Role of Nidogen-2 in diagnosis and prognosis of head and neck squamous cell carcinoma: A systematic review.

Context: Nidogen-2 (NID-2) hypermethylation has been implicated in many types of cancers, such as lung, bladder, and gastric carcinomas. However, its role has not yet been studied adequately in head and neck squamous cell carcinomas (HNSCC). HNSCCs constituting a major portion of the global cancer load, it is of importance to diagnose and treat them at earliest. This systematic review was performed to assess the role of NID-2 in HNSCCs and assess its utility as a diagnostic and prognostic marker. Materials and Methods: A systematic search was performed across multiple databases to identify studies pertaining to analysis of expression or methylation of NID-2 in HNSCCs. The sample size, type of cancer/premalignant condition studied, type of tissue/fluid analysed, and the various methodologies used and their results were extracted. PROSPERO registration number: CRD42021245326. Results: Four studies were identified after a systematic search of literature. The studies analysed NID-2 expression or methylation in conditions such as nasopharyngeal carcinoma, esophageal carcinoma, and oral squamous cell carcinoma (OSCC). NID-2 was found to be a highly specific marker for HNSCCs, and serum NID-2 levels also correlated with poor survival. Conclusion: Data from the reviewed studies indicate that hypermethylation of NID-2 is highly specific for HNSCC. The high specificity is maintained in salivary and serum samples, facilitating accurate and non-invasive prognostication of HNSCC. The relatively lower sensitivity of NID-2 methylation may be overcome by analysing it along with a panel of multiple biomarkers such as HOX-A2 and YKL20.

Demographic study of 366 cases of oral leukoplakia and immunohistochemical analysis - An institutional study.

Background: It has been reported that oral squamous cell carcinoma (OSCC) is associated with the presence of potentially malignant disorders (PMDs) in 15%-48% of cases. Among PMDs, oral leukoplakia (OL) is the most common, with 16%-62% of cases associated with OSCC. Hence, in the present study, we have analyzed demographic data and re-evaluated immunohistochemical (IHC) data of OL cases and aimed to correlate the clinical, histopathological and IHC aspects of OL. Materials and Methods: The data of histopathologically diagnosed cases of OL were retrieved from the archives. These data were further evaluated for age, gender, duration, site, size, side, habits, clinical staging and histopathological grading. IHC re-evaluation of OL tissues was done using epithelial cadherin (E-cadherin), n = 20; human MutL homolog 1 (hMLH1), n = 30; CD1a (n = 30); vimentin (n = 30); Ki-67 (n = 30); heat shock protein-70 (HSP-70), n = 30; p16INK4, n = 20; and mucin-1 (MUC1), n = 30. All the results and observations were subjected to descriptive statistical analysis. Results: The male: female ratio was 7.5:1; right side and buccal mucosa were more commonly affected. The duration of the lesion ranged from 1 to 30 years. One hundred and twelve patients were habituated to tobacco chewing, while 171 patients came with a combined habit of smoke and smokeless tobacco usage. Clinically, most of the lesions were of stage 2 while histopathologically they were of mild dysplasia. There was a decrease in the immunoexpression of E-cadherin, hMLH1 and CD1a, while there was an increase in the immunoexpression of vimentin, Ki-67, HSP-70, MUC1 and p16INK4. Conclusion: The study of different biomarkers such as cytoplasmic, membranous and nuclear in OL will help in better understanding and application of a reliable marker for diagnostic and prognostic purpose.

Ultrasound-Assisted Facile Synthesis of Nanostructured Hybrid Vesicle for the Nasal Delivery of Indomethacin: Response Surface Optimization, Microstructure, and Stability.

This work is devoted to design a novel nanostructured hybrid vesicle (NHV) made of lecithin and an acrylate/C10-C30 alkyl acrylate for the nasal delivery of a model active indomethacin (IND), and further to probe its microstructure, intermolecular interactions, drug release behavior, ex vivo permeation, and stability. NHVs were prepared by cavitation technology employing RSM-based central composite design (CCD). Amount of lecithin (X1), power of ultrasound (X2), and sonication time (X3) were selected as three independent variables while the studied response included Z-Avg (nm), polydispersity index (PDI), and zeta potential (mV). The designed system (NHV) was investigated through dynamic (DLS) and electrophoretic light scattering (ELS), attenuated total reflectance (ATR-FTIR), oscillatory measurement (stress and frequency sweep), and transmission electron microscopy (TEM). CCD was found useful in optimizing NHV. An optimized formulation (S6) had Z-Avg 80 nm, PDI 0.2, and zeta potential of - 43.26 mV. Morphology investigation revealed spherical vesicles with smaller TEM diameters (the largest particle being 52.26 nm). ATR analysis demonstrated significant intermolecular interactions among the drug (IND) and the components of vesicles. The designed vesicles had an elastic predominance and displayed supercase II (n > 1) type of drug release. Besides, the vesicles possessed potential to transport IND across the nasal mucosa with the steady-state flux (µg/cm2/h) and permeability coefficient (cm/h) of 26.61 and 13.30 × 10-3, respectively. NHV exhibited an exceptional stability involving a combination of electrostatic and steric interactions while the histopathology investigation confirmed their safety for nasal administration.

