PTHrP participates in the bone destruction of middle ear cholesteatoma via promoting macrophage differentiation into osteoclasts induced by RANKL. / PTHrP促进RANKLè¯±å¯¼å·¨å™¬ç»†èƒžåˆ†åŒ–ä¸ºç ´éª¨ç»†èƒžå‚ä¸Žä¸­è€³èƒ†è„‚ç˜¤éª¨ç ´å.

OBJECTIVES: 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.

m6A modification of lncRNA in middle ear cholesteatoma. / 中耳胆脂瘤中lncRNA的m6A修饰.

OBJECTIVES: 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.

Comparison of Total Endoscopic Ear Surgery and Microscopic Postauricular Canal-Wall-Down Approach on Primary Acquired Cholesteatoma.

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.

Postoperative Late Hearing Deterioration in Cholesteatoma with Labyrinthine Fistulas.

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.

Efficacy of Otoendoscopy for Residual Cholesteatoma Detection During Microscopic Chronic Ear Surgery.

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.

Long-Term Results of Sodium 2-Mercaptoethane Sulfonate Usage on Cholesteatoma Surgery.

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.

Bezold's abscess, an uncommon complication of otitis media and cholesteatoma: a case report.

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. CASE PRESENTATION: 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.

[The effect of different degrees of Eustachian tube dysfunction on hearing threshold in patients with acquired primary middle ear cholesteatoma after balloon eustachian tuboplasty].

Objective:To investigate the changes in hearing threshold of the acquired primary cholesteatoma of the middle ear with different degrees of eustachian tube dysfunction after balloon eustachian tuboplasty. Methods:This retrospective study included forty cases with middle ear cholesteatoma and eustachian tube dysfunction who underwent open mastoidectomy + tympanoplasty + balloon eustachian tuboplasty were enrolled. All patients were admitted from November 2020 to April 2022. The preoperative eustachian tube score of 0-2 were defined as the lower group, and the scores of 3-5 were defined as the higher group. Pure tone audiometry was measured preoperatively and 1, 3, 6 and 12 months postoperatively. The average value of bone conduction threshold and air conduction threshold of 250-4 000 Hz were calculated, and the air-bone gap was calculated simultaneously. SPSS 25.0 was used for statistical analysis. P<0.05 was considered statistically significant. Results:In the lower group, the air conduction threshold and air-bone gap at 3 months postoperatively were significantly decreased in comparison with those preoperatively（P<0.05），as was the air-bone gap at 6 months postoperatively（P<0.05）. In the higher group, the air conduction threshold and air-bone gap were significantly decreased at 3, 6 and 12 months postoperatively（P<0.05）. Conclusion:The air conduction threshold and air-bone gap of patients with the acquired primary cholesteatoma of the middle ear and eustachian tube dysfunction were significantly decreased after eustachian tube balloon dilatation. Hearing improvement lasted longer in patients with slight eustachian tube dysfunction.

[Therapeutic effect of ß-tricalcium phosphate in mastoid cavity obliterationunder endoscope].

Objective:To investigate the therapeutic effect of ß-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 ß-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 ß-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.

Ectodermal dysplasia and cholesteatoma: A cross-sectional analysis of otologic issues.

OBJECTIVES: 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.

Identification of miRNA expression profile in middle ear cholesteatoma using small RNA-sequencing.

