Surgical treatment compared with "wait and see" in patients affected by oral leukoplakia to prevent oral cancer: Preliminary data from a multicenter randomized controlled trial.

OBJECTIVE: Oral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in the clinical management of OL. Surgical removal of OL is performed by most clinicians, although its effectiveness in reducing OSCC onset has still not been established by randomized controlled trials (RCT). Wait and see approach is characterized by frequent clinical examinations and periodical biopsies of OL, avoiding unnecessary surgical procedures. This is the first multicenter RCT in literature aiming at comparing the effectiveness of surgical removal and the "wait and see" approach in preventing OSCC onset in patients affected by dysplastic and non-dysplastic OL. METHODS: Two Italian referral care centres for oral diseases were involved in this multicenter two-arm RCT comparing the surgical removal of OL (group A) and the "wait and see" approach (group B), with the aim of reducing oral cancer onset. RESULTS: This report shows preliminary data on the first 161 patients, with a mean follow-up of 19.14 ± 11.25 months. Eight cases of OSCC occurred (6 out 8 involving the tongue): one case in group A and seven cases in group B. Moreover, OL recurred in 13 (20%) cases after surgical excision. CONCLUSIONS: Within the limitations of this preliminary report, these initial data underline the increased risk of OSCC onset in the case of OL of the tongue in the presence of epithelial dysplasia in group B ("wait and see") compared to group A (surgery). This RCT is currently ongoing at the same clinical departments, with the aim of enrolling 310 patients and collecting data at 5-year follow-up, in order to achieve conclusive results, in an evidence-based medicine approach.

Oral leukoplakia diagnosis and treatment in Europe and Australia: Oral Medicine Practitioners' attitudes and practice.

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.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

Oral potentially malignant disorders - An assessment of knowledge and attitude to future education in undergraduate dental students.

INTRODUCTION: The aim of this study was to assess the knowledge and clinical experience of oral potentially malignant disorders (OPMDs) in undergraduate dental students in six European countries (Croatia, France, Italy, Portugal, Spain and United Kingdom) and assess student's attitude and preference to future education on the topic. A secondary aim was to identify gaps in student's knowledge and clinical practice. The study was a part of the Erasmus+ project "Oral Potentially Malignant Disorders: Healthcare Professionals Training" (Grant No: 2020-1-UK01-KA202-078917). MATERIALS AND METHODS: An online questionnaire was distributed to all final-year students in six partner universities. This consisted of four parts assessing: (1) knowledge on OPMDs, (2) clinical experience with this group of patients, (3) self-rated competence in the management of OPMDs and (4) preferences with regard to future education. RESULTS: Two hundred and sixty final-year dental students from six partner universities responded to the questionnaire. Response rates varied from 12% to 92% between partner universities. Significant differences in clinical experience and knowledge were found between students. Students with more clinical exposure to OPMDs rated their knowledge and competence in the management of OPMDs higher than students with less clinical experience. The majority of students were interested in future education on OPMDs, preferably via short educational videos. CONCLUSION: The majority of students have received theoretical knowledge of OPMDs during their undergraduate studies, however, not all had clinical exposure to this group of patients. Students were open to further education on OPMDs. Important deficiencies in knowledge were identified that need to be addressed and it is anticipated that the e-learning platform and e-book that are in development by partner institutions will help to improve overall knowledge of OPMDs.

Herpes simplex virus type 1 in subgingival plaque and periodontal diseases. Meta-analysis of observational studies.

BACKGROUND AND OBJECTIVES: This meta-analysis of observational studies (PROSPERO registration number CRD42021236054) sought to investigate strength and generalizability of the association of herpes simplex virus type 1 (HSV-1) in subjects with plaque-induced gingivitis and periodontitis, since the data from literature are contrasting. MATERIAL AND METHODS: Case-control and cross-sectional studies, investigating HSV-1 in subgingival plaque/crevicular fluid and periodontal status, were searched through MEDLINE via PubMed, Scopus, Web of Science and Google Scholar. From each study the crude odds ratio (OR) with 95% confidence interval (95CI) was extracted, and the pooled OR was assessed for periodontitis, chronic and aggressive, and gingivitis. The meta-analytic method was chosen based on the level of heterogeneity. The generalizability of results, determined by the meta-analysis bias, was investigated through secondary analyses including sensitivity analyses for study quality, publication bias, and study inclusion, and subgroup analyses for quality of scientific journals that published the primary studies, world Region, subgingival plaque sampling method and study design. RESULTS: Twelve studies were included (738 cases, 551 controls). The pooled ORs were 4.4 (95CI, 1.9-10.2) for any periodontitis; specifically, 2.8 (95CI, 1.0-8.3) for chronic periodontitis, 11.8 (95CI, 5.4-25.8) for aggressive periodontitis and 4.8 (95CI, 2.1-11.0) for gingivitis. These estimates were statistically significant, excluding for chronic periodontitis, resulting marginally significant (p = .05). Secondary analyses on any and aggressive periodontitis, and, partly, chronic periodontitis corroborated the results, while the material was insufficient for secondary analyses on gingivitis. CONCLUSIONS: The results obtained indicated that HSV-1 is associated with periodontitis, while data about gingivitis are inconclusive. HSV-1 investigation in subgingival plaque could help assess periodontitis risk and severity and, if causal association were confirmed, could contribute to its control.

