MiR-26a and miR-191 are upregulated while PLAG1 and HIF2 are downregulated in pleomorphic adenomas of the salivary glands compared to Warthin tumors.

BACKGROUND: Salivary gland tumors (SGTs) are a heterogenous group of pathologies, which still represents a challenge regarding differential diagnosis and therapy. Although histological findings govern SGTs management, detection of molecular alterations is emerging as an effective additional tool. The aim of this study was to analyze the relative expression levels of three micro RNAs (miR-26a, miR-26b, and miR-191), and three pro-oncogenic molecular markers (PLAG1, MTDH, and HIF2) in SGTs and normal salivary gland (NSG) tissues and evaluate them as potential differential diagnosis markers. METHODS: This cross-sectional study included 58 patients with SGTs (23 pleomorphic adenomas, 27 Warthin tumors, and 8 malignant SGTs) and 10 controls (normal salivary gland tissues). Relative gene expression levels of all investigated molecules were determined by reverse transcriptase-real-time polymerase chain reaction. RESULTS: All three micro RNAs exhibited highest expression levels in benign SGTs, whereas miR-26a And miR-191 were significantly more expressed in PAs compared to WTs (p = 0.045 and p = 0.029, respectively). PLAG1 And HIF2 were both overexpressed in WTs compared to PAs (p = 0.048 and p = 0.053, respectively). Bioinformatic analysis suggested that all investigated micro RNAs function as negative regulators of MTDH. CONCLUSION: The results of this study suggest that all three micro RNAs have a considerable negative impact on MTDH oncogene expression in malignant tumors, while the differences between levels of miR-26a, miR-191, PLAG1, and HIF2 in PA and WT represent possible differential diagnosis markers.

Management of maxillofacial trauma in the elderly: A European multicenter study.

BACKGROUND/AIMS: Management of maxillofacial trauma in the geriatric population poses a great challenge due to anatomical variations and medical comorbidities. The aim of this study was to analyze the management variables, timing, and outcomes of facial fractures in elderly patients (aged 70 years or more) at several European departments of oral and maxillofacial surgery. MATERIALS AND METHODS: This study was based on a systematic computer-assisted database that allowed the recording of data from all geriatric patients with facial fractures from the involved maxillofacial surgical units across Europe between 2013 and 2017. RESULTS: A total of 1334 patients were included in the study: 665 patients underwent closed or open surgical treatment. A significant association (P < .005) was found between the presence of concomitant injuries and a prolonged time between hospital admission and treatment. The absence of indications to treatment was associated with comorbidities and an older age (P < .000005). CONCLUSIONS: Elderly patients require specific attention and multidisciplinary collaboration in the diagnosis and sequencing of trauma treatment. A prudent attitude may be kept in selected cases, especially when severe comorbidities are associated and function is not impaired.

Immunohistochemical expression of caspases 9 and 3 in adenoid cystic carcinoma of salivary glands and association with clinicopathological parameters.

PURPOSE: Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. It is characterized by a high rate of recurrence, perineural invasion and development of distant metastases many years after removal of the primary tumor. Disorders of the induction of apoptosis and its cascade reactions where caspases are involved may be significant in the pathogenesis of this tumor. METHODS: The immunohistochemical expression of caspase 9 and caspase 3 was analyzed by tissue microarray (TMA) in 50 cases of ACC in relation with different clinicopathological parameters (gender, age, localization, histological type and overall survival). RESULTS: Caspase 9 was expressed in the cytoplasm and nuclei of ACC tumor cells with varying degrees of staining intensity (1+, 6%; 2+, 54%, 3+, 40%). Comparison of caspase 9 expression in tumor cells with clinicopathological parameters (gender, age, localization, histological type and overall survival) showed no statistically significant difference except that the expression was more pronounced in females. Caspase 3 was expressed in the cytoplasm of tumor cells with varying degrees of staining intensity (1+, 22%; 2+, 36%; 3+, 42%). No correlation between the expression of caspase 3 and clinicopathological parameters was noticed. CONCLUSIONS: The expression of caspases 9 and 3 in ACC of the salivary glands can contribute in the better characterization of molecules involved in apoptosis of tumor cells.

