Targeted therapies in ameloblastomas and amelobastic carcinoma-A systematic review.

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.

Efficacy of natural enzymes mouthwash: a randomised controlled trial.

OBJECTIVES: Natural enzymes mouthwash has been proposed as salivary substitutes to treat xerostomia. This study aims to evaluate the efficacy of the mouthwash to treat xerostomia. MATERIALS AND METHODS: A double-blind, parallel group randomised control clinical trial involving N = 49 adult participants with xerostomia was carried out. Intervention group received natural enzymes moisturising mouthwash (with active ingredients lactoferrin, lysozyme, lactoperoxidase and glucose oxidase); while control group received benzydamine mouthwash. Mouthwashes were repacked, labelled with specific code, and were given to participants by third-party. Subjects were instructed to rinse with the mouthwash 4 times per day at a specific period, for 2 weeks. Symptoms of xerostomia were assessed using Xerostomia Inventory at day 0 and 14; together with the assessment of Clinical Oral Dryness Score (CODS), and measurement of resting and stimulated salivary flow rate. RESULTS: 48 participants completed the clinical follow-up, and n = 1 had lost of follow-up. From the 48 participants, n = 23 received natural enzymes mouthwash, while n = 25 received benzydamine mouthwash. Intervention group achieved reduction in symptoms of xerostomia from baseline. Intervention group also showed significantly better improvements in the cognitive perception of dry mouth and oromotor function such as chewing, swallowing and speech of the participants; and reduction in waking up at night to drink water (p < 0.05). The CODS and resting salivary flow rate were also significantly improved in intervention group (p < 0.05). CONCLUSION: Use of natural enzymes mouthwash improved signs and symptoms of xerostomia. CLINICAL RELEVANCE: Natural enzymes mouthwash is potentially effective to treat xerostomia, well-tolerated and safe to be used by xerostomia patients. CLINICAL TRIAL REGISTRATION NUMBER: This study was retrospectively registered in ClinicalTrials.gov ID NCT05640362 on 7 December 2022.

Effects of glycation end-products on the dental pulp in patients with type 2 diabetes.

AIM: This ex vivo study aimed to compare protein expression of advanced glycation end-products (AGE) and receptor (RAGE), and the levels of selected genes associated with inflammation and collagen within dental pulp tissue from patients with type 2 (T2D) diabetes and non-T2D. METHODOLOGY: Noncarious extracted permanent molar teeth from patients with well-controlled T2D (n = 19) and non-T2D (controls) (n = 19) were collected and compared. The coronal pulp was examined using immunohistochemistry (IHC) (n = 10 per group) for anti-AGE and anti-RAGE. Quantitative PCR (n = 9 per group) was used to analyse the gene expression levels of NFKB, S100A12 and COLIA1. Data analyses were performed between the groups using GraphPad Prism using Pearson correlation, Shapiro-Wilk and Mann-Whitney U-tests, and multiple regression using SPSS. RESULTS: AGEs were distributed diffusely throughout the pulp extracellular matrix associated with collagen fibres and were present on several cell types. RAGE was expressed at the pulp-dentine interface and was observed on odontoblasts, immune cells, endothelial cells and fibroblasts. Semi-quantitative analysis of IHC samples showed significantly increased expression of AGE (p < .0001) and RAGE (p = .02) in T2D samples compared with controls. The expression of NFKB (p < .0001), S100A12 (p < .0001) and COLIA1 (p = .01) genes were significantly higher in the T2D pulp, and multivariate logistic regression analysis showed that these findings were not affected by age. CONCLUSION: T2D may exert a similar glycation response in the dental pulp to other body sites. This could occur through activation of NF-κB pathways with a concomitant increase in genes associated with inflammation and collagen.

A Cell Culture Method for the Isolation and Study of Primary Human Dental Pulp Cells.

Primary human dental pulp cell (HDPC) cultures contain dental pulp stem cell (DPSC) populations. DPSCs are multipotent mesenchymal cells residing inside the dental pulp where they can contribute to the regenerative potential of this and other tissues throughout the body. These cells are promising tools for cell-based therapies, including regenerative endodontic procedures. HDPCs can be readily isolated and expanded from extracted teeth either by the dental tissue explant method or enzymatic digestion method. This chapter describes the explant method, whereby cells outgrow from dissected pulp tissue, to generate HDPC cultures. We also provide protocols for HDPC passaging, cryopreservation, and basic immunocytochemical characterization.

Immunohistochemistry and Immunofluorescence.

