Impact of worst pattern of invasion on prognosis of oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The relationship between the worst pattern of invasion (WPOI) and the prognosis of oral squamous cell carcinoma (OSCC) remains controversial. This systematic review and meta-analysis was performed to determine the impact of the WPOI on the prognosis of OSCC. METHODS: Studies from six databases were assessed for quality using the Newcastle-Ottawa Scale, and data were analyzed using Stata software. RESULTS: Eighteen studies involving 3954 patients showed that patients with a WPOI of 4 to 5 had significantly worse overall survival, disease-specific survival, and disease-free survival than patients with a WPOI of 1 to 3. Significant associations of the WPOI with locoregional recurrence and mortality were found. CONCLUSION: A higher WPOI was significantly associated with a worse prognosis of OSCC across various outcomes. Incorporating the WPOI into standard histopathological assessments may guide personalized treatments and improve outcomes.

The value of a specialized second-opinion pathological diagnosis for oral and maxillofacial lesions.

OBJECTIVES: An error in the diagnosis of an oral or maxillofacial lesion could potentially be detrimental to a patient's prognosis and management. Major discrepancies between the initial and subsequent diagnoses of head and neck pathologies range from 7 to 53%. This study determined the rate of discrepancies found in the diagnoses of oral and maxillofacial lesions after a second opinion in Saudi Arabia. METHODS: A retrospective single-center study was conducted by oral and maxillofacial pathology consultants to review all cases referred for a second opinion to the oral and maxillofacial pathology laboratory between January 2015 and December 2020. If the second-opinion diagnosis matched the original diagnosis, this was described as "agreement." If the second-opinion diagnosis did not match the original diagnosis but would not change the management or prognosis of a patient, this was classified as a "minor disagreement." If the second-opinion diagnosis resulted in the changing of a patient's management or prognosis, this was categorized as a "major disagreement." Chi-square test and Fisher's exact test were used to compare data between original and second-opinion diagnoses. A p-value of less than 0.05 was considered significant. RESULTS: Of 138 cases, 59 (43%) had an initial diagnosis and a second-opinion diagnosis that were in major disagreement. The most common tumor for which there was a major disagreement was squamous cell carcinoma. No single factor influenced the occurrence of major disagreements. CONCLUSIONS: Our evaluation reiterates the importance of obtaining a second opinion from a specialist in oral and maxillofacial pathology to improve the diagnostic accuracy for lesions. A formal system for this step, in addition to the obtaining of adequate clinical and radiographic information about a patient, is mandatory for the review of difficult cases.

Oral Manifestations of COVID-19: A Cross-Sectional Study of Their Prevalence and Association with Disease Severity.

BACKGROUND: COVID-19, caused by SARS-CoV-2, has impacted the world in an unprecedented way since December 2019. SARS-CoV-2 was found in the saliva of patients, and entry points for the virus may have been through the numerous angiotensin-converting enzyme 2 receptors in the oral cavity. Oral manifestations of COVID-19 could contribute to the burden of oral disease. OBJECTIVE: To determine the prevalence of oral manifestations of COVID-19 in patients and their association with disease severity. METHODS: Interviews were conducted with adult participants diagnosed with COVID-19 between October 2021 and March 2022 to document their demographic and health status data, symptoms, and the presence of oral manifestations of COVID-19. Chi-square and the Fisher's exact test were used to compare data on the presence or absence of oral manifestations of COVID-19. RESULTS: Of 195 participants interviewed, 33% were 18 to 24 years old, 33% were 25 to 34 years old, and 75% were female. A total of 57 (29%) had oral manifestations; the most common were taste disorders (60%), xerostomia (42%), and oral ulcers (11%). There was no relationship between the severity of COVID-19 and the presence of the oral manifestations. CONCLUSION: Oral manifestations of COVID-19 were common among female patients and linked to certain general COVID-19 symptoms regarding frequency and extent.

