Plausible mechanisms in malignisation of non-habit related chronic nonhealing traumatic ulcers of oral cavity.

ABSTRACT: Chronic nonhealing ulcers of the oral mucosa and lateral tongue, in particular, can transform into invasive oral squamous cell carcinoma (OSCC). Sometimes these ulcers do not heal even after the removal of the etiological agent that actually initiated these lesions, something similar to what happens in "neoplasia." Numerous factors have been postulated in the literature; however, the exact mechanism remains unclear. We hereby would suggest few plausible factors that could be considered for future studies to shed light on some untapped territories in the pathogenesis of OSCC arising from chronic nonhealing traumatic ulcers in purview of chromoanagenesis and the concepts of "quantum entanglement and coherence."

Optimizing Ideal Thickness of Sections for Epidermis in Intra-Operative Frozen Sections.

AIM AND OBJECTIVES: To estimate and evaluate the optimal thickness of tissue section for skin and dermal appendages intra-operatively and to compare the morphology and architecture of the epidermis and its appendages at 7 and 10 microns. METHODOLOGY: After obtaining clearance from the institutional human ethical committee, 101 skin margins were prospectively analyzed using a two-step embedding technique. After multiple trials and errors, 7- and 10-micron thicknesses were selected for the present study. Artefacts, staining characteristics, cellular morphology, cellular outline, and nuclear outline were assessed and scored as unacceptable or acceptable. The data were entered in a Microsoft Excel spreadsheet and analyzed using SPSS software. RESULTS: There was a statistically significant difference between the sections obtained at 7 microns and 10 microns (p-value: <0.001), the latter were better in all the parameters analyzed. However, no difference was noted in the characteristics of the dermal appendages (p-value: >0.05). CONCLUSION: While mucosal margins can be obtained at the usual 5-7 microns, the same thickness is not optimal for skin margins intra-operatively. Frozen sections for the skin margins may be set at 10 microns, to save time, minimize artefacts, and for better readability.

Estimation of Tooth Dimensions and Golden Divine Ratio in Extracted Human Permanent Maxillary and Mandibular Canines in a Cohort of Tamil Ethnicity.

Background Teeth serve many functions, and aesthetics is one of the most important aspects served by teeth, perceived by the limbic system of the human brain. The golden divine ratio is the unique proportion often correlated with beauty. The present study was devised to estimate the dimension of human permanent canines and approximation to the golden divine ratio. Materials and methods The present study included 47 extracted human permanent canines retrieved from the tooth repository of our institute's Department of Oral Biology. Using digital vernier calipers (Themisto TH-M61 digital vernier caliper, 0-150mm/ 6 inch, JIPVI Ecommerce Pvt. Ltd, India, 2022), the following measurements were taken: Mesio-distal and labiolingual dimensions of the crown, crown length, root length, root to crown ratio (R/C) and the tooth to root ratio (T/R). The data were analyzed using Statistical Package for Social Sciences (SPSS) software version 26. Results All the dimensions' mean and standard deviations were calculated for both maxillary and mandibular canines. While the means of mesio-distal and labiolingual dimensions of the crown approximated the values reported in the literature, there was some variation in crown and root lengths. The mean crown lengths of the upper and lower canines were 10.34mm and 9.76mm, respectively, while the root lengths were 16.52 and 15.54mm, respectively. The R/C of both sets and the T/R of the upper canine only followed the golden ratio. T/R of the lower canine was slightly higher (1.64) Conclusion Although the number of included teeth was less, owing to the fact that canines are rarely extracted, our results provided new values of canines for updation in a unique population. More studies are required for comparative anthropological data updates.

Osteogenic and Biomedical Prospects of Hafnium and Its Compounds: A Scoping Review.

