Predictors of malignant transformation in oral leukoplakia and proliferative verrucous leukoplakia: An observational prospective study including the DNA ploidy status.

BACKGROUND: This prospective observational study investigated the determinants of malignant transformation (MT) in localized oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL). METHODS: Demographic, clinical, histological, and DNA ploidy status data were collected at enrolment. Survival analysis was performed (MT being the event of interest). RESULTS: One-hundred and thirty-three patients with OL and 20 patients with PVL entered the study over 6 years (mean follow-up 7.8 years). The presence of OED, DNA ploidy, clinical presentation, and lesion site were associated with MT in patients with OL in a univariate analysis. In a multivariate model, OED was the strongest predictor of MT in patients with OL. Adding DNA ploidy increased the model's predictive power. None of the assessed predictors was associated with MT in patients with PVL. CONCLUSIONS: DNA ploidy might identify a subset OL with low risk or minimal risk of MT, but it does not seem to be a reliable predictor in patients with PVL.

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 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.

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.

Gingival Overgrowths Revealing PTEN Hamartoma Tumor Syndrome: Report of Novel PTEN Pathogenic Variants.

PTEN hamartoma tumor syndrome (PHTS), is a spectrum of disorders caused by mutations of PTEN, in which non-cancerous growths, called hamartomas, develop in different areas of the body, often including the oral mucosa. PHTS also implies a recognized increased risk of malignancies, as PTEN is a tumor suppressor gene capable of inhibiting progression of several cancers. One of the main and most common clinical manifestation of PHTS are gingival overgrowths presenting as warty lumps. The current study describes patients with gingival or mucosal enlargements leading to the diagnosis of PHTS associated to novel PTEN pathogenic variants. Patients referred to us for gingival lumps suggestive of PHTS associated overgrowths were submitted to genetic analysis in the PTEN gene. Two related and two unrelated patients were investigated. PTEN novel pathogenic variant was found in all of them. Two patients also fulfilled diagnostic criteria of Cowden syndrome (CS). Mucocutaneous lesions, and particularly diffuse gingival overgrowths, are both early and major clinical signs revealing a potential diagnosis of PHTS. Further genetic and clinical assessments are needed in order to confirm and clarify the diagnosis within the PHTS spectrum, including, among others, the CS. A correct interpretation of oral clinical features potentially associated to PHTS is mandatory for diagnosis and a surgical approach can be useful just in case of impairment of periodontal health or for aesthetic needs. The increased risk of malignancies associated to PHTS makes a correct diagnosis pivotal to set up an appropriate lifelong surveillance, aiming at secondary cancer prevention.

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.

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.

A multicenter observational study on Medication-Related Osteonecrosis of the Jaw (MRONJ) in advanced cancer and myeloma patients of a cancer network in North-Western Italy / Un estudio observacional multicéntrico sobre osteonecrosis relacionada con medicamentos de la mandíbula (MRONJ) en pacientes con cáncer avanzado y mieloma de una red contra el cáncer en el noroeste de Italia

Background: Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) related to cancer and myelomatreatments is undetermined, with scarce data varying from 2 to 7.8/million/year in limited investigated popula-tions. A 9-years [2009-2018] regional-wide survey was conducted, deploying the North-Western Italy Cancer Net-work (“Rete Oncologica Piemonte e Valle d’Aosta”), to assess number and main characteristics of MRONJ casesamong myeloma/cancer patients, within a population of 4.5 million inhabitants.Material and Methods: MRONJ cases were collected retrospectively from January 2009 to June 2015; from July2015 to December 2018, data were collected prospectively. Number of new MRONJ cases per year, underlyingdisorder, drug(s) administered, treatment duration, site and onset timing of MRONJ were detailed.Results: 459 MRONJ cases were identified. Primary diseases were breast cancer (46%), prostate cancer (21%),myeloma (19%), and other types of carcinoma (14%). Patients received antiresorptive treatment either alone (399;88.47%) or in combination with biological agents (52; 11.53%); 8 patients (1.7%) received only antiangiogenicdrugs. Zoledronic acid [388] and denosumab [59] were the most frequently administered drugs. Mandible was involved in 296 (64,5%) cases. Number of new MRONJ cases was stable from 2009 to 2015, with a mean of 51.3 casesper year (raw incidence: 11.6/million/year), declining in the 2016-2018 years to 33.3 cases per year (raw incidence:7.5/million/year).Conclusions: With such discrepancy of cases overtime being partially explicable, number of new MRONJ cases peryear are consistent with those observed in a previous study [2003-2008] in the same region, being instead higher thanthose reported in other populations.(AU)

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.

Clinical validation of 13-gene DNA methylation analysis in oral brushing samples for detection of oral carcinoma: Italian multicenter study.

BACKGROUND: The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. METHODS: Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. RESULTS: DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative. CONCLUSION: These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.

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.

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.

Interobserver and intraobserver variability affecting the assessment of loss of autofluorescence of oral mucosal lesions.

OBJECTIVES: The assessment of loss of tissue autofluorescence (LAF) has been proposed as an adjunct to comprehensive oral examination to enhance the detection of mucosal lesions harbouring dysplasia or carcinoma. The assessment of LAF is not based on completely objectified parameters therefore intraobserver and interobserver variability cannot be neglected alongside the issue of correct interpretation of LAF. The present study evaluated intraobserver and interobserver variability in the clinical assessment of LAF as performed by oral medicine practitioners (OMPs) or general dental practitioners (GDPs). MATERIALS AND METHODS: Couples of clinical pictures, acquired under white incandescent dental operatory light and during the assessment of LAF performed by VELscope were retrieved. Four OMPs and eight GDPs were asked to assess the pictures and to score the LAF. Kappa statistics allowed the assessment of intra- and inter-observer related variability. RESULTS: Pictures of 109 lesions representative of all oral mucosal sites and clinical appearances were selected. OMPs had a better intraobserver agreement than GDPs (substantial versus moderate). The moderate (k = 0.506) interobserver agreement observed among both OMPs and GDPs in a 2-score model (positive versus negative), lowered down to poor values only among GDPs when a 3-score or 4-score model (including uncertain judgements) was applied. CONCLUSIONS: A good agreement (k>0.8) was never observed and the present results are similar to previously reported data about conventional oral examination. Irrespective of the diagnostic accuracy, the assessment of AF seems not to be able to improve observer-related variability in the clinical assessment of oral mucosal lesions.

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

PURPOSE: To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. CONCLUSIONS: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.

World Workshop on Oral Medicine VII: Functional pathways involving differentially expressed lncRNAs in oral squamous cell carcinoma.

Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.

World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review.

BACKGROUND: Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis. OBJECTIVES: To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma. METHODS: PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival. RESULTS: Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs. CONCLUSIONS: Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.