Pulpal and periapical tissue response after direct pulp capping with endosequence root repair material and low-level laser application.

BACKGROUND: The study aims to investigate the pulp and periapical reaction and healing after capping with EndoSequence Root Repair Material (ERRM) combined with low-level laser application. METHODS: In 6 rabbits, pulps were exposed via class V, half of the samples received a low-level diode laser at 980 nm. Thereafter, cavities were capped with regular-set ERRM. The specimens were processed for histomorphological examination after 2 weeks and two months. RESULTS: After 2 weeks, images show mild inflammation and organized odontoblasts in lased group. The non-lased group shows more severe inflammation. The predentin thickness was thicker in the lased group with statistical significance (p < 0.05). After 2 months, inflammatory cells were sparse in both lased and non-lased groups. In the periapical area, group one showed dilated blood vessels and thick fibrous connective tissues. In group two, there were more numerous maturations of PDL fibers with scattered inflammatory cells and congested blood vessel. CONCLUSIONS: Using low-level laser therapy in combination with ERRM for pulp capping shortens the inflammatory phase and enhances healing.

Why do students skip classroom lectures: A single dental school report.

BACKGROUND: Conventional classroom lectures continue to represent a major component of the dental education system to ensure optimum delivery of knowledge. Certain number of students are less compliant and likely to skip classes which may impact the overall academic performance. The aim of this study was to investigate dental students' attitude towards classroom attendance and potential reasons for absenteeism at King Abdulaziz University-Faculty of Dentistry (KAU-FD). METHODS: This was a cross-sectional survey of all dental students actively enrolled at KAU-FD from January to June 2019. The survey included questions on demographics, average travel time to school, current dental year, most recent GPA, student's perspective toward classroom lectures. The survey was validated and distributed to all students at a pre-selected time frame. Data were analysed and presented as frequencies and percentages; chi-square test was used to explore parameters association. RESULTS: A total of 678 students consented and completed the survey. Overall, 44.3% of students were more likely to skip two classes or less per month. Second year dental students were more likely to be absent from classroom lectures (31.3%), while 3rd year dental students were less likely to do so (15.4%). Reported students' justifications for missing classes included early morning classes (47.9%), exams preparation (42%), and lecturer's weak presentation skills (41.9%). CONCLUSION: Compliance of dental students with classroom attendance has been an ongoing challenge for most programs. The current data suggests a multifactorial module for students' attitude toward classroom attendance. Future studies focusing on reasons behind classroom attendance behavior and addressing students' concerns are needed.

The application of teledentistry for Saudi patients' care: A national survey study.

BACKGROUND/PURPOSE: Teledentistry has emerged as a new communication tool in various dental disciplines around the world. The aim of this study was to investigate the applicability and reliability of teledentistry in the field of diagnostic dentistry and explore the perception of Saudi dentists of its benefits and concerns. MATERIALS AND METHODS: An electronic survey with 40 questions was developed, validated and distributed electronically by email and social media channels to dentists from different specialty in Saudi Arabia. Collected data were analyzed for statistical significance. RESULTS: A total of 148 dentists completed the survey. The current data demonstrated that 50% of study participants have had applied teledentistry in their clinical practice. Out of all, 90% have computers in their dental offices and 72% have been using electronic medical records in which radiographs and clinical images are uploaded. Most participants had smart phones (91%), in which they were used more commonly (74.3%) than conventional cameras (54.1%) to capture and share patients' clinical images over communication applications (74.3%) and less likely through emails (62.2%). Overall, 83% were confident that teledentistry can improve daily dental practice, specifically in the fields of oral radiology followed by endodontics and oral medicine. CONCLUSION: Teledentistry is an emerging tool with potential to improve the delivery of diagnostic dental care for communities with limited or no access to dental specialists. As of today, teledentistry has not been truly implemented by the Saudi dental community. Development of national programs to educate the public and promote teledentistry among dental practitioners are warranted.

Medication-Induced Oral Hyperpigmentation: A Systematic Review.

