Endoscopic otological surgery has revolutionized ear surgery. Endoscopes are frequently used in myringoplasty and tympanoplasty, and their use in attic reconstruction (atticoplasty) is gaining popularity. While microscopic surgery for limited attic cholesteatoma and attic retraction (grade III and IV) is difficult especially anterior area, the endoscope has emerged as a new treatment option, offering a 360-degree view of the attic and facilitating the complete removal of diseased tissue.1 We had performed atticoplasty with rigid nasal endoscopes (Karl Storz) of 4 mm diameter and 18-cm length. Our preliminary results showed that transcanal endoscopic atticoplasty is a reliable and safe technique for the surgical management either attic retraction pocket (grade III or IV) or limited attic cholesteatoma.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
目的: 中耳胆脂瘤是一种非肿瘤性疾病，通常会引起听力丧失、骨质破坏和其他严重并发症。尽管手术是主要的治疗方法，但其复发率较高。因此，探讨胆脂瘤的分子机制对寻找新的治疗方法具有重要意义。本文旨在探究长链非编码RNA(long non-coding RNA，lncRNA)中N6-甲基腺嘌呤(N6-methyladenosine，m6A)甲基化参与中耳胆脂瘤的生物学功能及相关通路。方法: 利用lncRNA m6A转录组芯片分析中耳胆脂瘤组织(n=5)和正常耳后皮肤组织(n=5)的m6A修饰模式。采用基因本体(Gene Ontology，GO)和京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)途径分析中耳胆脂瘤发病的可能生物学功能和信号通路。并运用甲基化RNA免疫沉淀(methylated RNA immunoprecipitation，MeRIP)-PCR验证中耳胆脂瘤和正常皮肤组织中的lncRNA m6A修饰。结果: 与正常皮肤对照组相比，中耳胆脂瘤组织中m6A甲基化修饰了1 525个lncRNAs(高甲基化1 048个，低甲基化477个)，差异有统计学意义[差异倍数(fold change，FC)≥3或<1/3，P<0.05]。GO富集分析表明：高甲基化的lncRNA参与蛋白磷酸酶抑制剂活性、神经元间突触和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid，AMPA)受体活性的调节。低甲基化lncRNA参与mRNA甲基转移酶活性、分泌颗粒膜和mRNA甲基化。KEGG分析表明：高甲基化lncRNAs主要与5条通路相关，包括Hedgehog信号通路、病毒蛋白与细胞因子及细胞因子受体的相互作用、丝裂原活化蛋白激酶(mitogen-activated protein kinases，MAPK)信号通路、细胞因子-细胞因子受体相互作用和心肌细胞的肾上腺素能信号通路。低甲基化lncRNA主要与4种途径相关：肾细胞癌、肿瘤坏死因子信号通路、癌症的转录失调以及细胞因子-细胞因子受体相互作用。此外，通过MeRIP-PCR验证了NR_033339、NR_122111、NR_130744和NR_026800中m6A甲基化水平的改变，与微距阵分析相一致。并且通过real-time PCR验证了MAPK信号通路的关键基因MAPK1和NF-κB表达量显著上调。结论: 本研究揭示了中耳胆脂瘤中lncRNA的m6A修饰模式，提示lncRNA m6A修饰在胆脂瘤病因学中的研究方向，为中耳胆脂瘤的治疗提供了潜在的靶点。.

OBJECTIVE: Progressive bone resorption and destruction is one of the most critical clinical features of middle ear cholesteatoma, potentially leading to various intracranial and extracranial complications. However, the mechanisms underlying bone destruction in middle ear cholesteatoma remain unclear. This study aims to explore the role of parathyroid hormone-related protein (PTHrP) in bone destruction associated with middle ear cholesteatoma.