Assessment of sleep disturbance in oral lichen planus and validation of PSQI: A case-control multicenter study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. METHODS: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. RESULTS: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values < 0.001**). Moreover, OLPs had higher scores in the HAM-D, HAM-A, NRS, and T-PRI (p-values < 0.001**). No differences in the PSQI sub-items' scores were found between the K-OLPs and nK-OLPs, although nK-OLPs suffered from higher levels of anxiety, depression, and pain (p-values: HAM-A, 0.007**, HAM-D, 0.009**, NRS, <0.001**, T-PRI, <0.001**). The female gender, anxiety, depression (p-value: 0.007**, 0.001**, 0.020*) and the intensity of pain, anxiety, and depression (p-value: 0.006**, <0.001**, 0.014*) were independent predictors of poor sleep (PSQI > 5) in K-OLPs and nK-OLPs, respectively. The PSQI's validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. CONCLUSIONS: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Single versus multiple visits for endodontic treatment of permanent teeth.

BACKGROUND: Root canal treatment (RoCT), or endodontic treatment, is a common procedure in dentistry. The main indications for RoCT are irreversible pulpitis and necrosis of the dental pulp caused by carious processes, coronal crack or fracture, or dental trauma. Successful RoCT is characterised by an absence of symptoms (i.e. pain) and clinical signs (i.e. swelling and sinus tract) in teeth without radiographic evidence of periodontal involvement (i.e. normal periodontal ligament). The success of RoCT depends on a number of variables related to the preoperative condition of the tooth, as well as the endodontic procedures. RoCT can be carried out with a single-visit approach, which involves root canal system obturation (filling and sealing) directly after instrumentation and irrigation, or with a multiple-visits approach, in which the treatment is completed in two or more sessions and obturation is performed in the last session. This review updates the previous versions published in 2007 and 2016. OBJECTIVES: To evaluate the benefits and harms of completion of root canal treatment (RoCT) in a single visit compared to RoCT over two or more visits, with or without medication, in people aged over 10 years. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 25 April 2022. SELECTION CRITERIA: We included randomised controlled trials and quasi-randomised controlled trials in people needing RoCT comparing completion of RoCT in a single visit compared to RoCT over two or more visits.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. tooth extraction and 2. radiological failure after at least one year (i.e. periapical radiolucency). Our secondary outcomes were 3. postoperative and postobturation pain; 4. swelling or flare-up; 5. analgesic use and 6. presence of sinus track or fistula after at least one month. We used GRADE to assess certainty of evidence for each outcome. We excluded five studies that were included in the previous version of the review because they did not meet the current standard of care (i.e. rubber dam isolation and irrigation with sodium hypochlorite). MAIN RESULTS: We included 47 studies with 5805 participants and 5693 teeth analysed. We judged 10 studies at low risk of bias, 17 at high risk of bias and 20 at unclear risk of bias. Only two studies reported data on tooth extraction. We found no evidence of a difference between treatment in one visit or treatment over multiple visits, but we had very low certainty about the findings (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.09 to 2.50; I2 = 0%; 2 studies, 402 teeth). We found no evidence of a difference between single-visit and multiple-visit treatment in terms of radiological failure (RR 0.93, 95% CI 0.81 to 1.07; I2 = 0%; 13 studies, 1505 teeth; moderate-certainty evidence). We found evidence of a higher proportion of participants reporting pain within one week in single-visit groups compared to multiple visit groups (RR 1.55, 95% CI 1.14 to 2.09; I2 = 18%; 5 studies, 638 teeth; moderate-certainty evidence).  We found no evidence of a difference in the proportion of participants reporting pain until 72 hours postobturation (RR 0.97, 95% CI 0.81 to 1.16; I2 = 70%; 12 studies, 1329 teeth; low-certainty evidence), pain intensity until 72 hours postobturation (mean difference (MD) 0.26, 95% CI -4.76 to 5.29; I2 = 98%; 12 studies, 1258 teeth; low-certainty evidence) or pain at one week postobturation (RR 1.05, 95% CI 0.67 to 1.67; I2 = 61%; 9 studies, 1139 teeth; very low-certainty evidence). We found no evidence of a difference in swelling or flare-up incidence (RR 0.56 95% CI 0.16 to 1.92; I2 = 0%; 6 studies; 605 teeth; very low-certainty evidence), analgesic use (RR 1.25 95% CI 0.75 to 2.09; I2 = 36%; 6 studies, 540 teeth; very low-certainty evidence) or sinus tract or fistula presence (RR 1.00, 95% CI 0.24 to 4.28; I2 = 0%; 5 studies, 650 teeth; very low-certainty evidence). Subgroup analysis found no differences between single-visit and multiple-visit RoCT for considered outcomes other than proportion of participants reporting post-treatment pain within one week, which was higher in the single-visit groups for vital teeth (RR 2.16, 95% CI 1.39 to 3.36; I2 = 0%; 2 studies, 316 teeth), and when instrumentation was mechanical (RR 1.80, 95% CI 1.10 to 2.92; I2 = 56%; 2 studies, 278 teeth). AUTHORS' CONCLUSIONS: As in the previous two versions of the review, there is currently no evidence to suggest that one treatment regimen (single-visit or multiple-visit RoCT) is more effective than the other. Neither regimen can prevent pain and other complications in the 12-month postoperative period. There was moderate-certainty evidence of higher proportion of participants reporting pain within one week in single-visit groups compared to multiple-visit groups. In contrast to the results of the last version of the review, there was no difference in analgesic use.

