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1.
Lancet ; 403(10441): 2339-2348, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38621397

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Otitis Media, Suppurative , Humans , Otitis Media, Suppurative/therapy , Otitis Media, Suppurative/complications , Chronic Disease , Anti-Bacterial Agents/therapeutic use , Child , Hearing Loss/etiology , Tympanic Membrane Perforation/therapy , Tympanic Membrane Perforation/etiology , Adult , Cholesteatoma, Middle Ear
2.
Mol Cell Proteomics ; 22(9): 100628, 2023 09.
Article in English | MEDLINE | ID: mdl-37532176

ABSTRACT

Cholesteatoma is a chronic inflammatory ear disease with abnormal keratinized epithelium proliferation and tissue damage. However, the mechanism of keratinized epithelium hyperproliferation in cholesteatoma remains unknown. Hence, our study sought to shed light on mechanisms affecting the pathology and development of cholesteatoma, which could help develop adjunctive treatments. To investigate molecular changes in cholesteatoma pathogenesis, we analyzed clinical cholesteatoma specimens and paired ear canal skin with mass spectrometry-based proteomics and bioinformatics. From our screen, alpha-synuclein (SNCA) was overexpressed in middle ear cholesteatoma and might be a key hub protein associated with inflammation, proliferation, and autophagy in cholesteatoma. SNCA was more sensitive to lipopolysaccharide-induced inflammation, and autophagy marker increase was accompanied by autophagy activation in middle ear cholesteatoma tissues. Overexpression of SNCA activated autophagy and promoted cell proliferation and migration, especially under lipopolysaccharide inflammatory stimulation. Moreover, inhibiting autophagy impaired SNCA-mediated keratinocyte proliferation and corresponded with inhibition of the PI3K/AKT/CyclinD1 pathways. Also, 740Y-P, a PI3K activator reversed the suppression of autophagy and PI3K signaling by siATG5 in SNCA-overexpressing cells, which restored proliferative activity. Besides, knockdown of SNCA in RHEK-1 and HaCaT cells or knockdown of PI3K in RHEK-1 and HaCaT cells overexpressing SNCA both resulted in attenuated cell proliferation. Our studies indicated that SNCA overexpression in cholesteatoma might maintain the proliferative ability of cholesteatoma keratinocytes by promoting autophagy under inflammatory conditions. This suggests that dual inhibition of SNCA and autophagy may be a promising new target for treating cholesteatoma.


Subject(s)
Cholesteatoma, Middle Ear , Humans , Cholesteatoma, Middle Ear/metabolism , Cholesteatoma, Middle Ear/pathology , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Lipopolysaccharides , Proteomics , Signal Transduction , Cell Proliferation , Autophagy , Inflammation , alpha-Synuclein
3.
Pediatr Radiol ; 54(4): 620-634, 2024 04.
Article in English | MEDLINE | ID: mdl-38393651

ABSTRACT

Congenital cholesteatoma is a rare, non-neoplastic lesion that causes conductive hearing loss in children. It is underrecognized and often diagnosed only when there is an established hearing deficit. In the pediatric population, hearing deficiency is particularly detrimental because it can impede speech and language development and, in turn, the social and academic well-being of affected children. Delayed diagnosis leads to advanced disease that requires more extensive surgery and a greater chance of recurrence. A need to promote awareness and recognition of this condition has been advocated by clinicians and surgeons, but no comprehensive imaging review dedicated to this entity has been performed. This review aims to discuss the diagnostic utility of high-resolution computed tomography and magnetic resonance imaging in preoperative and postoperative settings in congenital cholesteatoma. Detailed emphasis is placed on the essential preoperative computed tomography findings that facilitate individualized surgical management and prognosis in the pediatric population.


Subject(s)
Cholesteatoma, Middle Ear , Cholesteatoma/congenital , Humans , Child , Cholesteatoma, Middle Ear/diagnosis , Cholesteatoma, Middle Ear/pathology , Cholesteatoma, Middle Ear/surgery , Diffusion Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging , Radiologists
4.
Am J Otolaryngol ; 45(2): 104121, 2024.
Article in English | MEDLINE | ID: mdl-38056195