The direct engagement of hafnium (Hf) in biological processes or its critical function in living things is not well understood as of now. Unlike key elements like oxygen, carbon, hydrogen, and nitrogen, which are necessary for life, Hf is not known to have any biological activities or functions. It is essential to acknowledge that scientific research is ongoing and that new findings may have been made. This systematic review aimed to aggregate and analyze the studies that discuss biomedical applications of Hf metal. This systematic review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The following search strategy was used: two independent researchers conducted electronic searches in databases including PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar. The search was conducted up to August 2023 using the Medical Subject Headings (MeSH) terms "transition elements," "hafnium," and "biomedical research." Boolean operators "AND" and "OR" were used to refine the search. Electronic databases, along with hand searches, identified a total of 38 studies. The various database searches resulted in a total of 38 studies, of which 12 were excluded as duplicates, and five were unavailable for full-text data. The remaining 21 full-text articles were then assessed for their eligibility based on the inclusion and exclusion criteria, and finally, a total of 12 studies were included in the present systematic review. Among the 12 chosen studies, six were on cancer-related targeted radiotherapy or chemoradiotherapy, five were on bone or apatite-forming capabilities, and one was on the treatment of inflammatory bowel disease. The common outcome measures included cell proliferation, osteoblast formation, radiotherapy intensification, and immunotherapy. This review outlines an overall picture of the biomedical uses of Hf metal, a transition element, as a potent biomaterial. In conclusion, this transition element, Hf, has some promising scope in the fields of biomedicine, with a special focus in terms of cancer radiotherapy and osteogenic capabilities.

Literature Review, Case Presentation and Management of Non-ossifying Fibroma of Right Angle of Mandible: More Than just a Cortical Defect!

Non-ossifying fibroma (NOF) of jaw bones are rare. While NOF is the most common benign bone tumor of long bones with pathognomonic radiological features and bear a tendency for self-regression, gnathic NOF appears to be comparatively larger in size and behave more aggressively. A 16 years old female patient reported with painless swelling of the right side of the face of 4 months duration. Radiographic analysis showed a unilocular radiolucent lesion of right angle of the mandible with ill-defined margins, cortical perforation and thinning of inferior border. The lesion was provisionally diagnosed as odontogenic keratocyst/unicystic ameloblastoma and incisional biopsy was performed. The histopathological features and immunohistochemical characteristics favored a diagnosis of NOF. The lesion was excised and reconstructed. The excised specimen confirmed the diagnosis. There are no signs of recurrence at 18 months follow-up. NOF should be considered in the differential diagnosis of uni-/multilocular radiolucencies of jaws particularly the posterior mandible.

Comparison of Broder's and Bryne's Grading System for Oral Squamous Cell Carcinoma With Lymph Node Metastases and Prognosis: A Scoping Review.

Oral squamous cell carcinoma (OSCC) has the highest mortality rate of any type of head and neck squamous cell carcinoma. For many eons, the clinical TNM (tumor size, nodal metastasis, and distant metastasis) classification and histological grading of malignancies have been used to predict clinical behavior, confusing it with prognosis and overall survival. This review aimed to systematically identify and evaluate the prognostic value of Broder's and Bryne's grading system for OSCC. Electronic resources such as PubMed, Cochrane Database of Systematic Reviews, Google Scholar, Scopus, and direct web searches were used to conduct a thorough search. The titles were examined to identify relevant papers, which were then reviewed for inclusion by reading the abstract. To incorporate studies published outside of the electronic database, the bibliography of all recognized papers was scanned. This review examined all research that investigated the prognostic value of Broder's and Bryne's grading systems in OSCC. The electronic database search identified 221 articles. After reading full articles, based on the titles and abstracts and after removing duplicates, six articles were screened. Finally, six articles were selected based on their ability to meet the inclusion criteria and answer the research question. All studies analyzed the competence of this histological grading system in predicting the prognosis of OSCC patients. Four studies evaluated lymph node metastasis and two studies analyzed the histological grading of OSCC. While evaluating the histological grade, we recommend the application of Bryne's (1992) system for grading OSCC. The standardization of a single, effective method would make it easier to compare results from various studies. This grading system yields better interobserver agreement and bears a prognostic value which may help in devising a treatment strategy for better patient outcomes.

Immunohistochemical Expression of CK14 and Bcl-2 in Odontogenic Keratocyst and Its Variants.

Odontogenic keratocysts (OKCs) are aggressive cystic jaw lesions with a high epithelial turnover rate and increased propensity for recurrence. Sometimes, the characteristic histopathological features of OKCs are either completely lost or seen focally due to previous marsupialization or inflammation. This research aimed to determine whether specific patterns of CK14 and Bcl-2 staining could assist in diagnosing OKCs with altered epithelial features and provide clues in elucidating their aggressive nature. CK14 expression was restricted to basal and suprabasal layers near satellite cysts and in areas showing subepithelial split. The entire epithelial lining showed CK14 expression in areas of inflammation and after marsupialization. The typical basal/suprabasal staining of Bcl-2 was lost in areas of inflammation and intensity is decreased in OKCs after marsupialization. These new findings could offer a hint into the biological nature and pathogenesis of OKCs. Because of its therapeutic consequences and high recurrence rate, proper recognition and diagnosis are essential for treatment planning.