BACKGROUND: The present study aims to identify the differential miRNA expression profile in middle ear cholesteatoma and explore their potential roles in its pathogenesis. METHODS: Cholesteatoma and matched normal retroauricular skin tissue samples were collected from patients diagnosed with acquired middle ear cholesteatoma. The miRNA expression profiling was performed using small RNA sequencing, which further validated by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs in cholesteatoma were predicted. The interaction network of 5 most significantly differentially expressed miRNAs was visualized using Cytoscape. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were processed to investigate the biological functions of miRNAs in cholesteatoma. RESULTS: The miRNA expression profile revealed 121 significantly differentially expressed miRNAs in cholesteatoma compared to normal skin tissues, with 56 upregulated and 65 downregulated. GO and KEGG pathway enrichment analyses suggested their significant roles in the pathogenesis of cholesteatoma. The interaction network of the the 2 most upregulated (hsa-miR-21-5p and hsa-miR-142-5p) and 3 most downregulated (hsa-miR-508-3p, hsa-miR-509-3p and hsa-miR-211-5p) miRNAs identified TGFBR2, MBNL1, and NFAT5 as potential key target genes in middle ear cholesteatoma. CONCLUSIONS: This study provides a comprehensive miRNA expression profile in middle ear cholesteatoma, which may aid in identifying therapeutic targets for its management.

The Impact of Piezoelectric Device in Cholesteatoma Endoscopic Surgery: Retrospective Evaluation of Safety and Functional Results.

OBJECTIVE: Atticotomy represents an essential surgical step within the management of attical cholesteatoma during endoscopic ear surgery. The aim of the present study was to evaluate the safety and functional results of an endoscopic atticotomy performed with piezosurgery, in terms of audiological outcomes and tissue's healing. METHODS: This is an observational retrospective study on patients with attical cholesteatoma who underwent endoscopic ear surgery with piezoelectric atticotomy and subsequent scutum reconstruction either with tragal cartilage or temporalis muscle fascia. Scutumplasty's status was evaluated via scheduled outpatient controls through an endoscopic check and classified as stable or unstable at least 10 months after surgery. A pre- and postoperative audiometric examination was performed in each patient. RESULTS: Eighty-four patients were enrolled. In 50 out of 84 patients (59.52%), an exclusive endoscopic procedure was performed, whereas in 34 patients (40.48%) a combined microscopic/endoscopicapproach was adopted. In 72 cases (85.71%), scutum's reconstruction appeared to be normally positioned, whereas 12 patients developed a retraction pocket, which was self-cleaning in 8 of them and non-self-cleaning in the remaining 4. In 17 patients, a slight sensorineural hearing loss (between 5 and 15 dBHL) was observed, and in 2 patients, the loss was greater than 15 dBHL. Overall, no significative differences between pre- and postoperative pure-tone average bone thresholds resulted (p = 0.4983), though a mild significant hearing deterioration was detected by the specific analysis at 4000 Hz (p = 0.0291). CONCLUSION: Piezosurgery represents an extremely useful tool in performing atticotomy during endoscopic tympanoplasties. Our data seem to support the safety of its usage in this specific step, as it did not lead to any significant sensorineural damage on overall pure-tone average. Moreover, satisfactory tissue healing in regard to scutum reconstruction was observed.

Risk factors for middle ear cholesteatoma surgery based on Korean population data.

BACKGROUND: Studies of risk factors for middle ear cholesteatoma surgery using population-based data are lacking. OBJECTIVES: To investigate the risk factors for cholesteatoma surgery in adults based on population data from Korea. MATERIALS AND METHODS: For this retrospective study, we used Korean National Health Insurance Service National Sample Cohort data. Patients who were 20 years or older and underwent mastoidectomy from 2006 through 2015 under the diagnostic codes of cholesteatoma were defined as patients with middle ear cholesteatoma surgery. The control group was comprised of the remaining database sample in 2006. Sociodemographic factors in 2006 and histories of medical diseases, allergic diseases, and chronic sinusitis from 2003 through 2005 were compared between cholesteatoma surgery and control groups. RESULTS: A total of 459 patients underwent cholesteatoma surgery. In multivariate Cox regression analysis, age 40-59 years and residence in metropolitan cities and small- and medium-sized cities and counties were significant risk factors for cholesteatoma surgery whereas allergic rhinitis, asthma, atopic dermatitis, and chronic sinusitis were not significant risk factors for middle ear cholesteatoma surgery. CONCLUSIONS AND SIGNIFICANCE: The present study found no evidence of associations between allergic diseases or chronic sinusitis and cholesteatoma surgery in adults.