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the graft outcomes and iatrogenic cholesteatomas for 3 years following cartilage-perichondrium over-underlay technique with perichondrial graft covering the epithelium for large-sized tympanic membrane (TM) perforations. MATERIALS AND METHODS: This prospective case series enrolled patients with large-sized perforation who underwent endoscopic cartilage-perichondrium over-underlay technique. The graft success rate, hearing outcomes, and development of iatrogenic middle ear cholesteatomas and graft cholesteatomas were assessed at 3 years postoperatively. RESULTS: This study included 62 ears of 62 patients. The mean follow-up duration was 47.3 ± 10.8 (38-64) months. Neovascularization was observed in the lateral perichondrium graft in 55 (88.7 %) patients, which inosculated into the TM remnant at 4-5 weeks. However, graft neovascularization was not observed in the four patients with excessive perichondrium graft that migrated into the external auditory canal and the three patients with middle ear infections. The graft failure rate was 6.5 % at 6 months, 11.3 % at 12 months, 6.5 % at 24 months, and the overall graft success rate was 91.8 % at the last follow-up. Granular myringitis developed in 11.3 % (7/62) of the patients. High-resolution computed tomography revealed well-pneumatized mastoids and middle ear at the final follow-up. However, graft cholesteatomas were observed in 3 (4.8 %) patients at 7-24 months postoperatively. CONCLUSIONS: The cartilage-perichondrium over-underlay technique with perichondrial graft covering TM epithelium is safe and effective for the repair of large perforations, with good short- and long-term graft outcomes, minimal risk of graft cholesteatoma development, and no risk of iatrogenic middle ear cholesteatomas.


Subject(s)
Cholesteatoma, Middle Ear , Otitis Media , Tympanic Membrane Perforation , Humans , Tympanic Membrane/surgery , Follow-Up Studies , Cholesteatoma, Middle Ear/surgery , Treatment Outcome , Cartilage/transplantation , Tympanic Membrane Perforation/etiology , Tympanic Membrane Perforation/surgery , Otitis Media/surgery , Iatrogenic Disease , Myringoplasty/methods
5.
Am J Otolaryngol ; 45(4): 104263, 2024.
Article in English | MEDLINE | ID: mdl-38547748

ABSTRACT

OBJECTIVES: To describe a rare complication of cholesteatoma. METHODS: Case report with literature review. RESULTS: We report a case of a 37-year-old male who presented for evaluation of otorrhea, headache, and progressive left sensorineural hearing loss. Clinical and radiologic evaluation demonstrated a large recurrent attic cholesteatoma with erosion into the lateral and superior semicircular canals, and diffuse enhancement of the internal auditory canal and cerebellopontine angle suggestive of hypertrophic pachymeningitis secondary to cholesteatoma. After treatment with a course of antibiotics and canal wall down mastoidectomy surgery for cholesteatoma exteriorization, he experienced improvement of his symptoms and resolution of hypertrophic pachymeningitis. CONCLUSION: Hypertrophic pachymeningitis is a rarely described complication of cholesteatoma. In the context of cholesteatoma, treatment with antibiotics and surgical removal or exteriorization of cholesteatoma are effective treatments for HP.


Subject(s)
Cerebellopontine Angle , Cholesteatoma, Middle Ear , Hypertrophy , Meningitis , Humans , Male , Adult , Meningitis/etiology , Meningitis/complications , Cerebellopontine Angle/surgery , Cerebellopontine Angle/diagnostic imaging , Cholesteatoma, Middle Ear/complications , Cholesteatoma, Middle Ear/surgery , Recurrence , Ear, Inner/diagnostic imaging , Ear, Inner/surgery , Magnetic Resonance Imaging , Mastoidectomy/methods , Tomography, X-Ray Computed
6.
Eur Arch Otorhinolaryngol ; 281(7): 3557-3568, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38351408

ABSTRACT

PURPOSE: To investigate the rate of residual disease in the Potsic staging system for congenital cholesteatomas. METHODS: A protocol registration was published on PROSPERO (CRD42022383932), describing residual disease as a primary outcome and hearing improvement as secondary. A systematic search was performed in four databases (PubMed, Embase, Cochrane Library, Web of Science) on December 14, 2022. Articles were included if cholesteatomas were staged according to the Potsic system and follow-up duration was documented. Risk of bias was evaluated using the Quality In Prognosis Studies (QUIPS) tool. In the statistical synthesis a random effects model was used. Between-study heterogeneity was assessed using I2. RESULTS: Thirteen articles were found to be eligible for systematic review and seven were included in the meta-analysis section. All records were retrospective cohort studies with high risk of bias. Regarding the proportions of residual disease, analysis using the χ2 test showed no statistically significant difference between Potsic stages after a follow-up of minimum one year (stage I 0.06 (confidence interval (CI) 0.01-0.33); stage II 0.20 (CI 0.09-0.38); stage III 0.06 (CI 0.00-0.61); stage IV: 0.17 (CI 0.01-0.81)). Postoperative and preoperative hearing outcomes could not be analyzed due to varied reporting. Results on cholesteatoma location and mean age at staging were consistent with those previously published. CONCLUSION: No statistically significant difference was found in the proportions of residual disease between Potsic stages, thus the staging system's applicability for outcome prediction could not be proven based on the available data. Targeted studies are needed for a higher level of evidence.