Anesthesia Considerations in Modified Osteo-odonto-keratoprosthesis.

PURPOSE: To elucidate anesthesia-related challenges in patients who underwent modified osteo-odonto-keratoprosthesis (MOOKP). DESIGN: Retrospective cohort study. METHODS: Medical records of consecutive patients who underwent MOOKP surgery between January 2007 and January 2015 were reviewed. Data including demographic details, systemic comorbidities, indications for MOOKP, and anesthesia techniques at various stages of MOOKP were collected and analyzed. RESULTS: A total of 74 patients (47 men, 27 women) were included in this study. The mean age of the patients was 29.7 ± 9.1 years. The most common indication for MOOKP was Stevens-Johnson syndrome (53%), followed by chemical burn (38%). In all stages of the MOOKP procedure, 94.6% of patients were American Society of Anesthesiologists (ASA) grade II, whereas 5.4% were ASA grade III. Mallampati score 1 was found in 79.7% of patients in stage 1A, 82.4% of patients in stage 1B + 1C, and 81.1% of patients in stage 2. Recovery grade of 10 was noted in all patients at all stages of the MOOKP procedure. Intubation in the second attempt was carried out in 8 patients and oral intubation in stage 1B + 1C was performed in 4 patients. Difficulty in intubation was noted in 3 patients in stage 1A, 4 patients in stage 1B + 1C, and 1 patient in stage 2. CONCLUSIONS: In patients undergoing MOOKP, a good preoperative anesthetic evaluation and intraoperative anesthesia plan before each stage could help in successful administration of anesthesia in these patients.

Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.

BACKGROUND: Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products. Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling. An aberrant expression of MUC1 has been demonstrated in various human cancers. Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region. In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM). AIMS: This study aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique. SETTINGS AND DESIGN: Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM). Formalin-fixed paraffin wax blocks were prepared from the tissue samples obtained. MATERIALS AND METHODS: Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied. STATISTICAL ANALYSIS: Pearson's Chi-square test was used. P <0.05 was considered to be statistically significant. RESULTS: In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30. All the samples in control group were negative for MUC1 immunoexpression. The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square). CONCLUSIONS: MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.

Odontogenic tumors: A 35-year retrospective study of 250 cases in an Indian (Maharashtra) teaching institute.

CONTEXT: This retrospective study was planned to ascertain the relative frequency of odontogenic tumors (OTs) in an Indian population in the light of the latest World Health Organization (WHO) classification. AIM: To compare data with various reports from other parts of the world. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: The histopathology records and archived slides of all lesions diagnosed as "OT" in the Department of Oral Pathology and Microbiology of Government Dental teaching institute, Mumbai, Maharashtra, India, were recovered from the period January 1981-December 2016. A total of 250 lesions thus classified were reviewed for age, gender, site of tumor, and histopathologic typing. The tumors were reclassified according to the WHO 2017 criteria. STATISTICAL ANALYSIS: Microsoft Excel 2010 was used for statistical analysis. RESULTS: In all, 250 cases of OTs were reported in a 35-year period. OTs in this study constituted 7.14% of all the 6797 registered biopsies. The most frequent histological type was ameloblastoma (AML) (30.8%), followed by odontoma (19.2%), unicystic ameloblastoma (18.4%), adenomatoid OT (14%), cementifying fibroma (6%), odontogenic myxoma and cementoblastoma (2.4% each), calcifying epithelial OT and odontogenic fibroma (2% each), ameloblastic fibroma (1.2%), squamous OT, dentinogenic ghost cell tumor, peripheral ameloblastoma, ameloblastic carcinoma and ameloblastic fibrosarcoma (odontogenic sarcoma) (0.4% each). CONCLUSION: A frequency of 7.14% of OTs was observed in this study. AML comprised the single most common tumor of all OTs. This study observed geographic variations in the frequency and distribution of OTs.