The Role of Trublue Laser in Cholesteatoma Surgery.

OBJECTIVE: The retrospective cohort study aimed to determine the safety and efficacy of TruBlue laser application in cholesteatoma surgeries. METHODS: All cholesteatoma surgeries conducted from January 2018 to January 2022 in two tertiary referral hospitals in Hong Kong, with and without use of TruBlue laser, were included. Pure tone audiogram was done pre- and post-operatively to assess hearing. Disease extent was graded with ChOLE score and ChOLE staging. Residual disease was determined clinically, radiologically, or surgically with second look operation. RESULTS: One hundred twenty cholesteatoma cases were identified. There are 39.2% (n = 47) of the cholesteatoma surgeries that utilized TruBlue laser, while 60.8% (n = 73) did not. Overall follow-up duration was 21 ± 12.4 months, ranging from 2 to 47 months. Both groups were similar in demographics, pre-operative hearing and ChOLE staging. The length of stay was comparable in both groups (2 ± 2 days in nonlaser, 1 ± 1 day in laser, p = 0.31). There was no facial nerve injury related to surgery in both groups, and overall complication rates were similar (4.1% in nonlaser, 4.3% in laser, p = 0.97). The postoperative hearing was comparable with good hearing preservation in both groups. Residual cholesteatoma occurred in 17.8% (n = 13) in nonlaser group, and 21.3% (n = 10) in laser group, which was not statistically significant (p = 0.64). Seventy percent of the cholesteatoma residual in laser group occurred at area that TruBlue LASER cannot be applied. CONCLUSION: TruBlue LASER was safe in cholesteatoma surgeries, though no added benefits were shown in reducing cholesteatoma residual rate. A larger controlled study is warranted to discern the true effect of TruBlue LASER. LEVEL OF EVIDENCE: Level 3.

Cholesteatoma in the pediatric aerodigestive population.

OBJECTIVES: To report the prevalence of cholesteatoma and related comorbidities in pediatric aerodigestive patients requiring tracheostomy or airway reconstruction procedures. To use study findings to inform clinical management of these complex patients. METHODS: A repository of clinical data drawn from our institution's electronic medical records was queried to identify airway reconstruction (airway) and complex hospital control (control) patient cohorts. Retrospective chart review was then performed to investigate the occurrence of cholesteatoma and related pathologies in these patients, as well as clinical management. RESULTS: The prevalence of cholesteatoma in airway and control patients was 6/374 (1.60 %) and 35/30,565 (0.11 %), respectively. The relative risk of cholesteatoma diagnosis in airway patients was 14.01 (95 % CI 6.06-32.14). Airway patients were more likely than control patients to have pressure equalization tube history (relative risk 3.25, 95 % CI 2.73-3.82). Age at cholesteatoma diagnosis and first surgical intervention was younger in airway compared to control patients (5.43 vs. 8.33, p = 0.0182, and 6.07 vs. 8.82, p = 0.0236). However, time from diagnosis to intervention and extent of surgery were similar between the groups. CONCLUSION: This is the first study to investigate the prevalence of cholesteatoma in the pediatric aerodigestive population. The relative risk of cholesteatoma diagnosis was found to be 14 times higher in patients with tracheostomy or airway reconstruction history. Underlying eustachian tube and palatal dysfunction are likely contributing factors to the elevated risk. Additionally, cholesteatoma in this population was diagnosed and required surgical intervention at a younger age, which may suggest a more aggressive disease course. Providers should maintain a high degree of suspicion for cholesteatoma in this complex population.

Evaluation of magnetic resonance imaging to detect cholesteatoma in clinical healthcare.