Immunohistochemistry (IHC) is one of the most widely used protein detection techniques. The principle of this technique is based on the binding of a specific antibody to a matching specific antigen in tissue. The bound antigen-antibody complex then is visualized using a range of detection techniques. IHC uses a number of different enzymatic labels, such as peroxidase and alkaline phosphatase, for the detection of the antigens of interest whereas immunofluorescence (IF) uses a fluorescent signal. In this chapter, IHC will be described using the peroxidase label. Both IHC and IF can be used on formalin-fixed paraffin-embedded (FFPE) or appropriately processed fresh tissues. IHC/IF can be multiplexed to detect more than one antigen at a time, or may be sequentially stained to detect multiple targets. These techniques are routinely used in diagnostic pathology laboratories, not just for diagnostic purposes but many biomarkers are used for patient staging, treatment allocation, and prognostication. Immunofluorescence is routinely used for the detection of antibodies and antigens in freshly biopsied tissues, particularly for immune-mediated and vesiculobullous lesions. In this chapter, the principles of IHC are reviewed followed by examples of IHC and IF staining using readily available antibodies. Steps and processes involved in IHC/IF double staining are also described.

Potentiality and Inflammatory Marker Expression Are Maintained in Dental Pulp Cell Cultures from Carious Teeth.

OBJECTIVES: This investigation aimed to isolate and culture human dental pulp cells from carious teeth (cHDPCs) and compare their growth characteristics, colony-forming efficiency, mineralization potential and gene expression of Toll-like receptors (TLR)-2, TLR-4, TLR-9, tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, IL-17A, 1L-17R, IL-23A, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK1), dentin matrix protein (DMP)-1, dentin sialophospho protein (DSPP), sex determining region Y-box 2 (SOX2) and marker of proliferation Ki-67 (MKi67) with cells isolated from healthy or non-carious teeth (ncHDPCs). METHODS: Pulp tissues were obtained from both healthy and carious teeth (n = 5, each) to generate primary cell lines using the explant culture technique. Cell cultures studies were undertaken by generating growth curves, a colony forming unit and a mineralization assay analysis. The expression of vimentin was assessed using immunocytochemistry (ICC), and the gene expression of above-mentioned genes was determined using quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: ncHDPCs and cHDPCs were successfully isolated and cultured from healthy and inflamed human dental pulp tissue. At passage 4, both HDPC types demonstrated a typical spindle morphology with positive vimentin expression. No statistical difference was observed between ncHDPCs and cHDPCs in their growth characteristics or ability to differentiate into a mineralizing phenotype. ncHDPCs showed a statistically significant higher colony forming efficiency than cHDPCs. The gene expression levels of TLR-2, TLR-4, TLR-9, TNF-α, IL-6, IL-8, IL-17R, IL-23A, NF-κB, MAPK1, DMP1, DSPP and SOX2 were significantly higher in cHDPCs compared with ncHDPC cultures. CONCLUSION: cHDPCs retain their differentiation potential and inflammatory phenotype in vitro. The inflamed tooth pulp contains viable stem/progenitor cell populations which have the potential for expansion, proliferation and differentiation into a mineralizing lineage, similar to cells obtained from healthy pulp tissue. These findings have positive implications for regenerative endodontic procedures.

Lyophilised Platelet-Rich Fibrin: Physical and Biological Characterisation.

BACKGROUND: Platelet-rich fibrin (PRF) has gained popularity in craniofacial surgery, as it provides an excellent reservoir of autologous growth factors (GFs) that are essential for bone regeneration. However, the low elastic modulus, short-term clinical application, poor storage potential and limitations in emergency therapy use restrict its more widespread clinical application. This study fabricates lyophilised PRF (Ly-PRF), evaluates its physical and biological properties, and explores its application for craniofacial tissue engineering purposes. MATERIAL AND METHODS: A lyophilisation method was applied, and the outcome was evaluated and compared with traditionally prepared PRF. We investigated how lyophilisation affected PRF's physical characteristics and biological properties by determining: (1) the physical and morphological architecture of Ly-PRF using SEM, and (2) the kinetic release of PDGF-AB using ELISA. RESULTS: Ly-PRF exhibited a dense and homogeneous interconnected 3D fibrin network. Moreover, clusters of morphologically consistent cells of platelets and leukocytes were apparent within Ly-PRF, along with evidence of PDGF-AB release in accordance with previously reports. CONCLUSIONS: The protocol established in this study for Ly-PRF preparation demonstrated versatility, and provides a biomaterial with growth factor release for potential use as a craniofacial bioscaffold.

