructions). Following the remaining 5/17 surgeries (three with a fat flap and two without any reconstructions), abnormal FDG uptake was not observed at the postoperative bed.CT features of postoperative sites included: non-homogeneous mixed iso/hyperdense structures (hollow or filled) with multiple surrounding and/or inside air bubbles ("sponge appearance") and mucosal thickening along the postoperative bed wall (in all cases with obturator implants); rich fat density material in reconstructions with a fat flap and in closures without reconstruction, and radiopaque elongated structures in mesh reconstructions.No correlation was found of the mean SUVmax in initial scans, with the time from the surgery date (10 ± 6 months; r=0.04, P=0.90), or with the mean SUVmax in final scans (at 25± 17 months, P=0.17). CONCLUSIONS:: Increased FDG uptake, together with corresponding non-specific CT features, may persist for a prolonged period after surgery with obturators and mesh implantations, mimicking malignancy or infection. Awareness of variations in postoperative PET-CT appearance can help avoid false interpretations and redundant invasive procedures.

Tumor Microenvironment in Oral Cancer Following Neoadjuvant Pembrolizumab: Preliminary Analysis of the Histopathologic Findings.

Background: The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is associated with immune suppression, one of the pathways being the programmed death receptor 1 (PD-1) and its ligands (PD-L1/PD-L2). Checkpoint inhibitors of PD-1/PD-L1, like pembrolizumab, have been recently approved for treatment of OSCC. We described the histologic findings in OSCC following neoadjuvant pembrolizumab, including identification of immune-related cell populations and cancer-associated fibroblasts (CAFs). Materials and Methods: Patients with OSCC clinical stages 3 and 4 and a combined PD-L1 score >1 were randomized either to the standard oncologic protocol or to the pembrolizumab arm of MK-3475-689 study for Head and Neck, Lip, and Oral Cavity. The latter were given two standard doses of 200 mg of pembrolizumab, 3 weeks apart, and then underwent surgical oncologic procedure according to the initial stage. Sections from the resection specimens were analyzed for pathological response to pembrolizumab. Various populations of immune-related cells within the tumor microenvironment were characterized by immunohistochemistry, as were the CAFs. Results: Three patients who were randomized to the pembrolizumab study were described. One patient presented with a tongue SCC, the other two had SCC of the mandibular ridge with bony involvement. Only the patient with tongue SCC showed clinical complete response. Microscopically, the tumor was replaced by a granulomatous type of inflammation. Immunohistochemical stains revealed massive T cell rich (CD3+) infiltrate, with approximately equal amounts of CD4+ and CD8+ cells, numerous macrophages of CD68+ and CD163+ phenotypes; no CAFs were identified. The other two patients were regarded as non-responders as at least 50% of the tumor was viable. The tumor microenvironment of these tumors was generally associated with a lesser extent of inflammatory response compared to the tongue tumor, a variable CD4+/CD8+ ratio and presence of CAFs. Neither T regulatory cells (FOXP3+) nor natural killer cells (CD56+, CD57+) were identified in any of the cases. Conclusion: We showed that characterizing the specific populations of immune-related cells and CAFs after treatment with pembrolizumab, may add to our understanding of the tumor-TME interactions in this setting. These findings should be investigated in future studies on a larger number of patients.

Restricted Mouth Opening in Head and Neck Cancer: Etiology, Prevention, and Treatment.

Restricted mouth opening or trismus is often encountered in patients with head and neck cancer. The restriction may be the presenting sign of malignancy, a sequela of tumor site or growth, an adverse effect of oncologic treatment, or a first sign of tumoral recurrence. In general, any insult to the temporomandibular joint, masticatory muscles, or their neural innervation may cause limitation in mouth opening. The etiologies leading to trismus are as follows: myospasm secondary to tumor infiltration; reflectory myospasm; radiation-induced myositis and myofibrosis; temporomandibular joint involvement with tumor; unfavorable postsurgical scarring; muscle and joint atrophy secondary to immobilization; pain; jaw fracture and hardware failure; and infection. Preventive measures should be implemented before, during, and after treatment. These measures include identification of high-risk patients, utilization of dose-sculpting radiation techniques whenever possible, performing reconstruction at the same time of resective surgery whenever feasible, and initiating mobilization exercises as early as possible. When trismus develops, treatments are often challenging and disappointing. These include physical therapy, mouth opening appliances, drug therapy, and release surgery. All medical specialties dealing with head and neck cancer should be familiar with the diagnosis and prevention of trismus and make an effort to ensure patients are referred to the appropriate care when needed. Trismus should not be considered a trivial sequela of head and neck cancer.