Subject(s)
Cholesteatoma, Middle Ear , Humans , Cholesteatoma, Middle Ear/surgery , Cholesteatoma, Middle Ear/complications , Cholesteatoma/pathology , Cholesteatoma/surgery , Cholesteatoma/congenital , Prognosis
7.
Eur Arch Otorhinolaryngol ; 281(2): 711-718, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37542562

ABSTRACT

PURPOSE: In primary cholesteatoma patients, incus destruction with an intact and mobile stapes is a frequent finding. Different techniques have been described to restore the ossicular chain, including incus interposition, stapes augmentation and type III tympanoplasty. Controversy about postoperative hearing results in open versus closed surgical techniques exist. METHODS: We performed a retrospective analysis of clinical, surgical and audiometric data of patients with primary cholesteatoma surgery operated between 2010 and 2020, and a mobile stapes and one-stage ossicular reconstruction. Pre- and post-operative audiograms were compared for the different surgical groups, mainly focusing on postoperative air-bone gap. Mastoid pneumatization and ventilation was also considered. RESULTS: The mean postoperative air-bone gap (0.5-4 kHz) of the 126 included patients was 20 dB. Hearing after type III tympanoplasty (26 dB) was worse than incus interposition (19 dB) and stapes augmentation (20 dB). Hearing after an open (23 dB) versus closed (19 dB) surgical technique was significantly different. No improvement in air-bone gap was observed for the higher frequencies. CONCLUSION: A residual postoperative air-bone gap should be considered after primary cholesteatoma surgery with intact and mobile stapes. Incus interposition in closed cavity operation is the optimal situation, but open cavity surgery should not be avoided because of hearing. Extent of the disease is prioritized and poorer ventilation before and after surgery may affect postoperative hearing.


Subject(s)
Cholesteatoma, Middle Ear , Ossicular Prosthesis , Ossicular Replacement , Humans , Stapes , Tympanoplasty/methods , Incus/surgery , Retrospective Studies , Cholesteatoma, Middle Ear/complications , Cholesteatoma, Middle Ear/surgery , Treatment Outcome , Ossicular Replacement/methods
8.
Eur Arch Otorhinolaryngol ; 281(8): 4081-4087, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38517544

ABSTRACT

PURPOSE: Exploring a possible link between upper airway inflammation and the development of cholesteatoma by studying the association between mucosa-affecting diseases of the upper airways and cholesteatoma surgery. METHODS: This is a nationwide case-control study of 10,618 patients who underwent surgery for cholesteatoma in Sweden between 1987 and 2018. The cases were identified in the National Patient Register and 21,235 controls matched by age, sex and place of residency were included from national population registers. Odds ratios (OR) and corresponding 95% confidence intervals were used to assess the association between six types of mucosa-affecting diseases of the upper airways and cholesteatoma surgery. RESULTS: Chronic rhinitis, chronic sinusitis and nasal polyposis were more common in cholesteatoma patients than in controls (OR 1.5 to 2.5) as were both adenoid and tonsil surgery (OR > 4) where the strongest association was seen for adenoid surgery. No association was seen between allergic rhinitis and cholesteatoma. CONCLUSION: This study supports an association between mucosa-affecting diseases of the upper airways and cholesteatoma. Future studies should aim to investigate the mechanisms connecting mucosa-affecting diseases of the upper airways and cholesteatoma formation regarding genetic, anatomical, inflammatory and mucosa properties.