Methylation of tumour suppressor genes in benign and malignant salivary gland tumours: a systematic review and meta-analysis.

The aim of the present systematic review was to critically analyse the relationship between tumour suppressor genes (TSGs) promoter methylation, a potent mechanism of gene silencing, and the development of salivary gland tumours, as well as the possible effect on clinical/histological characteristics. Review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (registration ID CRD42020218511). A comprehensive search of Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials was performed utilizing relevant key terms, supplemented by a search of grey literature. Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for the quality assessment of included studies. Sixteen cross-sectional and 12 case-control studies were included in the review, predominantly dealing with methylation in TSGs related to DNA repair, cell cycle, and cell growth regulation and differentiation. Quantitative synthesis could be performed on P16 (inhibitor of cyclin-dependent kinase 4a), RASSF1A (Ras association domain family 1 isoform A) and MGMT (O6-methylguanine DNA methyltransferase) genes only. It showed that P16 and RASSF1A genes were more frequently methylated in salivary gland tumours compared to controls (P = .0002 and P < .0001, respectively), while no significant difference was observed for MGMT. Additionally, P16 did not appear to be related to malignant transformation of pleomorphic adenomas (P = .330). In conclusion, TSG methylation is involved in salivary gland tumour pathogenesis and several genes might play a considerable role. Further studies are needed for a better understanding of complex epigenetic deregulation during salivary gland tumour development and progression.

Epidemiological, clinical, and forensic aspects of chainsaw, circular saw, and grinding saw injuries in the maxillofacial region.

The aim of this article was the epidemiological, clinical, and forensic evaluation of the chainsaw, circular saw, and grinding saw maxillofacial injuries. A retrospective analysis of the medical records at the Clinic of Maxillofacial Surgery, School of Dentistry, University of Belgrade, was performed. A total of 133 patients were treated during a period of 19 years (1989-2008). Grinding saw injuries were more frequent (62%) in comparison to chainsaw and circular saw injuries that were present in 23% and 15% of patients, respectively. All injured individuals were men, and most of them were aged 31 to 40 years. Accident by self injuring was the only mechanism of all the analyzed injuries. There were no suicide or homicide attempts. Isolated injuries of the facial soft tissues, which were mainly lacerations, were present in most patients. Less frequently, soft tissues injuries were compounded with bone fractures of the face and teeth injuries. Surgical debridement, revision, and suturing were performed in all patients where only soft tissues were injured. Patients with compound injuries of the soft tissues, facial bones, and teeth were treated according to the common surgical protocol for the type of the injuries. Most often, these injuries were accidental without fatalities. The number of these injuries increased in the recent years owing to the "do-it-yourselfers" for home hobbies. To avoid these types of injuries, users should be carefully instructed, and attention should be paid to the use of accurately guarded saws and appropriate safety equipment.

Surgical management of unilateral body fractures of the edentulous atrophic mandible.

