口腔黏膜癌前病变和口腔癌动物模型的研究进展

口腔黏膜癌前病变和口腔癌是发展中国家的常见疾病尤其是在南亚地区,其癌变机制尚不明确,目前缺乏有效防治措施,因此口腔黏膜癌前病变及口腔癌动物模型建立显得尤为重要。本文结合相关研究,就近年来口腔黏膜癌前病变及口腔癌动物模型建立方法的进展作一综述。     

Successful treatment of mucous membrane pemphigoid with tacrolimus

Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune, chronic inflammatory subepithelial vesiculobullous disorders. It predominantly affects the mucous membranes of the oral cavity and eyes of the elderly population. Oral manifestations of pemphigoid include desquamative gingivitis, ulcers, erythematous patches, erosions, vesicles and bullae located on the attached gingiva, palate, buccal mucosa, labial mucosa, and tongue. Diagnosis is based on history, clinical features and a biopsy stained with hematoxylin and eosin (H&E), and also direct and indirect immunofluorescence. Topical and systemic corticosteroids are the most commonly used medications for managing pemphigoid. Recently, topical tacrolimus has been successfully used in the treatment of ocular and skin pemphigoid. In this report we present a patient with longterm recalcitrant MMP that did not respond to conventional treatment but was treated successfully with tacrolimus ointment.     

Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients

To cite this article:
Int J Dent Hygiene 10 , 2012; 138–141
DOI: 10.1111/j.1601‐5037.2010.00527.x Arduino PG, Lopetuso E, Carcieri P, Giacometti S, Carbone M, Tanteri C, Broccoletti R. Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients. Abstract: Objectives: The aim of this prospective case series was to assess the clinical efficiency of an oral hygiene protocol in patients affected by mucous membrane pemphigoid (MMP) with specific gingival localization, before starting any medical treatment. Methods: Patients received oral hygiene instruction followed by non‐surgical periodontal therapy including oral hygiene instructions in a 3‐week cohort study. Clinical outcome variables were recorded at baseline and 5 weeks after intervention and included, as periodontal parameters, full mouth plaque (FMPS) and bleeding (FMBS) scores and patient‐related outcomes (visual analogue score of pain). Results: A total of 12 patients were recruited. The mean age at presentation was 59.5 ± 14.52 years. Five weeks after finishing the oral hygiene and periodontal therapy protocol, a statistical significant reduction was observed for FMPS (P = 0.001), FMBS (P = 0.022) and reported pain (P = 0.0028). Conclusions: Professional oral hygiene procedures and non‐surgical periodontal therapy are connected with improvement of gingival status and decrease in gingival‐related pain, in female patients affected by MMP with specific gingival localization.     

Benign mucous membrane pemphigoid with linear IgA deposits in oral mucosa

Two patients with severe oral ulcerations and concomitant lesions in the nose, eyes and genitals were examined. The immunofluorescence (IFL) studies of buccal and genital mucosa revealed that the only deposited immunoglobulin was IgA. Immunoelectron microscopy confirmed the linear pattern of IgA deposition and localized IgA in lamina lucida in both patients. Dapsone 50 mg daily was effective in controlling the disease activity partially in the first and completely in the second patient. The results suggest that our patients had benign mucous membrane pemphigoid (BMMP) with linear IgA deposition but do not exclude a mucosal form of a newly recognized bullous skin disease termed linear IgA disease.     

The management of oral mucous membrane pemphigoid with dapsone and topical corticosteroid

Statement of problem:  Mucous membrane pemphigoid (MMP) is a chronic autoimmune subepithelial disease that primarily affects the mucous membranes of patients over the age of 50 years, resulting in mucosal ulceration and subsequent scarring.
Purpose:  The purpose of this study was to investigate the efficacy of dapsone in combination with topical corticosteroids to treat the oral lesions of MMP.
Materials and methods:  Twenty-two patients who had been diagnosed with MMP were selected. The oral features were graded according to severity of disease from 1 to 3. Each patient was assigned to one of four groups according to his or her response to therapy.
Results:  Five patients with mild to moderate disease were treated with topical corticosteroids alone for the duration of the study; 15 patients with moderate to severe disease were treated by topical corticosteroid with dapsone therapy. All of 15 patients had significant benefits.
Conclusions:  The use of dapsone in combination with topical corticosteroids is one of the most useful methods for the treatment of MMP.     