Changing face of medication-related osteonecrosis of the jaw: Sheba Medical Center experience-fifteen years.

INTRODUCTION: Our aim is to track the development of the epidemiological characteristics in patient populations diagnosed with MRONJ at the Sheba Medical Center. MATERIALS AND METHODS: The files of patients diagnosed with MRONJ from 2003 until December 2017 were retrieved. Data on demographics, medical background, type and duration of drug use and triggering events at presentation was collected. RESULTS: The study included 448 patients, 336 females and 112 males. A decrease in the proportion of multiple myeloma patients (p < 0.05) and an increase in the proportion of patients with bone metastases of solid tumors has been observed recently. An increase in the proportion of cases in osteoporosis patients compared with oncology patients is evident (p < 0.01). Overtime a higher proportion of patients presented at an earlier stage of MRONJ (p < 0.01). CONCLUSIONS: As a result of changes in treatment protocols and increased awareness of oncology caregivers, including referral and consultation with Oral Medicine specialists, there has been a change in the demographics and presentation of the disease.

Cancer-associated fibroblasts in the tumor microenvironment of tongue carcinoma is a heterogeneous cell population.

OBJECTIVES: To examine different immunophenotypes of cancer-associated fibroblasts (CAFs) in tongue squamous cell carcinoma (TSCC) and to investigate how they related to clinical outcomes. METHODS: Serial sections from 54 cases of TSCC were immunohistochemically stained with α-smooth muscle actin (αSMA, CAF marker) to determine CAF density, and double-immunostained with αSMA combined with CD80 and CD86 (myeloid/monocytic-derived cell markers), Nanog (mesenchymal stem cell marker) and CD133 (hematopoietic/endothelial stem cell marker). Density of cells co-expressing these marker combinations was semi-quantitatively assessed in 5 randomly selected high power fields within the tumor area and scored as 1 - one-to-five stained cells in each field, 2 - more than 5 stained cells in each field; any finding less than score 1, was allocated a score of 0. RESULTS: There were 26 CAF-poor, 16 CAF-rich and 12 CAF-intermediated cases. CD86+αSMA+ cells were the most frequent (80.4%) followed by CD80+αSMA+ (72%) and Nanog+αSMA+ cells (56%). The CD133+αSMA+ phenotype was found only in association with blood vessels. High density of αSMA+ CAFs was associated with disease recurrence and poor survival (p < 0.05). Increased density of CD86+αSMA+ cells was significantly associated with CAF-rich tumors and with poor survival (p < 0.05). CONCLUSION: In TSCC, CAFs demonstrate heterogeneous and overlapping phenotypes with the myeloid/monocytic type being the most frequent and having an impact on the clinical outcomes. Further studies are needed in order to further characterize CAF phenotypes in carcinomas of various oral sites, as this may open new frontiers for personalized medicine.

Metastatic tumors in oral mucosa and jawbones: Unusual primary origins and unusual oral locations.

AIM: To perform clinico-pathological characterization of a large series of oral metastases, collected from 3 main medical centers in Israel and compare findings to data on frequency of primary cancer types in the population. MATERIALS: Pathology archives were searched for cases of metastatic tumors to the oral soft tissues and jawbones, 1990 - 2016. Metastases to the skin of face or to major salivary glands have been excluded. Demographic data and histopathological features were analyzed. RESULTS: Study population included 60 patients, 35 females and 25 males (ratio of 1.4:1). The age range was 17-87 years, mean 67.7 + 14.36 years. Only 3 (5%) patients were under 40 years, the remaining clustered predominantly in the 60-80 year age group. The mean age of females (59 + 13.84) was significantly lower than that of males (67.44 + 14) (p = 0.03). There was an almost equal distribution between the oral soft tissue and the jawbones (48.3% and 51.7%, respectively). The five most common organs from which metastases were distributed to the oral cavity and jawbones combined were kidney (20%), breast (15%), cutaneous (predominately melanoma, 13%), lung (11.7%) and soft tissue-sarcomas (8.3%). For comparison, Israel National Cancer Registry 2013 reported that the most frequent malignancies were breast (25.8%), colorectal cancer (16.3%), lung (12%) and prostate (10%). Malignant melanoma was 6th (5.4%), kidney malignancy was only 9th in frequency (4.2%). Although the gingiva and jawbones were the most frequent locations, some cases presented in unusual locations, (mandibular vestibule, lower lip, posterior dorsal tongue), without any specific clinical feature to suggest metastasis. CONCLUSIONS: The most frequent primary origins for oral metastasis do not correspond to the relative frequency of the primary tumors in the population, indicating that metastatic spread is not a random process. Although the majority of metastasis involves the gingiva and jawbones, any other oral mucosal location might be involved. Thus, in adult/older patients, metastasis from a distant site should be included in the differential diagnosis of oral masses at any oral location, whether the existence of a primary tumor is reported or not.

