Treatment Of Middle Ear Cholesteatoma Research Articles

N6-methyladenosine methylation analysis of circRNAs in acquired middle ear cholesteatoma.

Middle ear cholesteatoma is a chronic middle ear disease characterized by severe hearing loss and adjacent bone erosion, resulting in numerous complications. This study sought to identify pathways involved in N6-methyladenosine (m6A) modification of circRNA in middle ear cholesteatoma. A m6A circRNA epitranscriptomic microarray analysis was performed in middle ear cholesteatoma tissues (n = 5) and normal post-auricular skin samples (n = 5). Bioinformatics analyses subsequently explored the biological functions (Gene Ontology, GO) and signaling pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG) underlying middle ear cholesteatoma pathogenesis. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was performed to verify the presence of circRNAs with m6A modifications in middle ear cholesteatoma and normal skin samples. Microarray analysis identified 3,755 circRNAs as significantly differentially modified by m6A methylation in middle ear cholesteatoma compared with the normal post-auricular skin. Among these, 3,742 were hypermethylated (FC ≥ 2, FDR < 0.05) and 13 were hypomethylated (FC ≤ 1/2, FDR < 0.05). GO analysis terms with the highest enrichment score were localization, cytoplasm, and ATP-dependent activity for biological processes, cellular components, and molecular functions respectively. Of the eight hypermethylated circRNA pathways, RNA degradation pathway has the highest enrichment score. Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway was hypomethylated. To validate the microarray analysis, we conducted MeRIP-qPCR to assess the methylation levels of five specific m6A-modified circRNAs: hsa_circRNA_061554, hsa_circRNA_001454, hsa_circRNA_031526, hsa_circRNA_100833, and hsa_circRNA_022382. The validation was highly consistent with the findings from the microarray analysis. Our study firstly presents m6A modification patterns of circRNAs in middle ear cholesteatoma. This finding suggests a direction for circRNA m6A modification research in the etiology of cholesteatoma and provides potential therapeutic targets for the treatment of middle ear cholesteatoma.

M6A modification of lncRNA in middle ear cholesteatoma.

Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss, bone destruction, and other severe complications. Despite surgery being the primary treatment, the recurrence rate remains high. Therefore, exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches. This study aims to explore the involvement of N6-methyladenosine (m6A) methylation in long non-coding RNAs (lncRNAs) in the biological functions and related pathways of middle ear cholesteatoma. The m6A modification patterns of lncRNA in middle ear cholesteatoma tissues (n=5) and normal post-auricular skin tissues (n=5) were analyzed using an lncRNA m6A transcriptome microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma. Methylated RNA immunoprecipitation (MeRIP)-PCR was used to validate the m6A modifications in cholesteatoma and normal skin tissues. Compared with normal skin tissues, 1 525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues, with 1 048 showing hypermethylation and 477 showing hypomethylation [fold change (FC)≥3 or <1/3, P<0.05]. GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity, neuron-neuron synapse, and regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activity. Hypomethylated lncRNAs were associated with mRNA methyltransferase activity, secretory granule membrane, and mRNA methylation. KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways: the Hedgehog signaling pathway, viral protein interaction with cytokines and cytokine receptors, mitogen-activated protein kinase (MAPK) signaling pathway, cytokine-cytokine receptor interaction, and adrenergic signaling in cardiomyocytes. Hypomethylated lncRNAs were mainly involved in 4 pathways: Renal cell carcinoma, tumor necrosis factor signaling pathway, transcriptional misregulation in cancer, and cytokine-cytokine receptor interaction. Additionally, MeRIP-PCR confirmed the changes in m6A methylation levels in NR_033339, NR_122111, NR_130744, and NR_026800, consistent with microarray analysis. Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB, key genes in the MAPK signaling pathway. This study reveals the m6A modification patterns of lncRNAs in middle ear cholesteatoma, suggests a direction for further research into the role of lncRNA m6A modification in the etiology of cholesteatoma. The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.