BACKGROUND: Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact pathogenesis of tissue pigmentation varies greatly and is not completely known. This systematic review aimed to present data on the causal association between medications and the development of oral/mucosal pigmentation as an adverse drug reaction. METHODS: A systematic review and analysis of literature were conducted using the following databases: PubMed, Science Direct, ProQuest, Web of Science, and Scopus. The systematic review included original articles written in English and published between January 1982 and June 2020. Following the PRISMA statement, eligible articles were systematically reviewed, and data were extracted from eligible studies and analyzed. RESULTS: A total of 235 articles were identified, of which 57 met the inclusion criteria and were included in this review. The mean age of included patients was 46.2±16.38 years (range: 10-90 years) with a male to female ratio of 1:1.45. Oral mucosal hyperpigmentation was reported following the use of several classes of medications such as antiviral (eg, zidovudine), antibiotic (eg, minocycline), antimalarial (eg, chloroquine), anti-fungal (eg, ketoconazole), antileprotic (eg, clofazimine), antihypertensive (eg, amlodipine), chemotherapeutic, and antineoplastic drugs. The risk of developing oral pigmentation was significantly higher with antimalarial medications, antibiotics, antineoplastic and chemotherapeutic agents. Medication-induced oral hyperpigmentation was most frequent among women and in the hard palate. CONCLUSION: Future research is warranted to better understand the pathogenesis and risk factors for medication-induced oral hyperpigmentation in order to reassure patients during prescription and management.

Retraction notice to Plexin-B1 and Semaphorin 4D Cooperate to Promote Perineural Invasion in a RhoA/ROK-Dependent Manner Am J Pathol 180 (2012) 1232-1242.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article is being retracted following correspondence from the Office of Accountability and Compliance at the University of Maryland, Baltimore. An internal investigation into this manuscript by the University of Maryland, Baltimore, found evidence that there are errors with the presentation of the standard deviations and statistical significance shown in Figure 6 which are not supported by the original data, and that these inaccuracies warrant retraction to correct the scientific record. Despite extensive efforts, the journal was unable to contact Dr. Ying-hua Yang and Dr. Hua Zhou with regard to this retraction.

Retraction Note to: Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression.

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figures 1B and 1D, the cell lines are different and all published histograms show SEMA4D mRNA level whereas Excel data have two histograms showing SEMA4D expression and two histograms showing VEGF expression. In Figure 2B, the metadata for one image shows different treatment conditions than those reported in the article. The published image labelled "VEGF + VEGFR-2 shRNA" has a metadata label of S4d-plexinB1 shRNA2". In Figure 2E, statistical significance was shown in the published figure for four comparisons, but upon recalculation, one comparison noted as significant was not. In Figure 6A, the lower left image is labelled "VEGF shRNA" in the published figure, but the metadata label is "S4DshRNA-HN121-20X". In Figure 6C, specifically, within columns 2-4, for each antibody used for immunocytochemistry, the three images have been swapped so that the original images do not match the shRNA labels in the figure (the labels for the two antibodies were correct). In Figure 7D, the first published image is labelled as "IgG" in the paper, but the metadata show a label of "Restore (V+S).tif". The third published image has a label of "anti-VEGF IgG", and the metadata show a label of "con sh.tif". Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.

Correction to: Rho-mediated activation of PI(4)P5K and lipid second messengers is necessary for promotion of angiogenesis by Semaphorin 4D.

Figure 3c of this article originally contained standard deviation values which had not been calculated correctly. A single standard deviation value was used for all 5 time points for each condition.

Prevalence and policy of occupational violence against oral healthcare workers: systematic review and meta-analysis.