Subject(s)
Cholesteatoma, Middle Ear , Nasal Polyps , Rhinitis , Sinusitis , Humans , Case-Control Studies , Female , Male , Cholesteatoma, Middle Ear/epidemiology , Cholesteatoma, Middle Ear/surgery , Sweden/epidemiology , Adult , Middle Aged , Rhinitis/epidemiology , Rhinitis/complications , Rhinitis/surgery , Sinusitis/epidemiology , Adolescent , Nasal Polyps/epidemiology , Nasal Polyps/complications , Nasal Polyps/surgery , Child , Chronic Disease , Young Adult , Aged , Adenoids/pathology , Adenoids/surgery , Child, Preschool , Registries
9.
Int Tinnitus J ; 27(2): 242-246, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38512871

ABSTRACT

A cholesteatoma is an expansion of keratinizing squamous epithelium that enters the middle ear cleft from the outer layer of the tympanic membrane or ear canal. Choleatomas are always treated surgically. Recurrence of the illness presents another challenge for the patient and the surgeon, though. There have been reports of recurrence rates as high as 30% in adults and as high as 70% in children. Here, we describe a case of persistent recurrent otorrhea following revision surgery, along with acquired recurrent cholesteatoma following canal wall down surgery. A 38-year -male with underlying Diabetes Mellitus and Hypertension presented with left scanty and foul-smelling ear discharge for 2 years and left reduced hearing. He was diagnosed with left chronic active otitis media with cholesteatoma for which he underwent left modified radical mastoidectomy, meatoplasty and tympanoplasty in 2017. Five months post operatively, he presented with left otorrhea. However, he defaulted followed up and presented in April 2018 for similar complaints. Otoscopy examination revealed left tympanic membrane perforation at poster superior quadrant of pars tensa and bluish discoloration behind pars flacida. He was diagnosed as recurrent left cholesteatoma and subsequently he underwent left mastoid exploration under general anesthesia in June 2018. Postsurgery, he developed recurrent ear discharge which was treated with topical antibiotics and ear toileting. We report a case of recurrent Cholesteatoma despite canal wall down procedure requiring a second redo procedure and with persistent recurrent otorrhea after the redo procedure.However, this case demonstrates the need for regular follow ups even after a canal wall down procedure for detecting recurrence of disease. Moreover, this case denotes some of the patient factors and surgeon factors involved in disease recurrence. Furthermore, importance of opting for an imaging study in case of high suspicion of the disease.


Subject(s)
Cholesteatoma, Middle Ear , Otitis Media , Adult , Humans , Male , Cholesteatoma, Middle Ear/complications , Cholesteatoma, Middle Ear/diagnosis , Cholesteatoma, Middle Ear/surgery , Chronic Disease , Otitis Media/complications , Otitis Media/diagnosis , Retrospective Studies , Treatment Outcome , Tympanic Membrane , Tympanoplasty/methods
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(5): 667-678, 2024 May 28.
Article in English, Zh | MEDLINE | ID: mdl-39174880

ABSTRACT

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.


Subject(s)
Adenosine , Cholesteatoma, Middle Ear , RNA, Long Noncoding , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Humans , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/genetics , Cholesteatoma, Middle Ear/genetics , Cholesteatoma, Middle Ear/metabolism , Methylation , Signal Transduction , Gene Ontology , Gene Expression Profiling , Transcriptome
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(5): 655-666, 2024 May 28.
Article in English, Zh | MEDLINE | ID: mdl-39174879

ABSTRACT

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.


Subject(s)
Bone Resorption , Cell Differentiation , Cholesteatoma, Middle Ear , Macrophages , Osteoclasts , Osteoprotegerin , Parathyroid Hormone-Related Protein , RANK Ligand , Animals , Humans , Male , Mice , Bone Resorption/metabolism , Cholesteatoma, Middle Ear/metabolism , Cholesteatoma, Middle Ear/pathology , Macrophages/metabolism , NFATC Transcription Factors/metabolism , NFATC Transcription Factors/genetics , Osteoclasts/metabolism , Osteoprotegerin/metabolism , Parathyroid Hormone-Related Protein/metabolism , RANK Ligand/metabolism , RANK Ligand/genetics , RAW 264.7 Cells
12.
Funct Integr Genomics ; 23(2): 138, 2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37106264