Potential of Lyophilized Platelet Concentrates for Craniofacial Tissue Regenerative Therapies.

OBJECTIVE: The use of platelet concentrates (PCs) in oral and maxillofacial surgery, periodontology, and craniofacial surgery has been reported. While PCs provide a rich reservoir of autologous bioactive growth factors for tissue regeneration, their drawbacks include lack of utility for long-term application, low elastic modulus and strength, and limited storage capability. These issues restrict their broader application. This review focuses on the lyophilization of PCs (LPCs) and how this processing approach affects their biological and mechanical properties for application as a bioactive scaffold for craniofacial tissue regeneration. MATERIALS AND METHODS: A comprehensive search of five electronic databases, including Medline, PubMed, EMBASE, Web of Science, and Scopus, was conducted from 1946 until 2019 using a combination of search terms relating to this topic. RESULTS: Ten manuscripts were identified as being relevant. The use of LPCs was mostly studied in in vitro and in vivo craniofacial bone regeneration models. Notably, one clinical study reported the utility of LPCs for guided bone regeneration prior to dental implant placement. CONCLUSIONS: Lyophilization can enhance the inherent characteristics of PCs and extends shelf-life, enable their use in emergency surgery, and improve storage and transportation capabilities. In light of this, further preclinical studies and clinical trials are required, as LPCs offer a potential approach for clinical application in craniofacial tissue regeneration.

Titanium particles: An emerging risk factor for peri-implant bone loss.

OBJECTIVE: To investigate the presence of titanium particles in peri-implant tissues in cases diagnosed with peri-implantitis, and to identify immunological reactions that these particles may elicit. METHODS: Ten peri-implant tissue biopsies of patients diagnosed clinically and radiographically with peri-implantitis were obtained from the archives of Oral Pathology Centre, University of Otago. The inclusion criteria involves: bleeding on probing, ≥6 mm probing depth and ≥3 mm radiographic bone loss around the dental implant. Peri-implant tissue samples were evaluated using scanning electron microscopy-energy dispersive x-ray spectroscopy (SEM-EDS) to identify of sites with/without titanium particles. Antibodies against human transforming growth factor beta 1 (TGF-ß1), receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin 33 (IL-33) and cluster of differentiation 68 (CD68) were used to stain the specimens. ImageJ software was used to standardise the sampling area, compare and characterise the inflammatory infiltrate in tissues with/without titanium particles. Inflammatory cytokines positivity was assessed using the immunoreactive scores (IRSs). RESULTS: Light microscopy and SEM-EDS analysis identified titanium wear particles in 90% of the tissue samples, associated with a mixed chronic inflammatory infiltrate. Quantification analysis of RANKL revealed significantly higher IRS and intensity scores (p < 0.05) in areas containing titanium. High intensity, proportion and IRSs of TGF-ß1 and IL-33 were observed in areas with titanium. CD68 had higher IRSs in the absence of titanium particles. CONCLUSIONS: Significant overexpression of the cytokine RANKL was observed, with a trend for over-expression of IL-33 and TGF-B1 in areas with titanium. Further studies with large sample size and appropriate control group for quantification analysis is needed to confirm the role of titanium particles in initiating bone loss.

Mechanical properties of human oral mucosa tissues are site dependent: A combined biomechanical, histological and ultrastructural approach.

AIM: To investigate load-deformation properties of Thiel-embalmed human oral mucosa tissues and to compare three different anatomical regions in terms of mechanical, histological and ultrastructural characteristic with focus on the extracellular matrix. MATERIALS AND METHODS: Thirty specimens from three different regions of the oral cavity: attached gingiva, buccal mucosa and the hard palate were harvested from two Thiel-embalmed cadavers. Mechanical properties were obtained, combining strain evaluation and digital image correlation in a standardised approach. Elastic modulus, tensile strength, strain at maximum load and strain to failure were computed and analysed statistically. Subsamples were also analysed using scanning electron microscopy (SEM) and histological analysis. RESULTS: The highest elastic modulus of 37.36 ± 17.4 MPa was found in the attached gingiva group, followed by the hard palate and buccal mucosa. The elastic moduli of attached gingiva differed significantly to the buccal mucosa (p = .01) and hard palate (p = .021). However, there was no difference in the elastic moduli between the buccal mucosa and hard palate (p > .22). The tensile strength of the tissue samples ranged from 1.54 ± 0.5MPa to 3.81 ± 0.9 MPa, with a significant difference between gingiva group and buccal mucosa or hard palate (p = .001). No difference was found in the mean tensile strength between the buccal mucosa and hard palate (p = .92). Ultrastructural imaging yielded a morphological basis for the various mechanical properties found intraorally; the attached gingiva showed unidirectional collagen fibre network whereas the buccal mucosa and hard palate showed multi-directional network, which was more prone to tension failure and less elasticity. CONCLUSION: This is the first study assessing the various morphological-mechanical relationships of intraoral soft tissues, utilising Thiel-embalmed tissues. The findings of this study suggest that the tissues from different intraoral regions showed various morphological-mechanical behaviour which was also confirmed under the SEM and in the histological analysis.