Osteopontin-driven partial epithelial-mesenchymal transition governs the development of middle ear cholesteatoma

ABSTRACT Cholesteatoma is a common disease of the middle ear. Currently, surgical removal is the only treatment option and patients face a high risk of relapse. The molecular basis of cholesteatoma remains largely unknown. Here, we show that Osteopontin (OPN), a predominantly secreted protein, plays a crucial role in the development of middle ear cholesteatoma. Global transcriptome analysis revealed the loss of epithelial features and an enhanced immune response in human cholesteatoma tissues. Quantitative RT-PCR and immunohistochemical staining of middle ear cholesteatoma validated the reduced expression of epithelial markers, as well as the elevated expression of mesenchymal markers including Vimentin and Fibronectin, but not N-Cadherin, α-smooth muscle actin (α-SMA) or ferroptosis suppressor protein 1 (FSP1), indicating a partial epithelial-mesenchymal transition (EMT) state. Besides, the expression of OPN was significantly elevated in human cholesteatoma tissues. Treatment with OPN promoted cell proliferation, survival and migration and led to a partial EMT in immortalized human keratinocyte cells. Importantly, blockade of OPN signaling could remarkably improve the cholesteatoma-like symptoms in SD rats. Our mechanistic study demonstrated that the AKT-zinc finger E-box binding homeobox 2 (ZEB2) axis mediated the effects of OPN. Overall, these findings suggest that targeting the OPN signaling represents a promising strategy for the treatment of middle ear cholesteatoma.

Prognostic role of EAONO/JOS, STAMCO, and ChOLE Staging for Exclusive Endoscopic and Endoscopic-Microscopic Tympanoplasty.

The aim of the study is to evaluate cholesteatoma's surgical outcomes in patients treated with endoscopic ear surgery (EES) or a combined endoscopic-microscopic approach (cEMA) according to STAM, STAMCO, ChOLE, and EAONO/JOS system (EJS) classifications and staging. Retrospective study. Monocentric study in a tertiary referral center. One-hundred sixty-eight patients who underwent EES or cEMA for cholesteatoma between 2010 and 2018 were classified according to the abovementioned classification and staging. Data on cholesteatoma's recurrence and residual rates were collected. Inferential statistical analysis was performed to evaluate surgical outcomes and the prognostic value of classifications and staging. The recurrence rate was significantly lower in cholesteatomas classified in EJS stage 1 (2.6%) and STAM stage 1 (0%). A comparison of the different stages of the disease showed a significantly lower recurrence only for stage 1 versus the superior stages of both classifications. Involvement of mastoid bone was associated with a higher risk of recurrence (odds ratio [OR]: 4.12; p = .031). Attical involvement was associated with a higher risk of residual cholesteatoma (OR: 1.165; p = .046). EES or cEMA represents an effective treatment for middle ear cholesteatoma. The STAM classification and the EJS have shown a prognostic value, with STAM 1 and EAONO-JOS 1 stages associated with a better prognosis. Mastoid involvement represents a risk factor for recurrence. Attic localization is associated with residual disease. Localization at difficult access sites did not implicate a higher risk for recurrence or residual. ChOLE classification, Ossicular chain status, and complication status did not provide prognostic information regarding recurrence or residual cholesteatoma.

Epigenetic Regulation as a New Therapeutic Target for Middle Ear Cholesteatoma.

To evaluate the effectiveness of the menin-MLL inhibitor, MI503, as a conservative treatment of middle ear cholesteatoma (cholesteatoma) in a mouse model and to confirm its safety profile regarding auditory function in vivo. Cholesteatoma is a mass formed by the keratinizing squamous epithelium in the tympanic cavity and/or mastoid and subepithelial connective tissue and by the progressive accumulation of keratin debris with/without a surrounding inflammatory reaction. Although the main treatment is surgical therapy, the techniques to prevent recurrence remain a critical area of research. Recently, the use of MI503 in experiments resulted in the inhibition of the growth of cholesteatoma in vivo under histone modification. After cholesteatoma was induced in ICR mice (n = 7) by keratinocyte growth factor expression vector transfection, MI503 (50 μM) or phosphate-buffered saline was topically injected for 14 days. The effects of MI503 against cholesteatoma were analyzed by micro-computed tomography images. For the in vivo ototoxicity study, a single intratympanic injection of MI503 (50 or 500 μM) or phosphate-buffered saline (n = 4 each) was done in the ICR mice. An auditory brainstem response was performed at days 0, 1, and 14. For morphological analysis, immunostaining for Phalloidin/F-actin and Myo7a was performed. MI503 reduced keratinocyte growth factor-induced cholesteatoma in vivo (4 of 4 [100%]). No difference was found in the mean variation of the average of the auditory brainstem response thresholds between the three groups in the in vivo ototoxicity study, thus confirming its safety profile regarding auditory function. MI503 does not demonstrate any deleterious effects on murine hair cells when assessed by immunostaining. These findings demonstrate an encouraging safety profile for the use of menin-MLL inhibitor for the conservative treatment of cholesteatoma.