BACKGROUND: Non-Echo-Planar Diffusion Weighed Magnetic Resonance Imaging (non-EPI DW MRI) plays a role in the planning of cholesteatoma surgery. OBJECTIVES: To outline the usage of Non-EPI DW MRI in cholesteatoma diagnostics and to determine its accuracy, using otosurgery diagnostics as reference standard. MATERIAL AND METHODS: A retrospective descriptive study. All subjects operated, with suspicion of cholesteatoma as indication, that had a preceding examination with non-EPI DW MRI, between October 2010 and March 2019. Calculating sensitivity, specificity, predicative values, and likelihood ratios, using non-EPI DW MRI as index test and diagnosis from otosurgery as reference standard. RESULTS: Fifty-two subject episodes were included. Non-EPI DW MRI had a sensitivity of 0.50, specificity of 0.75, positive and negative predictive values of 0.74 and 0.52 and, positive and negative likelihood ratios of 2.0 and 0.67 respectively. CONCLUSIONS AND SIGNIFICANCE: There is a clear annual trend with increased numbers of executed examinations during the study period. The diagnostic accuracy of non-EPI DW MRI does not reach acceptable levels in the existing everyday routine practice conditions. The accuracy of the examination increases when interpreted by an experienced radiologist and when using the definition of cholesteatoma recommended by EAONO/JOS.

Chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is a leading global cause of potentially preventable hearing loss in children and adults, associated with socioeconomic deprivation. There is an absence of consensus on the definition of CSOM, which complicates efforts for prevention, treatment, and monitoring. CSOM occurs when perforation of the tympanic membrane is associated with severe or persistent inflammation in the middle ear, leading to hearing loss and recurrent or persistent ear discharge (otorrhoea). Cholesteatoma, caused by the inward growth of the squamous epithelium of the tympanic membrane into the middle ear, can also occur. The optimal treatment of discharge in CSOM is topical antibiotics. In resource-limited settings where topical antibiotics might not be available, topical antiseptics are an alternative. For persistent disease, surgery to repair the tympanic membrane or remove cholesteatoma might offer long-term resolution of otorrhoea and potential improvement to hearing. Recent developments in self-fitted air-conduction and bone-conduction hearing aids offer promise as new options for rehabilitation.

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

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.

Cost-Effectiveness of Diffusion Weighted MRI Versus Planned Second-Look Surgery for Cholesteatoma.

OBJECTIVE: To compare the cost-effectiveness of serial non-echo planar diffusion weighted MRI (non-EP DW MRI) versus planned second look surgery following initial canal wall up tympanomastoidectomy for the treatment of cholesteatoma. METHODS: A decision-analytic model was developed. Model inputs including residual cholesteatoma rates, rates of non-EP DW MRI positivity after surgery, and health utility scores were abstracted from published literature. Cost data were derived from the 2022 Centers for Medicare and Medicaid Services fee rates. Efficacy was defined as increase in quality-adjusted life year (QALY). One- and 2-way sensitivity analyses were performed on variables of interest to probe the model. Total time horizon was 50 years with a willingness to pay (WTP) threshold set at $50 000/QALY. RESULTS: Base case analysis revealed that planned second-look surgery ($11 537, 17.30 QALY) and imaging surveillance with non-EP DWMRI ($10 439, 17.26 QALY) were both cost effective options. Incremental cost effectiveness ratio was $27 298/QALY, which is below the WTP threhshold. One-way sensitivity analyses showed that non-EP DW MRI was more cost effective than planned second-look surgery if the rate of residual disease after surgery increased to 48.3% or if the rate of positive MRI was below 45.9%. A probabilistic sensitivity analysis at WTP of $50 000/QALY found that second-look surgery was more cost-effective in 56.7% of iterations. CONCLUSION: Non-EP DW MRI surveillance is a cost-effect alternative to planned second-look surgery following primary canal wall up tympanomastoidectomy for cholesteatoma. Cholesteatoma surveillance decisions after initial canal wall up tympanomastoidectomy should be individualized. LEVEL OF EVIDENCE: V.