METHODS: A total of 25 cholesteatoma specimens and 13 normal external auditory canal skin specimens were collected from patients with acquired middle ear cholesteatoma. Immunohistochemical staining was used to detect the expressions of PTHrP, receptor activator for nuclear factor-kappa B ligand (RANKL), and osteoprotegerin (OPG) in cholesteatoma and normal tissues. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the presence of TRAP positive multi-nucleated macrophages in cholesteatoma and normal tissues. Mono-nuclear macrophage RAW264.7 cells were subjected to interventions, divided into a RANKL intervention group and a PTHrP+ RANKL co-intervention group. TRAP staining was used to detect osteoclast formation in the 2 groups. The mRNA expression levels of osteoclast-related genes, including TRAP, cathepsin K (CTSK), and nuclear factor of activated T cell cytoplasmic 1 (NFATc1), were measured using real-time polymerase chain reaction (real-time PCR) after the interventions. Bone resorption function of osteoclasts was assessed using a bone resorption pit analysis.
RESULTS: Immunohistochemical staining showed significantly increased expression of PTHrP and RANKL and decreased expression of OPG in cholesteatoma tissues (all P<0.05). PTHrP expression was significantly positively correlated with RANKL, the RANKL/OPG ratio, and negatively correlated with OPG expression (r=0.385, r=0.417, r=-0.316, all P<0.05). Additionally, the expression levels of PTHrP and RANKL were significantly positively correlated with the degree of bone destruction in cholesteatoma (r=0.413, r=0.505, both P<0.05). TRAP staining revealed a large number of TRAP-positive cells, including multi-nucleated osteoclasts with three or more nuclei, in the stroma surrounding the cholesteatoma epithelium. After 5 days of RANKL or PTHrP+RANKL co-intervention, the number of osteoclasts was significantly greater in the PTHrP+RANKL co-intervention group than that in the RANKL group (P<0.05), with increased mRNA expression levels of TRAP, CTSK, and NFATc1 (all P<0.05). Scanning electron microscopy of bone resorption pits showed that the number (P<0.05) and size of bone resorption pits on bone slices were significantly greater in the PTHrP+RANKL co-intervention group compared with the RANKL group.
CONCLUSIONS: PTHrP may promote the differentiation of macrophages in the surrounding stroma of cholesteatoma into osteoclasts through RANKL induction, contributing to bone destruction in middle ear cholesteatoma.
目的: 骨质进行性吸收破坏是中耳胆脂瘤最重要的临床特征之一，可导致一系列颅内外并发症，而目前中耳胆脂瘤骨破坏的机制尚未明确。本研究旨在探究甲状旁腺激素相关蛋白(parathyroid hormone-related protein，PTHrP)参与中耳胆脂瘤骨破坏的机制。方法: 收集后天性中耳胆脂瘤患者的25例胆脂瘤标本和13例外耳道正常皮肤组织标本。采用免疫组织化学染色方法检测PTHrP、核因子κB受体活化因子配体(receptor activator for nuclear factor-kappa B ligand，RANKL)和骨保护素(osteoprotegerin，OPG)在中耳胆脂瘤和外耳道正常皮肤组织中的表达，抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase，TRAP)染色法检测中耳胆脂瘤和外耳道正常皮肤组织中是否存在TRAP阳性多核巨噬细胞。选取小鼠单核巨噬细胞RAW264.7细胞进行干预，分为RANKL干预组和PTHrP+RANKL共同干预组，采用TRAP染色法检测2组破骨细胞的生成情况，实时聚合酶链反应(real-time polymerase chain reaction，real-time PCR)检测干预后2组破骨细胞相关基因TRAP、组织蛋白酶K(cathepsin K，CTSK)和活化T细胞核因子1(nuclear factor of activated T cell cytoplasmic 1，NFATc1)的mRNA表达水平，骨吸收陷窝实验检测2组破骨细胞的骨吸收功能。结果: 免疫组织化学染色结果显示，PTHrP和RANKL在中耳胆脂瘤组织中的表达均显著增高，OPG表达降低(均P<0.05)，且PTHrP的表达与RANKL、RANKL/OPG比值均呈显著正相关，与OPG表达呈显著负相关(分别r=0.385、r=0.417、r=-0.316，均P<0.05)。同时，PTHrP、RANKL的表达水平与中耳胆脂瘤的骨破坏程度均呈显著正相关(分别r=0.413、r=0.505，均P<0.05)。TRAP染色结果显示中耳胆脂瘤上皮周围基质中有大量TRAP阳性细胞，并存在细胞核数量为3个或3个以上的TRAP阳性破骨细胞。RANKL或PTHrP+RANKL联合干预5 d后，与RANKL干预组相比，PTHrP+RANKL联合干预组的破骨细胞数量显著增加(P<0.05)，且破骨细胞相关基因TRAP、CTSK和NFATc1的mRNA表达水平均升高(均P<0.05)。骨吸收陷窝扫描电镜结果显示RANKL干预组、PTHrP+RANKL联合干预组的骨片表面均形成骨吸收陷窝；与RANKL干预组相比，PTHrP+RANKL联合干预组的骨片表面骨吸收陷窝数量显著增加(P<0.05)，面积也更大。结论: PTHrP可能通过促进RANKL诱导胆脂瘤组织周围基质中的巨噬细胞分化为破骨细胞，参与中耳胆脂瘤骨破坏。.

