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BACKGROUND: We present a series of 10 patients with osteonecrosis of the jaws (ONJ) that appeared following cancer chemotherapy. MATERIAL AND METHODS: Of the 10 cases with ONJ, six had bone metastases from breast cancers and the other four had multiple myeloma. We analysed the location of bone metastases, as well as the characteristics of the ONJ, and the drugs with which they had been treated for their bone metastases. RESULTS: Of the 10 patients, all had ONJ in the mandible; 50% also had maxillary involvement. The average number of areas of painful exposed was 2.1 per patient (range 1-5). In seven patients a tooth extraction preceded the onset of ONJ. Two patients developed oroantral communications and another a cutaneous fistula to the neck with suppuration. In all the 10 patients the histopatholological diagnosis was of chronic osteomyelitis without evidence of metastatic disease to the jaws. All the patients had received treatment for their malignant bone disease with bisphosphonates. These were the only drugs that all patients had received. CONCLUSION: ONJ appears to have a relationship with the use of bisphosphonates. [ABSTRACT FROM AUTHOR]

The management of oral potentially malignant disorders (OPMD) including oral leukoplakia (OL) is not currently structured according to agreed guidelines. The current report presents survey data gathered from Oral Medicine Practitioners (OMPs) in Europe and Australia and is aimed to investigate attitudes and practice in the diagnosis, risk stratification and treatment of OL. In the presence of a clinical provisional diagnosis of OL, respondents reported always undertaking biopsy in 83% of cases, with most OMPs also relying on diagnostic adjuncts. The potential for malignant transformation is almost invariably assessed through epithelial dysplasia status, with other biomarkers described in the literature used less often. Active treatment of OL was considered mandatory by 20% of OMPs, while others reserve treatment for selected cases only. OMPs are mostly driven to active treatment by lesion-related features which are frequently jointly considered including lesion site, clinical appearance and dysplasia status. Inconsistent assessment was observed regarding mild dysplasia, lesion size, presence of unavoidable trauma, exposure to tobacco and patient age. Frequently observed geographical variations were seldom statistically significant. In agreement with previous surveys, a lack of consensus around the management of OL was observed, supporting claims from learned academies and societies for treatment guidelines aiming to reduce inter-practitioner variability., (© 2022 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Oral Medicine is a young dental specialty born almost a century ago and deals with orofacial conditions not directly attributable to the most prevalent tooth pathologies such as dental caries or periodontal diseases. Presentations may reflect local disease or orofacial manifestations of more widespread pathology affecting other parts of the body. Due to its recency as a distinct discipline and to heterogeneous global settings, Oral Medicine has not yet achieved a shared scope and definition, as well as a recognized status across the globe. The current report presents survey data gathered from Oral Medicine practitioners in Europe and Australia and aimed to identify practitioner characteristics including demographics, training, clinical and research activity. As expected, Oral Medicine clinical practice commonly deals with conditions such as immune-mediated disorders, potentially malignant disorders, oral mucosal infections and chronic pain disorders, but geographical heterogeneities are observed. The present data, representative of current clinical practice, are valuable in order to understand the evolution of Oral Medicine as a distinct discipline and should be taken into consideration in order to create or update postgraduate training curricula able to meet the needs of future practitioners and the communities they serve., (wileyonlinelibrary.com/journal/odi.)

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer., (© 2020 Wiley Periodicals LLC.)