INTRODUCTION: Management of body fractures in patients with edentulous atrophic mandibles represents a challenging task due to patient's age, medical comorbidities, poor bone quality, and vascularity, as well as reduced contact area between the fracture ends. The aim of the study was to assess the demographic and clinical variables, the surgical technique, and outcomes of unilateral body fractures of the edentulous atrophic mandible managed at several European departments of oral and maxillofacial surgery. METHODS: This study is based on a systematic computer-assisted database that allowed the recording of data of all patients with fractures of the atrophic edentulous mandible from the involved maxillofacial surgical units across Europe between 2008 and 2017. The following data were recorded for each patient: gender, age, comorbidities, etiology, synchronous body injuries, degree of atrophy of the mandible according to Luhr classification, type of surgical approach and fixation, length of hospitalization, and presence and type of complications. RESULTS: A total of 43 patients were included in the study: 17 patients' mandibles were classified as class I according to Luhr, 15 as class II, and 11 as class III. All patients underwent open reduction and internal fixation by extraoral approach in 25 patients, intraoral in 15 patients, and mixed in 3 patients. A single 2.0 miniplate was used in 16 patients, followed by a single 2.4 reconstruction plate in 13 patients, by two 2.0 miniplates, and three 2.0 miniplates. Outcome was considered to be satisfying in 30 patients, with no complications. Complications were observed in 13 cases. CONCLUSIONS: Treatment of unilateral body fractures of the edentulous mandible must still be based on the type of fracture, degree of atrophy, experience of the surgeon, and patients' preference. An adequate stability can be obtained by different plating techniques that have to be appropriately tailored to every single specific patient.

The epidemiology of edentulous atrophic mandibular fractures in Europe.

INTRODUCTION: The objective of the present study was to assess the demographic variables, causes, and patterns of edentulous atrophic fractures of the mandible managed at several European departments of oral and maxillofacial surgery. The results of this multicenter collaboration over a 10-year period are presented. METHODS: The data of all patients with fractures of the atrophic edentulous mandible from the involved maxillofacial surgical units across Europe between January 1, 2008, and December 31, 2017 were recorded: gender; age; voluptuary habits; comorbidities; etiology; fracture sites; synchronous body injuries; atrophy of the mandible according to Luhr classification; eventual type of treatment; timing of the eventual surgery; length of hospital stay. RESULTS: A total of 197 patients (86 male and 111 female patients) with 285 mandibular fractures were included in the study. Mean age of the study population was 75 years. Statistically significant associations were found between Luhr classes I - II and condylar fractures on one hand (p < .0005), and between Luhr class III and body and parasymphyseal fractures on the other hand (p < .05). Finally, 135 patients underwent open reduction and internal fixation, 56 patients did not undergo any intervention, and 6 patients underwent closed reduction. No statistically significant association was observed between treatment, timing of treatment, comorbidities, and concomitant injuries. CONCLUSIONS: The management of edentulous atrophic mandibular fractures remains challenging. Treatment decisions should continue to be based on the clinician's previous experience and on the degree of bone resorption in edentulous mandible in relation to fracture subsites.

P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population.

OBJECTIVE: To investigate the prevalence of p16INK4 a, p14ARF, tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. STUDY DESIGN: DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing. RESULTS: The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P<.001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P< .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively). CONCLUSIONS: Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters.

High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors.

OBJECTIVES: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. MATERIALS AND METHODS: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. RESULTS: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms - between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P=0.00), and significantly decreased in comparison to the carcinoma group (P=0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P=0.044 and P=0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P=0.013). CONCLUSION: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and p14(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands.

[Positional changes of the lower and upper anterior teeth after surgical correction of mandibular prognathism].

BACKGROUND/AIM: To establish the influence of surgical corrections of mandibular prognathism upon the position of the lower and upper anterior teeth (incisors). METHODS: The changes in position of the lower and upper anterior teeth (incisors) after the surgical correction of mandibular prognathism were analyzed by means of x-ray craniometry in 183 patients (female: n = 110, male: n = 73) in which the correction had been made in accordance with the principles of sagital osteotomy of the mandibular ramus. There were 4 angular and 2 linear parameters determined in the pre- and postoperative tele-x-ray-pictures. The changes of these parameters were tested by means of the parametric statistic tests. RESULTS: The performed surgical procedures did not cause statistically significant changes in the angular parameters. The changes of both linear parameters were thought highly statistically significant. CONCLUSION: Under the influence of the performed surgical procedures no changes were found in the position of anterior teeth (incisors) in relation to SN and the mandibular plane. They were actually moved along with the medium fragment of the lower jaw and that fragment was moved linearly backwards along the occlusal plane with a practically insignificant rotation in the cranial direction.