Pre-chemoradiotherapy high platelet counts predict jaw osteoradionecrosis in locally advanced nasopharyngeal carcinoma patients.

INTRODUCTION: This retrospective study aimed to investigate if pretreatment platelet (PLT) levels can predict the risk of osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) who received concurrent chemoradiotherapy (CCRT). MATERIAL &METHODS: ORNJ instances were identified from LA-NPC patients' pre- and post-CCRT oral exam records. All pretreatment PLT values were acquired on the first day of CCRT. Receiver operating characteristic curve analysis was used to determine the optimal PLT cutoff that divides patients into two subgroups with distinctive ORNJ rates. The primary outcome measure was the association between pretreatment PLT values and ORNJ incidence rates. RESULTS: The incidence of ORNJ was 8.8 % among the 240 LA-NPC patients analyzed. The ideal pre-CCRT PLT cutoff which divided the patients into two significantly different ORNJ rate groups was 285,000 cells/µL (PLT ≤ 285,000 cells/µL (N = 175) vs. PLT > 285,000 cells/µL (N = 65)). A comparison of the two PLT groups revealed that the incidence of ORNJ was substantially higher in patients with PLT > 285,000 cells/L than in those with PLT≤285,000 cells/L (26.2% vs. 2.3 %; P < 0.001). The presence of pre-CCRT ≥3 tooth extractions, any post-CCRT tooth extractions, mean mandibular dose ≥ 34.1 Gy, mandibular V57.5 Gy ≥ 34.7 %, and post-CCRT tooth extractions > 9 months after CCRT completion were also associated with significantly increased ORNJ rates. A multivariate Cox regression analysis demonstrated that each characteristic had an independent significance on ORNJ rates after CCRT. CONCLUSION: An affordable and easily accessible novel biomarker, PLT> 285,000 cells/L, may predict substantially higher ORNJ rates after definitive CCRT in individuals with LA-NPC.

Geniospasm: A systematic review on natural history, prognosis, and treatment.

BACKGROUND: Geniospasm is a rare and generally benign movement disorder of the chin yet with potentially debilitating complications. Due to its rarity, previous literature was limited to only case reports or series with critical knowledge gap on its natural history, prognosis, and management. We aimed to establish the natural history, prognosis, and treatment for geniospasm. METHODS: A systematic review on case reports or series was performed with literature search on PubMed and Google Scholar, from inception through December 2021. The quality of the reports was assessed with low-quality articles excluded for analyses other than demographics. RESULTS: Forty-one articles were included for demographic analysis (n = 489) while forty articles for other analyses (n = 451). There was only slight male preponderance of this disease in our cohort (Male:Female = 1.2:1) with 98.6% having family history of geniospasm, 68.1% having onset below 1 year of age, 91.4% having emotional triggers of the symptoms, 25.7% having geniospasm in sleep, 100% involving mentalis muscles, 4.9% involving muscles adjacent to mentalis, 55.2% having regular paroxysms (≥1/week, but brief in 56.3% of the cases) and only 11.1% having complications. The paroxysms reduced with age, but complete remission only happened in 9.9%. Females (p = 0.010) and those without geniospasm in sleep (p = 0.048) were associated with good outcome of the disease. Geniospasm was usually refractory to treatment except for regular botulinum toxin injections. CONCLUSION: Generally, geniospasm improved with age but complete remission was rare. Considering our review limitations, our findings should be interpreted with caution. Future studies of higher evidence level are crucial.

Predictors of osteoradionecrosis following irradiated tooth extraction.

