Challenging management of gingival squamous cell carcinoma: a 10 years single-center retrospective study on Northern-Italian patients.

BACKGROUND: Aim of this study was to describe the outcome of patients with gingival squamous cell carcinoma (GSCC), and to recognize aspects affecting clinical course and to consider survival rate. MATERIAL AND METHODS: The case records of patients, over a 10-year period, were retrospectively examined. Differences in distribution of the potential risk factors by prognosis were investigated through non-parametrical tests (Wilcoxon Rank-Sum and Fisher's Exact). Survival curves for age, therapy and stage were built by the Kaplan-Meier method and compared with Log-Rank test. RESULTS: 79 patients were analysed. Significant increase in mortality for patients older than 77 and for those with advanced stages was found. Cumulative survival rate 5 years after the diagnosis was 43%, while at 10 years was of 11%. CONCLUSIONS: With a statistical relationship between age and tumour stage with survival rates, and 70% of GSCC cases identified as stage IV, early GSCC diagnosis remains challenging.

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.

BACKGROUND: Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) related to cancer and myeloma treatments is undetermined, with scarce data varying from 2 to 7.8/million/year in limited investigated populations. A 9-years [2009-2018] regional-wide survey was conducted, deploying the North-Western Italy Cancer Network ("Rete Oncologica Piemonte e Valle d'Aosta"), to assess number and main characteristics of MRONJ cases among 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 July 2015 to December 2018, data were collected prospectively. Number of new MRONJ cases per year, underlying disorder, 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 antiangiogenic drugs. 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 cases per 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 per year are consistent with those observed in a previous study [2003-2008] in the same region, being instead higher than those reported in other populations.

Can atrophic-erosive oral lichen planus promote cardiovascular diseases? A population-based study.

OBJECTIVE: Lichen planus has been recently associated with an increased risk of cardiovascular diseases (CVDs). The oral manifestations can be divided into white hyperkeratotic lesions (WL) and atrophic and erosive lesions (RL). The aim of this report was to compare the presence of CVDs between patients affected by WL or RL, to test the hypothesis that RL are associated with an increased incidence of CVDs. SUBJECTS AND METHODS: Patients were analysed through a complete collection of all the risk factors for CVDs. The primary endpoint was the occurrence of a cardiovascular event-acute coronary syndrome (ACS), any revascularization or stroke/TIA. A multivariable logistic regression model, adjusted for age at diagnosis, body mass index, smoking, alcohol consumption, diabetes, hypertension, CVDs familiarity and periodontitis, was performed. RESULTS: A prospective cohort of 307 patients has been evaluated; 185 (60.3%) had WL and 122 RL (39.7%). Twenty-four patients had a CVD. ACS occurred more frequently in RL (adjusted odds ratio 5.83; 95% CI: 1.16-29.39), mainly due to the higher risk of it after the histological diagnosis of Oral lichen planus OLP (odds ratio 4.23; 95% CI: 0.66-27.23). CONCLUSION: Patients with RL could possibly have a higher risk of developing ACS. Further analysis on larger cohort is however warranted.

Randomized, placebo-controlled, double-blind trial of clobetasol propionate 0.05% in the treatment of oral lichen planus.

OBJECTIVE: To perform a randomized, placebo-controlled, double-blind study, with a follow-up period of 6 months, for the use of topical clobetasol in cases of symptomatic oral lichen planus (OLP). SUBJECTS AND METHODS: Thirty-two participants were analyzed, with the aims of: (I) to compare the usefulness of topically applied clobetasol propionate 0.05% (mixed with 4% hydroxyethyl cellulose gel) and 4% hydroxyethyl cellulose gel alone (considered as placebo) in the management of OLP; (II) to describe which of them is quicker in decreasing signs and reported symptoms, and (III) which is able to give the proper longer remission in the follow-up. RESULTS: Symptoms improved in all clobetasol-treated patients during the first 2 months of therapy, while only 50% of placebo control group (p = .005) displayed similar results; of the remaining half, 12.5% did experienced a worsening while 37.5% remained stable. Regarding clinical signs, 87.5% of clobetasol-treated patients improved, while only 62.5% of the placebo-treated patients had a positive response (p = .229). CONCLUSIONS: It is possible to report that clobetasol, at this dosage, has been more effective than a placebo at provoking symptoms improvement in subjects affected by atrophic-erosive oral lesions.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Describing the gingival involvement in a sample of 182 Italian predominantly oral mucous membrane pemphigoid patients: A retrospective series.