Background: A systematic review and meta-analysis were made of the incidence of recurrences in patients with proliferative verrucous leukoplakia (PVL) subjected to different types of treatment., Methods: The study was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. A literature search was made in the Medline (PubMed), EMBASE, and Web of Science databases, together with a manual search, covering the period from 1985 to January 2020, with no language restrictions. Studies were included if they described treatments applied to at least 10 patients with the corresponding outcomes. Methodological quality was evaluated using Jadad scale and Newcastle-Ottawa tool. Global incidence was calculated by random effects meta-analysis using the Comprehensive Meta-analysis version 3.0 software. Publication bias was assessed using funnel plots and the Duval and Tweedie trim and fill method., Results: Of the 922 identified articles, 12 were found to meet the inclusion criteria. Most of them presented moderate or low risk of bias. A total of 397 patients were analyzed. The mean age was 62.34 years and 248 were women (62.5%). The mean follow-up was 79.3 months. The most frequent treatment was surgical removal with a cold scalpel or laser (339 patients). A total of 232 subjects presented lesion recurrence. The combination of proportions global effect meta-analysis yielded a recurrence rate of 67.2% (95% CI: 48.3-81.8), with the absence of publication bias., Conclusions: There is not enough scientific evidence to conclude that any treatment strategy is able to reduce the recurrence in PVL., (© 2021 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

Objectives: To explore the pathophysiology of proliferative verrucous leukoplakia, a rare oral disorder that exhibits high rates of recurrence and malignant transformation, through a RNAseq case-control study., Material and Methods: We obtained oral biopsies from 10 patients with verrucous leukoplakia lesions and from the mucosa of 5 healthy individuals for sequencing using RNAseq technology. Using bioinformatic methods, we investigated gene expression and enrichment differences between patients both with and without the disorder. We applied network biology methods to investigate functional relations among those genes that were differentially deregulated., Results: We detected 140 differentially expressed genes with distinct roles in immune surveillance, tissue and organ morphogenesis, development, and organization. Of these 140 genes, 111 have been previously described as cancer expression biomarkers, being oral squamous cell carcinoma the most represented type of cancer among them. Of these 140 genes, 26 were prioritized for further investigation as biomarkers using larger sample sizes., Conclusions: The gene expression patterns of healthy and unhealthy patients differed in 140 genes whose deregulation has a functional impact on normal functioning of the immune system. This immune expression profile provides a plausible hypothesis to explain the transformation to oral squamous cell carcinoma observed in 6 of the 10 assayed cases., Clinical Relevance: By determining the molecular bases of the proliferative verrucous leukoplakia disorder and identifying early biomarkers of malignancy, this can allow us to develop new treatment strategies.

Background: A study is made of the association between maxillary sinus pathology and odontogenic lesions in patients evaluated with cone beam computed tomography., Material and Methods: A literature search was made in five databases and OpenGrey. Methodological assessment was carried out using the Newcastle-Ottawa tool for observational studies. The random-effects model was used for the meta-analysis., Results: Twenty-one studies were included in the qualitative review and 6 in the meta-analysis. Most presented moderate or low risk of bias. The periodontal disease showed to be associated with the thickening of the sinus membrane (TSM). Mucous retention cysts and opacities were reported in few studies. The presence of periapical lesions (PALs) was significantly associated to TSM (OR=2.43 (95%CI:1.71-3.46); I2=34.5%) and to odontogenic maxillary sinusitis (OMS) (OR=1.77 (95%CI: 1.20-2.61); I2=35.5%)., Conclusions: The presence of PALs increases the probability of TSM and OMS up to 2.4-fold and 1.7-fold respectively. The risk differences suggests that about 58 and 37 of out every 100 maxillary sinuses having antral teeth with PALs are associated with an increased risk TSM and OMS respectively. The meta-evidence obtained in this study was of moderate certainty, and although the magnitude of the observed associations may vary, their direction in favor sinus disorders appearance, would not change as a result.