BACKGROUND: Occupational violence is considered unlawful in professional environments worldwide. In the healthcare industry, including dentistry, the safety of workers is essential, and it is of the utmost importance to ensure patient and employee safety and provide quality care. This study aimed to evaluate the prevalence of violence and associated workplace policies among oral healthcare professionals. Additionally, it aimed to identify the factors associated with violence and their impact on oral healthcare workers. METHODS: A systematic review and analysis of the literature was conducted using PubMed, ScienceDirect, Scopus, Web of Science, Cochrane Library and ProQuest. Original articles written in English and published between January 1992 and August 2019 were included in the analysis. RESULTS: A total of 980 articles were found, and eight were selected for analysis. The violence experienced by healthcare workers included both physical and non-physical forms, such as shouting, bullying, and threatening; it also included sexual harassment. The impact of violence on workers manifested as impaired quality of work, psychological problems, and, although rare, quitting the job. With regard to dental healthcare, awareness of occupational violence policies among dental professionals has not been previously reported in the literature. CONCLUSIONS: The increasing incidence of occupational violence against oral healthcare workers indicates the need for the implementation of better protective measures to create a safe working environment for dental professionals. There is a current need for increasing awareness of workplace violence policies and for the detection and reporting of aggression and violence at dental facilities.

The Agreement Rate between Radiographic Interpretation and Histopathologic Diagnosis of Jaw Lesions.

BACKGROUND: To determine the agreement rate between histopathologic diagnosis and radiographic interpretation of jaw lesions. METHODS: Cases with jaw pathologies that have diagnostically adequate histopathologic samples and radiographic examinations were reviewed retrospectively. Two board-certified oral and maxillofacial pathologists (OMFP) independently determined the histopathologic diagnosis, while two board-certified oral and maxillofacial radiologists (OMFR) determined the radiographic interpretations independently. Then the histopathologic diagnosis and the radiographic interpretation were compared for agreement. RESULTS: A total of 104 cases (53% females) were included with a mean age of 31 years. The agreement rate between histopathologic diagnosis and radiographic interpretation was 49%. OMFP required OMFR consultations to reach a diagnosis in 16% of cases. The most commonly encountered lesions were by far odontogenic cysts of inflammatory origin and the agreement for this disease category was 49.1%. However, agreement rates were highest for the disease category of tumors (62.5%). CONCLUSION: The agreement rate between OMFP and OMFR was higher for tumors than cysts. Agreement rates between OMFP and OMFR improved with efficient consultation between the two disciplines.

A retrospective study of oral and maxillofacial pathology lesions diagnosed at the Faculty of Dentistry, King Abdulaziz University.

BACKGROUND: Oral and maxillofacial lesions (OMFL) comprise a broad spectrum of benign and malignant lesions that affect the oral cavity. However, few epidemiological studies have evaluated oral cavity lesions, and very few have focused on oral soft tissue pathology. The purpose of this study was to identify the prevalence and distribution of OMFL that had been diagnosed histologically at the Oral Pathology Laboratory, Faculty of Dentistry, King Abdulaziz University. MATERIALS AND METHODS: A retrospective study was conducted to assess the distribution of OMFL among the oral cavity biopsies submitted to the Oral Pathology Laboratory during the period from 1996 to 2016. Information on sex, age, location of the lesion, and histopathologic diagnosis was analyzed. RESULTS: A total of 1,218 cases were examined. Among these, reactive/adaptive lesions were the most common type (n=245; 20.1%) and cystic lesions were the second most common (n=214; 17.6%), followed by inflammatory lesions (n=152; 12.5%) and epithelial pathology (n=115; 9.4%). CONCLUSION: The results of the present study provide valuable information on the prevalence of OMFL in Jeddah, Saudi Arabia. Reactive conditions were the most frequently diagnosed pathologies. Most oral and maxillofacial biopsies were soft tissue lesions, benign in nature, and inflammatory in origin. Further studies are necessary to provide more information on head and neck diseases in the general population to develop better future oral health policies.

Histopathologic analysis of gingival lesions: A 20-year retrospective study at one academic dental center.