BACKGROUND: The oral cavity has been frequently described as the only site of involvement or as the first manifestation of mucous membrane pemphigoid (MMP), being the gingival tissues often involved, but usually this has been effusively detailed in limited case series. This is a retrospective evaluation of the gingival involvement in 182 Italian patients with oral MMP. MATERIAL AND METHODS: The diagnosis of MMP was established by both clinical morphology and direct immunofluorescence finding. Patient information (age, gender, risk factors and medical status) and parameters of manifestation (lesions' distribution, site and type) were detailed. RESULTS: The mean age was 62 years for women (n=137) and 67 years for men (n=45). Patients had several sites of oral involvement; the gingiva was the most common one, affecting 151 patients (82.96%; 119 f - 32 m). Female subjects had more possibilities to develop gingival lesions than male patients (P = 0.005). Sixty-five patients (35.7%; 58 f - 7 m) had pure gingival involvement. Patients with lower gingival involvement statistically had more complaints (P = 0.006). CONCLUSIONS: This report is one of the largest about predominantly oral MMP cases, detailing the very frequent gingival involvement; this could be crucial not only for oral medicine specialists but also for primary dental healthcare personnel and for periodontists.

A report on the clinical-pathological correlations of 788 gingival lesion.

BACKGROUND: The diagnosis and treatment of a variety of non-plaque related gingival diseases have become an integrated aspect of everyday dentistry. The aim of this study was to analyse the relationship between clinical appearance and histopathological features of gingival lesions in a large Northern Italian population. MATERIAL AND METHODS: A retrospective study of 788 cases of gingival and alveolar mucosal biopsies was set up. Statistical analysis was performed by calculating the odds ratio and 95% confidence interval (C.I.), in order to assess the degree of association between the clinical parameters considered (primary lesions) and the single pathologies, statistically evaluated by Mantel-Haenszel tests. The correlation between clinical and histological diagnosis was classified as follow: 1) expected data (ED): provisional clinical diagnosis; 2) real data (RD): final histopathology diagnosis; 3) concordant data (CD): correspondence between the expected data and real data. The correlation was calculated as follow: CC (complete concordance) = CD x 100 / ED, this expressing the percentage in which the clinical and the histological diagnosis overlapped. RESULTS: The most frequently observed and biopsied primary lesions resulted to be exophytic, followed by mucosal colour changes and finally by losses of substance. The statistically significant association between primary lesion and their manifestation in gingival pathologies was reported. Volume increases, for instance, were positively correlated to plasma cell epulis, pyogenic granuloma, fibrous reactive hyperplasia and hemangioma. Verrucous-papillary lesions were most often seen in verrucous carcinoma, verrucous leukoplakia and mild dysplasia. White lesion resulted to be related to leukoplakia or oral lichen planus. Red lesions resulted to be related only oral lichen planus. Erosive vesicle-bullous lesions were linked to disimmune pathologies. Ulcerative lesions were positively associated to oral squamous cell cancer. Finally, potentially malignant disorders have the most percentage high concordance. Among the malignant lesions, the correlation increased up to the squamous cell carcinoma and leukaemia. CONCLUSIONS: This article presented the frequency and the clinico-pathological concordance of all primary lesions and the histopathological diagnosis of gingival lesions. For every primary lesion, it is possible to correlate a specific histopathological diagnosis in a statistical manner. This can be a valuable aid for not specialist clinicians who daily observe mucosae and have the opportunity to intercept major diseases.