Oral medicine practice in Europe and Australia: Identifying practitioner characteristics and their clinical activity.

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.

Chronic mechanical trauma/irritation and oral carcinoma: A systematic review showing low evidence to support an association.

BACKGROUND: Chronic trauma of oral mucosa, resulting from repeated and persistent mechanical irritative action of an intraoral injury agent, has repeatedly been reported to be possibly implicated in the development of oral squamous cell carcinoma (OSCC). OBJECTIVES: The present systematic review aimed to assess whether chronic mechanical trauma can be considered a risk factor for OSCC. DATA SOURCES: PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus; EMBASE, Web of Science. STUDY ELIGIBILITY CRITERIA: Cohort studies comparing OSCC incidence among subjects with/without chronic mechanical trauma or case-control or cross-sectional studies comparing chronic mechanical trauma among subjects with/without OSCC. RESULTS: Only one prospective case-control study fulfilled the inclusion criteria, but the quality of the evidence provided is not enough to define trauma as a risk factor for OSCC. The main limitation is the presence of only one case-control study at high risk of bias. In the absence of strong evidence supporting the role of trauma in OSCC, a thorough discussion on trauma and carcinogenesis has been performed. CONCLUSIONS: Available evidence does not support an active role for chronic trauma in oral carcinogenesis, neither as promoter nor as progressor factor. Prospective cohort studies able to better assess trauma in OSCC are needed.

Where do you live? North versus Central-South differences in relation to Italian patients with oral lichen planus: a cross-sectional study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: Oral lichen planus (OLP) is an immune-mediated inflammatory chronic disease of the oral mucosa, with different patterns of clinical manifestations which range from keratotic manifestations (K-OLP) to predominantly non-keratotic lesions (nK-OLP). The aim of the study was to analyze the differences in the clinical, psychological profile and symptoms between Italian patients of the North and Central-South with K-OLP and nK-OLP. METHODS: 270 K-OLP and 270 nK-OLP patients were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The Central-South K-OLP (CS-K-OLP) patients reported a higher frequency of pain/burning compared with the K-OLP patients of the North (N-K-OLP) with higher scores in the NRS and T-PRI (p value < 0.001**). The CS-K-OLP and the CS-nK-OLP patients showed higher scores in the HAM-D, HAM-A, PSQI and ESS compared with the Northern patients (p value < 0.001**). Multivariate logistic regression revealed that the NRS and T-PRI showed the greatest increase in the R2 value for the CS-K-OLP (DR2 = 9.6%; p value < 0.001**; DR2 = 9.7% p value < 0.001**; respectively) and that the oral symptoms (globus, itching and intraoral foreign body sensation) and PSQI showed the greatest increase in the R2 value for the CS-nK-OLP (DR2 = 5.6%; p value < 0.001**; DR2 = 4.5% p value < 0.001** respectively). CONCLUSIONS: Pain and mood disorders are predominant in patients with OLP in the Central-South of Italy. Clinicians should consider that the geographical living area may explain the differences in oral symptoms and psychological profile in OLP.