Markers of the pre-metastatic niche "knock on the door" of metastasis-free cervical lymph nodes in patients with oral cancer.

AIM: To assess expression of some markers of the pre-metastatic niche (PMN) in lymph nodes (LNs) of oral cancer patients. MATERIALS: LNs from metastatic-free neck dissections (LN0/N0, N = 43) and metastatic-free LNs in the vicinity of metastasis-containing LNs (LN0/N+, N = 30) were immuno-histochemically stained for lysyl oxidase (LOX), fibronectin (FN), vascular-endothelial growth factor receptor (VEGFR)-1 and matrix metalloproteinase (MMP)-9. Staining was assessed as 0 (no or weak staining), 1 (strong stain in 25% cells or extracellular area), 2 (same as 1 but in up to 50%) and 3 (same as 1 but in > than 50% of cells/area). Assessment was performed in the lymph node capsule (CAP), sub-capsular sinus (SCS) and medullary sinus (MS). In addition, sections were stained with picrosirius red and examined with polarized microscopy for assessing the distribution of polarization colors of the collagen fibers in the LN capsular area. RESULTS: All examined LNs were positive for markers of the PMN. In general, the distribution and intensity of the immunoreactivity was similar between the LN0/N0 and LN0/N+, with only a few differences regarding expression of LOX in the capsule (p = 0.002) and VEGFR1 and MMP9 in the SCS (p = 0.023 and p < 0.001, respectively). Picrosirius red stain and polarized microscopy revealed a disrupted arrangement and distribution of the collagen fibers in both LN0/N0 and LN0/N + . CONCLUSION: Markers for PMN were shown for the first time to be expressed in cervical LN0/N0 from patients with oral cancer, suggesting the increased permissive pathway remotely paved by the primary oral tumor for the incoming metastatic cells.

Rare variants of head and neck squamous cell carcinoma -differential immunohistochemical profiles.

We aimed to immunohistochemically characterize the pattern of expression of epithelial markers in rare head and neck squamous cell carcinoma (HNSCC) variants: carcinoma cuniculatum (CC) and adenosquamous carcinoma (ASC). We also present an additional variant of HNSCC with concomitant basaloid and squamous components that has overlapping morphological features with odontogenic and non-odontogenic tumors, which we termed basalo-squamous carcinoma (BSC). The selected markers included CK5/6, p40, CK19, BerEP4, p16 and SOX10. All tumors were CK5/6 and p40 positive. CK19 and BerEP4 were positive in BSC and focally in ASC but negative in CC. p16 was positive in 3 (60%) of the CCs, focally positive in ASC and negative in BSC. SOX10 was negative in all three variants. Our results highlight the plasticity of the lining epithelium revealing differential profiles of immuno-expression of the selected molecular markers, possibly reflecting their diverse histopathogenesis.

Datasets of RT spoofing attacks on MIL-STD-1553 communication traffic.

The datasets in this article are produced to evaluate the ability of MIL-STD-1553 intrusion detection systems to detect attacks that emulate normal non-periodical messages, at differing attack occurrence rates. And different data representations. We present three streams of simulated MIL-STD-1553 traffic containing both normal and attack messages corresponding to packets that were injected into the bus by a malicious remote terminal. The implemented attacks emulate normal non-periodical communication so detecting them with a low false positive rate is non-trivial. Each stream is separated into a training set of normal messages and a test set of both normal and attack messages. The test sets differ by the occurrence rate of attack messages (0.01%, 0.10%, and 1.00%). Each stream is also preprocessed into a dataset of message sequences so that it can be used for sequential anomaly detection analysis. The sequential test sets differ by the occurrence rate of attack sequences (0.14%, 1.26%, and 11.01%). All dataset files can be found in Mendeley Data, doi:10.17632/jvgdrmjvs3.3.

