Leukocyte and platelet rich fibrin in the management of medication-related osteonecrosis of the jaw: A systematic review and meta-analysis.

BACKGROUND: Osteonecrosis of the jaw (ONJ) has a frequent adverse effect after the administration of nitrogenous bisphosphonates, as non-nitrogenous bisphosphonates are metabolized more rapidly and would produce this effect to a lesser extent. The objective of this study is to analyze the results obtained in the literature with the use of L-PRF in the treatment of ONJ through a systematic review and meta-analysis. MATERIAL AND METHODS: Medline (via PubMed), Cochrane, Web of Science and Grey Literature Database was screened from which 10 were selected. RESULTS: In the meta-analysis with full resolution, combining the use of L-PRF in the treatment of ONJ, a weighted proportion (PP) of 94.3% of complete resolution is obtained (95% CI: 91.2-97.4, p<0.001), with a low degree of heterogeneity, statistically significant (I2 = 29.02%; p<0.001). When analyzing the non-resolution data, a weighted proportion (PP) of 7.7% (95% CI: 3.6-11.9; p<0.001) was obtained with moderate heterogeneity (I2: 41.87%; p=0.112). In the meta-regression, no significant correlation was found between complete resolution and year of publication (intercept = 2.88, p=0.829). In consistency analysis no major changes in PP are identified when any of the studies are eliminated, demonstrating a high reliability in the combined results. CONCLUSION: L-PRF alone or in combination with other therapies in treatment of ONJ achieved high percentages of complete lesion resolution (94.3%). In studies where L-PRF is combined with other therapies, and where the effectiveness of the other therapy alone is analyzed, L-PRF has been shown higher percentages of resolution.

Management options for low-dose methotrexate-induced oral ulcers: A systematic review.

BACKGROUND: Oral ulcers caused by methotrexate (MTX) at low doses are a known side effect of this drug. Although increasingly more patients are medicated with MTX, these painful ulcers, without traumatic origin and resistant to any type of treatment, are not usually identified by health professionals as a side effect of the medication. MATERIAL AND METHODS: In the absence of a consensus protocol for the effective treatment of oral lesions produced by MTX, the objective of this article was to review and analyse the information from articles related to oral ulcers produced by low-dose MTX and to record the clinical management performed and the MTX dose given to the patient. Data sources - Medline, Web of Science, and Cochrane Library. Participants - Patients treated with low-dose MTX (less than 25 mg/week). Interventions - Management of oral lesions caused by MTX. Study eligibility criterion, study appraisal and synthesis method: An initial search was carried out in the aforementioned databases with the terms 'methotrexate AND oral OR ulcer'. The search was carried out using both medical subject heading (MeSH) terms and a free search between January 2003 and January 2018. Of the results obtained, two independent researchers analysed abstracts that met the search criteria, that is, those that mentioned oral ulcers produced by MTX at low doses. Next, both researchers read the complete article and determined whether it met the following inclusion criteria: written in English, specified the dose of MTX prescribed for the patient and specified the protocol of action for the ulcers. A third investigator acted as a mediator in cases of dispute. Agreement was calculated using Cohen's kappa coefficient, with a k value of 0.82. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide for systematic reviews was used. RESULTS: The initial search resulted in a total of 66 articles, of which 30 were selected to assess their inclusion in this study. Finally, 16 met the inclusion criteria. Using the Pierson and Newcastle-Ottawa scales and Bradford Hill criteria modified for studies of case series and "in relation to a case", 2 were rated as high quality, 2 were rated as low quality and 12 were rated as medium quality. The limitations of this study are based on the fact that all of the articles available to carry out the systematic review were "in relation to a case or series of cases", with the heterogeneity of data that this implies. CONCLUSIONS: Evidence on the management of oral ulcers in the oral cavity produced by MTX at low doses is scarce due to the heterogeneity of data and the measures adopted in the selected studies. Therefore, it seems that this management is relegated to the perception of the clinician rather than to a specific protocol of action. Studies with a longer follow-up duration and larger sample size are needed to guide different health professionals on the management of these lesions.

Expression of ATP6V1C1 during oral carcinogenesis.

We investigated the gene and protein expressions of V-type ATPase protein subunit C1 (ATP6V1C1) in cases of oral squamous cell carcinoma (OSCC) and contralateral normal mucosa in smokers, nonsmokers and former smokers. Subjects were separated into five groups of 15: group 1, smokers with OSCC; group 2, normal contralateral mucosa of OSCC patients; group 3, chronic smokers; group 4, former smokers who had stopped smoking 1 year earlier; group 5, individuals who had never smoked. Exfoliative cytology specimens from oral mucosa of smokers, former smokers and nonsmokers showed normal gene and protein expression. We found significantly greater gene expression in the OSCC group than in the nonsmoker groups. No difference in gene expression was observed between normal contralateral mucosa and nonsmoker groups, smoker and nonsmoker groups or former smoker and nonsmoker groups. We observed intense immunostaining for ATP6V1C1 protein in all cases of OSCC and weak or no staining in smoker, former smoker and nonsmoker groups. Significantly greater expression of ATP6V1C1 protein was observed in the OSCC group compared to the other groups, which supports the role of ATP6V1C1 in effecting changes associated with oral cancer. Analysis of the mucosae of chronic smokers, former smokers and the normal contralateral mucosa of patients with OSCC showed unaltered ATP6V1C1 gene and protein expression. Early stages of carcinogenesis, represented by altered epithelium of chronic smokers, had neither gene nor protein alterations as seen in OSCC. Therefore, we infer that the changes in ATP6V1C1 occur during later stages of carcinogenesis. Our preliminary study provides a basis for future studies of using ATP6V1C1 levels for detecting early stage OSCC.

HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is being described for the first time in this study. A combination of O6-methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a possible biomarker in therapy choice. Interestingly, survival data shows a similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen methylation rates of different genes and evaluate the association between genes methylation and clinicopathologic variables. Our study is the first of its kind to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of methylated ones) and could be new markers in the study of GBM prognosis, especially in the therapy selection.

Adjuvant treatment with infusional 5-fluorouracil in high risk adenocarcinoma of the stomach or gastroesophageal junction.

PURPOSE: In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme. METHODS: We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m(2) iv with leucovorin 200 mg/m(2) iv and 1200 mg/m(2) in 46-hour infusion of 5-fluorouracil (D'Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m(2)/day and four additional infusions of chemotherapy one month after complete radiochemotherapy. RESULTS: Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3-102.1 months), and the 3-year survival rates were 52.7 %. CONCLUSIONS: This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results.