Antibiotics to prevent complications following tooth extractions.

BACKGROUND: The most frequent indications for tooth extractions, generally performed by general dental practitioners, are dental caries and periodontal infections. Systemic antibiotics may be prescribed to patients undergoing extractions to prevent complications due to infection. This is an update of a review first published in 2012. OBJECTIVES: To determine the effect of systemic antibiotic prophylaxis on the prevention of infectious complications following tooth extractions. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health Trials Register (to 16 April 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 3), MEDLINE Ovid (1946 to 16 April 2020), Embase Ovid (1980 to 16 April 2020), and LILACS (1982 to 16 April 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials of systemic antibiotic prophylaxis in patients undergoing tooth extraction(s) for any indication. DATA COLLECTION AND ANALYSIS: At least two review authors independently performed data extraction and 'Risk of bias' assessment for the included studies. We contacted trial authors for further details where these were unclear. For dichotomous outcomes, we calculated risk ratios (RR) and 95% confidence intervals (CI) using random-effects models. For continuous outcomes, we used mean differences (MD) with 95% CI using random-effects models. We examined potential sources of heterogeneity. We assessed the certainty of the body of evidence for key outcomes as high, moderate, low, or very low, using the GRADE approach. MAIN RESULTS: We included 23 trials that randomised approximately 3206 participants (2583 analysed) to prophylactic antibiotics or placebo. Although general dentists perform dental extractions because of severe dental caries or periodontal infection, only one of the trials evaluated the role of antibiotic prophylaxis in groups of patients affected by those clinical conditions. We assessed 16 trials as being at high risk of bias, three at low risk, and four as unclear.  Compared to placebo, antibiotics may reduce the risk of postsurgical infectious complications in patients undergoing third molar extractions by approximately 66% (RR 0.34, 95% CI 0.19 to 0.64; 1728 participants; 12 studies; low-certainty evidence), which means that 19 people (95% CI 15 to 34) need to be treated with antibiotics to prevent one infection following extraction of impacted wisdom teeth. Antibiotics may also reduce the risk of dry socket by 34% (RR 0.66, 95% CI 0.45 to 0.97; 1882 participants; 13 studies; low-certainty evidence), which means that 46 people (95% CI 29 to 62) need to take antibiotics to prevent one case of dry socket following extraction of impacted wisdom teeth. The evidence for our other outcomes is uncertain: pain, whether measured dichotomously as presence or absence (RR 0.59, 95% CI 0.31 to 1.12; 675 participants; 3 studies) or continuously using a visual analogue scale (0-to-10-centimetre scale, where 0 is no pain) (MD -0.26, 95% CI -0.59 to 0.07; 422 participants; 4 studies); fever (RR 0.66, 95% CI 0.24 to 1.79; 475 participants; 4 studies); and adverse effects, which were mild and transient (RR 1.46, 95% CI 0.81 to 2.64; 1277 participants; 8 studies) (very low-certainty evidence).  We found no clear evidence that the timing of antibiotic administration (preoperative, postoperative, or both) was important. The included studies enrolled a subset of patients undergoing dental extractions, that is healthy people who had surgical extraction of third molars. Consequently, the results of this review may not be generalisable to all people undergoing tooth extractions. AUTHORS' CONCLUSIONS: The vast majority (21 out of 23) of the trials included in this review included only healthy patients undergoing extraction of impacted third molars, often performed by oral surgeons. None of the studies evaluated tooth extraction in immunocompromised patients. We found low-certainty evidence that prophylactic antibiotics may reduce the risk of infection and dry socket following third molar extraction when compared to placebo, and very low-certainty evidence of no increase in the risk of adverse effects. On average, treating 19 healthy patients with prophylactic antibiotics may stop one person from getting an infection. It is unclear whether the evidence in this review is generalisable to patients with concomitant illnesses or patients at a higher risk of infection. Due to the increasing prevalence of bacteria that are resistant to antibiotic treatment, clinicians should evaluate if and when to prescribe prophylactic antibiotic therapy before a dental extraction for each patient on the basis of the patient's clinical conditions (healthy or affected by systemic pathology) and level of risk from infective complications. Immunocompromised patients, in particular, need an individualised approach in consultation with their treating medical specialist.