Ultrasound-Guided Botulinum Toxin Injections into the Salivary Glands for the Treatment of Drooling.

BACKGROUND: Drooling is the unintentional loss of saliva from the mouth, usually caused by poor coordination of the swallowing mechanism. It is commonly seen in patients with chronic neurologic disorders, such as Parkinson's disease, amyotrophic lateral sclerosis (ALS), cerebral palsy, and stroke, as well as in patients with cognitive impairment and dementia. OBJECTIVES: To evaluate the efficacy and safety of ultrasound-guided botulinum toxin injections into the parotid and submandibular salivary glands for the treatment of drooling. METHODS: We conducted a retrospective analysis of the medical records of 12 consecutive patients treated with botulinum toxin injections into the parotid and submandibular glands for the first time. The primary outcome variable was the subjective improvement of drooling on a 5-point scale. Secondary outcome variables were duration of the therapeutic effect, request to undergo additional treatment, and adverse events. RESULTS: Of 12 patients, 8 (67%) reported considerable improvement after treatment, 3 reported slight improvement, and 1 reported development of dry mouth. All patients stated that they felt the effects 1 week after the injections; the mean duration of the therapeutic effect was 4.5 months (range 3-9 months). One patient suffered from local hematoma and ecchymosis that did not require medical care. Another patient complained of difficulty swallowing, which did not require medical treatment and resolved spontaneously within 1 month. CONCLUSIONS: Ultrasound-guided botulinum toxin injections into the parotid and submandibular glands seem to be a safe and effective therapy for the treatment of drooling. Further long-term prospective studies with varying doses are warranted.

FTIR-based spectrum of salivary exosomes coupled with computational-aided discriminating analysis in the diagnosis of oral cancer.

PURPOSE: To determine the Fourier-transform infrared (FTIR) spectra of salivary exosomes from oral cancer (OC) patients and healthy individuals (HI) and to assess its diagnostic potential using computational-aided models. METHODS: Whole saliva samples were collected from 21 OC patients and 13 HI. Exosomes were pelleted using differential centrifugation (12,000g, 120,000g). The mid-infrared (IR) absorbance spectra (900-5000 cm- 1 range) were measured using MIR8025 Oriel Fourier-transform IR equipped with a PIKE MIRacle ZnSe attenuated total reflectance attachment. Machine learning techniques, utilized to build discrimination models for the absorbance data of OC and HI, included the principal component analysis-linear discriminant analysis (PCA-LDA) and support vector machine (SVM) classification. Sensitivity, specificity and the area under the receiver operating characteristic curve were calculated. RESULTS: IR spectra of OC were consistently different from HI at 1072 cm- 1 (nucleic acids), 2924 cm- 1 and 2854 cm- 1 (membranous lipids), and 1543 cm- 1 (transmembrane proteins). The PCA-LDA discrimination model correctly classified the samples with a sensitivity of 100%, specificity of 89% and accuracy of 95%, and the SVM showed a training accuracy of 100% and a cross-validation accuracy of 89%. CONCLUSION: We showed the specific IR spectral signature for OC salivary exosomes, which was accurately differentiated from HI exosomes based on detecting subtle changes in the conformations of proteins, lipids and nucleic acids using optimized artificial neural networks with small data sets. This non-invasive method should be further investigated for diagnosis of oral cancer at its very early stages or in oral lesions with potential for malignant transformation.

Three-Dimensional Orofacial Changes Occurring After Proportional Condylectomy in Patients With Condylar Hyperplasia Type 1B (Unilateral Hemimandibular Elongation).