Prevalence of oral cancer, oral potentially malignant disorders and other oral mucosal lesions in Cambodia.

OBJECTIVES: To obtain data on the prevalence of oral mucosal lesions (OMLs) among Cambodians, and to assess the relationship between known risk habits of oral diseases with prevalence of oral potentially malignant disorders (OPMDs). DESIGN: This was a population-based, cross-sectional study whereby subjects were adults aged 18 years old and above. A workshop on the identification of OML was held to train and calibrate dental officers prior to data collection in the field. Sociodemographic and risk habits data were collected via face-to-face interview, whilst presence of OML and clinical details of lesions such as type and site were collected following clinical oral examination by the examiners. Data analysis was carried out using the Statistical Package for Social Science (SPSS) version 12.0. The association between risk habits and risk of OPMD was explored using logistic regression analysis. RESULTS: A total of 1634 subjects were recruited. Prevalence of OML for this population was 54.1%. Linea alba was the most common lesion seen (28.7%). This study showed an overall OPMD prevalence of 5.6%. The most common type of OPMD was leukoplakia (64.8%), followed by lichen planus (30.8%). Subjects who only smoked were found to have an increased risk for OPMD of almost four-fold (RR 3.74, 95%CI 1.89-7.41). The highest risk was found for betel quid chewers, where the increased risk observed was more than six times (RR 6.75, 95%CI 3.32-13.72). Alcohol consumption on its own did not seem to confer an increased risk for OPMD, however when practiced concurrently with smoking, a significant risk of more than five times was noted (RR 5.69 95%CI 3.14-10.29). CONCLUSION: The prevalence of OML was 54.1%, with linea alba being the most commonly occurring lesion. Smoking, alcohol consumption and betel quid chewing were found to be associated with the prevalence of OPMD, which was 5.6%.

Stevens-Johnson Syndrome following Failure of Genetic Screening prior to Carbamazepine Prescription.

Failure to screen susceptible individuals for human leucocyte allele B∗1502 leads to the onset of Stevens-Johnson syndrome (SJS). We report a case of a 27-year-old Malay female who was treated with carbamazepine following the diagnosis of trigeminal neuralgia without a genetic screening. She was prescribed 150 mg of carbamazepine initially and the dose was increased to 300 mg following the initial dose. A sudden development of skin and mucous membrane ulcers was observed and this warranted immediate hospitalization. A diagnosis of SJS was made and she was treated immediately with intravenous corticosteroids. Genetic screening prior to carbamazepine prescription is essential especially in susceptible populations.

Exophytic Verrucous Hyperplasia of the Oral Cavity ­ Application of Standardized Criteria for Diagnosis from a Consensus Report

Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC) need to be further clarified for better understanding of their predictable biologic behavior and appropriate treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of the 'First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity' held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named 'Exophytic Verrucous Hyperplasia'. Previously described clinical features of OVH such as the 'blunt' or 'sharp' variants; and the 'mass' or 'plaque' variants can now collectively fall under this newly described entity. This paper discusses in detail the application of the standardized criteria guidelines of 'Exophytic Verrucous Hyperplasia' as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool of OVH cases and facilitate a better understanding of OVH malignant potential.

Toll-like receptors and cancer, particularly oral squamous cell carcinoma.

It is becoming increasingly apparent that the tumor microenvironment plays an important role in the progression of cancer. The microenvironment may promote tumor cell survival and proliferation or, alternatively may induce tumor cell apoptosis. Toll-like receptors (TLRs) are transmembrane proteins, expressed on immune cells and epithelial cells, that recognize exogenous and endogenous macromolecules. Once activated, they initiate signaling pathways leading to the release of cytokines and chemokines, which recruit immune cells inducing further cytokine production, the production of angiogenic mediators and growth factors, all of which may influence tumor progression. This paper examines the actions of TLRs in carcinogenesis with particular emphasis on their role in oral squamous cell carcinoma.

A retrospective study of oral and maxillofacial injuries in Seremban Hospital, Malaysia.