Comparison of Clinico-Demographic and Histological Parameters Between Young and Old Patients With Oral Squamous Cell Carcinoma.

INTRODUCTION: Among the epithelial malignancies of the head and neck region, oral squamous cell carcinoma (OSCC) arising from the oral mucosa is the commonest type. OSCC is common in the older population; however, recent epidemiological data indicate an increase in the incidence in the younger age group. The present study was designed to compare the clinicopathological characteristics of OSCC between young and old South Indian patients. METHODS: All the histopathologically confirmed cases of OSCC were retrieved from the department archives. Patients aged more than 40 years were considered Group I, and patients aged less than or equal to 40 were considered Group II. Age, gender, laterality, site, degree of keratinization, nuclear pleomorphism, pattern of invasion, lymphoplasmacytic infiltration, grade, tumor budding (TB), and tumor stroma ratio (TSR) were assessed. RESULTS: Among 510 patients reported with OSCC, 442 were aged above 40 years, and 68 were aged 40 years or younger. Nuclear pleomorphism, TB, and stroma-rich ratio were statistically higher in younger OSCC patients (p=0.00). CONCLUSION: The results of our study support the fact that OSCC in younger individuals is more aggressive. Targeting TB and tumor stroma could provide new strategies for the management of OSCC.

An In Vitro Evaluation of Anti-inflammatory and Antioxidant Activities of Cocos nucifera and Triticum aestivum Formulation.

Background Medicinal plants are traditionally used in Ayurveda, Unani medicine, and Siddha as primary sources of drugs, and mankind has exploited the therapeutic properties of these herbs throughout history. Coconut (Cocos nucifera), a common ingredient of Indian sub-continental cuisine, has been proven to possess various medicinal properties; similarly, wheatgrass (Triticum aestivum) is of greater medicinal value and is known as the powerhouse of nutrients and vitamins. These have been used individually, but there is limited data on the synergistic use of these products. Thus, the present in vitro study was designed to prepare an oral gel from the extract of C. nucifera and T. aestivum and to assess its cumulative anti-inflammatory and antioxidant activity. Materials and methods C. nucifera extract and T. aestivum extract were prepared separately, and gel formulation was done. The formulated gel was tested for its anti-inflammatory and antioxidant activity. Results The results of the present study demonstrated that the anti-inflammatory property of the gel formulation was greater as compared to the standard (diclofenac), with the highest percentage of inhibition of 90.1% at 50 µl. With regard to the antioxidant property, we found that it was comparable to the standard (ascorbic acid) at various concentrations, with greater activity at 50 µl. Conclusion The oral gel formulation of coconut (C. nucifera) and wheatgrass (T. aestivum) showed better anti-inflammatory and a comparable antioxidant activity. Thus, this formulation may be employed as an adjunct to the commercially available oral gel preparations.

Application of InceptionV3, SqueezeNet, and VGG16 Convoluted Neural Networks in the Image Classification of Oral Squamous Cell Carcinoma: A Cross-Sectional Study.

Background Artificial intelligence (AI) is a rapidly emerging field in medicine and has applications in diagnostics, therapeutics, and prognostication in various malignancies. The present study was conducted to analyze and compare the accuracy of three deep learning neural networks for oral squamous cell carcinoma (OSCC) images. Materials and methods Three hundred and twenty-five cases of OSCC were included and graded histologically by two grading systems. The images were then analyzed using the Orange data mining tool. Three neural networks, viz., InceptionV3, SqueezeNet, and VGG16, were used for further analysis and classification. Positive predictive value, negative predictive value, specificity, sensitivity, area under curve (AUC), and accuracy were estimated for each neural network. Results Histological grading by Bryne's yielded significantly stronger inter-observer agreement. The highest accuracy was found for the classification of poorly differentiated squamous cell carcinoma images irrespective of the network used. Other values were variegated. Conclusion AI could serve as an adjunct for improvement in theragnostics. Further research is required to achieve the modification of mining tools for greater predictive values, sensitivity, specificity, AUC, accuracy, and security. Bryne's grading system is warranted for the better application of AI in OSCC image analytics.

Correlation Between Clinical and Histopathological Stagings of Oral Submucous Fibrosis: A Clinicopathological Cognizance of 238 Cases From South India.