Management of oral potentially malignant disorders.

Patients with oral potentially malignant disorders (OPMDs), including oral leukoplakia and erythroplakia, proliferative verrucous leukoplakia, oral submucous fibrosis, and oral lichen planus/lichenoid lesions, can be challenging to manage. A small proportion will undergo cancer development and determining a patient's cancer risk is key to making management decisions. Yet, our understanding of the natural history of OPMDs has not been fully elucidated, and a precision approach based on the integration of numerous predictive markers has not been validated by prospective studies. Evidence-based health promotion by clinicians and healthcare systems is not embraced universally. Medical and surgical interventions evaluated by rigorous research measuring important endpoints, such as cancer development, mortality, or survival, are difficult and expensive to run. Most of these studies employ non-ideal surrogate endpoints and have deep methodologic flaws. Diagnostic criteria for enrolling research subjects are not uniform, and patients with the highest risk for cancer development comprise small proportions of those enrolled. Few studies explore quality of life and patient preferences. It is time to rethink how we approach the management of these patients, across each OPMD, and considering the healthcare infrastructure and cost-effectiveness. Global networks with well-characterized patient populations with OPMDs and well-designed interventional trials using validated outcome measures are needed.

Development of lung metastases in mouse models of tongue squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) represents 3%-4% of all cancers. Despite the increasing incidence of OSCC distant metastasis and poor prognosis, few animal models of OSCC distant metastasis have been reported. In this study, we established mouse models of OSCC lung metastasis by orthotopic and tail vein injection of new OSCC cell lines. METHODS: For the tail vein model, we used a novel cell line isolated from lung metastases reproduced in vivo after intravenous injection of HSC-3 GFP/luciferase cells and sorted for GFP expression (HSC-3 M1 GFP/luciferase). Lung metastases were assessed by imaging techniques and further confirmed by histology. For the orthotopic model, HSC-3 GFP/luciferase cells were injected into the tongue of athymic nude mice. The primary tumor and metastases were assessed by in vivo imaging, histology, and immunohistochemistry. RESULTS: The orthotopic model presented spontaneous lung metastases in 50% of the animals and lymph node metastases were present in 83% of cases. In the tail vein model, a lung metastasis rate of 60% was observed. CONCLUSIONS: Lung metastases were successfully reproduced by orthotopic and tail vein injection. Since lymph node metastases were present, the orthotopic model with HSC-3 GFP/luciferase cells may be suitable to investigate metastatic dissemination in OSCC.

Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer.

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.

Psychological profile and unexpected pain in oral lichen planus: A case-control multicenter SIPMO studya.

OBJECTIVES: To analyze psychological profiles, pain, and oral symptoms in patients with oral lichen planus (OLP). MATERIALS AND METHODS: 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes), and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value < .001** ). A positive correlation between the NRS, T-PRI, HAM-A, HAM-D, and PSQI was found with the number of oral symptoms and number of oral sites involved. Pain was reported in 67.3% of nK-OLP and 49.7% of K-OLP cases with poor correspondence between the site of lesions and the site of the symptoms. CONCLUSIONS: Mood disorders are frequently associated with OLP with an unexpected symptomatology correlated with the number of oral symptoms and with the extension of disease suggesting a peripheral neuropathy.

Posture Assessment in Dentistry for Different Visual Aids Using 2D Markers.

Attention and awareness towards musculoskeletal disorders (MSDs) in the dental profession has increased considerably in the last few years. From recent literature reviews, it appears that the prevalence of MSDs in dentists concerns between 64 and 93%. In our clinical trial, we have assessed the dentist posture during the extraction of 90 third lower molars depending on whether the operator performs the intervention by the use of the operating microscope, surgical loupes, or with the naked eye. In particular, we analyzed the evolution of the body posture during different interventions evaluating the impact of visual aids with respect to naked eye interventions. The presented posture assessment approach is based on 3D acquisitions of the upper body, based on planar markers, which allows us to discriminate spatial displacements up to 2 mm in translation and 1 degree in rotation. We found a significant reduction of neck bending in interventions using visual aids, in particular for those performed with the microscope. We further investigated the impact of different postures on MSD risk using a widely adopted evaluation tool for ergonomic investigations of workplaces, named (RULA) Rapid Upper Limb Assessment. The analysis performed in this clinical trial is based on a 3D marker tracker that is able to follow a surgeon's upper limbs during interventions. The method highlighted pros and cons of different approaches.

Interventions for treating oral lichen planus: corticosteroid therapies.