This study aimed to compare total endoscopic ear surgery (TEES) and microscopic postauricular canal-wall-down tympanomastoidectomy (CWD) in cholesteatoma surgery in our clinic. This study included 59 patients, of whom 30 and 29 were operated on with CWD in 2016-2018 and TEES in 2019-2021, respectively and compared regarding intraoperative findings, hearing outcomes, long-term outcomes, and recidivism rates between groups. This study excluded patients in stage IV according to the European Academy of Otology and Neurotology/Japan Otological Society Staging System on Middle Ear Cholesteatoma, aged < 18, with congenital cholesteatoma, who underwent revision surgery. Two patients in the TEES group had recidivism (6.9%), with recurrent disease observed in both patients and residual disease in none, whereas 3 patients in the CWD group had recidivism (10%), including recurrent disease in 2 and residual disease in 1 patient. Tympanic membrane perforation occurred in 2 (6.9%) and 1 (3.3%) patients in the TEES and CWD groups, respectively. The 2 groups revealed no significant difference in terms of recidivism and perforation rates (P=1.000, P = .612). The CWD group had a longer mean operation time (225.54 ± 47.86 minutes) than the TEES group (160.55 ± 24.98 minutes) (P < .001). The 2 groups demonstrated no significant difference regarding pre- and postoperative air-bone gap (ABG) and ABG gain (P = .105, P=.329, P=.82, respectively). Total endoscopic ear surgery provides similar results in terms of hearing, recidivism, and long-term outcomes with the microscopic CWD approach. However, the CWD approach is still important, especially in patients in advanced stages.

Although advanced technologies and surgical procedures are used, cholesteatoma is a disease with the possibility of recurrence. The aim of this study was to determine the long-term effect of sodium 2-mercaptoethane sulfonate (MESNA) on cholesteatoma surgery. Patients who underwent cholesteatoma surgery between January 2009 and July 2014 by the same surgeon were divided into 2 groups: those where MESNA was used and those where it was not. Otomicroscopic examinations were performed to see the presence of cholesteatoma recurrence in the patients who had surgery at least 8 years ago. Pure-tone audiometry was performed to evaluate the hearing results. Sodium 2-mercaptoethane sulfonate was used in 23 patients and was not used in 39 patients who came to the control. In the MESNAused group, cholesteatoma was seen in only 1 of the patients who underwent a canal wall-down (CWD) mastoidectomy. In the MESNA non-used group, cholesteatoma was seen in 3 patients who underwent CWD. The difference was not statistically significant. Although there was no statistically significant difference, recurrence of cholesteatoma was seen less frequently in patients who received MESNA during surgery. Studies to be conducted in larger patient series may clarify this issue.