ABSTRACT

In this study, the bacterial diversity of acquired middle ear cholesteatoma (MEC) was evaluated to reveal its pathogenesis and provides a guide for the use of antibiotics. Twenty-nine cases of acquired MEC and eight cases of healthy middle ears undergoing cochlear implantation (CI) were evaluated. Full-length 16S rRNA gene sequencing was performed to profile the bacterial communities in lesions and healthy tissues of the middle ear. ACE (P = 0.043) and Chao1 (P = 0.039) indices showed significant differences in alpha diversity (P < 0.05). Analysis of PERMANOVA/Anosim using the Bray-Curtis distance matrix results suggested that the between-group differences were greater than the within-group differences (R = 0.238, P < 0.05, R2 = 0.066, P < 0.05). Bacterial community analysis revealed that Alphaproteobacteria at the class level and Caulobacterales and Sphingomonadales at the order level were significantly different (P < 0.05). In the LefSe (Linear discriminant analysis effect size) analysis, Porphyromonas bennonis was elevated, and Bryum argenteum and unclassified Cyanobacteriales were reduced at the species level in MEC (P < 0.05). Fifteen metabolic pathways were found to be significantly different between the two groups by analysing the abundance of metabolic pathways in level 2 of the Kyoto Encyclopaedia of Genes and Genomes (KEGG). Seven and eight metabolic pathways were significantly elevated in the MEC and control groups, respectively (P < 0.05). The role of bacteria in the pathogenesis of acquired MEC was further refined through analysis of metabolic pathways. These findings indicate that the acquired MEC and healthy middle ear contain more diverse microbial communities than previously thought.


Subject(s)
Cholesteatoma, Middle Ear , Humans , Cholesteatoma, Middle Ear/genetics , RNA, Ribosomal, 16S/genetics , Genes, rRNA , Bacteria/genetics , China
13.
Calcif Tissue Int ; 113(6): 609-617, 2023 12.
Article in English | MEDLINE | ID: mdl-37872266

ABSTRACT

Cholesteatoma can lead to progressive destruction of the auditory ossicles along with conductive hearing loss but precise data on the microstructural, cellular, and compositional aspects of affected ossicles are not available. Here, we obtained incus specimens from patients who had cholesteatoma with conductive hearing loss. Incudes were evaluated by micro-computed tomography, histomorphometry on undecalcified sections, quantitative backscattered electron imaging, and nanoindentation. Results were compared with two control groups taken from patients with chronic otitis media as well as from skeletally intact donors at autopsy. The porosity of incus specimens was higher in cholesteatoma than in chronic otitis media, along with a higher osteoclast surface per bone surface. Histomorphometric assessment revealed higher osteoid levels and osteocyte numbers in cholesteatoma incudes. Incudes affected by cholesteatoma also showed lower matrix mineralization compared with specimens from healthy controls and chronic otitis media. Furthermore, the modulus-to-hardness ratio was higher in cholesteatoma specimens compared with controls. Taken together, we demonstrated increased porosity along with increased osteoclast indices, impaired matrix mineralization, and altered biomechanical properties as distinct features of the incus in cholesteatoma. Based on our findings, a possible impact of impaired bone quality on conductive hearing loss should be further explored.


Subject(s)
Cholesteatoma, Middle Ear , Otitis Media , Humans , Incus , Hearing Loss, Conductive , X-Ray Microtomography , Chronic Disease
14.
J Comput Assist Tomogr ; 47(1): 144-150, 2023.
Article in English | MEDLINE | ID: mdl-36395525

ABSTRACT

OBJECTIVE: The aim of the study is to evaluate the application of high-resolution computed tomography (HRCT) and turbo spin-echo diffusion-weighted imaging (TSE-DWI) fusion imaging for localization of middle ear cholesteatomas. METHODS: Eighty-six patients with clinically suspected middle ear cholesteatomas were enrolled prospectively. Ear TSE-DWI and HRCT scans were performed using a postprocessing workstation to generate a TSE-DWI-CT fusion image. Subsequently, all the enrolled patients received surgical treatment. According to the STAM system (difficult access sites [S], the tympanic cavity [T], the attic [A], and the mastoid [M]), the agreement between the localization of lesions evaluated by HRCT, TSE-DWI, and TSE-DWI-CT fusion images and the intraoperatively recorded localization were computed using Cohen κ statistic. RESULTS: Based on the pathological results, the enrolled patients were divided into a cholesteatoma (n = 50) and a noncholesteatoma group (n = 36). The area under the receiver operator characteristic curve for diagnosis of cholesteatoma with TSE-DWI-CT fusion imaging was identical to that using the TSE-DWI images (0.924 vs 0.924, P > 0.05), but was significantly higher than that with HRCT imaging (0.924 vs 0.767, P = 0.0005). Furthermore, the diagnostic sensitivity and specificity of TSE-DWI-CT fusion imaging for cholesteatomas were 96.0% and 88.9%, respectively. Depending on whether the cholesteatoma extended to the mastoid, TSE-DWI-CT fusion imaging demonstrated good agreement with the intraoperative record for localization of lesions (κ = 0.808) and had a high accuracy of localization by the STAM system. CONCLUSIONS: Turbo spin-echo-DWI-CT fusion images have a very high diagnostic value for the preoperative localization of cholesteatomas.