BACKGROUND: Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease, which can cause significant pain, particularly in its erosive or ulcerative forms. As pain is the indication for treatment of OLP, pain resolution is the primary outcome for this review. This review is an update of a version last published in 2011, but focuses on the evidence for corticosteroid treatment only. A second review considering non-corticosteroid treatments is in progress. OBJECTIVES: To assess the effects and safety of corticosteroids, in any formulation, for treating people with symptoms of oral lichen planus. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases to 25 February 2019: Cochrane Oral Health's Trials Register, CENTRAL (2019, Issue 1), MEDLINE Ovid, and Embase Ovid. ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. There were no restrictions on language or date of publication. SELECTION CRITERIA: We considered randomised controlled clinical trials (RCTs) of any local or systemic corticosteroid treatment compared with a placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug, or the same corticosteroid plus an adjunctive treatment. DATA COLLECTION AND ANALYSIS: Three review authors independently scanned the titles and abstracts of all reports identified, and assessed risk of bias using the Cochrane tool and extracted data from included studies. For dichotomous outcomes, we expressed the estimates of effects of an intervention as risk ratios (RR), with 95% confidence intervals (CI). For continuous outcomes, we used mean differences (MD) and 95% CI. The statistical unit of analysis was the participant. We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE. MAIN RESULTS: We included 35 studies (1474 participants) in this review. We assessed seven studies at low risk of bias overall, 11 at unclear and the remaining 17 studies at high risk of bias. We present results for our main outcomes, pain and clinical resolution measured at the end of the treatment course (between one week and six months), and adverse effects. The limited evidence available for comparisons between different corticosteroids, and corticosteroids versus alternative or adjunctive treatments is presented in the full review. Corticosteroids versus placebo Three studies evaluated the effectiveness and safety of topical corticosteroids in an adhesive base compared to placebo. We were able to combine two studies in meta-analyses, one evaluating clobetasol propionate and the other flucinonide. We found low-certainty evidence that pain may be more likely to be resolved when using a topical corticosteroid rather than a placebo (RR 1.91, 95% CI 1.08 to 3.36; 2 studies, 72 participants; I² = 0%). The results for clinical effect of treatment and adverse effects were inconclusive (clinical resolution: RR 6.00, 95% CI 0.76 to 47.58; 2 studies, 72 participants; I² = 0%; very low-certainty evidence; adverse effects RR 1.48, 95% 0.48 to 4.56; 3 studies, 88 participants, I² = 0%, very low-certainty evidence). Corticosteroids versus calcineurin inhibitors Three studies compared topical clobetasol propionate versus topical tacrolimus. We found very low-certainty evidence regarding any difference between tacrolimus and clobetasol for the outcomes pain resolution (RR 0.45, 95% CI 0.24 to 0.88; 2 studies, 100 participants; I² = 80%), clinical resolution (RR 0.61, 95% CI 0.38 to 0.99; 2 studies, 52 participants; I² = 95%) and adverse effects (RR 0.05, 95% CI 0.00 to 0.83; 2 studies, 100 participants; very low-certainty evidence) . One study (39 participants) compared topical clobetasol and ciclosporin, and provided only very low-certainty evidence regarding the rate of clinical resolution with clobetasol (RR 3.16, 95% CI 1.00 to 9.93), pain resolution (RR 2.11, 95% CI 0.76 to 5.86) and adverse effects (RR 6.32, 95% CI 0.84 to 47.69). Two studies (60 participants) that compared triamcinolone and tacrolimus found uncertain evidence regarding the rate of clinical resolution (RR 0.86, 95% CI 0.55 to 1.35; very low-certainty evidence) and that there may be a lower rate of adverse effects in the triamcinolone group (RR 0.47, 95% CI 0.22 to 0.99; low-certainty evidence). These studies did not report on pain resolution. AUTHORS' CONCLUSIONS: Corticosteroids have been first line for the treatment of OLP. This review found that these drugs, delivered topically as adhesive gels or similar preparations, may be more effective than placebo for reducing the pain of symptomatic OLP; however, with the small number of studies and participants, our confidence in the reliability of this finding is low. The results for clinical response were inconclusive, and we are uncertain about adverse effects. Very low-certainty evidence suggests that calcineurin inhibitors, specifically tacrolimus, may be more effective at resolving pain than corticosteroids, although there is some uncertainty about adverse effects and clinical response to tacrolimus showed conflicting results.

Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis.