An Effect of Cyclosporin A in a Treatment of Temporal Bone Defect Using hBM-MSCs.

Background. The treatment of middle ear cholesteatoma requires surgical treatment and the reconstruction of the temporal bone, which represents an ongoing problem. Otologists have focused on the research of materials allowing an airy middle ear and the preservation of hearing function to reconstruct the temporal bone. Methods. This study evaluated the effect of cyclosporin A (CsA) and a combined biomaterial in the healing process of postoperative temporal bone defects in an animal model. Cultured human Bone Marrow Mesenchymal Stromal Cells (hBM-MSCs) were mixed with hydroxyapatite (Cem-Ostetic®), and subsequently applied as a bone substitute after middle ear surgery, showing that the therapeutic potential of hBM-MSCs associated with bone regeneration and replacement is directly influenced by CsA, confirming that it promotes the survival of MSCs in vivo. Results. The therapeutic efficacy of the combination of MSCs with CsA is greater than the sole application of MSCs in a hydroxyapatite carrier. Conclusion. The reconstruction of a temporal bone defect using hBM-MSCs requires an immunosuppressant to improve the results of treatment.

Advances in the surgical treatment of cholesteatoma of the middle ear

Middle ear cholesteatoma, as a common ear disease, has been further understood in terms of its molecular mechanism, classification and staging, and it is generally believed that surgical treatment is the first choice, but there is no final conclusion on its surgical choice. Microscopic surgery includes complete or open radical mastoidectomy with or without reconstruction of the middle ear cavity, and their pros and cons have been debated for decades. In the past decade, a variety of surgical methods have been developed, including various improvements and combined operations that combine the advantages of traditional open radical mastoidectomy and complete mastoidectomy. On the other hand, the emergence of ear endoscopic surgery has opened up new surgical methods, as well as the use of laser and other new technologies to improve the surgical effect and prognosis, but also can not avoid their limitations and shortcomings. The purpose of this paper is to summarize the advantages and disadvantages of various surgical treatments for middle ear cholesteatoma in order to provide guidance and help for otologists in the treatment of middle ear cholesteatoma.

Mastoid cavity obliteration in treatment of middle ear cholesteatoma

Objective: The primary goal in the surgical management of chronic otitis media with cholesteatoma is the creation of a dry and safe ear. The method of choice for management of cholesteatoma is the inside out or reverse mastoidectomy. If external auditory canal reconstruction after complete cholesteatoma removal is not possible, mastoid cavity obliteration techniques are recommended to reduce the size of the open mastoid cavity. The goal of our study is to evaluate the frequency of postoperative ear secretion and hearing situation in patients with mastoid cavity obliteration in treatment of middle ear cholesteatoma. Methods: Retrospective study of 155 patients with middle ear cholesteatoma were surgically treatment during 52 months from 01.06.2014 to 30.09.2018 in Hospital Trakia Park, Stara Zagora (Bulgaria) with canal wall reconstruction or mastoid cavity obliteration with cartilage, bone pate or bone replacement alloplastic materials. Results: After complete cholesteatoma removal we perform ear canal reconstruction in 51.61% of cases (80; n=155), and in others 41.94% of cases (65; n=155) we perform mastoid cavity obliteration. In our patient group we perform type I tympanoplasty in 36.77% (57; n=155), type III tympanoplasty in 46.45% (72; n=155), Secondlook operations in 14% (21, n = 155) and only in 5 cases we left the operating cavity open (3.23%; n=155). After mean follow-up period from 11.34 months (1÷48 months; SD 13.10 months) our frequency of postoperative ear secretion is 6.45% (10; n=155) and our cholesteatoma residual rate is 9.03% (14; n=155). Conclusion: Mastoid cavity obliteration procedures can prevent the development of postoperative retraction pockets by isolation the tympanic cavity from the attic and mastoid. This is a safe and effective technique for rehabilitation of mastoid cavities. Hearing results of this technique is variable according to the involvement of the middle ear ossicles, but with the possibility of fitting a hearing aids or middle ear implants.