Background: To analyze the presence of salivary Epstein-Barr virus (EBV) DNA in oral squamous cell carcinoma and potentially malignant oral disorders., Material and Methods: Three groups were studied: Group 1 (12 oral squamous cell carcinomas (OSCC)), Group 2 (12 potentially malignant oral disorders (PMD)) and Group 3 (47 healthy controls). EBV DNA salivary analysis was performed by PCR., Results: The highest percentage of positive salivary EBV DNA corresponded to the OSCC group (58.3%), followed by the PMD group (41.7%) and the controls (40.4%). The differences between groups were not statistically significant, however (p>0.05)., Conclusions: Salivary EBV DNA was more prevalent in OSCC than in PMD or the controls.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is usually initiated by dental surgery, but is occasionally exacerbated by other antiresorptive (denosumab) and anti-angiogenic therapies, and in such cases is currently termed medication-related osteonecrosis of the jaws (MRONJ). The case of a 58-year-old female with breast cancer who developed multiple and ultimately fatal metastases despite 3 years of treatment with chemotherapeutic drugs and intravenous bisphosphonates, is presented herein. Her malignant disease worsened and she was started on mitoxantrone. She developed a severe adverse reaction to this drug soon after starting treatment. As well as diarrhoea and vomiting, she had a very aggressive gingival inflammation with multiple ulcerations in both jaws and wide areas of necrotic bone, affecting the attached gingiva, and seemingly unrelated to dental plaque. These ulcerations and the exposed necrotic bone persisted for more that 6 months, until her death. This report describes a case in which severe gingival ulcerations that occurred after mitoxantrone treatment for metastatic breast cancer were a local factor that initiated MRONJ., (Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Oral medicine (stomatology) is a recognized and increasingly important dental specialty in many parts of the world that recognizes and fosters the interplay between medical health and oral health. Its dental activities rely greatly on the underlying biology of disease and evidence-based outcomes. However, full recognition of the importance of oral medicine to patient care, research, and education is not yet totally universally acknowledged. To address these shortcomings, we outline the birth, growth, and future of oral medicine globally, and record identifiable past contributions to the development of the specialty, providing an accurate, unique, and valuable resource on oral medicine. Although it was challenging to gather the data, we present this information as a review that endeavors to summarize the salient points about oral medicine, based on MEDLINE, other internet searches, communication with oral medicine and stomatological societies across the world, the web page http://en.wikipedia.org/wiki/List_of_dental_organizations, and discussions with a wide range of key senior persons in the specialty., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We analysed the degree of sclerosis in the different stages of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and studied the relation between the grade of sclerosis, the clinical symptoms, and the depth of lucency. We compared 43 patients with mandibular BRONJ with a control group of 40 cases with no bony lesions. The presence of sclerotic bone, cortical irregularities, radiolucency, fragmentation or sequestration, periostitis, and narrowing of the mandibular canal were studied from computed tomographic (CT) scans using the program ImageJ 1.47v (National Institute of Health, Bethesda, USA) to measure the radiolucency, width of the cortices, and degree of sclerosis. Patients with BRONJ had more severe sclerosis than controls (p<0.01). There was also a significant difference among the different stages of BRONJ, with the highest values found in stage III (p=0.02). The degree of sclerosis differed according to sex, type of bisphosphonate, and the clinical characteristics such as pain, or suppuration, but not significantly so (p>0.05). We conclude that the degree of sclerosis increases with the clinical stage of BRONJ, and is correlated with the depth of lucency., (Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: The objectives of this study are to describe the distinctive characteristics of extra-nodal B-cell non-Hodgkin's lymphomas (BNHLs) located in the head and neck in a series of patients, to discuss patient survival, and to compare the oral versus the non-oral locations of the extra-nodal BNHLs of the head and neck., Material and Methods: We studied 68 patients with BNHL of the head and neck. We analyzed the clinical and survival characteristics. Additionally, we performed Kaplan-Meier and Cox regression analyses to determine the influence of the different factors on survival., Results: This study included 68 non-nodal lymphomas; 30 lymphomas (31.9%) were located intraorally, with the gingiva as the most frequent location. The oral lymphomas in stages 1 and 2 showed a prevalence of 60% (18/30). The Kaplan-Meier analysis showed that the stage of disease and the oral versus non-oral extranodal lymphomas were significant prognostic factors (p<0.05). However, the multivariate Cox analysis indicated that only complete remission and oral versus non-oral location were significant prognostic factors (p<0.01)., Conclusions: The gingiva was the most common location of the intraoral lymphomas. Complete remission and non-oral location were the only significant survival factors in the multivariate Cox regression analysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: This study aimed to survey the presence of known oncoviruses in oral biopsies from patients diagnosed with the aetiologically undetermined proliferative verrucous leukoplakia and compare results to those from milder oral leukoplakia (OL) cases, oral squamous cell carcinoma, a common outcome of the lesions of interest, and healthy controls., Design: Blind, retrospective, case-control study., Setting: A stomatology unit in an academic Hospital and a Public Health laboratory., Participants: Forty patients were divided in four groups. Ten patients had been diagnosed with proliferative verrucous leukoplakia, 10 with OL and 10 with OSCC, and 10 were healthy subjects., Main Outcome Measures: The presence or absence of oncovirus DNA was assayed with the amplification of viral genetic markers using PCR and subsequent gel electrophoresis confirmation. Amplified fragments were sequenced and identified bioinformatically., Results: No DNA from the herpesvirus, papillomavirus or polyomavirus species was detected in the samples., Conclusions: No association between proliferative verrucous leukoplakia and target viruses was detected. A higher throughput viral metagenomic approach may prove valuable for future analyses, as it would not be restricted to a priori knowledge of potential targets., (© 2014 John Wiley & Sons Ltd.)

