Is the use of Pentoxifylline and Tocopherol effective in the treatment of Osteoradionecrosis of the jaws or for the treatment of medicationosteonecrosis of the jaw? An overview.

PURPOSE: The aim of the present study was to determine the methodological quality of systematic reviews that evaluated the effectiveness of pentoxifylline and tocopherol (PENTO) in the treatment of osteoradionecrosis of the jaw (ORNJ) and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Searches were performed in Databases including PubMed, Scopus, LILACS, DARE, Cochrane Library, and SIGLE through OpenGrey until March 2024, were evaluated by two independent reviewers to answer the following question: Is the use of PENTO protocol effective in the treatment of ORNJ or for the treatment of MRONJ? RESULTS: A total of 256 articles were initially identified; however, following the use of appropriate inclusion and exclusion criteria, five systematic reviews were identified for detailed analysis. The final study sample comprised 588 patients: 397 patients with ORN and 197 patients with MRONJ who were treated with PENTO. The total recovery of individuals who used the PENTO protocol was 62,2 % for ORN and 100 % for MRONJ, with a follow-up period of 1 month to 10 years. The methodological quality of the studies was assessed using the AMSTAR 2 tool, in which four were of low quality and 1 moderate quality. CONCLUSION: The treatment of ORN and MRONJ with pentoxifylline and tocopherol has shown good results in the studies presented, with a partial or total reduction in bone exposure. However, the low quality of the relevant reports highlights the need for primary and secondary studies with better methodological rigor to reduce bias and provide reassurance for this treatment option.

New perspectives in the differential diagnosis of jaw lesions: Machine learning and inflammatory biomarkers.

This study aimed to assess the diagnostic performance of a machine learning approach that utilized radiomic features extracted from Cone Beam Computer Tomography (CBCT) images and inflammatory biomarkers for distinguishing between Dentigerous Cysts (DCs), Odontogenic Keratocysts (OKCs), and Unicystic Ameloblastomas (UAs). This retrospective study involves 103 patients who underwent jaw lesion surgery in the Maxillofacial Surgery Unit of Federico II University Of Naples between January 2018 and January 2023. Nonparametric Wilcoxon-Mann-Whitney and Kruskal Wallis tests were used for continuous variables. Linear and non-logistic regression models (LRM and NLRM) were employed, along with machine learning techniques such as decision tree (DT), k-nearest neighbor (KNN), and support vector machine (SVM), to predict the outcomes. When individual inflammatory biomarkers were considered alone, their ability to differentiate between OKCs, UAs, and DCs was below 50 % accuracy. However, a linear regression model combining four inflammatory biomarkers achieved an accuracy of 95 % and an AUC of 0.96. The accuracy of single radiomics predictors was lower than that of inflammatory biomarkers, with an AUC of 0.83. The Fine Tree model, utilizing NLR, SII, and one radiomic feature, achieved an accuracy of 94.3 % (AUC = 0.95) on the training and testing sets, and a validation set accuracy of 100 %. The Fine Tree model demonstrated the capability to discriminate between OKCs, UAs, and DCs. However, the LRM utilizing four inflammatory biomarkers proved to be the most effective algorithm for distinguishing between OKCs, UAs, and DCs.

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.

Multiple central giant cell granuloma of the jaws: diagnostic signposts of Noonan syndrome and RASopathy.

Noonan syndrome (NS) is a phenotypically variable inherited multi-system disorder. Maxillofacial findings can be diagnostic, especially in the evaluation of discrete facial dysmorphia. Diagnostic landmark findings of therapeutic relevance for the jaws such as central giant cell granuloma (CGCG) are rare in NS. However, recent molecular genetic studies indicate that these rare, benign lesions are neoplasms and more common in specific syndromes grouped under the umbrella term RASopathies. A specialist surgical diagnosis can be helpful in identifying the underlying disease. This report outlines diagnosis and treatment of a case of CGCG for which jaw diagnosis became the key to identifying a syndromic disease.

Implant presence-triggered osteonecrosis: A scoping review.