BACKGROUND: Systemic antimicrobials can be used as an adjunct to mechanical debridement (scaling and root planing (SRP)) as a non-surgical treatment approach to manage periodontitis. A range of antibiotics with different dosage and combinations are documented in the literature. The review follows the previous classification of periodontitis as all included studies used this classification. OBJECTIVES: To assess the effects of systemic antimicrobials as an adjunct to SRP for the non-surgical treatment of patients with periodontitis. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases to 9 March 2020: Cochrane Oral Health's Trials Register, CENTRAL, MEDLINE, and Embase. The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) which involved individuals with clinically diagnosed untreated periodontitis. Trials compared SRP with systemic antibiotics versus SRP alone/placebo, or with other systemic antibiotics. DATA COLLECTION AND ANALYSIS: We selected trials, extracted data, and assessed risk of bias in duplicate. We estimated mean differences (MDs) for continuous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 45 trials conducted worldwide involving 2664 adult participants. 14 studies were at low, 8 at high, and the remaining 23 at unclear overall risk of bias. Seven trials did not contribute data to the analysis. We assessed the certainty of the evidence for the 10 comparisons which reported long-term follow-up (≥ 1 year). None of the studies reported data on antimicrobial resistance and patient-reported quality of life changes. Amoxicillin + metronidazole + SRP versus SRP in chronic/aggressive periodontitis: the evidence for percentage of closed pockets (MD -16.20%, 95% CI -25.87 to -6.53; 1 study, 44 participants); clinical attachment level (CAL) (MD -0.47 mm, 95% CI -0.90 to -0.05; 2 studies, 389 participants); probing pocket depth (PD) (MD -0.30 mm, 95% CI -0.42 to -0.18; 2 studies, 389 participants); and percentage of bleeding on probing (BOP) (MD -8.06%, 95% CI -14.26 to -1.85; 2 studies, 389 participants) was of very low certainty. Only the results for closed pockets and BOP showed a minimally important clinical difference (MICD) favouring amoxicillin + metronidazole + SRP. Metronidazole + SRP versus SRP in chronic/aggressive periodontitis: the evidence for percentage of closed pockets (MD -12.20%, 95% CI -29.23 to 4.83; 1 study, 22 participants); CAL (MD -1.12 mm, 95% CI -2.24 to 0; 3 studies, 71 participants); PD (MD -1.11 mm, 95% CI -2.84 to 0.61; 2 studies, 47 participants); and percentage of BOP (MD -6.90%, 95% CI -22.10 to 8.30; 1 study, 22 participants) was of very low certainty. Only the results for CAL and PD showed an MICD favouring the MTZ + SRP group. Azithromycin + SRP versus SRP for chronic/aggressive periodontitis: we found no evidence of a difference in percentage of closed pockets (MD 2.50%, 95% CI -10.19 to 15.19; 1 study, 40 participants); CAL (MD -0.59 mm, 95% CI -1.27 to 0.08; 2 studies, 110 participants); PD (MD -0.77 mm, 95% CI -2.33 to 0.79; 2 studies, 110 participants); and percentage of BOP (MD -1.28%, 95% CI -4.32 to 1.76; 2 studies, 110 participants) (very low-certainty evidence for all outcomes). Amoxicillin + clavulanate + SRP versus SRP for chronic periodontitis: the evidence from 1 study, 21 participants for CAL (MD 0.10 mm, 95% CI -0.51 to 0.71); PD (MD 0.10 mm, 95% CI -0.17 to 0.37); and BOP (MD 0%, 95% CI -0.09 to 0.09) was of very low certainty and did not show a difference between the groups. Doxycycline + SRP versus SRP in aggressive periodontitis: the evidence from 1 study, 22 participants for CAL (MD -0.80 mm, 95% CI -1.49 to -0.11); and PD (MD -1.00 mm, 95% CI -1.78 to -0.22) was of very low certainty, with the doxycycline + SRP group showing an MICD in PD only. Tetracycline + SRP versus SRP for aggressive periodontitis: we found very low-certainty evidence of a difference in long-term improvement in CAL for the tetracycline group (MD -2.30 mm, 95% CI -2.50 to -2.10; 1 study, 26 participants). Clindamycin + SRP versus SRP in aggressive periodontitis: we found very low-certainty evidence from 1 study, 21 participants of a difference in long-term improvement in CAL (MD -1.70 mm, 95% CI -2.40 to -1.00); and PD (MD -1.80 mm, 95% CI -2.47 to -1.13) favouring clindamycin + SRP. Doxycycline + SRP versus metronidazole + SRP for aggressive periodontitis: there was very low-certainty evidence from 1 study, 27 participants of a difference in long-term CAL (MD 1.10 mm, 95% CI 0.36 to 1.84); and PD (MD 1.00 mm, 95% CI 0.30 to 1.70) favouring metronidazole + SRP. Clindamycin + SRP versus metronidazole + SRP for aggressive periodontitis: the evidence from 1 study, 26 participants for CAL (MD 0.20 mm, 95% CI -0.55 to 0.95); and PD (MD 0.20 mm, 95% CI -0.38 to 0.78) was of very low certainty and did not show a difference between the groups. Clindamycin + SRP versus doxycycline + SRP for aggressive periodontitis: the evidence from 1 study, 23 participants for CAL (MD -0.90 mm, 95% CI -1.62 to -0.18); and PD (MD -0.80 mm, 95% CI -1.58 to -0.02) was of very low certainty and did not show a difference between the groups. Most trials testing amoxicillin, metronidazole, and azithromycin reported adverse events such as nausea, vomiting, diarrhoea, mild gastrointestinal disturbances, and metallic taste. No serious adverse events were reported. AUTHORS' CONCLUSIONS: There is very low-certainty evidence (for long-term follow-up) to inform clinicians and patients if adjunctive systemic antimicrobials are of any help for the non-surgical treatment of periodontitis. There is insufficient evidence to decide whether some antibiotics are better than others when used alongside SRP. None of the trials reported serious adverse events but patients should be made aware of the common adverse events related to these drugs. Well-planned RCTs need to be conducted clearly defining the minimally important clinical difference for the outcomes closed pockets, CAL, PD, and BOP.