Comprehensive Treatment of Middle Ear Cholesteatoma

Comprehensive treatment of middle ear cholesteatoma involves preoperative treatment, followed by a radical inside-out aticoanthromastoidectomy with cartilage-perichondrium reconstruction of the tympanic membrane. If possible, a reconstruction of the posterior wall of the external auditory canal is done. In all other cases mastoid obliteration with bone pate, cartilage or artificial bone is performed. In case of intact stapes a type III tympanoplasty is performed; in the absence of stapes suprastructures TORP ossicular chain reconstruction is performed when there are no indications for a second-look surgery. Post-operative follow-up of patients includes regular checkups and DW-MRT in some cases.

Autophagy Is Deficient and May be Negatively Regulated by SERPINB3 in Middle Ear Cholesteatoma.

Whereas autophagy has been linked to various human diseases, whether it also plays a role in cholesteatoma is virtually unknown. This study aimed to investigate the activity and regulation of autophagy in cholesteatoma. The treatment of middle ear cholesteatoma has been challenging due to an insufficient understanding of the underlying disease mechanism. Expression of microtubule-associated protein 1A/1B-light chain 3 (LC3), the autophagy protein marker, and phosphorylated Akt (p-Akt), and mammalian target of rapamycin (p-mTOR), the known autophagy regulators, in fresh retroauricular skin and cholesteatoma tissue samples was analyzed by immunoblotting. The results were further confirmed by immunohistochemistry and statistical analyses. Cell proliferation of primary retroauricular skin- and cholesteatoma-derived fibroblasts was evaluated by methyl thiazol tetrazolium (MTT) assay. Ectopic expression of serine proteinase inhibitor, clade B, member 3 (SERPINB3) in the fibroblasts was achieved by electroporation and the expression was detected by immunoblotting. LC3 expression was significantly decreased in cholesteatoma in most of the 15 paired retroauricular skin/cholesteatoma tissue samples. However, p-Akt and p-mTOR expression in the cholesteatoma samples was not significantly different from that in the control subjects. Immunohistochemical studies further demonstrated an inverse correlation between LC3 expression and cholesteatoma. The cholesteatoma fibroblasts proliferated faster than the retroauricular skin fibroblasts, and had higher SERPINB3 but lower LC3 expression. Furthermore, overexpression of SERPINB3 in the retroauricular skin fibroblasts enhanced cell proliferation and downregulated LC3 expression. Autophagy is significantly suppressed in cholesteatoma tissues, which may not involve the Akt/mTOR signaling pathway. More importantly, SERPINB3 may promote cell proliferation and negatively regulate autophagy in cholesteatoma fibroblasts. Together, these findings warrant further investigation into the pathogenic mechanism of cholesteatoma.

Expression of PTHrP and RANKL in acquired middle ear cholesteatoma epithelium

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.

Age aspects of the course of chronic otitis media with cholesteatoma in children (clinical and immunological characteristics)

Cholesteatoma of the middle ear is the disease, the course and prognosis of which can not be considered without taking into account the patients age. In pediatric otorhinolaryngology, such patients require special attention due to the aggressiveness of cholesteatoma in children. The rapid growth and a high number of recurrences after surgical treatment are features of the course of this disease in children. The causes of the aggressiveness of this disease in children have not been studied. Objective: to identify clinical and immunological features in children with middle ear cholesteatoma in different age groups that contribute to the aggressive course of the disease. A retrospective analysis of 143 medical case reports of children from 1 to 17 years old who received surgical treatment of middle ear cholesteatoma was carried out in the Department of othorhinolaryngology (St. Petersburg State Pediatric Medical University) from 2000 to 2018. Comparative analysis of clinical manifestation, anamnesis of ear disease, concomitant diseases, immunological reactivity (the content of lymphocytes, their subpopulations and interleukin-2 in peripheral blood) and results of surgical treatment of middle ear cholesteatoma in different age groups has been performed. Cholesteatoma is more aggressive in young children. Frequent infections of the upper respiratory tract, eustachian tube dysfunctions, immune disorders in children under 7 years of age lead to an unfavorable course and prognosis of middle ear cholesteatoma.