Urban legend series: mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune subepithelial blistering diseases affecting primarily mucous membranes showing marked degree of clinical and immunological variability. We investigated four controversial topics: (i) Does oral pemphigoid (OP) really exist as a separate entity? (ii) Is mucous membrane pemphigoid curable? (iii) What is the best therapeutic option for MMP? (iv) Does exclusive oral IgA dermatitis exist as a distinct entity from MMP? Results from extensive literature searches suggested that (i) it is still unclear whether patients with OP could be considered as a distinct subset of MMP with specific clinical and immunological features; (ii) it is uncertain whether treatment regimens that get MMP under control can be eliminated to allow patients to be in drug‐free remission or they should be continuously administered in some capacities; (iii) there is a concerning paucity of good‐quality trials on MMP and available recommendations are solely based on generally small patients' cohorts or case series. Some of the 2002 consensus experts' opinions should be possibly updated, particularly regarding the safety of sulfa drugs; (iv) we did not find any strong evidence to support an exclusive oral (and perhaps also mucosal) form of LAD as a separate entity.     

异体软组织修复材料在口腔颌面部缺损中的应用

目的 探讨异体软组织修复材料(异体脱细胞真皮基住)在口腔颌面外科应用的可行性。方法 选择口腔粘膜组织缺损患者46例，在创面上采用异体脱细胞真皮基质覆盖，并对修复后创面情况和组织病理进行观察。结果 所有口腔粘膜创面愈合良好，无1例出现排斥反应。经4～6月后组织学观察，异体脱细胞真皮基质处所生成的组织与正常粘膜组织不易区分。结论 异体脱细胞真皮基质可以作为口腔粘膜缺损的修复材料推广使用。     

Serum soluble CD44v6 levels in patients with oral and maxillofacial malignancy

Objective:  To determine the levels of serum sCD44v6 in patients with oral cancer and evaluate the value of serum sCD44v6 in adjuvant diagnosis, staging and monitoring treatment response in these patients.
Materials and Methods:  A total of 112 hospitalized patients with oral and maxillofacial malignancy and 28 healthy individuals were examined for serum sCD44v6 levels. Venous blood was collected from these patients and the healthy individuals. One week after treatment, venous blood was collected once again in 60 patients with oral and maxillofacial squamous cell carcinoma (OSCC).
Results:  The sCD44v6 concentration was not significantly different between patients with oral and maxillofacial malignancy and control group ( P  > 0.05). The levels of serum sCD44v6 in patients with OSCC and salivary carcinoma showed no difference with those in control group ( P  > 0.05). The sCD44v6 level in patients with stage III and IV disease was higher than that of patients with stage I and II and that of the control group, but the difference was not significant ( P  > 0.05).  Serum sCD44v6 levels in patients with OSCC after treatment became lower than that prevailed during pretreatment ( P  < 0.05).
Conclusion:  The possible roles of CD44v6 in the diagnosis of oral and maxillofacial malignancy deserve further elucidation and evaluation. Serum sCD44v6 may be a valuable marker in monitoring treatment response in patients with OSCC.     