The aim of this article is to determine the efficacy of otoendoscopy during microscopic cholesteatoma surgery on residual cholesteatoma rates postoperatively. The medical records of patients (aged 4-90) with primary acquired cholesteatoma who underwent microscopic cholesteatoma surgery (exclusively transcanal approach or canal wall-up tympano-mastoidectomy) with subsequent otoendoscopic examination (80 ears) for intraoperative cholesteatoma residues were retrospectively reviewed. All cases with mixed microscopic/endoscopic, fully endoscopic, or fully microscopic dissection were excluded, as well as cases where a canal wall-down technique was used. After microscopic cholesteatoma removal, the otoendoscope was used to inspect the middle ear recesses for intraoperative cholesteatoma residues. The intra- and postoperative cholesteatoma residue rate were evaluated. On endoscopic examination, intraoperative cholesteatoma residues were encountered in 24 patients (30%). A total of 30 foci were detected. Most of them were found in the superior retrotympanum (15 foci). In 9 cases an antral remnant guided the surgeon to convert to a canal wall up tympanomastoidectomy. During the postoperative follow-up period, residual cholesteatoma was detected on postoperative magnetic resonance imaging in 6 patients (7.5%). Adding an otoendoscopic examination to microscopic cholesteatoma surgery reduced the postoperative cholesteatoma residues rate (odds ratio=0.16). A negative otoendoscopic examination led to a cholesteatoma residue-free follow-up period in 95% of cases(NPV=0.95). Otoendoscopy is effective in identifying intraoperative cholesteatoma residues after microscopic cholesteatoma surgery. It reduces the postoperative cholesteatoma residue rate, and a negative otoendoscopic examination increases the likelihood of a cholesteatoma residue-free follow-up.

A labyrinthine fistula is a severe complication of middle ear cholesteatoma that can cause profound sensorineural hearing loss and vertigo. However, there is no consensus regarding the transition to postoperative hearing. Although hearing deteriorates gradually with a delay in some cases of labyrinthine fistula, insufficient consideration has been given to this point. We examined perioperative changes in cases of middle ear cholesteatoma with labyrinthine fistulas. We retrospectively reviewed the medical records of 578 patients with middle ear cholesteatoma who underwent tympanoplasty at our hospital between 2016 and 2021. Patients with labyrinthine fistulas were selected; their perioperative bone-conduction hearing was assessed. Fistula depth was determined following the classification reported by Dornhoffer et al. The hearing was compared preoperatively, early postoperatively (3-6 months), and 1 year postoperatively. Forty-eight patients (8.3%) had labyrinthine fistulas. Regarding depth, 21 cases were type I, 14 were type IIa, 3 were type IIb, and 10 were type III. Preoperative bone-conduction hearing was significantly poor in invasion type IIb or deeper cases. Cases with type IIb or deeper fistulas, multiple fistulas, or vertigo deteriorated postoperatively. Type III cases or those with multiple fistulas deteriorated further from the early postoperative period to 1 year postoperatively. Concerning frequency, 500 and 2000 Hz showed a delayed deterioration. This is a valuable report of delayed hearing loss after surgery in patients with a labyrinthine fistula. This change is associated with the labyrinthine fistula\'s depth and multiple fistulas-this is important during preoperative counseling of patients undergoing surgery.

OBJECTIVE: Previous studies have also associated cleft palate with increased cholesteatoma risk. Despite this close relation, the incidence of cholesteatoma and associated otologic issues in patients with ectodermal dysplasia types highly associated with cleft palate (EDT-ACPs) has not been formally analyzed. This study provides insight to guide clinicians caring for patients with ED types associated with cleft palate.
METHODS: Individuals with TP63 disorders and Goltz syndrome/Focal Dermal Hypoplasia in the National Foundation for Ectodermal Dysplasia database were contacted for participation in an online REDCap survey from Sept-Dec \'22. Descriptive statistics were generated using SAS JMP Pro 17 statistical software.
RESULTS: 65 individuals participated in the survey (response rate approx. 18 %). The median [IQR] age was 22 [14, 43], 41 (63 %) were female, and Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome (EEC) was most common (n = 26, 40 %). We found that, among our respondents with a history of cleft palate, the incidence of cholesteatoma was 39 %. Among respondents without a history of cleft palate, the incidence of cholesteatoma was 13 % CONCLUSIONS: Otologic issues, such as cholesteatoma, can have permanent implications including hearing loss that can be minimized by early identification and treatment. The estimated incidence of cholesteatoma among our participants is far above the estimated incidence of cholesteatoma in the general population with and without a history of cleft palate, suggesting an independent contribution of EDT-ACPs to the risk of cholesteatoma.

BACKGROUND: Mastoiditis frequently occurs in children as they are more susceptible to middle ear infections, but infrequently occurs in adults. A rare complication that results from mastoiditis and an obstructing cholesteatoma is a Bezold\'s abscess, of which there are less than 100 reported cases in literature to date.