PURPOSE: To evaluate 3-dimensional orofacial changes that occurred after proportional condylectomy that was not followed by orthognathic surgery in patients with condylar hyperplasia type 1B (unilateral hemimandibular elongation). MATERIALS AND METHODS: This retrospective analysis used the medical records of 14 skeletally mature patients. Transverse, vertical, and horizontal cephalometric analyses of photographs and radiographs were undertaken. A comparison of preoperative and postoperative measurements was conducted. RESULTS: After proportional condylectomy, transverse chin position and vertical lip cant improved to various degrees, whereas ramus and condyle height and mandibular lower border discrepancy worsened to different extents. The prominence of the gonial angle of the affected (operated) side increased in all patients after surgery, and this contributed to better symmetry only when the preoperative prominence was small (flat), whereas the opposite occurred when the preoperative prominence was large (bulky). After condylectomy, there was posterior displacement of the pogonion point (setback), which was favorable in cases with a preoperative concave profile and unfavorable in cases with a preoperative convex profile. CONCLUSION: Proportional condylectomy can successfully arrest the hyperplastic growth of the affected condyle; however, it rarely achieves perfect symmetry of the face. Although it improves some facial features, other facial traits are worsened. Surgeons should have a full understanding of the 3-dimensional changes occurring after proportional condylectomy and should be able to predict, based on preoperative findings, the anticipated improvement or worsening of different facial features.

Role of oral examination in newly diagnosed multiple myeloma patients: A safe and simple way to detect light chain amyloidosis.

OBJECTIVE: Up to 30% of multiple myeloma (MM) patients have subclinical amyloid deposits. These patients are under-recognized and are more susceptible to drug toxicity, bleeding and death. Early diagnosis and adjustment of treatment are crucial. Biopsies of oral mucosa might be a potentially useful diagnostic tool. The objective of this study was to assess the prevalence and characteristics at presentation of oral amyloidosis in a large cohort of MM patients. METHODS: The prevalence and characteristics of oral amyloidosis in a large cohort of MM patients who were referred for oral evaluation before and during bisphosphonate therapy were assessed, retrospectively. RESULTS: Among 212 patients analysed, 13 (6%) were diagnosed with concomitant light chain (AL) amyloidosis. In 54% (n = 7), lesions in the oral cavity compatible with amyloid deposition were detected by examination. CONCLUSIONS: The salient feature of this study is the high prevalence of oral manifestations among MM patients with amyloidosis. These results highlight the value of routine oral cavity examination and biopsy as a safe and simple method for detecting light chain amyloidosis.

Rapid onset of osteonecrosis of the jaw in patients switching from bisphosphonates to denosumab.

OBJECTIVE: The aim of this study was to determine whether osteonecrosis of the jaw (ONJ) developed more rapidly in patients who switched from bisphosphonates (BP) treatment to denosumab than in patients who received only denosumab. STUDY DESIGN: This was a retrospective cohort study conducted at a tertiary referral center. Thirty-one patients with ONJ met the inclusion criteria. RESULTS: Twenty-two patients who had been on BP were switched to denosumab (BP + D), whereas 9 patients received only denosumab. Both groups were similar for the known ONJ risk factors, that is, age, diabetes mellitus, and smoking. The number and cumulative doses of denosumab before the onset of ONJ symptoms were significantly lower among the BP + D group compared with the denosumab-only group (P = .025 and .018, respectively). In the BP + D group, ONJ symptoms developed in 9 patients (41%) following the administration of ≤3 denosumab doses compared with ONJ developing in only 1 patient (11%) who was naïve to BP. ONJ developed spontaneously without any known triggering event in 72.7% of patients in the BP + D group and in 77.8% of patients in the denosumab-only group. CONCLUSIONS: Denosumab-induced ONJ might develop rapidly in patients previously treated with BP. ONJ developed spontaneously in most patients treated with denosumab. In light of our sample being small, there is need for further investigation on our conclusions.

Assessing the Different Oncologic Disease Distribution and Postoperative Complications of Octogenarian and Nonagenarian Head and Neck Oncology Patients.

