Micronucleus frequency in acquired middle ear cholesteatoma

Objective—To determine the micronucleus (MN) frequency of acquired cholesteatoma tissue using an MN assay.

Material and Methods—Eighteen patients were diagnosed as having chronic otitis media with acquired cholesteatoma and were divided into primary and secondary acquired cholesteatoma groups. Cholesteatoma tissue and normal tissue specimens from the external ear canal skin were taken from the patients during surgical operations. MN frequencies of cholesteatoma and control samples were determined according to standard criteria.

Results—The MN frequencies of the cholesteatoma and control tissues were 0.54%±0.31% and 0.24%±0.11%, respectively (p<0.01). MN frequencies for the primary and secondary acquired cholesteatoma groups were 0.63%±0.36% and 0.46%±0.26%, respectively (p>0.05). MN frequencies in cholesteatoma patients without and with complications were 0.42%±0.19% and 0.85%±0.37%, respectively (p<0.05).

Conclusion—MN frequencies were found to be increased in cholesteatoma tissues when compared with external ear canal skin. The MN frequency in five cases with complications was higher than in cases without complications. These results indicate that there could be associations between MN frequency and acquired cholesteatoma and between MN frequency and complications.     

TNF-R2 expression in acquired middle ear cholesteatoma

Acquired middle ear cholesteatoma is a disease which promotes bone erosion resulting in potentially serious complications. The tumor necrosis factor alpha (TNF-α) is present in cholesteatoma and it is related to bone erosion, as shown by different authors. To understand the aggressiveness characteristics of cholesteatoma is necessary, however, to better address the presence and distribution of their receptors.ObjectiveTo evaluate the expression of type 2 TNF-α receptor (TNF-R2) in fragments of cholesteatoma and correlate it to the degree of inflammation present.Material and methodsobservational cross-sectional study, which analyzed 33 fragments of cholesteatomas through histological analysis and immunohistochemistry (using as primary antibody to TNF-R2 LabVision ® brand). The evaluation was performed by means of a qualitative and semi-quantitative agreement with the observed intensity. For statistical analysis we used the Fisher exact test and Spearman's correlation coefficient (considered statistically significant when p ≤ 0.05).ResultsThe expression of TNF-R2 was present in all fragments, however a statistical analysis showed no correlation or association between inflammation and the expression of TNF-R2.ConclusionsTNF-R2 is present in cholesteatoma of the middle ear, however, its expression is not directly related to the degree of inflammation observed in patients with this disease.     

Congenital and acquired cholesteatoma middle ear in children

Cholesteatoma of the middle ear in children may cause hypoacusis. Early diagnosis and optimal treatment is neccessary for good functional effect. We present 57 children (58 ears) with cholesteatoma treated in ENT Department of Medical University in Gdańsk in 1991-2002. The age of patients ranged between 3 and 16 years, the most common 11-15 years. In 52 (89.6%) cases acquired cholesteatoma and in 6 (10.4%) congenital cholesteatoma was diagnosed. Epitympanal cholesteatoma was found in 32 children (55.1%) whereas in posterior part of tympanic cavity--in 20 children (34.5%). In 6 cases (10.4%) intact tympanic membrane was found. Mean air-bone gap in acquired cholesteatoma before treatment was 18.7 dB, after treatment 15.7 dB. In congenital cholesteatoma mean air-bone gap before treatment was 13.6 dB, after treatment 14 dB. The most frequent symptom was hearing loss (98.3%) and purulent otorrhea (85.4%). Positive bacteriological culture was obtained in 43.1% of the cases. X-ray revealed sclero-pneumatic mastoid in 26 (34.5%) cases, sclerotic in 25 (43.1%) and pneumatic mastoid in 7 (12.1%) cases. Intracranial complications were found in 2 cases, intratemporal in 2 cases and extracranial complication in 1 case. Radical surgery was performed in 23 cases (39.7%) and in each case, which required reoperation, modified radical mastoidectomy in 20 cases (34.4%), in another 15 children (25.9%) tympanoplasty was done. The most frequent failure was purulent otorrhea in 21 (36.2%) cases. Reoperation in cholesteatoma recurrence was performed in 17 children (29.3%). Improvement or the same as preoperatively hearing level was obtained in 35 (60.3%) ears, hearing loss was revealed in 23 (39.7%) ears. Treatment of temporal bone cholesteatoma in children is difficult due to silent beginning, aggressive growth and frequent recurrence. The best treatment results in children cholesteatoma are obtained in early clinical stage and with open tympanoplasty procedure.     