Background  This paper aims to descriptively present the clinico-demographic and pathological profile of 238 cases of oral submucous fibrosis (OSMF) with emphasis on the correlation between clinical and histopathological classification systems and the incidence of malignant transformation. Methods A total of 7098 oral biopsies were retrospectively retrieved over a period of 13 years, out of which 238 cases of OSMF were included in the present study. Data were analyzed for age, gender, habits, clinical symptoms, functional staging, histological staging, type and nature of epithelium, signet-ring cell changes, presence/absence of dysplasia or transformation squamous cell carcinoma, and treatment. Results Clinically and histologically, most cases were moderately advanced. Men outnumbered women. The prevalence of dysplasia was found to be 23.94% and the malignant transformation rate was estimated to be 13.8%. There was a significant correlation between clinical staging with age and histological grading. No correlation was found between histological staging and the age of the patients. Conclusions OSMF is a habit-related progressive chronic oral condition with a high malignant transformation rate. Multimodal treatment with auxiliary physiotherapy helps in the improvement of the clinical symptoms.

Morphometric analysis of papillary synovial metaplasia-like changes in oral mucoceles.

BACKGROUND: Oral mucoceles (OMs) are common cystic lesions seen mainly on the lower lip in young males. Histologically, OMs show variegated features such as clear cell changes, myxoglobulosis, calcifications, and papillary synovial metaplasia (PSM)-like changes. The aim of the present paper is to morphometrically analyze PSM-like changes seen in OMs. METHODOLOGY: Seventy-two cases of histologically proven OMs were retrospectively retrieved and divided into two groups: group I without PSM-like changes and group II with PSM-like changes. The internal area was measured using Image J software. SPSS version 26 was used to analyze the data. RESULTS: There were 50 cases in group I (mean age 19.23 years) and 22 cases in group II (mean age 30.25 years). The lower lip was the most commonly affected site for both groups. The mean age in group II was significantly higher than group I. In contrast, the mean internal area was significantly higher in group I. CONCLUSION: We speculate that PSM-like changes in OMs represent an incomplete repair phenomenon. Knowledge of such an innocuous process is essential for differentiation from malignant histopathological mimickers.

Qualitative Assessment of Collagen and Elastic Fibers in Oral Submucous Fibrosis (OSMF), OSMF with Dysplasia and Oral Squamous Cell Carcinoma Arising from OSMF: A Histochemical Study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a habit related potentially malignant disorder seen mainly in South Asian people. The malignancy arising from OSMF has been regarded as low grade with better outcome. The present study was orchestrated to histochemically analyze collagen and elastic fibres in OSMF without dysplasia, OSMF with dysplasia and OSMF turning malignant. MATERIALS AND METHODS: 100 cases (80 cases and 20 healthy controls) were included after obtaining clearance from ethical committee. All cases were subjected to Van Gieson staining for collagen and a novel simple method for elastic fibres (Orcein staining). Data were analyzed using SPSS software. RESULTS: Controls showed haphazard arrangement of collagen and elastic fibres. The collagen bundles were parallelly arranged in OSMF without dysplasia and OSMF with dysplasia; the collagen was however haphazard in cases of OSMF turning malignant. As with collagen, elastic fibres were also haphazardly arranged in the control group; in contrast, the elastic fibres were predominantly arranged in a criss-cross pattern in the other study groups. The difference in orientation and density among the groups was statistically significant. CONCLUSION: With advancement of stage there is increased collagenization of OSMF, as the condition acquires dysplastic changes and turns malignant, microenvironment alters resulting in increased activity of collagenases. However, the arrangement of more resistant elastic fibres depicts the better outcome, once OSMF shows malignant transformation, limiting locoregional and distant spread.

Correlation of Bony Invasion With Nodal Metastasis, Pattern of Invasion and Survival in Oral Squamous Cell Carcinoma: A Retrospective Analysis of 122 Primary Cases From Oral Cancer Centre of South India.