TNF-α expression and apoptosis-regulating proteins in oral lichen planus: a comparative immunohistochemical evaluation

Apoptosis appears to be the mode of cell death by which damaged cells are removed from the lesional tissue in oral lichen planus (OLP). In the present study, OLP biopsies were immunohistochemically evaluated for TNF-alpha and apoptosis-regulating proteins in an attempt to compare their phenotypic expression. Deparaffinized tissue sections from 22 OLP and 10 control oral biopsy specimens were immunohistochemically stained with anti-Bcl-2, anti-Bcl-x, anti-Bax and anti-TNF-alpha antibodies. Keratinocytes did not show any immunoreactivity for Bcl-2, while a uniform intense staining for this protein was evident in the lymphocytic infiltrate of OLP specimens. Immunoreactivity for TNF-alpha was seen in 17/22 OLP cases. All control tissues were TNF-alpha negative, thus indicating a possible involvement of this cytokine in the pathogenesis of OLP The differences in the staining intensities of Bcl-x and Bax between OLP and normal epithelium were slight; therefore an obvious association of the phenotypic TNF-alpha expression with these apoptosis-regulating proteins was not apparent.     

Periodontal status in oral mucous membrane pemphigoid: initial results of a case‐control study

Oral Diseases (2010) 17 , 90–94 Objective: To evaluate the periodontal status of mucous membrane pemphigoid (MMP) patients and compare it with that of healthy controls. Methods: A prospective study was undertaken to examine the impact of gingival MMP lesions on the human periodontium of 29 patients. Parameters evaluated included full mouth plaque score (FMPS), full mouth bleeding upon probing scores, probing depths (PD), gingival recession, clinical attachment level (CAL), mobility score, furcation involvement, number of missing teeth and Machtei criteria. Results: All periodontal parameters recorded were increased in cases when compared to controls in univariate statistics. The mean differences between groups in PD (0.8 ± 0.2 mm, 95% CI 0.3–1.3), CAL (1.3 ± 0.4 mm, 95% CI 0.4–2.2), FMPS (41.0 ± 6.2%, 95% CI 28.7–53.4), FMBS (16.2 ± 6.6%, 95% CI 3.0–29.4) and tooth loss (2 ± 1 teeth, 95% CI 1–3) were all statistically significant (P < 0.01 for all). Substantial differences in domiciliary oral hygiene routines were observed (P < 0.0001). In multivariate models when FMPS was included as covariate the difference between groups in all clinical periodontal parameters was no longer statistically significant. Conclusions: Our results showed that periodontal status is worse in MMP patients if compared with healthy controls due to a substantial difference in oral hygiene. Oral health should be promoted in MMP.     

Alteration in peripheral blood mononuclear cell function and serum cytokines in oral lichen planus

Different activation parameters of peripheral blood mononuclear cells (PBMC) from 31 patients with oral lichen planus (OLP) were examined and compared with 23 healthy donors. Impaired spontaneous (450±241 vs 1290±480 cpm) and mitogen-induced (39580±14470 vs 67000±11810 cpm) lymphocyte blastogenesis was observed in OLP patients. Furthermore, reduced cytokine production was found after phytohemagglutinin A (PI1A) stimulation for all cytokines studied-tumour necrosis factor α(TNFα, 432.2±73.4 vs 979.8±46.3 units/ml), interleukin 2 (IL-2, (56.2±14.9 vs 572.6±12.9 pg/ml), interferon γ (IFNγ, 48.5±11.9 vs 82.6± 12.4 pg/ml) and interleukin 6 (IL–6. 253.6±57.7 vs 1.419.0±279.6 units/ ml)-except for interleukin 1ß (IL–lß) and lymphotoxin (LT). In contrast, unstimulated culture supernatants showed increased TNFα (38.2±13.1 vs 8.0±0.2 units/ml), LT (10.2±2.2 units/ml vs <0.4) and IL–6 (18.5±5.6 units/ml vs <0.5) activity. Similarly, elevated concentrations of TNFα (19.6±6.3 units/ml) and IL–6(22.9±4.7 units/ml) were detected in the sera of OLP patients. Combination of PHA and phorbol myristate acetate (PM A) could restore OLP proliferative T cell response and cytokine production to the level of healthy donors, whereas exogenous recombinant human IL-2 (rhuIL-2) plus PMA did not seem to be an effective stimulant for OLP T cells. These results indicate an alteration in the immune condition of OLP patients and an impairment in T lymphocyte function.     