Identification of Id1 in acquired middle ear cholesteatoma

OBJECTIVES: To determine (1) the relationship between chronic inflammatory changes in the ossicular chain area (OCA) and the formation of cholesteatoma and (2) the correlates between aberrant gene expression and abnormal proliferation of cholesteatoma. METHODS: Two hundred sixty-four ears with chronic otitis media that had undergone ear surgery were included in this study for statistical analysis of the relationship between abnormalities in the OCA and cholesteatoma. Fourteen middle ear cholesteatoma specimens were collected for immunohistochemical analysis of candidate molecules involved in the abnormal proliferation of keratinocytes. A cell model was used for verification of candidate molecule involvement. RESULTS: The formation of cholesteatoma was accompanied by chronic inflammatory changes in the OCA, including granulated tissue, adhesion, and stagnating effusion. The inhibitor of the DNA-binding (Id1) gene, which is involved in controlling cell cycle progression, was abundantly expressed in cholesteatoma epithelium. In vitro studies indicate that Id1 regulated the expression of nuclear factor kappaB, cyclin D1, proliferating cell nuclear antigen, and cell cycle progression of keratinocytes, CONCLUSIONS: Chronic inflammation in the OCA is closely related to the formation of cholesteatoma. The Id1/nuclear factor kappaB/cyclin D1/proliferating cell nuclear antigen signaling pathway is involved in the abnormal proliferation of keratinocytes in acquired cholesteatoma.     

Expression of PTHrP and RANKL in acquired middle ear cholesteatoma epithelium

Abstract

Background: Regarded as the most important clinical characteristic of middle ear cholesteatoma, the exact mechanism of bone resorption in cholesteatoma still remains unknown.

Objectives: To investigate protein expression of PTHrP and RANKL in acquired middle ear cholesteatoma epithelium and analyze their functional roles in the etiopathogenesis of bone resorption in middle ear cholesteatoma.

Material and methods: A total of 22 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. Protein expression of PTHrP and RANKL in middle ear cholesteatoma and normal postauricular skin was investigated by immunohistochemical staining. Correlations between bone resorption degree and expression of PTHrP and RANKL were also analyzed.

Results: Protein expression of PTHrP and RANKL in cholesteatoma epithelium significantly increased when compared with normal postauricular skin epithelium. In cholesteatoma epithelium, a significantly positive association was observed between PTHrP and RANKL expression. Meanwhile, obviously positive correlations between protein expression of PTHrP and RANKL and bone resorption degree were discovered.

Conclusions and significance: The increased protein expression of PTHrP and RANKL in cholesteatoma epithelium, and their associations with the degree of bone resorption, revealing that PTHrP might promote bone resorption process in middle ear cholesteatoma through RANKL signaling pathway.     

Current concepts of the pathogenesis of acquired middle ear cholesteatoma

The pathogenesis of acquired middle ear cholesteatoma is still unknown and subject of controversial discussions. Based on clinical and histological findings, several theories for cholesteatoma pathogenesis have been developed: 1) retraction pocket theory; 2) proliferation theory; 3) immigration theory, and 4) metaplasia theory. Additionally cholesteatoma development was grouped in particular stages. Immunohistochemical examinations of the matrix and perimatrix have considerably improved the knowledge of cholesteatoma pathogenesis. In this review the current concepts of cholesteatoma pathogenesis are discussed: a retraction pocket occurs due to a tubal dysfunction. Local infection leads to a disturbance of self-cleaning mechanisms, with cell debris and keratinocytes accumulate inside the retraction pocket, and this is followed by an immigration of immune cells, i. e. Langerhans' cells, T-cells, macrophages. There is an imbalance and a vicious circle of epithelial proliferation, keratinocyte differentiation and maturation, prolonged apoptosis, and disturbance of self-cleaning mechanisms. The inflammatory stimulus will induce an epithelial proliferation along with expression of lytic enzymes and cytokines. As a consequence, some "microcholesteatoma" occur which will confluent. Bacteria inside the retraction pocket produce some antigens which will activate different cytokines and lytic enzymes, i. e. ICAM, RANKL, IL-1, IL-2, IL-6, MMP-2, and MMP-9. These cytokines lead to activation and maturing of osteoclasts with the consequence of degradation of extracellular bone matrix and hyperproliferation, bone arrosion and finally progression of the disease. The question why not all cholesteatomas show the same progression process is still unclear. A probable explanation could be that in most retraction pockets migration and self-cleansing mechanisms for keratinocytes are well functioning, with normal migration of the squamous epithelium from the basal layers to the surface. Nevertheless, future research will have to evaluate this topic which might be crucial for the understanding of cholesteatoma pathogenesis and for therapy.     