Treatment of angular cheilitis: A narrative review and authors' clinical experience.

Angular cheilitis (AC) is a clinical entity first described in the XIX century, characterized by erythema, rhagades, ulcerations, and crusting of one or both lip commissures and perilabial skin, responsible of an unpleasant and painful discomfort. Aim of this manuscript was to examine and evaluate the therapeutic options actually available for AC. Despite antifungals being the first-line treatment for most of clinicians, very limited scientific evidence supports their reliability, with just two RCTs published between the 70's and the 80's. Furthermore, alternative topical treatments, various techniques of occlusal vertical dimension restoration, B-vitamin supplementation, anti-drooling prosthetic device, and photodynamic therapy have been experimented and proposed, mostly in the form of case reports or case series on a small number of individuals. Our group found in 1% isoconazole nitrate (ISN) and 0.1% diflucortolone valerate (DFV) ointment the most consistent AC treatment, due to the broad spectrum of ISN against many species of dermatohpytes and bacteria, and the anti-inflammatory properties displayed by DFV. However, further and well-designed trials on larger samples of patients are needed to assess the differential profile of consistency of the treatments outlined in literature and claimed by the authors of this paper.

Clinical Audit of Minimally Invasive Nonsurgical Techniques in Active Periodontal Therapy.

AIMS: Periodontitis is one of the most widespread diseases worldwide. Many efforts have been made to increase the efficacy of periodontitis therapy as much as possible. Recently, minimally invasive nonsurgical techniques (MINST) were introduced in the periodontal field as an alternative to minimally invasive surgical techniques (MIST). This clinical audit aims to evaluate the results of MINST in the initial phase of treatment for periodontitis. MATERIALS AND METHODS: One hundred seven patients with periodontitis who were treated with MINST between 2013 and 2017 and reevaluated after 2 months were included in this clinical audit. The primary outcome analyzed was the proportion of pocket closure. The secondary outcomes were tooth extraction before active periodontal therapy, full-mouth plaque score (FMPS) change, full-mouth bleeding score (FMBS) change, average probing pocket depth (PPD) reduction, and average clinical attachment level (CAL) gain between the baseline and reevaluation values. RESULTS: A total of 2,407 teeth were included in the analysis. At the patient level, the treatment resulted in a mean pocket closure rate of 71.6 ± 15.7% for sites with an initial PPD ≥5 mm. The treatment was statistically significantly (p < 0.001) more effective with respect to the primary outcome compared with expected values reported in a recent meta-analysis (57%). The subgroup analysis revealed statistically significant differences between single and multirooted teeth and between shallow (5-6 mm) and deep pockets (≥7 mm) at the baseline. CONCLUSION: Nonsurgical periodontal therapy with MINST achieved satisfactory results that were better than expected based on the scientific literature. Single-rooted and shallow pockets showed the best proportion of pocket closure at the reevaluation after treatment. CLINICAL SIGNIFICANCE: Minimally invasive nonsurgical techniques can be the treatment of choice when approaching periodontally diseased patients with nonsurgical periodontal therapy.