Favourably effective formulation of sodium iodide and salicylic acid plus professional hygiene in patients affected by desquamative gingivitis.

The aim of this prospective pilot study was to evaluate the efficiency of an oral hygiene protocol, in combination with a solution of sodium iodide associated to salicylic acid (SISA), in patients affected by desquamative gingivitis (DG). Twenty patients not totally responding to conventional topical therapies, were selected. They received oral hygiene instructions with non-surgical periodontal therapy in a 21-day cohort study (during 3 weekly appointments). The SISA was used at the end of each session, with an impregnated gauze (with 5 ml of the solution) applied for 15 minutes for the upper jaw, and for a further 15 minutes with a new gauze for the lower. Evaluated clinical outcome variables included the full mouth plaque (FMPS) and bleeding (FMBS) scores, probing depth, patient related outcome and clinical gingival signs. Two months after concluding the planned protocol, a statistically significant reduction was observed for FMPS (P=0.032), FMBS (P=0.038), reported pain (P=0.000) and gingival clinical improvement (P=0.005). Topical application of SISA and professional oral hygiene procedures are connected with improvement of gum status, and decrease of related pain in subjects affected by severe DG.

Pimecrolimus vs. tacrolimus for the topical treatment of unresponsive oral erosive lichen planus: a 8 week randomized double-blind controlled study.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease, affecting nearly 1-2% of the population; Proposed therapies are usually symptomatic and numerous drugs have been used, but recently, it has been published that there is insufficient evidence to support the effectiveness of any specific treatment as being superior. To the best of our knowledge, direct evaluation of the efficacy of topically applied pimecrolimus and tacrolimus in the treatment of atrophic-erosive OLP, refractory to topical steroids, is still lacking. OBJECTIVES: To assess the efficacy and safety of topical calcineurin inhibitors for unresponsive OLP. An 8 week randomized, double-blind controlled trial, followed by a 6 month follow-up period. Patients were treated with either pimecrolimus 1% cream or tacrolimus 0.1% ointment, both mixed with an equivalent amount of 4% hydroxyethyl cellulose gel. The medications were to be applied twice daily for 2 months. Each patient was examined at the beginning of therapy, and then every 2 weeks during the treatment and every 3 months of follow-up. Main outcome measures were: (i) to compare the effectiveness of topically applied pimecrolimus and tacrolimus; (ii) to evaluate which is more cost-effective; (iii) to determine which drug is faster in reducing signs and symptoms and (iv) which gives the longest remission. RESULTS: Thirty patients were involved in the study. Both drugs were effective at inducing clinical improvement, with no statistical difference. Pimecrolimus creams revealed a significantly better stability of the therapeutic effectiveness (P = 0.031). CONCLUSION: Both medications would currently appear to be a treatment of choice for patients with unresponsive atrophic-erosive OLP. Pimecrolimus seemed to be more effective in providing long-term resolution of signs and symptoms. Future efforts are however needed to obtain more objective evidence of the benefit of these medications in the treatment of immunologically mediated oral mucosal lesion.

Urban legends series: oral leukoplakia.

To date, the term oral leukoplakia (OL) should be used to recognize 'predominantly white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk of cancer'. In this review, we addressed four controversial topics regarding oral leukoplakias (OLs): (i) Do tobacco and alcohol cause OLs?, (ii) What percentage of OLs transform into oral squamous cell carcinoma (OSCC)?, (iii) Can we distinguish between premalignant and innocent OLs?, and (iv) Is proliferative verrucous leukoplakia (PVL) a specific entity or just a form of multifocal leukoplakia? Results of extensive literature search suggest that (i) no definitive evidence for direct causal relationship between smoked tobacco and alcohol as causative factors of OLs, (ii and iii) the vast majority of OLs follow a benign course and do not progress into a cancer, and no widely accepted and/or validated clinical and/or biological factors can predict malignant transformation, and (iv) the distinction between multifocal/multiple leukoplakias and PVL in their early presentation is impossible; the temporal clinical progression and the high rate of recurrences and development of cancer of PVL are the most reliable features for diagnosis.

Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients.

OBJECTIVES: The aim of this prospective case series was to assess the clinical efficiency of an oral hygiene protocol in patients affected by mucous membrane pemphigoid (MMP) with specific gingival localization, before starting any medical treatment. METHODS: Patients received oral hygiene instruction followed by non-surgical periodontal therapy including oral hygiene instructions in a 3-week cohort study. Clinical outcome variables were recorded at baseline and 5 weeks after intervention and included, as periodontal parameters, full mouth plaque (FMPS) and bleeding (FMBS) scores and patient-related outcomes (visual analogue score of pain). RESULTS: A total of 12 patients were recruited. The mean age at presentation was 59.5 ± 14.52 years. Five weeks after finishing the oral hygiene and periodontal therapy protocol, a statistical significant reduction was observed for FMPS (P = 0.001), FMBS (P = 0.022) and reported pain (P = 0.0028). CONCLUSIONS: Professional oral hygiene procedures and non-surgical periodontal therapy are connected with improvement of gingival status and decrease in gingival-related pain, in female patients affected by MMP with specific gingival localization.

Vascular endothelial growth factor genetic polymorphisms and haplotypes in female patients with bisphosphonate-related osteonecrosis of the jaws.

OBJECTIVE: To investigate the polymorphisms of the vascular endothelial growth factor (VEGF) gene in relation to female patients who developed bisphosphonate-related osteonecrosis of the jaws (BRONJ). METHODS: Test subjects were 30 Italian female patients with BRONJ (Group A). Control subjects were 30 female patients with a history of intravenous bisphosphonate use without any evidence of osteonecrosis (Group B) and 125 unrelated healthy volunteers (Group C). Three single-nucleotide polymorphisms were investigated: -634 G>C, occurring in 5' untranslated region (UTR); +936 C>T, occurring in 3' UTR; and -2578 C>A of the promoter region. RESULTS: The frequency of the VEGF CAC (+936/-2578/-634) haplotype was increased in patients with BRONJ, compared with female disease-negative controls [odds ratio (OR) = 2.76, 95% CI = 1.09-4.94, P = 0.039; corrected P value: P(c) = 0.117], and was also increased compared with female healthy controls (OR = 2.11, 95% CI = 1.14-3.89, P = 0.024; corrected P value: P(c) = 0.072). The CC homozygotes of -634G>C of VEGF gene and AA homozygotes of -2578C>A have also been significantly correlated in female patients who developed BRONJ compared with healthy controls (OR = 2.04, 95% CI = 1.12-3.70, P = 0.008; corrected P value: P(c) = 0.024). CONCLUSIONS: These results suggest a possible haplotype effect of VEGF polymorphisms expression in BRONJ Italian female patients. Studies with different and larger populations possibly using TagSNP to represent all haplotypes within the VEGF gene are needed to further delineate the genetic contribution of this gene to BRONJ.

Periodontal status in oral mucous membrane pemphigoid: initial results of a case-control study.