PURPOSE: The admission rate of patients aged 80 years or older (oldest-old) with head and neck (HN) oncologic disease is on the rise. Our goal was to study the demographic characteristics, reasons for admission, types of surgical procedures, and postoperative complications of the oldest-old patients with HN malignancy. MATERIALS AND METHODS: We conducted a retrospective cohort study including all inpatients aged 80 years or older who were admitted to the department of otolaryngology-head and neck surgery or department of oral and maxillofacial surgery because of HN oncologic disease between 2009 and 2013. The control group was composed of a matched number of randomly selected patients aged 60 to 79 years. We compared the demographic characteristics, diagnoses, comorbidities, surgical interventions, and postoperative complications of the 2 age groups to characterize the oldest-old patients' admissions and determine whether age alone increases the risk of postoperative complications. RESULTS: The study included 109 oldest-old patients (median age, 83 years) and 107 patients in the control group (median age, 68 years). Although the oldest-old patients had significantly more underlying diseases (4.41 vs 2.86) and drugs prescribed (4.76 vs 3.21), similar rates of postoperative complications occurred in both groups. An important finding was that ischemic heart disease and chronic lung disease were the only significant risk factors for postoperative complications among the oldest-old patients (odds ratio on multivariate analysis of 5.5 and 4.5, respectively). CONCLUSIONS: Although comorbidities and prescribed drugs are more prevalent in the oldest-old patients, the rate of postoperative complications did not differ between the age groups, suggesting that age alone should not be a factor in the surgical treatment of HN malignancies.

Involvement of the maxillary sinus in bisphosphonate-related osteonecrosis of the jaw: Radiologic aspects.

BACKGROUND: The use of bisphosphonates is very common among patients with osteoporosis and multiple myeloma as well as those with bone metastases from various malignancies. The benefits of bisphosphonates are well recognized, but it became evident during the past decade that these medications portend the major adverse effect of osteonecrosis of the jaw, known as bisphosphonate-related osteonecrosis of the jaw. OBJECTIVE: Our aim was to evaluate the specific manifestations of bisphosphonate use on the maxillary sinus in patients with documented bisphosphonate-related osteonecrosis of the jaw. METHODS: A retrospective review of all the patients diagnosed between October 2003 to August 2014 as having bisphosphonate-related osteonecrosis of the jaw in a large university-affiliated tertiary care medical center. The records of 173 patients diagnosed as having bisphosphonate-related osteonecrosis of the jaw during the study period were retrieved. The available head and neck computed tomographic images were analyzed for cases of involvement of the maxilla. MAIN OUTCOME MEASURES: Manifestations of bisphosphonate-related osteonecrosis of the jaw as observed on physical examination and on imaging studies. RESULTS: Seventy-one patients (41%) had involvement of the maxilla, 86 patients (49%) had involvement of the mandible, and 16 patients (9%) had involvement of both the maxilla and the mandible. Computerized tomography studies were available for 50 patients with involvement of the maxilla: 36 (72%) had evidence of maxillary sinus opacification (in comparison, the incidence of maxillary sinus opacification as an incidental finding in the general population is reported to be 19%, p < 0.0001). Sixteen patients (32%) had evidence of oroantral fistula, and five patients (10%) had oronasal fistula. CONCLUSION: In addition to its well-established effects on the mandible and maxilla, bisphosphonate-related osteonecrosis of the jaw significantly affected the maxillary sinus. Its radiologic manifestations should be recognized by clinicians and especially by otolaryngologists.

The Possible Role of Dental Implants in the Etiology and Prognosis of Osteomyelitis: A Retrospective Study.

PURPOSE: The aim of this study was to describe the clinical outcome of osteomyelitis of the mandible or maxilla following dental implants. A detailed treatment protocol is also proposed. MATERIALS AND METHODS: Electronic data of all the patients who were treated between October 2009 and November 2014, in three maxillofacial surgical departments, were reviewed. Computed databases were searched for the diagnosis of osteomyelitis of the mandible or maxillas (ICD9 code 526.2), and medical files were analyzed. Treatment outcome was considered successful if only primary treatment (debridement and antibiotic therapy) was applied. Statistical analysis was performed to compare treatment outcomes in the different etiologic groups. RESULTS: The cohort included 29 men and 25 women, with histologically and clinically proven osteomyelitis. The mean age was 59 years (range, 24 to 70 years). Forty patients had complete remission, as opposed to 14 patients who failed the primary treatment and required a more aggressive surgical intervention (11 had segmental mandibulectomy, 2 patients had marginal mandibulectomy, and 1 patient had maxillectomy). Most failures were in the dental implantation group. A previous dental implant was an independent factor for primary treatment failure and the need for aggressive surgical intervention (P = .0001). CONCLUSION: The results of this retrospective study suggest that a previous dental implant is an independent predictive factor of failure in primary treatment in osteomyelitis of the mandible or maxilla. Also, dental implant-induced osteomyelitis is a rare pathology, but it presents an aggressive subtype of osteomyelitis, and requires a broader and more comprehensive management.