BACKGROUND: Tooth extraction post radiotherapy is one of the most important risk factors of osteoradionecrosis of the jawbones. The objective of this study was to determine the predictors of osteoradionecrosis (ORN) which were associated with a dental extraction post radiotherapy. METHODS: A retrospective analysis of medical records and dental panoramic tomogram (DPT) of patients with a history of head and neck radiotherapy who underwent dental extraction between August 2005 to October 2019 was conducted. RESULTS: Seventy-three patients fulfilled the inclusion criteria. 16 (21.9%) had ORN post dental extraction and 389 teeth were extracted. 33 sockets (8.5%) developed ORN. Univariate analyses showed significant associations with ORN for the following factors: tooth type, tooth pathology, surgical procedure, primary closure, target volume, total dose, timing of extraction post radiotherapy, bony changes at extraction site and visibility of lower and upper cortical line of mandibular canal. Using multivariate analysis, the odds of developing an ORN from a surgical procedure was 6.50 (CI 1.37-30.91, p = 0.02). Dental extraction of more than 5 years after radiotherapy and invisible upper cortical line of mandibular canal on the DPT have the odds of 0.06 (CI 0.01-0.25, p < 0.001) and 9.47 (CI 1.61-55.88, p = 0.01), respectively. CONCLUSION: Extraction more than 5 years after radiotherapy, surgical removal procedure and invisible upper cortical line of mandibular canal on the DPT were the predictors of ORN.

[Thoughts on the prevention, clinical diagnosis and treatment of osteonecrosis of the jaw and future research directions].

With the progress and development of society, osteonecrosis of the jaw has appeared some new features and new problems in oral clinical work. The prevention, early diagnosis, and early treatments of osteonecrosis of the jaw are of great significance. This article describes the current clinical diagnosis and treatment status of osteoradionecrosis of the jaw and medication-related osteonecrosis of the jaw, and puts forward some thoughts on the prevention, clinical diagnosis and treatment and future research direction of osteonecrosis of the jaw.

[The past, present and future of diagnosis and treatment of osteoradionecrosis of the jaws].

Osteoradionecrosis of the jaw (ORNJ) is one of the most devastating complications caused by radiation therapy in head and neck region, which is among the greatest challenges within stomatology. Treatment methods have been enriched because of expanded understanding of the pathogenic mechanism of ORNJ. Meanwhile, the diagnosis and treatment of ORNJ have been uniformed and improved gradually in China, making progress on several aspects from the establishment of classification and hierarchy system and publication of the consensus on ORNJ treatment. In the present comment, the author reviewed the history and current situation of diagnosis and treatment of ORNJ and prospected the hot topics of basic, translational and clinical research.

In-house 3D-printed surgical guides for osseous lesions of the lower jaw: an experimental study.

BACKGROUND: The accuracy of computer-assisted biopsies at the lower jaw was compared to the accuracy of freehand biopsies. METHODS: Patients with a bony lesion of the lower jaw with an indication for biopsy were prospectively enrolled. Two customized bone models per patient were produced using a 3D printer. The models of the lower jaw were fitted into a phantom head model to simulate operation room conditions. Biopsies for the study group were taken by means of surgical guides and freehand biopsies were performed for the control group. RESULTS: The deviation of the biopsy axes from the planning was significantly less when using templates. It turned out to be 1.3 ± 0.6 mm for the biopsies with a surgical guide and 3.9 ± 1.1 mm for the freehand biopsies. CONCLUSIONS: Surgical guides allow significantly higher accuracy of biopsies. The preliminary results are promising, but clinical evaluation is necessary.

Jaw Pain and Oromandibular Dysfunction After a Complex Hospital Course: A Clinical Vignette.

ABSTRACT: A 38-yr-old man presented to the emergency department with severe chest pain and was found to have a type A aortic dissection. Forty-eight hours after an emergency mechanical Bentall and ascending hemiarch replacement, the patient developed agitation prompting administration of high-dose haloperidol. He was found to have evidence of multiple acute infarcts on head computed tomography/computed tomography angiography and brain magnetic resonance imaging. Four days later, he began to complain of jaw pain and difficulty opening his mouth. After admission to inpatient rehabilitation, he was found to have strong activity in the masseters bilaterally at rest on electromyography, indicating a diagnosis of oromandibular dystonia. Starting in the intensive care unit, the patient reported jaw pain and dysfunction for 40 days before having a diagnosis of oromandibular dystonia. At this point, treatment with onabotulinumtoxinA injections and baclofen did not provide relief. Because of an extended delay in diagnosis, it is believed that the patient has developed joint contractures. Oromandibular dystonia is an important diagnosis to consider in patients who experience jaw pain or difficulty with mouth opening. Treatment of this condition can decrease pain and trauma to oral structures as well as improve ability to perform oral hygiene, eat, and communicate.