Current Status of Surgical Treatment for Middle Ear Cholesteatoma in Japan

Current Status of Surgical Treatment for Middle Ear Cholesteatoma in Japan

Evaluation of the Effect of Diclofenac Sodium and 5-Fluourasil in a 3D Cholesteatoma Cell Culture Model.

Middle ear cholesteatoma is a benign disease with invasive and destructive clinical behaviors. It increases the rate of both chronic otitis media complications and revision surgeries. The most effective treatment of middle ear cholesteatoma is surgical excision, and there is no medical treatment for this disease. Exploring new medical treatment options may help to create treatment alternatives instead of surgery. Required cholesteatoma tissues for cell culture were excised from 4 different participants who underwent surgery in our clinic and agreed to give tissue for the study. Cholesteatoma-derived keratinocytes and fibroblasts were cocultured in temperature-sensitive culture dishes to make a three-dimensional (3D) cholesteatoma model. Then, the effects of 1% and 2% diclofenac sodium on viability and cell proliferation rates were examined using WST-1 and annexin-V tests. Cell viability and proliferation rates were found to be lower and apoptosis rates were higher in the diclofenac sodium group versus the negative and positive control groups. In this present study, we described a new 3D cholesteatoma cell culture model developed using cell sheet technology and demonstrated the efficacy of diclofenac sodium on cholesteatoma for the first time in the literature. It may be used in patients with chronic otitis media with cholesteatoma, but further studies investigating ototoxic and neurotoxic effects of this molecule are needed.

Taraxerol exerts potent anticancer effects via induction of apoptosis and inhibition of Nf-kB signalling pathway in human middle ear epithelial cholesteatoma cells

Purpose : To investigate the effect of taraxerol on the proliferation of middle ear epithelial cholesteatoma cells. Methods : The anti-proliferative effect of taraxerol was investigated by cell counting kit-8 (CCK8) and clonogenic assays. Apoptosis was measured using DAPI, while mitochondrial membrane potential was determined with the aid of rhodamine 123 staining. Protein expression was studied by western blotting. Results : Taraxerol induced concentration-dependent anti-proliferative effects on the middle ear epithelial cholesteatoma cells, and also inhibited their colony formation potential. The drug induced apoptosis in the middle ear epithelial cholesteatoma cells by reducing mitochondrial membrane potential, and also triggered sub-G1 cell cycle arrest in these cells. Moreover, taraxerol inhibited the expression of Nf-kB. Conclusion : These findings reveal that taraxerol may be a potential lead compound for the treatment of middle ear cholesteatoma. Keywords : Cholesteatoma, Epithelial tissues, Taraxerol, Apoptosis, Cell cycle arrest

The surgical treatment of middle ear cholesteatoma complicated with peripheral facial paralysis (with 22 cases)

Objective:To summarize the clinical characteristics, the surgical methods and the recovery of facial nerve function outcomes in patients with the middle ear cholesteatoma complicated with peripheral facial paralysis.Method:Retrospective analysis method was used on patients treated for middle ear cholesteatoma associated with peripheral facial paralysis. Facial nerve decompression and great auricular nerve grafting were performed for restoration of facial nerve. Facial nerve function was assessed with the House-Brackmann (H-B) grade scale. Spearman test was employed for statistic analysis.Result:Surgical exploration revealed that the cholesteatoma was mainly located in epitympanic cavity, mastoid and sinus tympani, which mainly damaged the tympanic segment of facial nerve. Nineteen cases with facial nerve edema, including complete sheath (n=15) and sheath defect (n=4), were performed decompression. Among which 15 recovered to H-B Ⅰ, 3 recovered to H-B Ⅱ, 1 recovered to H-B Ⅳ. Three cases with facial nerve disrupt underwent great auricular nerve grafting, 1 recovered to H-B Ⅳ, 2 recovered to H-BⅤ. The rate of recovery to H-B Ⅰ or Ⅱ in patients underwent surgery within 2 weeks was 92.3%(12/13).Conclusion:When the middle ear cholesteatoma complicated with peripheral facial paralysis, surgery should be carried out as soon as possible. After removed the cholesteatoma completely, facial nerve decompression could acquire a better facial nerve function recovery compared to great auricular grafting.

HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma

Conclusions: The heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays an essential role in the development and invasiveness of cholesteatoma. This study may help to realize the molecular mechanisms underlying the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug intervention of cholesteatoma.Objective: To detect HB-EGF expression in human surgical specimens of acquired middle ear cholesteatoma and analyze its functional role as a regulator of epithelial keratinocytes hyperproliferation.Methods: A total of 34 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. The mRNA and protein expression of HB-EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was investigated by real-time quantitative reverse-transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining, and western blot. The correlation between bone resorption degree and HB-EGF expression was also analyzed.Results: On average, compared with normal postauricular skin, expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32-fold by western blot. Positive HB-EGF immunostaining observed in the basal and suprabasal layers of cholesteatoma epithelium was significantly stronger than in normal postauricular skin. Meanwhile, an obviously positive correlation between HB-EGF protein expression and bone resorption degree was discovered.

The Diagnosis and Treatment of Middle Ear Cholesteatoma with Tuberculous Otitis Media Co-infection: A Series of 11 cases

The Diagnosis and Treatment of Middle Ear Cholesteatoma with Tuberculous Otitis Media Co-infection: A Series of 11 cases

Techniques of the Tympanomastoidectomy with Reconstruction of the Posterior Bone Wall of the External Auditory Canal.

A combined tympanoplasty method, the mobile-bridge tympanoplasty, has been applied at the Clinic for Ear, Nose and Throat Diseases in Novi Sad since 1998. Mobile-bridge tympanoplasty is performed at our Clinic by applying Feldmann's procedure utilizing a microsurgical oscillating saw. It is a combination of closed and open techniques for surgical treatment of middle ear diseases. In addition to this technique, a method for reconstruction of the posterior bone wall of the external auditory canal was introduced. This procedure is applied in cases of damage or impairment of the bony ear canal wall using mastoid cortical temporal bone graft or modeled cartilage of the concha. Maintenance of general anatomical relations in the middle ear enables good ventilation of pneumatic spaces of the middle ear and Eustachian tube permeability, thus providing good conditions for ossicular chain reconstruction. The incidence of recurrent cholesteatoma in combined mobile-bridge tympanoplasty and tympanoplasty with reconstruction of the posterior bone wall was 6% in total. The incidence values for the recurrent cholesteatoma in closed tympanoplasty and in cases of open techniques were 10%. Mobile-bridge tympanoplasty and reconstruction of the posterior bone wall of external auditory canal are methods of choice in surgical treatment of middle ear cholesteatoma that progressed to the attic space, sinus tympani and facial recess.

KGFR as a possible therapeutic target in middle ear cholesteatoma

Conclusion: We demonstrated that repression of keratinocyte growth factor (KGF) receptor (KGFR) could be a potentially useful strategy in the conservative treatment of middle ear cholesteatoma. Objectives: Recently, the use of a selective inhibitor of the KGFR, SU5402, in an in vitro experiment resulted in the inhibition of the differentiation and proliferation of epithelial cells through KGF secretion by fibroblasts isolated from the cholesteatoma. In this study, we investigated the effects of the KGFR inhibitor during middle ear cholesteatoma formation in vivo. Methods: Based on the role of KGF in the development of cholesteatoma, Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal of rats five times on every fourth day. Ears transfected with empty vector were used as controls. KGFR selective inhibitor (SU5402) or MEK inhibitor (PD0325901) was administered in the right ear of five rats after vector transfection. In the control, 2% DMSO in PBS was administered in the other ears after vector transfection. Results: The use of a selective KGFR inhibitor, SU5402, completely prevented middle ear cholesteatoma formation in the rats.