METHODS: Here, we present a case of a 72-year-old Caucasian man who has had no history of prior ear infections and was found to have a cholesteatoma and advanced acute coalescent mastoiditis complicated by a Bezold\'s abscess.
CONCLUSIONS: Bezold\'s abscess is a rare entity infrequently encountered in the modern era, likely owing to more prompt treatment of otitis media. Cholesteatoma poses a great risk for both the development of otitis media and further progression to mastoiditis and its associated complications, such as Bezold\'s abscess. Knowledge of said abscess is crucial; without prompt recognition, further spread of infection can occur with vascular or mediastinal involvement.

Objective:To investigate the therapeutic effect of β-tricalcium phosphate in mastoid cavity obliteration for middle ear cholesteatoma under endoscope. Methods:Sixty patients with middle ear cholesteatoma admitted to our department from September 2021 to March 2022 were included in this study. The observation group（n=30） received β-tricalcium phosphate during mastoid cavity obliteration. The control group（n=30） received autologous tissue during mastoid cavity obliteration. Pure tone audiometry was performed before surgery and after surgery in both groups, and the air conduction thresholds of 500, 1 000, 2 000 and 4 000 Hz were recorded. The external acoustic meatus cross-sectional area within 1 cm of the external acoustic meatus opening was measured during the operation and after the operation. The differences of postoperative ear drying time, hearing change and mastoid cavity healing were compared between the two groups. Results:The duration of postoperative dry ear in the observation group was 2-14 weeks, with an average of （9.4±2.7） weeks, while that in the control group was 4-26 weeks, with an average of（16.0±5.7） weeks. The difference in dry ear time between the two groups was statistically significant（P<0.05）. In the observation group, the threshold change was -19-27 dB, with an average of（6.4±10.7） dB, and in the control group, the threshold change was -9-17 dB, with an average of （4.7±7.1） dB. There was no significant difference in hearing change between the two groups（P>0.05）. In the observation group, the cross-sectional area of 1 cm inside the ear canal opening was -5.9-8.2 mm², with an average of （-0.6±2.6） mm², and in the control group, the cross-sectional area of 1 cm inside the ear canal opening was -5.5-5.2 mm², with an average of （-0.4±2.3） mm². There was no significant difference in intraoperative cavity changes between the two groups（P>0.05）. Conclusion:The application of β-tricalcium phosphate to fill the mastoid cavity during the operation of endoscopic middle ear cholesteatoma has no adverse effect on the hearing of patients, can shorten the postoperative dry ear time, and results in good postoperative healing, which is worth promoting.
目的：探讨耳内镜术中使用β-磷酸三钙填塞乳突术腔的治疗效果。 方法：将2021年9月至2022年3月收治的中耳胆脂瘤患者60例纳入研究。观察组30例，术中填塞β-磷酸三钙；对照组30例，术中填塞自体组织。2组患者术前、术后行纯音听阈测听，记录500、1 000、2 000、4 000 Hz气导阈值；测量术中乳突填塞完成后及术后外耳道口内1 cm处横截面积。比较2组患者术后干耳时间、听力改变情况、乳突术腔愈合情况差异。 结果：观察组患者术后干耳时间为4～14周，平均（9.4±2.7）周；对照组患者术后干耳时间为4～26周，平均（16.0±5.7）周；2组干耳时间差异有统计学意义（P<0.05）。观察组气导听阈较术前改变值为-19～27 dB，平均（6.4±10.7） dB；对照组气导听阈较术前改变值为-9～17 dB，平均（4.7±7.1） dB；2组听力改变差异无统计学意义（P>0.05）。观察组术后外耳道口内1 cm处面积较术中改变值为-5.9～8.2 mm²，平均为（-0.6±2.6） mm²；对照组术后外耳道口内1 cm处面积较术中改变值为-5.5～5.2 mm²，平均为（-0.4±2.3） mm²；2组术腔改变差异无统计学意义（P>0.05）。 结论：内镜中耳胆脂瘤术中应用β-磷酸三钙填塞乳突术腔对患者听力无不良影响，可缩短术后干耳时间，患者术后愈合良好，值得推广。.