Assessment of jaw osteonecrosis diagnostic criteria in cancer patients with a history of radiation therapy and exposure to bone-modifying agents.

BACKGROUND: Osteoradionecrosis (ORN) of the jaw is currently defined by the development of osteonecrosis in head/neck irradiated patients, regardless of lesion exposure. To diagnose medication-related osteonecrosis of the jaw (MRONJ), a history of any radiation therapy to the jaw region must be ruled out. The aim of this study was to assess the accuracy of current osteonecrosis criteria, while introducing new modifications for improved diagnosis and treatment. METHODS: One hundred and forty-one necrotic lesions were analyzed from patients exposed to bone-modifying agents (BMAs) and/or received head and neck regional radiation therapy, where the maximal dose of radiation exposure to the jaw osteonecrosis site was calculated. Modified diagnostic criteria were used to reassess all cases and a comparison of outcomes was performed using Pearson's Chi-Square/Fisher's exact test. RESULTS: Only in patients with primary head and neck carcinomas did the maximal mean radiation dose in the necrotic jaw site reach ranges associated with ORN formation (>40 Gy), with individual cases showing exposures as low as 0-2 Gy. Based on the modified diagnostic criteria almost 2/3 of the necrotic cases diagnosed as ORN should be diagnosed as MRONJ. CONCLUSIONS: ORN diagnosis should only be considered in cases of radiation exposure >40 Gy to prevent misdiagnosis and suboptimal treatment. A modified criterion for MRONJ diagnosis is recommended where radiation exposure <40 Gy in the necrotic site is included. In cases with exposure >40 Gy and BMA administration, an additional modification to diagnostic criteria of 'medication- and radiation-related osteonecrosis of the jaw', should be used.

Mucormycosis in the Jaw: A Report of 2 Cases and Literature Review.

Mucormycosis is a rare fungal infection with high morbidity and mortality and a very poor prognosis. However, aggressive medical and surgical management can result in survival rates exceeding 80%. The most common sites involved in mucormycosis infection are the sinus, lung, skin and soft tissues, gastrointestinal system, central nervous system, and rarely the mandible. Systemic risk factors for mucormycosis are diabetes mellitus (DM), neutropenia, corticosteroid use, hematologic malignancies, organ transplantation, metabolic acidosis, deferoxamine use, and advanced age. Local risk factors are a history of trauma, burns, surgery. We report on two patients with mucormycosis of the jaw. While one case presented as mucormycois involving the maxillary sinus in a patient with uncontrolled DM, the other was a rare case of mandibular mucormycosis in a patient with acute myeloid leukemia.

Effective Treatment of Geniospasm: Case Series and Review of the Literature.

Background: Geniospasm is a rare genetic disorder characterized by paroxysmal rhythmic or irregular movements of the chin and lower lip due to repetitive contractions of the mentalis muscle. Pathophysiology is poorly understood, and optimal treatment has not been established. Methods: Geniospasm was characterized in a series of patients after evaluation in our clinics, and a comprehensive review of all cases in the medical literature was performed. Results: We evaluated four patients (1 female) in four families with geniospasm, aged 4 months to 9 years. Bothersome symptoms were present in one patient, who was treated with regular injections of onabotulinumtoxinA, with complete resolution of symptoms and no adverse effects. 9 patients in the literature have had similar outcomes. Conclusions: Limited data exist with regard to the effective treatment of geniospasm. Several treatments have been used historically, with variable outcomes. Our results, together with those of prior reported cases, demonstrate benefit of the use of botulinum toxin injections for management of this condition.

Aromatase inhibitors associated osteonecrosis of jaw: signal refining to identify pseudo safety signals.