Purpose. To report the efficacy of conservative surgical treatment for stage I bisphosphonate-related osteonecrosis of the jaw (BRONJ). Materials and Methods. This study reports the clinical outcomes of 63 patients treated for BRONJ stage I (according to Ruggiero's staging system) at the Oral Pathology and Laser-Assisted Surgery Unit of the University of Parma between January 2004 and January 2011. Surgical interventions were performed, under local analgesia, in patients unresponsive for a period of six months to noninvasive treatments such as cycles of local or systemic antibacterial therapy combined or not to low level laser therapy, ozone therapy, or Hyperbaric Oxygen Therapy. All interventions were performed after the consultation of oncologist or physician. Results. In our experience, conservative surgical treatment is associated with the highest number of BRONJ healed sites in stage I disease. Complete healing was observed in 92.6% of sites surgically treated. Conclusions. This study confirms that treatment of patients affected by minimal bone exposition, (stage I of BRONJ), through conservative surgical strategies, possibly with laser, may result in a high control of the disease in the long term.

Purpose: An analysis was performed of the clinical and epidemiologic characteristics of a group of patients diagnosed with oral metastases of distant primary tumors or unknown primary malignancies., Material and Methods: The study series consisted of 16 patients with oral metastatic lesions seen in the Department of Stomatology and Maxillofacial Surgery, Valencia University General Hospital (Valencia, Spain) that had been diagnosed in the previous 15 years. A retrospective analysis was made of patient age and gender, clinical characteristics of metastatic lesions, location of the primary tumor, and time elapsed from diagnosis to the death of a patient., Results: There were 13 male and 3 female patients (mean age, 58.8 years). Ten patients had been diagnosed previously and were being treated for a primary tumor; 2 patients were diagnosed with a primary malignancy in the department; and 4 patients presented with an unidentified primary tumor (metastatic disease diagnosed from biopsy study). The predominant clinical presentation was mixed soft tissue and bone metastases followed by solely soft tissue lesions and solely bone lesions. Some patients showed no apparent oral lesions. Primary malignancies originated mainly from the lung followed by the prostate, gastrointestinal tract, thyroid gland, breast, and liver. Mean survival from diagnosis of oral metastases was 8.25 months., Conclusion: Oral metastatic lesions are infrequent, can affect male and female patients equally, can manifest at any age, and may constitute the first manifestation of a still unidentified primary malignancy. According to the literature, bone metastases are more common than soft tissue metastases. Nevertheless, in the present series, there was a clear male predominance, and the oral metastases showed a predominance of mixed presentations followed by solely soft tissue lesions and solely bone metastases., (Published by Elsevier Inc.)