Study of oral changes in patients with eating disorders

Abstract: Background: The prevalence of eating disorders is very high in industrialized countries, especially in young women. The principal orodental manifestations are erosion of the dental enamel, caries and dental sensitivity. Objectives: Our aim was to study oral complications in female with eating disorders. Methods: We study oral complications (dental, mucosal and salivary) in 17 female patients from the Hospitalized Patients Eating Disorders Unit. Results: We found alterations in salivary flow and pH, as well as salivary gland enlargement. Conclusions: A significant alteration in oral tissue occurs; this has an adverse impact on oral health, producing an accumulation of local irritants which favour the appearance of oral diseases. Preventative measures are therefore recommended for this group of patients.     

Putative periodontal pathogens colonizing oral mucous membranes in denture-wearing subjects with a past history of periodontitis

Abstract The prevalence of selected putative periodontal pathogens colonizing oral mucous membranes was investigated in 26 denture-wearing subjects with a history of periodontitis. The microbiota of the oral cavity of these subjects was examined on average 9.3 years after extraction (range: 1-40 years). Samples were taken from several locations on the oral mucous membranes, from saliva and from plaque attached to the upper and lower denture. Actinobacillus actinomycetemcomitans was not detected in any of the 26 edentulous subjects. Porphyromonas gingivalis was detected in 2 subjects (proportion of cultivable flora: 0.002% and 12.5%). Prevotella intermedia was recovered from 7 subjects with a mean proportion of 0.5% (range < 0.001%-6.3%). Analysis showed that subjects harbouring P. intermedia were wearing full dentures for a longer period of time (mean: 20.2 years) than subjects in which P. intermedia could not be detected (mean: 6.6 years). This result suggests that the absence of P. intermedia shortly after extraction may reflect only a temporary event. Other Prevotella species were found in 22 subjects, constituting < 2% of the total cultivable flora (range 0.01%-10.5%)). In conclusion, the low prevalence of P. gingivalis and the absence of A. actinomycetemcomitans, suggest that the oral cavity of edentulous subjects may not be regarded as a habitat for these species. The preferable habitat of the Prevotella spp. seems to be the oral mucous membranes, possibly with the exception of P. intermedia.     

微弧氧化AZ91D镁合金的口腔黏膜刺激实验

目的了解新型口腔植入材料微弧氧化AZ91D镁合金对口腔黏膜的刺激性。方法健康金黄地鼠10只,麻醉后将微弧氧化AZ91D镁合金的浸提液浸湿的脱脂棉球放入动物的左侧中央颊黏膜极低处,而将阴性对照材料置于动物右侧的中央颊黏膜极低处,分别于1h、4h、6h、8h后肉眼观察并做组织切片。结果实验动物均未出现局部及全身的不良刺激反应。结论微弧氧化AZ91D镁合金对口腔黏膜的没有不良刺激反应。     

Oral submucous fibrosis patients have altered levels of cytokine production

Oral submucous fibrosis (OSF) is a pre-malignant fibrotic lesion of the mouth in betel quid chewers and is characterised by dense bands of collagen in the juxta-epithelial region preceded by inflammation. We have investigated the spontaneous and stimulated production of cytokines by peripheral blood mononuclear cells (PBMC) from OSF patients and compared them with genetically-related relatives, Indian and Caucasian control subjects. The cytokines studied included: interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The results show: a) significant differences in the stimulated versus non-stimulated levels of IL-1beta, IL-6, IL-8 and TNF-alpha but not of IFN-gamma production by patients, and in the relatives' stimulated versus non-stimulated levels of IL-1beta, IL-6 and IFN-gamma; b) no difference in the spontaneous cytokine production between any two groups; and c) significant increases in the patients' stimulated cytokines compared to the Caucasian and Indian controls (P< or =0.050). These results demonstrate increased levels of proinflammatory cytokines and reduced anti-fibrotic IFN-gamma in patients with OSF, which may be central to the pathogenesis of OSF.