Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands

Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomorphic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detection). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p LT 0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c-myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter polymorphisms represent susceptibility factors for the development of PAs in the Serbian population

Manual versus rigid intraoperative maxillo-mandibular fixation in the surgical management of mandibular fractures:A European prospective analysis

Purpose: Intraoperative stabilisation of bony fragments with maxillo-mandibular fixation (MMF) is an essential step in the surgical treatment of mandibular fractures that are treated with open reduction and internal fixation (ORIF). The MMF can be performed with or without wire-based methods, rigid or manual MMF, respectively. The aim of this study was to compare the use of manual versus rigid MMF, in terms of occlusal outcomes and infective complications. Materials and methods: This multi-centric prospective study involved 12 European maxillofacial centres and included adult patients (age ≥16 years) with mandibular fractures treated with ORIF. The following data were collected: age, gender, pre-trauma dental status (dentate or partially dentate), cause of injury, fracture site, associated facial fractures, surgical approach, modality of intraoperative MMF (manual or rigid), outcome (minor/major malocclusions and infective complications) and revision surgeries. The main outcome was malocclusion at 6 weeks after surgery. Results: Between May 1, 2021 and April 30, 2022, 319 patients-257 males and 62 females (median age, 28 years)-with mandibular fractures (185 single, 116 double and 18 triple fractures) were hospitalised and treated with ORIF. Intraoperative MMF was performed manually on 112 (35%) patients and with rigid MMF on 207 (65%) patients. The study variables did not differ significantly between the two groups, except for age. Minor occlusion disturbances were observed in 4 (3.6%) patients in the manual MMF group and in 10 (4.8%) patients in the rigid MMF group (p &gt; .05). In the rigid MMF group, only one case of major malocclusion required a revision surgery. Infective complications involved 3.6% and 5.8% of patients in the manual and rigid MMF group, respectively (p &gt; .05). Conclusion: Intraoperative MMF was performed manually in nearly one third of the patients, with wide variability among the centres and no difference observed in terms of number, site and displacement of fractures. No significant difference was found in terms of postoperative malocclusion among patients treated with manual or rigid MMF. This suggests that both techniques were equally effective in providing intraoperative MMF.</p

Epidemiology of maxillofacial trauma in the elderly: a European multicenter study

ABSTRACT Introduction: The progressive aging of European population seems to determine a change in the epidemiology, incidence and etiology of maxillofacial fractures with an increase in the frequency of old patients sustaining craniofacial trauma. The objective of the present study was to assess the demographic variables, causes, and patterns of facial fractures in elderly population (with 70 years or more). Materials and Methods: The data from all geriatric patients (70 years or more) with facial fractures between January 1, 2013, and December 31, 2017, were collected. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, etiology, site of facial fractures, synchronous body injuries, Facial Injury Severity Score (FISS). Results: A total of 1334 patients (599 male and 735 female patients) were included in the study. Mean age was 79.3 years, and 66% of patients reported one or more comorbidities. The most frequent cause of injury was fall and zygomatic fractures were the most frequently observed injuries. Falls were associated with a low FISS value (p<.005). Concomitant injuries were observed in 27.3% of patients. Falls were associated with the absence of concomitant injuries. The ninth decade (p <.05) and a high FISS score (p <.005) were associated with concomitant body injuries too. Conclusions: This study confirms the role of falls in the epidemiology of facial trauma in the elderly, but also highlights the frequency of involvement of females, and the high frequency of zygomatic fractures.Peer reviewe

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 Pl4(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. (C) 2015 Elsevier Ltd. All rights reserved

Incidence and clinical relevance of T(11;19) translocation in salivary gland mucoepidermoid carcinoma

Mucoepidermoid carcinoma (MEC) harbors a recurring t(11;19) translocation with an associated novel fusion oncogene-MECT1-MAML2. The CRTC1-MAML2oncogene disrupts normal cell-cycle and differentiation, contributing to tumor development. The objectives of this study were to establish the incidence of CRTC1-MAML2 fusion in Serbian patients and estimate its relevance as a genetic marker of MEC behavior. In this retrospective study, 20 cases of MEC of salivary glands were tested for the presence of CRTC1-MAML2 fusion using reverse transcriptase-polymerase chain reaction. Clinicopathological parameters and survival data were examined in relation to fusion status. The CRTC1-MAML2 fusion was detected in 40% of MECs and its presence was associated exclusively with low-intermediate grade tumor histology (P = 0.02) and favorable clinical outcome, with 100 % overall survival rate (P=0.046). The study has shown that the presence of the CRTC1-MAML2 fusion can serve as an additional diagnostic and prognostic marker for mucoepidermoid carcinomas