Subject(s)
Cholesteatoma, Middle Ear , Humans , Cholesteatoma, Middle Ear/diagnostic imaging , Cholesteatoma, Middle Ear/surgery , Magnetic Resonance Imaging , Diffusion Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed , Ear, Middle/diagnostic imaging , Ear, Middle/surgery , Sensitivity and Specificity
15.
Am J Otolaryngol ; 44(2): 103751, 2023.
Article in English | MEDLINE | ID: mdl-36586321

ABSTRACT

BACKGROUND: There is ongoing debate over the optimal surgical approach for cholesteatoma treatment1-5. The aim of this review was to determine whether canal-wall down with mastoid obliteration is associated with favourable outcomes compared to either canal-wall down without obliteration or canal-wall up. The primary outcome was cholesteatoma reoccurrence with secondary outcomes including otorrhoea, reoperation and patient-reported outcome measures. METHODS: Medline, Embase, Cochrane databases and clinicaltrials.gov were searched for studies reporting outcomes of patients undergoing primary CWD-MO for cholesteatoma and directly compared with CWD and CWU mastoidectomies. Data were collated and meta-analysis performed. RESULTS: 2379 patients were included from 12 studies that met the inclusion criteria. CWD-MO was found to be associated with significantly less risk of recurrence when compared to CWU (OR = 0.330 (95 % CI 0.191-0.570, p < 0.001). When compared to CWD, CWD-MO was associate with significantly lower incidence of persistent otorrhoea (OR 0.405 (95 % CI 0.232-0.706, p < 0.001) while the rates of recurrence were comparable (OR: 1.231 [95 % CI: 0.550-2.757] p = 0.613). Otorrhoea rates between CWD-MO and CWU were equivalent as was reoperation. Quality of life and hearing outcomes were variably reported. CONCLUSIONS: This systematic review demonstrates that CWD-MO technique achieves lower recurrence rates comparable to CWD approaches and superior to CWU, while offering improved long-term control of otorrhoea. The final procedural choice should be decided based on surgeon experience, skill set and individual patient factors. To address the risk of selection bias, a randomised controlled trial is needed to answer this important research question.


Subject(s)
Cholesteatoma, Middle Ear , Mastoidectomy , Humans , Mastoid/surgery , Cholesteatoma, Middle Ear/surgery , Quality of Life , Tympanoplasty/methods , Retrospective Studies , Treatment Outcome
16.
Am J Otolaryngol ; 44(4): 103860, 2023.
Article in English | MEDLINE | ID: mdl-36996516

ABSTRACT

PURPOSE: Compare the audiological results and postoperative outcomes of the endoscopic approach versus the endaural microscopic approach for treatment of attic cholesteatomas, using a randomized prospective model. MATERIALS AND METHODS: Eighty patients were consecutively enrolled in the study and randomized into two groups of treatment of 40 patients: Group A -tympanoplasty with a microscopic endaural approach; Group B -tympanoplasty with an exclusive trans-meatal endoscopic approach. Preoperative, intraoperative and postoperative outcomes were evaluated. Hearing was assessed preoperatively and at 1 month, 3 months and 6 months after surgery in both groups. RESULTS: There were no differences in the parameters analyzed (CT findings, patient age, disease duration, intraoperative cholesteatoma characteristics,) between the group A and B patients. No statistical difference between the two groups regarding hearing improvement, abnormal taste sensation, dizziness, post-operative pain and healing times emerged. Graft success rate was 94.5 % and 92.1 % for MES and ESS respectively. CONCLUSION: Both microscopic and exclusively endoscopic endaural approaches offer similar and excellent results in the surgical treatment of attic cholesteatomas.