Primary intraosseous squamous cell carcinoma - A rare odontogenic malignancy.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare epithelial odontogenic malignancy affecting the jaws, especially in elderly population. It is a rare lesion, because very few cases of PIOSCC have been reported in the literature with not much of research done on this particular entity. In the present article, we report a case of PIOSCC with detailed discussion of clinical, radiographic and histopathologic features along with review of literature.

Human MutL homolog 1 immunoexpression in oral leukoplakia and oral squamous cell carcinoma: A prospective study in Indian population.

BACKGROUND: Mammalian mismatch repair system is responsible for maintaining genomic stability during repeated duplications, and human MutL homolog 1 (hMLH1) protein constitutes an important part of it. Various isolated studies have reported the altered expression of hMLH1 in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Research is lacking in the quantitative estimation and comparison of hMLH1 expression in OL and OSCC. AIMS: To evaluate, quantify and compare hMLH1 immunoexpression in normal oral mucosa, OL and OSCC. SETTINGS AND DESIGN: Thirty patients of OL and thirty patients of OSCC formed the study group and thirty patients were included in the control group (normal oral mucosa). Formalin-fixed paraffin wax blocks were prepared from the tissue samples. MATERIALS AND METHODS: Immunohistochemistry for hMLH1 was performed, and the total number of positive cells was counted in high-power fields, and based on that percentage positivity of hMLH1 was calculated in all the cases. STATISTICAL ANALYSIS: Kruskal-Wallis and t-test were used. P < 0.05 was considered to be statistically significant. RESULTS: The mean hMLH1 value in control group, leukoplakia and OSCC was 78.26, 54.33 and 40.97 respectively. hMLH1 immunoexpression showed decreasing indexes from control group to leukoplakia and then further to OSCC. hMLH1 expression was significantly lower in OSCC as compared to leukoplakia. There was no significant correlation of mean hMLH1 expression between different clinical and histopathological stages of leukoplakia and OSCC. CONCLUSIONS: hMLH1 immunoexpression was inversely related to the degree of dysplasia. These findings suggest that there is a progressive decrease in hMLH1 expression from control to leukoplakia and further to OSCC. Thus, it can be concluded that hMLH1 can be used as a reliable biomarker for malignant transformation.

Pathogenesis of Rushton bodies: A novel hypothesis.

Rushton bodies (RBs) are one of the characteristic features seen in the epithelial lining of odontogenic cysts mainly radicular, dentigerous and odontogenic keratocyst. It has two different histo-morphological appearances; granular and homogeneous. Although widely investigated, the exact pathogenesis and histogenesis of RBs is still an enigma. Many hypotheses were made in the literature but none has explained conceivably the two histo-morphological appearances of RBs and their association with inflammation. In the present paper the various pathogenesis for the formation of RBs proposed till date are discussed along with proposal for a novel hypothesis. The given hypothesis is mainly related to inflammation and its effect on pore size of basement membrane of odontogenic cystic epithelium. It explains RBs association with inflammation as well as existence of two histo-morphological appearances. The proposed hypothesis also justifies the RB's presence inside the lining epithelium of odontogenic cyst despite its hematogenous origin. Future studies are advocated for isolating RBs using laser capture microdissection and subsequent biochemical, histochemical and electron microscopic analysis to substantiate the proposed hypothesis.

Histopathological spectrum of polymorphous low-grade adenocarcinoma.

Polymorphous low-grade adenocarcinomas (PLGA) are distinctive salivary gland neoplasms, with an almost exclusive propensity to arise from the minor salivary glands. PLGA frequently manifests as an asymptomatic, slow-growing mass within the oral cavity, which must be separated from adenoid cystic carcinoma and benign mixed tumor for therapeutic and prognostic considerations. We report a case of a 67-year-old male, who presented with a long-standing mass in the palate. This lesion was diagnosed as PLGA based on histopathological findings, which was further confirmed by the immunohistochemical marker.

Leprous macrocheilia: A rare clinical presentation.

Oral leprosy, a granulomatous disease is classified under the term oro-facial granulomatosis which comprises a group of diseases characterized by noncaseating granulomas affecting the soft tissues of the oral and maxillofacial region. The most common clinical presentation of oro-facial granulomatous conditions is persistent swelling of one or both lips. Due to its rare incidence and clinical findings overlapping with other granulomatous conditions such as sarcoidosis, Crohn's disease, and cheilitis granulomatosa; it is practically difficult for a dental surgeon to easily diagnose this condition. This study presents a case of leprosy causing macrocheilia as the only clinical presentation and diagnosed initially as Miescher's cheilitis based on exclusion criteria.

Oral potentially malignant disorders: A proposal for terminology and definition with review of literature.

Several attempts to produce internationally accepted terminologies and definitions of 'oral precancer' have appeared in the literature. World Health Organizations (WHO) in 1972 subdivided 'precancer' into 'lesions' and 'conditions' with their definitions. Recent working group of WHO is not in favor of such subdivision and recommended the use of the term 'oral potentially malignant disorder (OPMD)'. This is mainly attributed to the recent advancement in molecular and genetic aspects of 'oral precancer'. But efforts to define OPMDs are few in the literature. 'Oral precancer' is ultimately colligated to oral squamous cell carcinoma (OSCC). With this semantics in mind, different OPMD and related terminologies in the literature used till date with their lexicographic analysis have been reviewed in the present paper. Attempt has also been made to propose desirable terminology and definition which suits to the current concept of OPMD. The proposed terminology and definition is based on the authors' opinions with a hope for further suggestions from readers.

Histological evaluation to study the effects of dental amalgam and composite restoration on human dental pulp: an in vivo study.

OBJECTIVE: To study and compare the effects of dental amalgam and composite restorations on human dental pulp. MATERIALS AND METHODS: One hundred sound premolars scheduled for orthodontic extraction were divided equally into two groups: group A, teeth restored with silver amalgam, and group B, teeth restored with composite resin. Each group was equally subdivided into two subgroups [extracted after 24 h (A-1 and B-1) or 7 days (A-2 and B-2)], and the histological changes in the pulp related to the two different materials at the two different intervals were studied. RESULTS: It was found that after 24 h, the inflammatory response of the pulp in teeth restored with amalgam and composite was similar (p = 1.00). However, after 7 days, the severity of the inflammatory response of the pulp in teeth restored with amalgam was less compared to that in teeth restored with composite (p = 0.045). CONCLUSION: This study confirmed that amalgam continues to be the mechanically as well as biologically more competent restorative material. Composite could be a promising restorative material to satisfy esthetic needs for a considerable period of time. However, its biological acceptance is still in doubt.

Efficacy of crystallization test for screening of oral squamous cell carcinoma with clinico-pathological correlation.

AIM: To determine the efficacy of crystallization test for screening oral squamous cell carcinoma (OSCC) with clinico-pathologic correlation. MATERIALS AND METHODS: Fifty patients of OSCC and 30 healthy individuals were selected. One drop of blood was collected into 1 cc of doubled distilled water at room temperature to give a final dilution of 6% hemolyzed blood. 0.1 to 0.2 cc of blood sample was then subjected to crystallization test using 10% cupric chloride solution. RESULTS: In healthy control group, the typical pattern was an eccentrically placed center of gravity with needles arranged in radiating fashion, while in OSCC group, there was 'transverse form' (TF) formation. The sensitivity and specificity of this test was found to be 96% and 96.66%, respectively. The positive and negative predictive values were found to be 97.96% and 98.55%, respectively. The mean TF frequency was found to be increasing from grade I (3.20 ± 1.5%) to grade II (653 ± 2.23%) and difference was statistically significant (P = 0.0001). However, there was no correlation between mean TF frequency and TNM stages of OSCC. CONCLUSION: Crystallization test is a simple, reliable, economical, less time-consuming, and less invasive screening procedure, which can be used for early detection of OSCC.

Early detection of oral cancer: PAP and AgNOR staining in brush biopsies.

AIM: The aim of this study was to determine the diagnostic accuracy of routine Papanicolaou stain (PAP) and Silver stained Nucleolar Organizer Regions (AgNOR) staining in brush biopsies taken from suspected oral lesions for early detection of oral cancer. MATERIALS AND METHODS: Brush biopsies were collected from macroscopically suspicious lesions of the oral cavity of 34 patients and 10 normal-aged and sex-matched controls. The numbers of AgNORs were counted in 100 squamous epithelial cell nuclei per slide after silver staining of the smears (Ploton's one-step method). RESULTS: Sensitivity and specificity of PAP analysis in the oral smears for detection of oral cancer and normal cells was 91.176% and 100%. The positive and negative prediction values were 100% and 76.92%, respectively. Sensitivity and specificity of AgNOR analysis in the oral smears for detection of oral cancer and normal cells was 100%. The positive and negative prediction values were 100% each. CONCLUSION: Based on the above facts, we conclude that brush biopsy in conjunction with AgNOR staining is an easily practicable, non-invasive, safe and accurate screening method for the detection of macroscopically suspicious oral cancerous lesions. Because of its simple technique and high reliability for cellular proliferation, AgNOR staining in brush smears can be used as an adjunct to other routine cytological diagnoses for the early detection of oral cancer. However, further investigations with more number of study samples will be needed to establish this correlation beyond doubt.