Unlike medication-related osteonecrosis of the jaw (MRONJ), implant presence-triggered osteonecrosis of the jaw (IPTO) is not well appreciated. Recent reports have suggested a mechanical aetiology unique to osseointegrated dental implants that may be responsible for this phenomenon. A scoping review was performed to consolidate the available evidence. Two reviewers independently searched the PubMed, EMBASE, CINAHL, and Cochrane Library databases. The study was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for scoping reviews. Studies that described or evaluated the development of IPTO in osseointegrated implants, which were placed prior to the commencement of anti-resorptive or anti-angiogenic agents, were included. Twenty-three (23) articles were included in this study. Patient characteristics, aetiopathogenesis, presentation, and treatment of the disease were evaluated. Most studies suggested a 6-month period between dental implant insertion and the commencement of anti-resorptive therapy as a criterion for IPTO. Both infective and mechanical processes were reported to be involved in the pathogenesis of IPTO. Most patients required surgical intervention to achieve resolution. While there are several knowledge gaps regarding IPTO, the evidence points towards a continuum in the pathogenesis of the disease, whereby there is a mechanical cause followed by secondary infection. Similar to typical MRONJ, the severity and treatment required also vary. Persistent peri­implantitis features around a dental implant should alert the clinician to the possibility of IPTO in patients taking anti-resorptive or anti-angiogenic agents. Prompt identification of the disease may play a role in timely management or appropriate referrals.

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.

[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.

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.

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.

[Statistical information about the inflammatory processes of the jaw-facial part in children].

OBJECTIVE: Introduction: The acute and chronic inflammatory processes prevail in the structure of the dental surgical diseases in children. Notably, various forms of lymphadenitis, adenophlegmon and odontogenous osteomyelitis dominate in the specialized surgical units; however, it is not possible to resolve a number of organizational problems without clear understanding of the statistical situation. The aim: The paper is aimed at the analysis of the incidence rate of major nosological forms of the acute suppurative inflammations of the maxillofacial area in children for the prospective planning of arrangements to provide them with high-quality specialized care. PATIENTS AND METHODS: Materials and methods: The paper involves findings of comprehensive examination and treatment of 537children with acute purulent lymphadenitis, adenophlegmon and odontogenous osteomyelitis that was carried out within 6 years. RESULTS: Results: The resulting clinical data have shown that three abovementioned nosological forms of the disease accounted for 42% of the overall number of the inpatient dental patients and 11% of the total number of children with acute surgical pathology. Out of 537 patients, 240 patients (44.8%) with acute purulent lymphadenitis, 150 (27,9%) patients with adenophlegmon and 147 (27.3%) patients with acute odontogenous osteomyelitis have been observed (318 (59,2%) boys and 219 (40,8%) girls aged from 2 months to 15 years). The study of the past history of the disease has established that in the majority of patients burdened premorbid history and occurrence of concomitant chronic general somatic diseases was presented prior to the onset of acute inflammation. CONCLUSION: Conclusions: The factors, mentioned above, greatly contributed to increase in protective-adaptive properties of child body and create the prerequisites for the formation of pathological symptomocomplex in children, which can be implemented even in the minimal effect of antigen load on the tissues of maxillofacial area. Such situation requires a balanced multidisciplinary approach to the planning of preventive measures in this category of patients at all stages of the observation.

Differences between osteoradionecrosis and medication-related osteonecrosis of the jaw.

PURPOSE: The appearance of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) is similar, but clinically important differences between ORN and MRONJ exist. The aim of this study was to compare the clinical data between ORN and MRONJ and to reveal the critical differences between these diseases. METHODS: We retrospectively reviewed the epidemiological data, clinical findings, and treatment in 27 ORN and 61 MRONJ patients. Radiographic signs before the initiation of treatment were also assessed. RESULTS: The median age (P = 0.0474) and the ratio of female to male patients (P < 0.0001) were significantly higher in MRONJ patients. There were significantly more MRONJ patients who reported a history of pain when compared with ORN patients (P = 0.0263). As an aetiological factor, tooth extraction was significantly more relevant to MRONJ than ORN (P = 0.0352). When assessing the radiographic signs on computed tomographic images, periosteal reaction was found only in MRONJ patients (P = 0.0158). Minimal debridement was performed significantly more frequently for MRONJ (P = 0.0093), and by contrast, surgical resection was performed more frequently for ORN (P = 0.0002). CONCLUSIONS: Understanding the clinical and underlying pathological differences between ORN and MRONJ probably contributes to the selection of appropriate treatment for each patient.