Background Signal generation through data mining algorithms is an innovative and emerging field in pharmacovigilance. Early detection of safety signals is important for public health safety. However, the possibility of generating pseudo signals should not be overlooked. Objective Our study aimed to identify potential signals of aromatase inhibitors associated Osteonecrosis of Jaw and assess the possibilities of the safety signal to be a pseudo signal/false positive in FDA Adverse Event Reporting System (FAERS). Setting Spontaneously reported data in FAERS database. Methods Data for this study were obtained from the public release of data in FAERS. OpenVigil, a pharmacovigilance analytical tool was used to access FAERS data. Reporting Odds Ratio (ROR) was used to assess the relation between the drug and adverse event. A value of ROR-1.96SE > 1, (SE-standard error) was considered positive. Main outcome measure Signal strength. Results FAERS database had a total of 15,178 reports for Osteonecrosis of Jaw. Amongst which 617 reports were associated with aromatase inhibitors. Signal strength ROR (lower bound of the 95% CI) for letrozole, anastrozole and exemestane associated Osteonecrosis of Jaw without any background correction was 8.34, 6.64 and 15.14 respectively. Upon removing the reports of concomitantly administered drugs (bisphosphonates and denosumab), signal strength drastically decreased to 0.03, 0.36 and 0.47 for letrozole, anastrozole and exemestane respectively. The signal strength of bisphosphonates and denosumab associated Osteonecrosis of Jaw was not changed significantly upon removal of aromatase inhibitors. Conclusion Our study concluded that the signal generated for aromatase inhibitors associated Osteonecrosis of Jaw in FAERS database can be false positive. Careful background corrections with identification of those risk factors are imperative to exclude false positive results.

Osteonecrosis of the jaw induced by arsenic trioxide therapy in a leukemia patient: A rare case report and literature review.

A patient suffering from acute promyelocytic leukemia (APL) was referred to the dental department before introduction of chemotherapy by all-trans retinoic acid and arsenic trioxide (ATO). A panoramic radiography showed his third upper maxillary left tooth included into the maxillary bone. The patient presented with a febrile episode. Consequently, the infectious gateway was researched. A left maxillary sinus migration of his third upper left tooth together with a bony sequestrum has been observed on a CT-scan. A surgery was then performed to remove the bony sequestrum and the tooth. The first hypothesis of tooth migration could be that the patient had an infection prior to introduction of chemotherapy. However, neither clinical or radiographic signs were observed during the initial check-up. The second hypothesis is that ATO caused osteonecrosis of the jaw (ONJ) induced the formation of a bony sequestrum associated to the tooth migration into the sinus. ONJ could be a potential adverse of ATO chemotherapy.

Cell-block as ancillary tool for the diagnosis of cystic and cyst-like jaw lesions.

BACKGROUND: The cell-block technique is a cytological diagnostic method that decreases cellular dispersion; however, its usefulness regarding intraosseous lesions is underexplored. Therefore, this study aimed to assess the diagnostic usefulness of cell-block for cystic and cyst-like jaw lesions. METHODS: Individuals with cystic or cyst-like jaw lesions who underwent aspiration biopsy were considered eligible. Aspiration of luminal content was prepared and processed by the cell-block technique. Cytological evaluations were blindly performed by two trained PhD students (in a single evaluation) and one oral and maxillofacial pathologist (OMP). Cohen's kappa statistic was used to measure inter-rater agreement. RESULTS: The sample was composed of 52 lesions, represented by 25 radicular cysts (RC), 17 odontogenic keratocysts (OKC), 5 idiopathic bone cavities (IBC), and 5 unicystic ameloblastomas (UA). The kappa coefficient of cell-block compared to histopathological diagnosis was 0.390 (95% confidence interval [95%CI], 0.195-0.585) for PhD students and 0.612 (95%CI, 0.433-0.791) for the OMP. The highest concordance rates between cell-block and histopathological diagnosis were observed for RC (PhD = 76.0%; OMP = 80.0%) and OKC (PhD = 58.8%; OMP = 76.5%). Conflicting results were found regarding IBC (PhD = 40.0%; OMP = 80.0%) and UA, that presented the overall lowest concordance rates (PhD = 20.0%; OMP = 40.0%). CONCLUSION: The cell-block technique presented a high diagnostic usefulness for detecting RC and OKC and, if associated with clinical and radiographic characteristics, might be sufficient for final diagnosis of these diseases. Regarding IBC and UA, an analysis with a higher number of cases is recommended to determine the true usefulness of the cell-block as ancillary tool for the diagnosis of these lesions.

Challenges in the treatment of parathyroid carcinoma: a case report.