Introduction: This preliminary study compared the epidermal growth factor receptor (EGFR) copy number in patients with potentially malignant oral disorders (PMODs) and oral squamous cell carcinoma (OSCC)., Material and Methods: Group 1 comprised 20 patients with oral leukoplakia and group 2 comprised 19 cases of OSCC. We estimated the EGFR copy number in both groups using real-time reverse-transcription polymerase chain reaction assays. We used laser microdissection (LMD) for EGFR amplification, and overexpression was performed., Results:   The EGFR copy number was higher in group 2 (9.1 ± 6.2) than in group 1 (3.8 ± 1.5). The greatest copy number was found in the non-homogeneous leukoplakias, but the difference in homogeneous cases was not significant (Mann-Whitney test, P>0.05). In group 2, the EGFR copy number was higher in advanced stages than in early stages, but again lacked statistical significance., Conclusions: The EGFR copy number may be a useful biomolecular marker to differentiate PMODs from OSCC. The EGFR was higher in non-homogeneous leukoplakias and in the advanced stages of OSCC., (© 2012 John Wiley & Sons A/S.)

Objective: The aim of this study was to validate the classification of bisphosphonate-related osteonecrosis of the jaws (BRONJ) published in 2009(17) in a series of cases., Material and Methods: This retrospective clinical study included a series of 102 cases (81%) of intravenous BRONJ (iBRONJ, group 1) and 24 cases (19%) of oral BRONJ (oBRONJ, group 2). We recorded all patients' symptoms and clinical findings and classified each patient into a BRONJ stage (0-3; stage 0=non-exposed BRONJ)., Results: Most BRONJ cases (n=120, 95.2%) could be classified according to the proposed stages. Exposed necrotic areas of bone were more prevalent in group 1 than in group 2 (p<0.05). In contrast, we observed more BRONJ cases without areas of exposed bone in group 2 (n=12, 50%) than in group 1 (n=14, 13.7%; p<0.05). We could not assign six cases to any of the proposed stages. These cases had no areas of exposed necrotic bone, but had mandibular fractures, extra-oral fistula or affected maxillary sinuses., Conclusions: In our series, iBRONJ cases showed more advanced stages of BRONJ than did oBRONJ cases. We found few cases that could not be classified into any proposed stage because they had findings associated with stages 0 and 3 but lacked exposed necrotic bone., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this study, we compared clinical differences between patients with proliferative verrucous leukoplakia (PVL) who did and did not develop oral cancer. This was a retrospective study of 55 PVL cases. All patients were followed for at least 1year, with a mean follow-up of 7.53 (SD=4.18) years. The mean age of the patients was 61.69 (SD=11.76) years. There were 36 (65.5%) females and 19 (34.5%) males. Group 1 included the 28 PVL patients who did not develop oral squamous cell carcinoma (OSCC) during the period. Group 2 included the 27 PVL patients who developed at least one OSCC during the period. The latter group was subdivided into patients with PVL who developed one (Subgroup 2a; n=16) or more than one (Subgroup 2b; n=11) OSCC during follow-up. There was no statistical difference in age or oral location of the PVL between Groups 1 and 2. Females had a greater tendency to develop cancer than males (58.3% vs. 31.6%). In Group 2, only six (22.2%) were smokers. There was no difference between Subgroups 2a and b in terms of age, gender, and oral location of the PVL. Subgroup 2b included fewer smokers, had higher gingival involvement rate, and lower frequency of PVL on the tongue. The PVL patients who develop oral cancers were more commonly female and non-smokers. Those patients who developed more than one OSCC were most likely to develop lesions of the gingiva., (Copyright © 2011 Elsevier Ltd. All rights reserved.)