儿童中耳先天性胆脂瘤的诊断和预后

目的:探讨儿童中耳先天性胆脂瘤的临床症状、位置、影像学特征、治疗及预后.方法:回顾性分析9例中耳先天性胆脂瘤患儿的临床资料.结果:患儿均行手术治疗,5例有听小骨破坏,术后复发4例,复发率为44.4%.平均随访7.4年,术前平均听阈为28 dB,术后平均听阈为26 dB.结论:中耳先天性胆脂瘤临床少见,发病隐匿,单侧传导性聋为主要表现.术前诊断可根据Levenson诊断标准和CT检查结果.其预后和复发率与病变范围、手术方式、是否2次手术有关.     

Condition of the anterior part of the middle ear cleft in acquired cholesteatoma

CONCLUSION: The high rate of flogistic suffering of the controlateral ear seems to suggest a correlation between tubal dysfunction and acquired cholesteatoma but the low rate of pathological reports regarding the anterior mesotympanic region exclude a eustachian tube dysfunction (EDT) at the time of surgery. These observations support the hypothesis that ETD is not a factor that may influence the evolution of the cholesteatoma. OBJECTIVES: To evaluate the role of eustachian tube function in the middle ear secondary acquired cholesteatoma. PATIENTS AND METHODS: This was a case series study. The study group consisted of 72 patients submitted to tympanoplasty for middle ear secondary acquired cholesteatoma. RESULTS: The contralateral ear was normal in 37 subjects (51%) and affected by chronic otitis media in 35 (49%); the anterior part of middle ear cleft was normal in 53 patients (74%). There was no significant relationship between the contralateral ear condition and the status of the anterior region of middle ear (p>0.05). The site of retraction or the presence of tympanic perforation with skin migration was not related to the condition of the protympanum. Otorrhea, cholesteatoma extension, and ossicular chain lesions were not significantly related to the status of the anterior part of the middle ear cleft (p>0.05).     

Colony-stimulating factor in middle ear cholesteatoma

Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in human middle ear cholesteatoma tissues by immunohistochemical technique using mouse monoclonal anti-(human) GM-CSF IgG. Immunofluorescent staining showed the presence of GM-CSF in the peribasal area, in some suprabasal cells of the epithelium, and in the inflammatory connective tissue, especially in the monocytes and fibroblasts. These findings were confirmed by the immunoperoxidase method. Staining of the external ear canal epithelium, however, was significantly weaker than that of the cholesteatoma epithelium. The presence of GM-CSF in cholesteatoma appears to be a response to inflammation occurring in the middle ear cavity. Moreover, our in vitro study showed that GM-CSF induced the proliferation and protein synthesis of basal keratinocytes. This study suggests that GM-CSF is involved in the development and destructive effects of middle ear cholesteatoma.     

Immunological problems in middle ear cholesteatoma

Regardless of the pathogenesis of congenital and acquired cholesteatoma two questions seem to be fundamental: what is the origin of the keratinizing squamous epithelium, and what influences invasive and hyperproliferative behavior of the epidermis. The authors of this paper advance a hypothesis that the similar mechanism of the skin infection could exist in psoriasis and atopic dermatitis as well as in cholesteatoma. The retraction pocket leads to the loss of the defense mechanisms and development of planctonic bacteria. Direct and indirect signalings of bacterial products, such as endotoxin stimulate the cytokine cascade and therefore the hyperproliferation of the epithelium keratynocytes. The mobilization of the immunological system may an important role in the perimatrix development.     

慢性化脓性胆脂瘤型中耳炎的高分辨CT诊断

目的探讨高分辨CT(HRCT)对慢性化脓性中耳炎(胆脂瘤型)的诊断价值.方法对238例经手术及病理证实的中耳胆脂瘤的CT征象与手术所见进行对照研究.结果(1)CT诊断胆脂瘤的敏感性最高在上鼓室(81.25%),最低在乳突(50%).(2)CT显示胆脂瘤的病理改变为①鼓室乳突腔内胆脂瘤影;②胆脂瘤周低密度环;③鼓室乳突腔边缘骨质硬化;④鼓室乳突腔扩大;⑤听骨链破坏.结论CT检查对于中耳胆脂瘤的诊断及指导手术有很大帮助.