Medication-Related Osteonecrosis of the Jaws: Two Center Retrospective Cohort Studies

This retrospective cohort study aims to describe characteristics of patients with MRONJ, to identify factors associated with MRONJ development, and to examine variables associated with favourable outcome. Totally 32 patients were followed and observed: 21 females and 11 males, in the age range 35-84 in the period from 2009 to 2018. Clinical, radiological examination (Orthopantomograph and CBCT) and biopsy were performed in order to achieve diagnosis. Demographic and clinical variables were taken into consideration: sex, age, primary disease, medication type, mode of delivery, anatomic location, drug treatment duration, timing of tooth extraction, chemotherapy, presence of bone metastasis, aetiology of MRONJ, disease stage, and treatment modality. MRONJ developed under osteoporosis and malignant disease in 11 and 21 patients, respectively. MRONJ development was triggered by tooth extraction or trauma in 30 out of 32 cases, whereas the two patients developed MRONJ spontaneously. Stages I, II, and III were confirmed in 5 (16%), 18 (58%), and 9 (28%) patients, respectively. Mandible was affected in 23 (72%) patients. MRONJ was treated in our department by conservative and surgical modality. In this study we found that 65% of all patients were classified in the cured/improvement group and 35% in the stable/progression group. The female gender, osteoporosis as primary disease, oral regime intake, shorter period on BPs, earlier stage of disease, and specific anatomic localisation (frontal and premolar maxilla) were factors associated with better response to therapy and favourable clinical outcome. Comprehensive treatment protocol and further randomized studies are necessary for further improvements

The "European Mandibular Angle" Research Project: The Epidemiologic Results From a Multicenter European Collaboration

The aim of this study was to analyze the demographic variables and causes and characteristics of mandibular angle fractures managed at several European departments of maxillofacial surgery

The \u201cEuropean Mandibular Angle\u201d research project: the analysis of complications after unilateral angle fractures

Objective: The aim of this study was to analyze the complications and outcomes of surgical treatment of angle fractures managed at departments of maxillofacial surgery in several European countries. Study Design: Patients hospitalized with unilateral isolated angle fractures between 2013 and 2017 were included. The following data were recorded: gender and age of patients, fracture etiology, presence of the third molar, maxillomandibular fixation, osteosynthesis technique, and complications. Results: In total, 489 patients were included in the study. The Champy technique was found to be the most frequently chosen osteosynthesis technique. Sixty complications were observed, at a rate of 12.3%. Complications were associated with the absence of third molars (P <.05). Instead, the Champy technique was associated with fewer complications (P <.05), in comparison with the other adopted techniques. Conclusions: The management of angle fractures still represents a challenging task with a significant complication rate. The Champy technique still seems to be a valid option for the treatment of such injuries

Patient's perception of recovery following surgical removal of mandibular third molars. A prospective european multi-center study

This study evaluated patient's perception of recovery following surgical removal of mandibular third molars (SRM3s) including analyze of potential risk factors associated with impaired convalescent. Patient related parameters combined with preoperative questionnaires including Modified Dental Anxiety Scale, Oral Health Impact Profile-14, and Decayed, Missing, Filled Teeth index were correlated with questionnaires assessing pain, swelling, trismus, sick leave, social and working isolation, physical appearance, eating and speaking ability, diet variations, sleep impairment, impaired sensation of the lip, chin, and tongue, one month following SRM3s. Totally, 412 patients (223 females, 189 males) with mean age of 29.4 years were included. Treatment satisfaction and willingness to undergo similar surgery were reported by 92% and 95%, although 21% reported that the surgery and postoperative period had been worse than expected. Mean days with pain, sick leave, and swelling were 3.6, 2.1, and 3.6, respectively. Preoperative symptoms, dental anxiety level, and prolonged surgical time were associated with increased pain and swelling (P &lt; 0.05). Pell and Gregory classification (I-IIIC) were associated with impaired sensation of the lower lip and chin (P &lt; 0.05). Consequently, results from this study improve the surgeon's ability to predict parameters that predisposed to impaired recovery and neurosensory disturbances following SRM3s.</p