INTRODUCTION: Parathyroid carcinoma (PC) is a rare neoplasm with a high rate of recurrence and an indolent course. It is frequently functional, causing nearly 1% of the cases of primary hyperparathyroidism (HPT), and in some cases, it may be complicated by brown tumors, mimicking bone metastases. Synchronous parathyroid and papillary thyroid carcinomas are rare. CASE REPORT: We present a patient with HPT due to PC, misdiagnosed at first evaluation, which exhibited multiple hypermetabolic lytic lesions in the skeleton, suggesting bone metastases. Their regression after PTH reduction suggested the diagnosis of brown tumors due to severe HPT. Given the persistence of HPT, the patient underwent a number of neck surgeries, and a papillary thyroid microcarcinoma with a nodal metastasis was diagnosed. A genetic test discovered a previously unreported mutation of the CDC73 (HRPT2) gene, codifying for parafibromin and resulting in a premature stop codon (c.580A>Tp.Arg194). Because of the persistence of HPT, cinacalcet therapy was started in order to control hypercalcemia. CONCLUSION: This is a very unusual patient with a newly discovered variant of the CDC73 gene and a phenotype characterized by recurrent PC, brown tumors, and N1a metastasized thyroid carcinoma. The present case confirms that PC may not exhibit clear malignant properties at first assessment, contributing to inadequate initial surgical treatment. Although infrequently, PC can be associated with papillary thyroid cancer. The diagnosis of brown tumor should be considered in patients with severe HPT and multiple destructive bone lesions mimicking metastases on PET/CT imaging.

Gorham disease of the mandible: a report of two cases and a literature review.

Gorham disease, a rare disorder of unknown etiology, is characterized by the clinical and radiologic disappearance of bone. Because the etiology is unknown, diagnosis is difficult. Therefore, radiographic manifestations play a vital role in the diagnosis of this disease. Thus far, there has been no completely effective treatment. Most remedies are limited to symptom management. Despite the fact that any bone can be affected, one of the most prevalent sites is the maxillofacial region. In this paper, 2 cases of Gorham disease involving the maxillofacial region are reported, including preoperative and postoperative radiographic features.

Acute and Chronic Suppurative Osteomyelitis of the Jaws: A 10-Year Review and Assessment of Treatment Outcome.

PURPOSE: To review cases of suppurative osteomyelitis of the jaws treated at the Massachusetts General Hospital (Boston, MA) over a 10-year period, evaluate specifics of disease presentation, and answer the clinical question: are there identifiable variables associated with treatment outcome? MATERIALS AND METHODS: A retrospective cohort study was completed using patients treated for suppurative osteomyelitis of the jaws at the Massachusetts General Hospital from April 2006 to October 2016. Inclusion criteria were a diagnosis of suppurative osteomyelitis of the jaw, age older than 18 years, and complete medical records. Patients with nonsuppurative disease, radiation history, or antiresorptive exposure were excluded. Candidate variables included demographic information, medical and dental history, presenting signs and symptoms, and radiologic and laboratory findings. The outcome variable was successful treatment, defined as resolution of symptoms and radiographic evidence of healing after initial treatment. Appropriate statistical analyses were performed with significance set a P value less than .05. RESULTS: Forty-two patients met the inclusion criteria. Mean age was 53 years (range, 20 to 80 yr) and 26 were women (62%). Common comorbidities included cardiovascular disease (52%), tobacco use (45%), and psychiatric disorders (45%). Pain (90%), swelling (86%), and neurosensory change (50%) were the most common findings. Common microbacterial isolates included Streptococcus milleri (74%) and coagulase-negative Staphylococcus species (43%), which showed marked antibiotic resistance. Surgical debridement was the most common intervention (93%). Successful treatment was found in 86%. Of 6 persistent cases, 4 resolved with a second debridement and continued antibiotics and 2 required resection. Increased white blood cell (WBC) count at presentation (P = .005) and associated psychiatric diagnoses (P = .037) were statistically associated with unsuccessful initial treatment. CONCLUSION: The results of this study indicate that antibiotic resistance is commonly encountered in this patient population, although it was not associated with unsuccessful outcome. Patients presenting with increased WBC count and concurrent psychiatric comorbidities required protracted treatment.