Correlation between Vascularity and Advancing Histological Grades of Oral Submucous Fibrosis with a Plausible Role in Malignisation: Systematic review of a persisting matter of conflict.

Objectives: This study aimed to quantify the vascularity in histological grades of oral submucous fibrosis (OSMF) and to determine if there is any connection between vasculogenesis and malignisation. Recent studies show no significant change in vascularity as the stage advances as opposed to the conventional concept. Methods: A comprehensive database search until December 2022 was conducted for published articles on vascularity in OSMF following preferred reporting items for systematic reviews and meta-analyses guidelines. Results: A total of 98 articles were screened of which 13 were included for systematic evaluation. The study included 607 cases, with a definite predilection for the male gender. Of the 13 studies, 11 evaluated mean vascular density. In more than half of the studies, the vascularity decreased as the stage advanced. Similar results were obtained for endothelial cells/µm2, mean vascular area percentage and mean vascular area. Conclusion: The present review supports the prevailing concept that vascularity decreases with the advancement of the OSMF stage. This denies the systemic absorption of carcinogens into the circulation with resultant longer exposure of compromised epithelium and malignisation.

Comparison Of Efficacy Of Steroids Alone And Combination Of Steroids With Hyaluronidase On Mouth Opening In Oral Submucous Fibrosis Patients.

BACKGROUND: Eventually Oral submucous fibrosis causes pronounced stiffness and failure to open the mouth. Objectives are to determine compare the efficacy of intralesional steroids alone and combination of steroids with hyaluronidase on mouth opening in oral submucous fibrosis. METHODS: It was a prospective comparative cohort study. Total of 74 patients both male and female having history of pan chewing and limited mouth opening and burning sensations were included in the study. Informed consent was taken and divided into two groups. Patients of group 1 were managed with mixture of betamethasone 1 ml and hyaluronidase 1500 IU and patients of group 2 were treated with only steroid injection of betamethasone 1 ml given intralesional, both injections were given intralesional, by multiple puncture technique and once a week and continued for twelve weeks (3 months). And data compiled and analyzed in SPSS-20. RESULTS: The mean age of group 1 was 40.027±6.97 years, and mean age of Group 2 was 37.351±5.48 years. In both groups, the greatest number of cases aged from 31-59 years. Compared to females in both groups, the majority of patients were males. In 32 (86.4)% patients of group 1 showed efficacy compared with 18[43.2] patients in group 2 [p-0.000]. Conclusion: In this study Intralesional steroids with hyaluronidase injections are more efficient for opening the mouth in patients with oral sub-mucus fibrosis.

Common benign and malignant oral mucosal disease.

BACKGROUND: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner. OBJECTIVE: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

Assessment of oral health-related quality of life instruments for oral submucous fibrosis: A systematic review using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist.

Quality of life (QoL) instruments are becoming increasingly important in research and often used in clinical practice. Various QoL instruments have been developed/ validated for assessment of oral health-related QoL (OHRQoL) in patients with oral submucous fibrosis (OSF). Selection of an adequate instrument is challenging in routine practice due to lack of information on psychometric quality of measurement instruments. This systematic review gives an extensive overview of quality of all the currently available measurement instruments for use in OSF patients. PubMed, Scopus, Web of Science and CINAHL were searched for relevant literature until December 2018 and the information was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the identified studies was assessed per measurement property according to the COnsensus-based Standards for the selection of health Measurements Instruments (COSMIN) checklist. Four studies that met the inclusion criteria were included. Three generic and one disease-specific QoL instruments were identified. Information regarding important measurement properties was often incomplete. The evidence for the quality of measurement instruments was found to be variable, none of the instruments performed sufficient on all measurement properties. Based on the available information, OHRQoL-OSF appeared to have adequate COSMIN measurement properties. As recently published, newer QoL instruments have not yet been evaluated in an adequate manner for use in OSF. We suggest future studies should implement OSF-specific OHRQoL-OSF to better understand OSF patients' perspectives and help inform clinicians to propose treatment strategies as per patients' needs.

Evaluation of Gustatory Function in Oral Submucous Fibrosis Patients and Gutka Chewers

Aim: The aim of the study is to assess and compare taste perception among Oral submucous fibrosis (OSMF) patients, Gutka chewers without OSMF and healthy subjects. Materials and methods: Ninety subjects (30 OSMF, 30 Gutka chewers without OSMF and 30 controls) were enrolled in the study for assessing taste perception by filter paper strips impregnated with different taste qualities. Taste perception assessment was also done in stage I, II and III OSMF subjects. The obtained data were analyzed using SPSS 20.0 software. Results: The gustatory defect was related to sweet, sour, bitter and salt, with significant changes in sour (33.3% showed hypoguesia) taste in OSMF subjects and 13.3%showed hypoguesia to all tastants in gutka chewers and hypoguesia to salt, sour and bitter to grade III compared in grade I and II. Conclusion: This study proved that there is significant alterations to taste perception with sour, salt, and bitter and then to sweet in OSMF subjects.

"Introducing Modified Dakkak and Bennett Grading System for Indian Food in Oral Submucous Fibrosis": A Dharwad Study.

Oral submucous fibrosis (OSMF) is one of the "diseases of civilization" because of the large differences in prevalence among races, geographic areas, and individuals at different socioeconomic levels. It is a premalignant condition strongly associated with the habit of chewing areca nuts. This study is to compare the scoring system in relation to the burning sensation of mouth and dysphagia using the visual analog scale (VAS) and Dakkak and Bennett grading system for Indian food, respectively, in OSMF patients. This study was a randomized clinical trial incorporating a total of 50 cases of OSMF divided into a control group (antioxidant therapy) and pentoxifylline test cases. Values for burning sensation of the mouth using the VAS and modified Dakkak and Bennett grading system for Indian food were recorded. Statistical analyses were done using t test, Mann -Whitney U test, and one-way analysis of variance (ANOVA) test. Patients subjected to pentoxifylline when compared to the control group showed significant reduction in dysphagia for Indian food. Burning sensation was recorded according to the visual analogue scale. Significant reduction in burning sensation was seen in the pentoxifylline group when compared to the control group. This grading system provides quantitative and qualitative parameters in patients with OSMF.

Validity of Chronic Oral Mucosal Diseases Questionnaire in oral submucous fibrosis.

OBJECTIVE: To validate the use of Chronic Oral Mucosal Diseases Questionnaire in oral submucous fibrosis. MATERIALS AND METHODS: Hundred consecutive oral submucous fibrosis (OSF) patients were requested to respond to Visual Analogue Scale (VAS) score and complete the Oral Health Impact Profile 14 (OHIP 14) and COMDQ. Spearman's rho correlation was used to assess the relationship between VAS and COMDQ score and COMDQ and OHIP 14 score. The reliability of the instrument was assessed using Cronbach's alpha analysis. Discriminant analysis was used to assess if COMDQ significantly differentiated between OSF population with and without any prior treatment done as well as OSF with mouth opening less than and more than or equal to 25 mm. RESULTS: The Spearman's correlation coefficient showed a high significance between the different domains of COMDQ and OHIP 14 and COMDQ and VAS. This study demonstrated a good convergent validity between the overall COMDQ and OHIP 14 scores (0.88).The overall Cronbach's alpha value was found to be 0.75 indicating an acceptable internal consistency reliability of COMDQ. The tool was unable to differentiate between patients with mouth opening between less than and more than or equal to 25 mm and patients with and without prior treatment. CONCLUSION: These results provide evidence that COMDQ can be used for OSF patients. CLINICAL RELEVANCE: COMDQ could be used as a valid and reliable tool for further clinical OSF research.

Impact of oral potentially malignant disorders on quality of life.

BACKGROUND: Oral potentially malignant disorders (OPMDs) could have a significant psychological impact on patients, principally because of the unknown risk of malignant transformation, while the physical and functional impairments could differ. This study aimed to assess the impact of three different OPMDs and their disease stages on the quality of life (QoL) of affected patients. METHODS: Oral leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF) patients who were undergoing treatment at an oral medicine clinic of a dental teaching hospital in India were the study population. All subjects completed the recently developed OPMDQoL questionnaire and a short form 12 item (version 2) health survey questionnaire (SF-12v2). OPMDQoL questionnaire consists of 20 items over four dimensions. A higher score denotes poor OHRQoL. SF-12v2 has two components, a Physical Component Summary (PCS) and Mental Component Summary (MCS). RESULTS: A total of 150 subjects (50 each of OL, OLP and OSF) participated. OL patients (37.7 ± 7.9) reported significantly better OPMDQoL scores than OLP (47.3 ± 5.8) and OSF (45.4 ± 9.2) patients. OLP patients reported significant problems in obtaining a clear diagnosis for their condition, more so than the other OPMDs. OL patients reported fewer problems for the dimension, "physical impairment and functional limitations" than the OLP and OSF patients. A significant trend was observed with the overall OPMDQoL and MCS, deteriorating as the disease stage increased. CONCLUSIONS: OLP and OSF have a significant impact on the QoL of affected individuals: OL less so. Increasing stage of the disease is associated with worsening QoL.

Evaluation of efficacy of aloe vera in the treatment of oral submucous fibrosis - a clinical study.

BACKGROUND: Oral submucous fibrosis is a chronic disease, treatment of which has largely been symptomatic. Aloe vera has immunomodulatory, anti-inflammatory, wound healing, antioxidant, and antineoplastic activities. All such properties of aloe vera suggest the possibility of its use in the management of oral submucous fibrosis. METHODS: Seventy-four patients of oral submucous fibrosis were randomly divided into 2 groups. Group A patients were treated with systemic (juice) and topical aloe vera (gel) for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with antioxidant supplements for 3 months. Patients were assessed for reduction in burning sensation and increase in mouth opening, cheek flexibility, and tongue protrusion at an interval of 1, 2, and 3 months. RESULTS: Both the groups showed statistically significant improvements in all the study parameters at the end of study period (P < 0.001). The clinical response to aloe vera was comparable to that of intralesional injections of hydrocortisone and hyaluronidase with antioxidant supplementation. CONCLUSION: The study concludes that aloe vera can be an alternative, safe, and effective treatment regime in the management of oral submucous fibrosis. Long-term follow-up studies with larger sample size are recommended.

Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies.

Limited mouth opening (LMO) in oral submucous fibrosis (OSF) has been attributed to both the submucosal and muscle fibrosis (MF). While reflectory trismus was proposed before as an auxiliary mechanism by another group, the stretch-mediated muscle damage (MSD), histopathological changes in blood vessels (such as endothelial dysfunction, endothelial hypertrophy, and endarteritis obliterans), and upregulated anaerobic isoforms of lactate dehydrogenase (LDH) have been proposed by us as complementary events leading to MF. Additionally, the amount of hypoxia-mediated upregulation of anaerobic isoforms of LDH determines the extent of MF. Radiotherapy (RT)-mediated release of reactive oxygen species causes vascular damage thereby worsening hypoxia. While the alteration in LDH levels secondary to hypoxia enhances fibrosis, RT worsens it. Oral squamous cell carcinoma occurring in the background of OSF is an absolute contraindication for RT as it augurs unfavorable prognosis. An algorithm to demonstrate this with evidence is clearly depicted. The role of HIF-1α in the progression of OSF and its malignant transformation, and the consideration of hyperbaric oxygen therapy as a therapeutic remedy in OSF are underscored.

Surgical defect coverage in oral submucous fibrosis patients with single-stage extended nasolabial flap.

PURPOSE: Long standing oral submucous fibrosis (OSMF) is associated with involvement of the oral submucosa and the muscles of mastication leading to difficulty in mouth opening. Various surgical modalities are mentioned for release but each has its own limitations. The aim of the study was to evaluate the postoperative mouth opening in patients of OSMF after excision of fibrous bands followed by coronoidotomy and surgical defect coverage by extended nasolabial flap. METHODS: We evaluated the use of extended nasolabial flaps and coronoidectomy in the management of 11 randomly selected patients with histologically confirmed oral submucous fibrosis. They all had interincisal opening of less than 25 mm and were treated by bilateral release of fibrous bands, coronoidectomy or coronoidotomy, and extended grafting with a nasolabial flap. RESULT: Their interincisal opening improved significantly from a mean of 8.68±7 mm to a mean of 36.75±4.05 mm at 6-month follow-up. CONCLUSION: The procedure was effective in the management of patients with oral submucous fibrosis, the main disadvantage being the extraoral scars.

Efficacy of buccal fat pad in the surgical management of oral submucous fibrosis: a prospective study.

PURPOSE: Various surgical treatment modalities have been advocated in the surgical management of oral submucous fibrosis with variable results. This prospective study evaluates the efficacy of buccal fat pad in the surgical treatment of oral submucous fibrosis. PATIENTS AND METHOD: In the present study, 20 patients were treated for oral submucous fibrosis with interincisal mouth opening less than 16 mm. Surgical procedure included fibrotomy, all third molar extractions, and coronoidotomy or coronoidectomy followed by reconstruction of fibrotomy defect with buccal pad of fat. Postoperatively, patients were prescribed nutritional and antioxidant supplements along with vigorous mouth opening exercise for 6 months. Regular follow-up was carried out for 2 years. RESULTS: Excellent increase in the interincisal mouth opening was noticed relieving trismus. Patient's ability of masticate and tolerance to regular food was increased significantly. Buccal fat pad underwent rapid epithelization within a period of 5-7 weeks. CONCLUSION: Buccal fat pad can be used effectively in the surgical management of oral submucous fibrosis with good functional and esthetic outcome, with only drawback of supple lobulated fat, which requires delicate handling and its limitation to reach anteriorly beyond the canine region.

Evaluation of hearing deficit in patients with oral submucous fibrosis.

Oral submucous fibrosis (OSMF) is a well recognized premalignant condition predominantly affecting the oral cavity, but sometimes extending to the pharynx, esophagus or even the larynx. OSMF may lead to stiffness of the oral cavity, resulting in trismus and inability to eat, difficulty with speech or swallowing, pain in the throat and ears, and a relative loss of auditory acuity. To evaluate the hearing deficit in patients with OSMF, we examined a study group comprising 40 patients, and also 10 age- and sex-matched healthy subjects as controls. All of the subjects were evaluated for hearing loss by pure tone audiometry. The OSMF group showed a significant degree of hearing loss relative to the control group. OSMF in advanced stages was significantly associated with mild conductive hearing loss (P < 0.01). The present study revealed a significant association between OSMF and hearing deficit. Involvement of the palatal muscles with OSMF may decrease the patency of the Eustachian tube, leading to conductive hearing loss. Therefore, all patients with OSMF should be evaluated for hearing deficit and advised about appropriate treatment.

Sphingosine-1-phosphate stimulated connective tissue growth factor expression in human buccal fibroblasts: Inhibition by epigallocatechin-3-gallate.

BACKGROUND/PURPOSE: Connective tissue growth factor (CCN2) has been associated with the pathogenesis of various fibrotic diseases, including oral submucous fibrosis (OSF). The chemical constituents of areca nut along with the mechanical trauma cause OSF. The coarse fibers of areca nut injure the mucosa and hence sphingosine-1-phosphate (S1P) is released at the wounded sites. Recent studies have shown that S1P is involved in wound healing and the development of fibrosis. The aims of this study were to investigate the effects of S1P on CCN2 expression in human buccal fibroblasts (HBFs) and identify the potential targets for drug intervention or chemoprevention of OSF. METHODS: Western blot analyses were used to study the effects of S1P on CCN2 expression and its signaling pathways in HBFs and whether epigallocatechin-3-gallate (EGCG), the main and most significant polyphenol in green tea, could inhibit this pathway. RESULTS: S1P significantly enhanced CCN2 synthesis in HBFs. This effect can be inhibited by c-Jun NH2-terminal kinase (JNK) inhibitor and extracellular signal-regulated kinase inhibitor but not by P38 mitogen-activated protein kinase inhibitor. Interestingly, EGCG completely blocked S1P-induced CCN2 expression via suppressing S1P-induced JNK phosphorylation. CONCLUSION: S1P released by repetitive mechanical trauma during AN chewing may contribute to the pathogenesis of OSF through upregulating CCN2 expression in HBFs. EGCG could be an adjuvant to the current offered therapy options or the prevention of OSF through suppression of JNK activation.

Restricted mouth opening and trismus in oral oncology.

Restricted mouth opening (RMO) and trismus are terms commonly used in oral oncology in instances where there is difficulty in mouth opening. The term trismus in oral oncology is mainly used to indicate the radiation-induced fibrosis of the muscles of mastication. The treatment given for RMO as reported in the literature is given for muscular dysfunction trismus, whereas RMO in oral oncology can occur owing to various reasons other than muscular dysfunction. RMO occurs in various conditions of the oral cavity; in posterior pharyngeal infection, where it is termed reflectory trismus; in oral submucous fibrosis; in oral mucosal disorders; in the use of certain drugs; and in minor dental procedures of the posterior oral cavity. The usage of the term trismus in all RMO cases would complicate the treatment; thus, the word should not be used in all RMO cases.

Assessment of cross-sectional thickness and activity of masseter, anterior temporalis and orbicularis oris muscles in oral submucous fibrosis patients and healthy controls: an ultrasonography and electromyography study.

OBJECTIVES: Oral submucous fibrosis (OSMF) is an insidious chronic disease that is associated with significant functional morbidity and an increased risk for malignancy. It initially affects the lamina propria of the oral mucosa, and, as the disease progresses, it involves the submucosa and deeper tissue, including muscles of the oral cavity, resulting in loss of fibroelasticity. OSMF is a pre-malignant condition mainly caused by areca nut chewing. The aim of this study was to find out the involvement of muscles of mastication and facial expression in patients with OSMF by assessing the cross-sectional thickness and activity of the masseter, anterior temporalis and orbicularis oris muscles by ultrasonography and electromyography and comparing with healthy controls and also to find out any correlation between the ultrasonographic cross-sectional thicknesses of the masseter, anterior temporalis and orbicularis oris muscles with electromyographic activity. METHODS: 40 patients with OSMF were included in the study group, and the patients were divided into four groups on the basis of interincisal mouth opening, i.e. Group I (mouth opening >35 mm), Group II (mouth opening between 30 and 35 mm), Group III (mouth opening between 20 and 30 mm) and Group IV (mouth opening <20 mm). Ultrasonographic cross-sectional thickness and electromyographic activity (amplitude and duration) of the masseter, anterior temporalis and orbicualris oris muscles were recorded in patients with OSMF and 20 controls. Intergroup comparison of ultrasonographic cross-sectional thickness and activity (amplitude and duration) was done, and Pearson's correlation coefficient was applied to find out any relation between ultrasonographic and electromyographic findings. RESULTS: Thickness and activity of the masseter muscle was significantly reduced in Group IV (mouth opening <20 mm) when compared with the control group. The anterior temporalis and orbicularis oris muscles remained unaffected. A positive correlation was observed between the thicknesses of the masseter muscle and the amplitude in Groups I, II and III; the anterior temporalis muscle in Group II and the control group; and the orbicularis oris muscle in Groups II, III and IV. CONCLUSIONS: It was concluded that, among the muscles studied, there was an early involvement of the masseter muscle in patients with OSMF compared with that of other muscles.

Expression of transforming growth factor â and its correlation with lipodystrophy in oral submucous fibrosis: An immunohistochemical study

Objective: In our routine review of Oral Submucous Fibrosis (OSMF) biopsies, we observed decreased adipose tissue even though most are from buccal mucosa. Pathogenesis of OSMF has demonstrated the role of Transforming Growth Factor â (TGF â), in causing fibrosis. This study aims to correlate the role of TGF â with loss of adipose tissue in OSMF. Study Design: From our archives, 84 OSMF cases (24 early and 60 advanced OSMF) were screened for adipose tissue. Immunoexpression of TGF â in these cases were investigated. Results: Adipose tissue was seen in 67% of early OSMF and in 13% of advanced cases. Early cases showed more intense TGF â staining of epithelium, fibroblast, macrophages and inflammatory cells than the advanced cases. Conclusion: These findings suggest that TGF â plays a key role in causing lipodystrophy in OSMF and is secreted more during early course of the disease than in advanced stage (AU)

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Extended nasolabial flap compared with the platysma myocutaneous muscle flap for reconstruction of intraoral defects after release of oral submucous fibrosis: a comparative study.

We compared extended nasolabial flaps and coronoidectomy with platysma myocutaneous muscle flaps in the management of 20 randomly selected patients with histologically confirmed oral submucous fibrosis. Ten patients were treated by release of fibrous bands, bilateral coronoidectomy, and reconstruction with an extended nasolabial flap (nasolabial group), and the other 10 by bilateral release of fibrous bands, coronoidectomy, and reconstruction with a platysma myocutaneous muscle flap (platysma group). In the nasolabial group the mean preoperative interincisal mouth opening was 12(range 3-14)mm, and in the platysma group it was 11 (3-13). All 20 patients were given vigorous postoperative physiotherapy, and were followed up for 3 years. The interincisal mouth opening improved to 47(35-45)mm in the nasolabial group and 48(41-52)mm in the platysma group. The procedures were equally effective in the management of the oral submucous fibrosis, except that the extraoral scar was not aesthetically acceptable in the nasolabial group.