Background Oral squamous cell carcinoma (OSCC) is considered to be the most common epithelial malignant neoplasm of the oral cavity. Despite advancements in diagnosis and therapeutics the clinical outcome of the disease has not improved much which may be attributed to tumor biology and heterogeneity. Bone invasion by cancer cells is currently staged as a moderately advanced disease. However, many low-grade carcinomas such as verrucous carcinoma and carcinoma cuniculatum show body invasion but less nodal metastases and better overall survival. The present study was orchestrated to analyze if bone invasion in OSCC has any impact on regional nodal metastases and survival. Materials and methods A total of 122 cases of OSCC who underwent excision and neck dissection were retrieved and included. These cases were then divided into two study groups. Group I comprised 56 OSCC cases with bone involvement and 66 cases with no bony involvement. The bone invasion was correlated with nodal metastases, survival and pattern of invasion. Statistical analysis was done using SPSS software (IBM Corp., Armonk, NY, USA). Results There was no statistically significant correlation between bone invasion with either nodal metastases or pattern of invasion, however, the worst pattern of invasion (WPOI)-4,5 showed a statistically higher incidence of nodal involvement in OSCC. No statistical difference was noted in overall survival between the two groups. Conclusion The worst pattern of invasion and not bone involvement, depicts nodal metastases in OSCC and thus, deserves consideration while staging and treatment planning.

Utility of CD44/CD24 in the Outcome and Prognosis of Oral Squamous Cell Carcinoma: A Systematic Review.

Cancer stem cells (CSCs) are characterized by their capacity for self-renewal and differentiation. CD44 and CD24 are two commonly used markers to identify these CSCs. Despite the enormous amount of data available in the literature, their specificity and coexistence remain elusive in oral squamous cell carcinoma (OSCC). In the present review, we aimed to assess the diagnostic utility of the CD44/CD24 combination in tumor development and metastasis in OSCC. Two investigators independently performed a systematic search to identify all the relevant studies from various electronic databases. Out of 694 articles, 9 were found eligible for further evaluation. Details including the number of patients, gender, site, tobacco and alcohol consumption, histological stage, CD24 expression, CD44 expression, CD44/CD24 expression, nodal status, disease-free survival, and overall survival were extracted. CD44+CD24- expression was noted in 35/207 (16.9%) cases, CD44+CD24+ in 53/207 (25.6%) cases, CD44-CD24- in 49/207 subjects (23.67%), and CD44-/CD24+ in 70/207 (33.81%) cases. CD44 or CD24 or their co-expression did not correlate with the disease-free survival rate, and double negatives (CD44-/CD24-) demonstrated a higher overall survival than other immunotypes. CD44/CD24 profile may be used on small incisional biopsies to predict the outcome and treatment planning. This finding may help in developing new therapeutic targets to suppress cancer metastasis and provide a better long-term prognosis for patients diagnosed with OSCC.

Necroptosis in human cancers with special emphasis on oral squamous cell carcinoma.

Necroptosis is a type of caspase independent 'programmed or regulated' necrotic cell death that has a morphological resemblance to necrosis and mechanistic analogy to apoptosis. This type of cell death requires RIPK1, RIPK3, MLKL, death receptors, toll like receptors, interferons, and various other proteins. Necroptosis is implicated in plethora of diseases like rheumatoid arthritis, Alzheimer's disease, Crohn's disease, and head and neck cancers including oral squamous cell carcinoma. Oral carcinomas show dysregulation or mutation of necroptotic proteins, mediate antitumoral immunity, activate immune response and control tumor progression. Necroptosis is known to play a dual role (pro tumorigenic and anti-tumorigenic) in cancer progression and targeting this pathway could be an effective approach in cancer therapy. Necroptosis based chemotherapy has been proposed in malignancies, highlighting the importance of necroptotic pathway to overcome apoptosis resistance and serve as a "fail-safe" pathway to modulate cancer initiation, progression, and metastasis. However, there is dearth of information regarding the use of necroptotic cell death mechanism in the treatment of oral squamous cell carcinoma. In this review, we summarise molecular mechanism of necroptosis, and its protumorigenic and antitumorigenic role in cancers to shed light on the possible therapeutic significance of necroptosis in oral squamous cell carcinoma.

Artificial Intelligence for Image Analysis in Oral Squamous Cell Carcinoma: A Review.

Head and neck tumor differential diagnosis and prognosis have always been a challenge for oral pathologists due to their similarities and complexity. Artificial intelligence novel applications can function as an auxiliary tool for the objective interpretation of histomorphological digital slides. In this review, we present digital histopathological image analysis applications in oral squamous cell carcinoma. A literature search was performed in PubMed MEDLINE with the following keywords: "artificial intelligence" OR "deep learning" OR "machine learning" AND "oral squamous cell carcinoma". Artificial intelligence has proven to be a helpful tool in histopathological image analysis of tumors and other lesions, even though it is necessary to continue researching in this area, mainly for clinical validation.