OBJECTIVE: To evaluate the periodontal status of mucous membrane pemphigoid (MMP) patients and compare it with that of healthy controls. METHODS: A prospective study was undertaken to examine the impact of gingival MMP lesions on the human periodontium of 29 patients. Parameters evaluated included full mouth plaque score (FMPS), full mouth bleeding upon probing scores, probing depths (PD), gingival recession, clinical attachment level (CAL), mobility score, furcation involvement, number of missing teeth and Machtei criteria. RESULTS: All periodontal parameters recorded were increased in cases when compared to controls in univariate statistics. The mean differences between groups in PD (0.8±0.2mm, 95% CI 0.3-1.3), CAL (1.3±0.4mm, 95% CI 0.4-2.2), FMPS (41.0±6.2%, 95% CI 28.7-53.4), FMBS (16.2±6.6%, 95% CI 3.0-29.4) and tooth loss (2±1 teeth, 95% CI 1-3) were all statistically significant (P<0.01 for all). Substantial differences in domiciliary oral hygiene routines were observed (P<0.0001). In multivariate models when FMPS was included as covariate the difference between groups in all clinical periodontal parameters was no longer statistically significant. CONCLUSIONS: Our results showed that periodontal status is worse in MMP patients if compared with healthy controls due to a substantial difference in oral hygiene. Oral health should be promoted in MMP.

Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review.

OBJECTIVES: Human papillomavirus (HPV) in oral carcinoma (OSCC) and potentially malignant disorders (OPMD) is controversial. The primary aim was to calculate pooled risk estimates for the association of HPV with OSCC and OPMD when compared with healthy oral mucosa as controls. We also examined the effects of sampling techniques on HPV detection rates. METHODS: Systematic review was performed using PubMed (January 1966-September 2010) and EMBASE (January 1990-September 2010). Eligible studies included randomized controlled, cohort and cross-sectional studies. Pooled data were analysed by calculating odds ratios, using a random effects model. Risk of bias was based on characteristics of study group, appropriateness of the control group and prospective design. RESULTS: Of the 1121 publications identified, 39 cross-sectional studies met the inclusion criteria. Collectively, 1885 cases and 2248 controls of OSCC and 956 cases and 675 controls of OPMD were available for analysis. Significant association was found between pooled HPV-DNA detection and OSCC (OR = 3.98; 95% CI: 2.62-6.02) and even for HPV16 only (OR = 3.86; 95% CI: 2.16-6.86). HPV was also associated with OPMD (OR = 3.87; 95% CI: 2.87-5.21). In a subgroup analysis of OPMD, HPV was also associated with oral leukoplakia (OR = 4.03; 95% CI: 2.34-6.92), oral lichen planus (OR = 5.12; 95% CI: 2.40-10.93), and epithelial dysplasia (OR = 5.10; 95% CI: 2.03-12.80). CONCLUSIONS: The results suggest a potentially important causal association between HPV and OSCC and OPMD.

Frequency and severity of dental caries in foster care children of Turin, Italy: a retrospective cohort study.

AIM: Aim of this retrospective cohort study was to assess the frequency and severity of dental caries (DC) among foster care children in the city of Turin, in North West Italy, and to compare these data with those of a general paediatric population. MATERIALS AND METHODS: From May 2016 to September 2018, 75 paediatric subjects between the age of 4 and 12, located in 11 residential child care communities were recruited. Instructions were provided concerning oral health, caries and correlation with dietary habits. Oral and dental examination were carried out to establish frequency and severity of caries (not-penetrating, nPC, corresponding to the International Caries Detection and Assessment System (ICDAS) codes: 1-4, vs. penetrating, PC, corresponding to ICDAS codes: 5-6). Decayed, missed, filled teeth (DMFT) index was used. Data for comparison were acquired from the WHO Collaboration Center For Epidemiology and Community Dentistry of Milan (WHO-CCOMS), belonging to a nationwide sample of 2,141 Italian children. RESULTS: Only 13 subjects (17%) were caries-free; 187 caries were identified: 133 were PC, whereas 54 were nPC. Overall, 76% of the caries were found in deciduous teeth. Mean DMFT was 3.43 (D = 2.97; M = 0.24; F = 0.22). When the study data were compared to those from WHO-CCOMS, a significantly higher DMFT (3.43 vs 0.96; p <0.00001) and D (2.97 vs 0.62; p <0.00001) was detected. CONCLUSION: A significant higher frequency of caries in foster care children in Turin, Italy compared to the general population was detected.