INTRODUCTION: Aetiology of oral and maxillofacial injuries in this country includes motorvehicle accident (MVA), fall, industrial accidents and others. Among these causes, MVA accident is the predominant cause of injury in Malaysia. MATERIALS AND METHODS: A retrospective record review was carried out using hospital records of all patients who sustained oral and maxillofacial injury at the Department of Oral Surgery, Seremban Hospital, Negeri Sembilan, Malaysia between 1998 and 2002. Information related to demographics, aetiology of trauma, vehicles involved in collision, location of injuries and treatment modalities were reviewed. RESULTS: Two thousand nine hundred and eighty-six patients sustained oral and maxillofacial injuries. Of these patients, 79.2% were men and the remaining were women. Among all the races, Malays had the highest involvement (50.6%) followed by Indians (24.5%), Chinese (19.6%) and others (5.3%). There were statistically significant results on the association of aetiology and the ethnic groups, in the age group of 30 years or less and male gender (P < 0.001). The most common injury was the soft-tissue injury followed by dental and dentoalveolar injuries and bony fracture. Among all facial fractures, 66.3% were managed conservatively, 13% were treated surgically and 19.7% did not have any intervention. In relation to dental and dentoalveolar injuries, 64.8% had treatment in the form of splinting, restorations or dental extraction. The rest of the patients (35.2%) were referred to their dentists or did not have any active treatment at Seremban Hospital. CONCLUSION: Most of the dental and facial injuries in Seremban Hospital were caused by MVA and were predominantly managed using conservative methods.

Facial trauma in geriatric patients in a selected Malaysian hospital.

BACKGROUND: Road traffic accidents are the main cause of trauma in Malaysia. It has been shown that there was an increase in admissions for trauma patients older than 60 years in the last decade. The purpose of this study was to determine the pattern of maxillofacial injuries in the geriatric patients referred to Seremban Hospital, Malaysia. METHODS: Records of patients aged 60 years or older who sustained oral and maxillofacial injuries between 1998 and 2002 were reviewed. Data related to age, sex, race, etiology, types of injuries and treatment modalities were obtained. RESULTS: A total of 134 geriatric patients with maxillofacial and dental injuries were seen in Seremban Hospital between January 1998 and December 2002. There were 101 (75.4%) men and 33 (24.6%) women. The age ranged 60-92 years with the mean age of 68.3 years (standard deviation, 7.48). Chinese made up the majority of the patients (51.8%), followed by Malays (37.2%), Indian (20.4%) and other ethnic groups (1.5%). The most common cause of injury was due to road traffic accidents (64.2%) However, falls were more common in those aged 76 years and above. The most common bone fracture documented was the mandible (35.7%) followed by fracture of the zygomatic complex (34.0%). The majority of treatment was conservative or closed reduction. CONCLUSION: All the elderly patients with facial trauma were managed conservatively or as closed reduction in this hospital. This was largely because of their comorbid state and financial constraints.

Maxillofacial trauma of pediatric patients in Malaysia: a retrospective study from 1999 to 2001 in three hospitals.

OBJECTIVE: Maxillofacial trauma in children is not common worldwide. Domestic injuries are frequently seen in younger children while older children are mostly involved in motor vehicle accidents (MVA). The objective of this study was to analyze the pattern of maxillofacial injuries in pediatric patients referred to three government main hospitals in different areas of West Malaysia. METHODS: Patients' records of three selected hospitals in Malaysia (National University of Malaysia Hospital, Kajang Hospital and Seremban Hospital) from January 1999 to December 2001 were reviewed. Data associated with demographics, etiology of injury in relation to age group, type of injuries whether soft tissues of hard tissue in relation to age group and treatment modalities were collected. RESULTS: A total of 521 pediatric patients' records were reviewed. Malays made up the majority of patients with maxillofacial injuries in the three hospitals. Males outnumbered females in all the three hospitals. Injuries commonly occur in the 11-16 years old. MVA was the most common etiology followed by fall and assault. Soft tissue injuries were the most common type of injuries in all the hospitals. In relation to fractures, mandible was the most common bone to fracture with condyle being the most common site. Orbital fracture was the most common fracture in the midfacial area. Most of the fractures were managed conservatively especially in the younger age groups. Open reduction with or without internal fixation was more frequently carried out in the 11-16 years old group. CONCLUSION: Children exhibit different pattern of clinical features depending on the etiology and stage of their bone maturation. A dedicated team, who is competent in trauma and aware of the unique anatomy, physical and psychological characteristics of children, should manage pediatric patient with trauma.