BACKGROUND: The gingiva is part of the periodontium supporting structures surrounding the teeth and commonly involved in gingival and periodontal conditions. Assessing the distribution of gingival lesions is important for evaluating the prevalence of periodontal disease in the population to optimize the oral health care services. The purpose of this study is to report the frequency and distribution of gingival lesions biopsied from 1996-2016. MATERIAL AND METHODS: This cross-sectional retrospective study retrieved data from all gingival lesions biopsied from 1996-2016 and sent to the King Abdulaziz University Dental Hospital oral pathology laboratory. Histologic sections were reviewed in a blinded manner by a certified oral pathologist to confirm the initial histologic diagnosis. RESULTS: Of the 1,248 oral-maxillofacial lesions, 119 (9.5%) gingival lesions were diagnosed. The mean age was 41.58 years. Gingival lesions were more prevalent in female patients than male patients (53.8%). The most common diagnoses were reactive lesions (41.2%). Pyogenic granuloma was the predominant lesion in the category (n=26, 21.8%), and followed by inflammatory conditions (24.4%), benign neoplasm (9.2%), malignant neoplasm (7.6%), epithelial lesions (7.6%), miscellaneous (5%), and immune-mediated diseases (5%). Squamous cell carcinoma was the only malignant neoplasm reported (7.6%; mean age, 57.44 years) and more common in male than female patients (2:1). Most biopsies were sent from oral and maxillofacial surgeons (55.6%) followed by general dentists (22.2%) and periodontists (12.8%). CONCLUSIONS: Pyogenic granuloma was the most common gingival lesion. Squamous cell carcinoma was the only malignant lesion in which histologic examination was the definitive diagnostic measure. This study provides information about the frequencies and distributions of gingival lesions over 20 years. Key words:Gingival biopsies, retrospective, reactive lesions, oral pathology.

The use of oral and maxillofacial pathology services by general pathologists and their attitude towards it in Saudi Arabia.

OBJECTIVES: To investigate the awareness and usage of oral and maxillofacial pathology (OMFP)  subspecialty services among pathologists in Saudi Arabia. Methods: In this cross-sectional study, we conducted an electronic questionnaire survey of pathologists in all regions of Saudi Arabia. The study was conducted between July 2015 and August 2016.  The questionnaire comprised 19 questions to evaluate the knowledge of pathologists regarding microscopic OMFP and their perceptions towards this subspecialty. Results: Most of the pathologists surveyed (94.6%) were aware of the OMFP subspecialty and its scope of practice. Although most of the pathologists recognized the importance and need of this subspecialty, 70% of them never referred or consulted an oral pathologist as they either diagnosed the cases themselves or  did not know any oral pathologist (57.7%). The pathologists had the greatest difficulty in identifying and diagnosing odontogenic tumors, salivary gland tumors, and odontogenic cysts.  Conclusion: Pathologists are aware of the OMFP subspecialty, but their utilization of the services offered by OMFP specialists in Saudi Arabia is quite low despite the strong demand for OMFP services.

Recruitment of Tiam1 to Semaphorin 4D Activates Rac and Enhances Proliferation, Invasion, and Metastasis in Oral Squamous Cell Carcinoma.

The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth. While plexins are the known functional receptors for the semaphorins, there is evidence that transmembrane semaphorins may transmit a signal themselves through their short cytoplasmic tail, a phenomenon known as 'reverse signaling.' We used computational methods based upon correlated evolution of sequences of interacting proteins, mutational analysis and in vitro and in vivo measurements of tumor aggressiveness to show that when bound to PB1, transmembrane S4D associates with the Rac GTPase exchange factor T lymphoma invasion and metastasis (Tiam) 1, which activates Rac and promotes proliferation, invasion and metastasis in oral squamous cell carcinoma (OSCC) cells. These results suggest that not only can S4D production by tumor cells affect the microenvironment, but engagement of this semaphorin at the cell surface activates a reverse signaling mechanism that influences tumor aggressiveness in OSCC.

Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells.

Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma.

Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors.