Histologic examination of pedicled buccal fat pad graft in oral submucous fibrosis.

PURPOSE: This report evaluates the wound healing process of buccal fat pad (BFP) grafted on a defect of the buccal mucosa for oral submucous fibrosis (OSF). PATIENTS AND METHODS: Sixteen patients with limitation of mouth opening under the diagnosis of OSF were surgically treated by cutting the fibrotic bands on the buccal mucosa (10 bilateral and 6 unilateral). The defects created were then covered by a BFP graft. The bulging BFP was trimmed postoperatively on a weekly basis until it was fully epithelialized. The specimens were stained and examined microscopically. RESULTS: Inflammatory cell infiltrate, blood vessel congestion, and fibrinous exudates covering the BFP were obvious by week 2. At week 3, blood vessel congestion and fat cell number decreased markedly. Evidence of stratified squamous epithelium with parakeratosis was seen in the margin of the BFP graft. At week 4, the number of fat cells decreased significantly and the original BFP was almost completely replaced by granulation tissue. The original BFP was fully covered by stratified squamous epithelium by week 5. CONCLUSIONS: The BFP graft has been widely used for covering exposed defects created by fibrotic band excision for the improvement of mouth opening limitation. The healing process was documented microscopically by weekly observation.     

p53 aberrations in oral submucous fibrosis and oral squamous cell carcinoma detected by immunocytochemistry and PCR-SSCP

Trivedy C, Warnakulasuriya KAAS, Tavassoli M, Steingrimsdottir H, Penhallow J, Maher R, Johnson NW: p53 aberrations in oral submucous fibrosis and oral squamous cell carcinoma detected by immunocytochemistry and PCR-SSCP. J Oral Pathol Med 1998; 27: 72–7. © Munksgaard, 1998.
An archival series of oral biopsies from Karachi, Pakistan, consisting of 21 cases of oral submucous fibrosis (OSF) and 27 cases of squamous cell carcinoma (SCC), of which 6 had arisen from OSF, were used to examine the aberrations in the structure and expression of the p53 tumour suppressor gene. The PCR-SSCP method was used for mutation analysis of exons 2–9, and (over)expression of p53 protein was detected by immunocytochemistry using monoclonal antibody DO 7. Positive immunostaining was observed in 15/20 (75%) of OSF specimens, 3/6 (50%) of SCC arising from OSF and 14/21 (67%) of SCC not arising from OSF. Mobility shifts in SSCP indicative of a mutation in p53 or loss of heterozygosity (deletion of a band) were seen in 13/21 cases of OSF and 15/27 cases of SCC. There was concordance between immunocytochemistry and SSCP results in a majority (33/48) of samples. Though the number of analysed SCC cases arising from OSF was limited, the results suggest that p53 mutation/protein stabilisation may play a part in the pathogenesis of OSF and its progression to SCC.     

口腔粘膜下纤维性变临床分型探讨

目的：为提高口腔粘膜下纤维性变（ＯＳＦ）的临床检出率和诊断率。方法：对湖南省湘潭市１１０４６人进行口腔普查将检出的３３５名ＯＳＦ患者按不同临床表现分为弥漫型和局限型,其中具有ＯＳＦ典型临床表现者为弥漫型,其它为局限型,并于１０年后复查了其中７２名患者。结果：３３５名患者中弥漫型仅１３例,占３．９％,局限型３２２例,占９６．１％。复查显示：在无适当治疗下,两型之间无相互转化。结论：局限型ＯＳＦ是湘潭     

Alterations in expression of retinoid receptor beta and p53 in oral submucous fibrosis

OBJECTIVE: Knowledge of the molecular pathogenesis of oral submucous fibrosis (OSF), a potentially malignant condition with high risk of transition to oral cancer, is meagre. Alterations in the expression of retinoic acid receptor beta (RARbeta) and tumor suppressor gene, p53 are early events in oral tumorigenesis. The aim of this study was to investigate the alterations in the expression of RARbeta and p53 in OSF lesions and determine their association with disease pathogenesis. METHODS: The expression of RARbeta and p53 proteins was analyzed by immunohistochemistry in 50 cases of OSF and 30 histologically normal oral tissues. RESULTS: No detectable RARbeta expression was observed in 35 of 50 (70%) OSF cases. p53 protein accumulation was observed in 24 of 50 (48%) OSF cases analyzed. Thirty-six percent OSF lesions showed loss of RARbeta and p53 overexpression. Interestingly, 41 of 50 (82%) of OSF lesions showed altered expression of at least one of these two proteins. CONCLUSION: Altered expression of either RARbeta or p53 in majority of OSF lesions suggests their association with disease pathogenesis and warrants follow-up to determine whether OSF lesions harboring concomitant alterations in RARbeta and p53 are at a high risk of transition to malignancy.     

Oral administration of milk from cows immunized with human intestinal bacteria leads to significant improvements of symptoms and signs in patients with oral submucous fibrosis

BACKGROUND: Previous studies have shown that the local and systemic upregulation of fibrogenic cytokines and downregulation of antifibrotic cytokine are central to the pathogenesis of oral submucous fibrosis (OSF). The milk from cows immunized with human intestinal bacteria (immune milk) contains an anti-inflammatory component that may suppress the inflammatory reaction and modulate cytokine production. Therefore, it was decided to test whether immune milk may have some beneficial effects on controlling the symptoms and signs in OSF patients. METHODS: In this preliminary study, 26 OSF patients who received immune milk treatment (45 g of immune milk powder twice a day) for 3 months and oral habit intervention were included in the experimental group. Another 20 OSF patients who received only oral habit intervention served as the control group. RESULTS: We found that the interincisor distance was significantly improved (> or =3 mm of the baseline measurement) in 18 of the 26 (69.2%) OSF patients in the experimental group at exit. However, in the control group none of the OSF patients had an increase in interincisor distance greater than 2 mm. In addition, disappearance or significant improvement of symptoms at exit was observed in 80% (16/20) of the patients with intolerance to spicy foods (P < 0.001) and 72.2% (13/18) of the patients with xerostomia (P < 0.005) in the experimental group, compared with 17.6% (3/17) of the patients with improvement of intolerance to spicy foods and 15.4% (2/13) of the patients with improvement of xerostomia in the control group. Partial regression of concomitant oral leukoplakia or erythroplakia (judged from the size reduction of the lesions) at exit was noted in 71.4% (5/7) of the patients in the experimental group (P < 0.05), compared with none (0/5) of the patients with improvement in the control group. CONCLUSION: We conclude that oral administration of immune milk leads to significant improvements of symptoms and signs in OSF patients.     

Treatment of oral submucous fibrosis by collagenase: effects on oral opening and eating function

OBJECTIVE: Patients with oral submucous fibrosis (OSF) suffer from the limitation of the oral opening. The aim of this study was to develop a simple and rapid method to improve the opening of the oral cavity and determine its effect on the incidence of developing oral carcinoma. METHODS: We first induced an OSF-like lesion in rabbits which histopathologically resembles OSF in betel nut chewers and evaluated the effects of exogenous collagenase on these lesions. We then applied the collagenase treatment regimen to patients with OSF. RESULTS: Endogenous collagenase activities in normal oral mucosa of patients exhibited 3- to 5-fold higher levels than that of OSF tissues. The collagenase treatment not only resulted in a significant improvement of oral opening, but patients also experienced a striking reduction in hypersensitivity to spices, sour, cold, and heat which helped restore eating function. Sub-mucosal fibrous proliferation, persistently good vascularization, and a mild increase in thickness of the sub-mucosal fibrous tissues were noticed 10 months after collagenase treatment. Within the 2-year follow-up period none of the treated patients developed an oral squamous cell carcinoma. CONCLUSION: A reduced content of functional collagenase observed in OSF mucosa of patients might be one mechanism responsible for collagen accumulation. Intervention of OSF by collagenase treatment at the early stage may reduce the incidence of developing oral carcinoma.     

Physiotherapeutic treatment improves oral opening in oral submucous fibrosis

Background:  In oral submucous fibrosis (OSF) fibrous bands and burning mucosal pain restrict oral opening to limit speech and eating. The pathogenesis of OSF remains unclear, while surgical and pharmacological treatments have limited success, and are often inaccessible in communities using areca nut where OSF is prevalent. Improved outcomes are reported for surgical treatment when followed by physiotherapy. We tested the hypothesis that physiotherapy alone can modify tissue remodelling in OSF to increase oral opening.
Materials and methods:  Fifty-four Nepali OSF patients were managed for 4 months in three randomly assigned groups receiving either: five times daily physiotherapy by inter-positioning tongue spatulas between teeth and adding a new spatula every 5–10 days; local injection of hyaluronidase with steroids; or no active treatment.
Results:  More males presented with OSF than females ( p  < 0.05). All patients reported reduced opening and 47% had mucosal pain. Progressive mucosal involvement was always in the same order, starting with the soft palate, and then progressing to the fauces, unilateral buccal mucosa, bilateral buccal mucosa, floor of mouth and finally lip mucosa ( p  < 0.006). Physiotherapy improved oral opening ( p  < 0.0005), but not oral pain, while no clear improvement was seen in untreated patients as well as patients managed by injection.
Conclusions:  We conclude OSF in the Nepali population progresses in a predictable pattern, and that physiotherapy is effective for increasing the oral opening. We further suggest physiotherapy can be readily used to improve OSF in communities with otherwise limited health resources.     

口腔黏膜下纤维化癌变过程中G2、M期细胞周期蛋白与存活素磷酸化的研究

目的 探讨细胞周期G2、M期重要分子细胞周期蛋白B1(Cyclin B1)、细胞分裂周期蛋白2(cell division cycle 2,p34cdc2)和存活素磷酸化在口腔黏膜下纤维化(oral submucosa fibrosis,OSF)癌变过程中的作用与意义.方法 应用Western blotting检测10例正常口腔黏膜上皮组织、40例OSF上皮组织及42例OSF癌变组织中Cyclin B1、p34cdc2和存活素磷酸化的表达情况,免疫共沉淀实验分析p34cdc2激酶与存活素的相关性.结果 Cyclin B1、p34cdc2、磷酸化p34cdc(p-p34cdc2)和存活素磷酸化在OSF组织中表达显著高于正常口腔黏膜(P＜0.05);在OSF癌变组织中的表达显著高于OSF组织(P＜0.05);但在OSF早、中、晚期3组间差异无统计学意义(P＞0.05).免疫共沉淀实验证实了p34cdc与存活素的结合.结论 细胞周期G2、M期重要分子Cyclin B1、p34cdc2及存活素磷酸化在OSF细胞分裂增殖过程中起促进作用,对OSF癌变的早期诊断和治疗具有重要的临床意义.     

PTPRZ1在口腔黏膜下纤维性变癌变中的表达及临床意义

目的:研究蛋白酪氨酸磷酸酶Z1型受体(PTPRZ1)蛋白在口腔黏膜下纤维性病变(OSF)癌变中的表达及分布特征,探讨其在OSF癌变发生、发展过程中的作用及临床意义.方法:利用免疫组织化学(immunohistochemistry,IHC)及蛋白印迹技术(Western blot,WB)检测36例OSF癌变患者、23例非OSF癌变鳞癌患者及21例身体健康者颊黏膜组织中PTPRZ1蛋白分布及表达差异.采用SPSS 21.0软件包对数据进行统计学分析.结果:免疫组织化学结果显示,PTPRZ1蛋白在OSF癌变组的颊黏膜中呈阳性表达,阳性表达率为72.22％;在非OSF癌变的颊黏膜鳞癌组织中呈弱阳性表达,表达率为43.47％;在正常颊黏膜组织中呈阴性表达.PTPRZ1蛋白在OSF癌变组及非OSF癌变组中的表达显著高于正常对照组(P＜0.01);OSF癌变组显著高于非OSF癌变的口腔癌组(P＜0.05).Western印迹结果显示,PTPRZ1在正常组织中不表达,在非OSF癌变的口腔鳞癌中微量表达,在OSF癌变组中显著表达.PTPRZ1与一般临床资料相关性分析发现,PTPRZ1与复发及转移呈显著正相关性(rk=0.642,P＜0.01;rk=0.656,P＜0.01).结论:PTPRZ1在OSF癌变的发生、发展及侵袭、转移过程中发挥重要作用,可作为早期诊断分子标志物及治疗的靶基因.     

口腔黏膜下纤维化中细胞凋亡及Bcl-2和Bax的表达

目的：检测口腔黏膜下纤维化（OSF）组织中细胞凋亡状况及Bcl-2和Bax的表达,探讨OSF的发病机制。方法：采用TUNEL测定法、免疫组织化学SP法分别检测45例OSF和10例正常口腔黏膜组织中凋亡细胞的数量及Bcl-2、Bax的表达情况。结果：OSF晚期上皮中的凋亡指数明显高于正常对照组和OSF早、中期组（P〈0.05）,以空泡变性的棘层细胞为主;Bcl-2在OSF晚期组表达高于正常对照组（P〈0.05）,Bax在OSF晚期表达高于早期组（P〈0.05）;Bcl-2/Bax的比值与AI无直线相关关系（P〉0.05）。结论：细胞凋亡可能是OSF晚期上皮萎缩的主要原因之一,Bcl-2、Bax参与了OSF的细胞凋亡,Bax在OSF晚期发挥重要作用。     

核受体共激活因子7在槟榔碱诱导的上皮间充质转化中的生物学功能

目的研究核受体共激活因子7(nuclear receptor coactivator 7,NCOA7)在口腔黏膜下纤维性变(OSF)中的表达及意义,并探讨其在人口腔角质细胞株HOKs间充质转化过程中的作用。方法收集OSF组织30例及正常口腔黏膜组织15例,采用免疫印迹法检测NCOA7、上皮间充质转化相关标记物在OSF组织及正常黏膜组织中蛋白水平的表达情况;以Western blot法检测槟榔碱刺激后HOKs中NCOA7、上皮及间充质标记物的蛋白水平变化。结果 NCOA7在30例OSF组织高表达(P<0.05);同时在细胞基底层出现间充质标记物的阳性表达。NCOA7在槟榔碱刺激的HOKs中高表达,且具有槟榔碱浓度依赖性(P=0.004 3);随着槟榔碱浓度的升高,上皮标志物表达逐渐下调,间充质标记物表达逐渐升高。结论口腔黏膜下纤维性变组织中高表达的NCOA7,可能参与调控上皮细胞间充质转化过程,进一步促进纤维化进程。     

口腔黏膜下纤维性变及其癌变组织中端粒酶逆转录酶表达

目的:探讨人端粒酶逆转录酶(hTERT)在口腔黏膜下纤维性变(OSF)癌变过程中的作用。方法:用免疫组织化学SP法检测10例正常口腔黏膜组织,46例OSF组织,14例OSF癌变组织以及10例相邻非癌变OSF组织中hTERT表达情况。结果:正常口腔黏膜组织上皮中无hTERT阳性表达,OSF癌变组织中hTERT阳性表达率(12/14)明显高于OSF组(7/46)(P<0.005),相邻非癌变OSF组织中hTERT阳性表达率(7/10)明显高于普通OSF组(7/46)(P<0.005)。结论:hTERT蛋白过度表达在OSF癌变过程中具有重要作用。     

Interferon gamma (IFN-γ) may reverse oral submucous fibrosis

Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity and oropharyngx characterised by fibrosis in the submucosa leading to progressive limitation of the mouth opening. Interferon gamma (IFN-gamma) is a known anti-fibrotic cytokine. In this study we have investigated: a) the effect of IFN-gamma on collagen synthesis by arecoline-stimulated OSF fibroblasts in vitro (n=5), b) the effect of intra-lesional IFN-gamma on the fibrosis of OSF patients (n=29) and c) the immunohistochemical analysis of pre- and post-treatment inflammatory cell infiltrates and cytokine levels in the lesional tissue (n=29). The results show that the increased collagen synthesis in vitro in response to arecoline was inhibited in the presence of IFN-gamma (0.01-10.0 U/ ml) in a dose-related way. In an open uncontrolled study intra-lesional IFN-gamma treatment showed improvement in the patients mouth opening from an inter-incisal distance before treatment of 21 +/- 7 mm, to 30 +/- 7 mm immediately after treatment and 30 +/- 8 mm 6-months later, giving a net gain of 8 +/- 4 mm (42%) (range 4-15 mm). Patients also reported reduced burning dysaesthesia and increased suppleness of the buccal mucosa. The post-treatment immunohistochemistry showed a decreased amount of inflammatory cell infiltrate and an altered level of cytokines compared with the pre-treatment lesional tissue. The effect of IFN-gamma on collagen synthesis appears to be a key to the treatment of these patients, and intra-lesional injections of the cytokine may have a significant therapeutic effect on OSF.     

Survivin磷酸化在口腔黏膜下纤维性变及其癌变组织中的表达

目的检测凋亡抑制蛋白Survivin活性形式——Survivin Thr34位磷酸化(p-Survivin)在口腔黏膜下纤维性变及其癌变组织中的表达,探讨Survivin在OSF癌变过程中的作用及意义。方法应用免疫组化SP法检测10例正常口腔黏膜组织、40例OSF组织及42例OSF癌变组织中p-Survivin的表达,并以Western Blot分析p-Survivin的表达。结果正常口腔黏膜上皮组织中无p-Survivin表达;OSF癌变组p-Survivin阳性表达率(97.6%)高于OSF组(50.0%);而OSF早、中、晚期3组间p-Survivin阳性表达率无显著性差异。Western Blot验证了免疫组化的检测结果。结论p-Survivin在OSF癌变过程中可能起促进作用,为OSF早期诊断和治疗提供理论依据。     

口腔黏膜下纤维性变的病因、致病机理、诊断与治疗

口腔黏膜下纤维性变是一种能形成瘢痕、组织纤维化的慢性疾病。流行病学研究显示,咀嚼槟榔是导致口腔黏膜下纤维性变的危险因素。在中国的口腔黏膜下纤维性变患者均有咀嚼槟榔的习惯。研究证实,嚼槟榔、吸烤烟和饮白酒可增加口腔黏膜下纤维性变的风险。口腔黏膜下纤维性变被广泛认为是一种口腔癌前病变,病理表现为慢性炎症、结缔组织内广泛的胶原纤维沉积、上皮固有层或其下结缔组织内的局部炎症改变。口腔黏膜下纤维性变的癌变发生率为7%~30%。口腔黏膜下纤维性变的治疗主要采用曲安奈德和丹参酮注射液行黏膜下局部注射,对改善患者的张口度及口腔黏膜的烧灼痛效果良好,其治疗总有效率可达93%。本文就口腔黏膜下纤维性变的病因、致病机理、诊断与治疗进行阐述,以供同道们临床参考之用。     

单核细胞趋化蛋白-1在口腔黏膜下纤维性变中的表达及意义

目的：探讨单核细胞趋化蛋白-1（MCP-1）在口腔黏膜下纤维性变（OSF）组织中的表达及其意义。方法：应用免疫组织化学SP法检测45例OSF和15例正常口腔黏膜组织中MCP-1的表达及分布情况。结果：OSF组织中MCP-1的表达较正常组织增加,差异有统计学意义（P〈0.01）,MCP-1在OSF早期组织与中、晚期组织中的表达有显著性差异（P〈0.05）。结论：MCP-1可能通过趋化、激活免疫和炎症细胞,在OSF发生发展中发挥重要作用。     

Is buccal fat pad a better option than nasolabial flap for reconstruction of intraoral defects after surgical release of fibrous bands in patients with oral submucous fibrosis? A pilot study: A protocol for the management of oral submucous fibrosis

PurposeThe aim this study was to compare the buccal fat pad (BFP) and nasolabial flap for reconstruction of intraoral defects after release of fibrous bands in patients with oral submucous fibrosis (OSF).Materials and methodsThis is a comparative study. The study sample was derived from the population of patients who presented, with restricted mouth opening of less than 20 mm, to the Department of Oral and Maxillofacial Surgery, Swargiya Dada Saheb Kalmegh Dental College and Hospital Hingna Nagpur. The patients were divided into two groups. In Group I (n = 10) reconstruction was performed with a nasolabial flap and in Group II (n = 10) with BFP. Both groups were analysed separately for mouth opening (interincisal distance in millimetres) preoperatively and 20 months postoperatively, time taken for epithelialization of BFP and nasolabial flaps. Statistical analysis was performed with SPSS statistical software for Windows, version 8.0 (SPSS, Inc, Chicago, IL) using the _2 test and Student's t test.ResultsIn all 20 patients the interincisal mouth opening was (mean) 11 mm (3–19 mm) preoperatively which improved to a mean of 42 mm (23–52 mm). In Group I there were more complications as compared to Group II such as partial flap necrosis particularly at the tips, temporary widening of oral commissure and subluxation of TMJ. The unsightly extraoral scar and intraoral growth of hairs were not seen in Group II.ConclusionBFP is the better choice for reconstruction in comparison to nasolabial flap.     

Oral submucous fibrosis in Asian countries

Oral submucous fibrosis (OSF) is a chronic, insidious, and progressive oral mucosal disease that affects entire oral cavity and sometimes pharynx. This oral potentially malignant disorder has a high rate of malignant transformation (7%-30%) to oral squamous cell carcinoma (OSCC), posing global problems for public health. Due to enormous efforts dedicated to this disease in the past decades, there have been significant advances in identification of its etiology and pathogenesis as well as development of corresponding therapeutic approaches, in spite of several challenges. This study reviewed the existing literature concerning OSF in Asian countries, encompassing its etiology, histopathology, pathogenesis, clinical manifestations, diagnosis and differential diagnosis, and treatments. For improving treatment of OSF, the multifactorial etiology analysis, incorporation of effective molecular pathways, cytokines and cells for mechanism illustration, and integration of multidisciplinary modalities were also expounded to guide future research and clinical practice.     

RUNX3和RASSF1A在口腔黏膜下纤维性变及其癌变组织中的表达

目的：研究Runt相关转录因子3（RUNX3）、RAS相关区域家族1A（RASSF1）在口腔黏膜下纤维性变（OSF）及其癌变组织中的表达与分布,初步探讨二者在OSF癌变过程中的作用。方法：采用免疫组织化学SP法检测10例正常口腔黏膜组织、35例OSF组织、10例OSF癌变组织中RUNX3、RASSF1A蛋白的表达及分布。结果：RUNX3在正常口腔黏膜组阳性表达率为90.00%（9/10）,OSF组为85.71%（30/35）,OSF癌变组为30.00%（3/10）,正常对照组与OSF组无统计学差异,OSF癌变组显著低于正常对照组（P〈0.05）及OSF组（P〈0.05）。RASSF1A在正常口腔黏膜组阳性表达率为80.00%（8/10）,OSF组为62.86%（22/35）,OSF癌变组为20.00%（2/10）,正常对照组与OSF组无统计学差异,OSF癌变组织组显著低于正常对照组（P〈0.05）及OSF组（P〈0.05）。结论：RUNX3和RASSF1A表达下调或缺失与OSF癌变有关。