Subject(s)
Cholesteatoma, Middle Ear , Cholesteatoma , Humans , Ear, Middle/surgery , Cholesteatoma/surgery , Tympanoplasty/methods , Endoscopy/methods , Hearing , Treatment Outcome , Retrospective Studies , Cholesteatoma, Middle Ear/surgery
17.
Am J Otolaryngol ; 44(5): 103928, 2023.
Article in English | MEDLINE | ID: mdl-37245325

ABSTRACT

OBJECTIVE: Investigation of ossicular chain (OC) status before surgery is important for preoperative patient consultation. This research aimed to investigate the relationship between pre-operative audiometric values and intra-operative OC condition in a relatively large population of chronic otitis media (COM) surgeries. METHODS: In this descriptive-analytic cross-sectional study, we evaluated 694 patients who underwent COM surgeries. We analyzed pre-operative audiometric data and intraoperative findings including ossicular anatomy, ossicular mobility, and the condition of middle ear mucosa. RESULTS: The optimal cut-off values of pre-operative speech reception threshold (SRT), mean air-conduction (AC), and mean air-bone gap (ABG) for predicting OC discontinuity were 37.5 dB, 37.2 dB, and 28.4 dB, respectively. For the prediction of OC fixation, the optimal cut-off points of SRT, mean AC, and mean ABG were 37.5 dB, 40.3 dB, and 32.8 dB, respectively. The computing of Cohen's d (95 % confidence interval) demonstrated the greater mean ABG in ears with OC discontinuity in comparison with ears with normal ossicles in all types of pathologies. There was a descending trend of Cohen's d from cholesteatoma to tympanosclerosis and then to granulation tissue and hypertrophic mucosa. There was a substantial relation between the type of pathology and OC status (P < 0.001). Ears with tympanosclerosis plaque had the most fixed OC among all types of pathologies (40 ears, 30.8 %), and ears with no pathology had the most normal OC (135 ears, 83.3 %). CONCLUSIONS: The results supported the view that pre-operative hearing is a key determining factor for the prediction of OC status.


Subject(s)
Cholesteatoma, Middle Ear , Ossicular Prosthesis , Otitis Media , Humans , Cross-Sectional Studies , Audiometry, Pure-Tone , Bone Conduction , Ear Ossicles/surgery , Otitis Media/diagnosis , Otitis Media/surgery , Otitis Media/pathology , Cholesteatoma, Middle Ear/diagnosis , Cholesteatoma, Middle Ear/surgery , Cholesteatoma, Middle Ear/pathology , Chronic Disease , Retrospective Studies , Treatment Outcome
18.
Am J Otolaryngol ; 44(2): 103743, 2023.
Article in English | MEDLINE | ID: mdl-36580740

ABSTRACT

PURPOSE: To describe the presentation, diagnosis, and management of chronic otitis media recidivism after subtotal petrosectomy and ear canal closure (STP). MATERIALS AND METHODS: Patients with temporal bone pathology detected during follow-up after STP were identified in the electronic medical record. Pertinent clinical details regarding surveillance plan, presentation, imaging findings, and revision surgery were collected and analyzed. RESULTS: A total of 10 patients were identified with recurrent or persistent pathology after STP. The median time to detection was 46 months (IQR 24-84). Five patients (50 %) had non-specific symptomatology, 4 patients (40 %) were completely asymptomatic, and 1 patient (10 %) was asymptomatic outside of two instances of mastoiditis with cochlear implant device infection treated with incision and drainage. One patient (10 %) was noted to have proptosis on examination, but no other patients had objective signs of disease at detection of disease recidivism. Nine (90 %) patients had pathology identified on preoperative imaging. All patients underwent revision surgery, with identification of cholesteatoma in 8 cases (80 %) and cholesterol granuloma in 2 cases (20 %). Extensive disease was noted in 6 patients (60 %), all of whom followed-up greater than 3 years from surgery. All patients tolerated revision surgery without complication. CONCLUSIONS: Recidivistic disease often remains clinically silent for extended periods of time after STP. Planned follow-up - with imaging or second look surgery - to facilitate early detection should be considered. Undetected disease recurrence or development may result in morbidity in a proportion of patients if surveillance is not performed.


Subject(s)
Cholesteatoma, Middle Ear , Cochlear Implantation , Cochlear Implants , Otitis Media , Recidivism , Humans , Ear Canal/surgery , Cochlear Implantation/methods , Otitis Media/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Cholesteatoma, Middle Ear/surgery , Chronic Disease
19.
Am J Otolaryngol ; 44(2): 103698, 2023.
Article in English | MEDLINE | ID: mdl-36470009

ABSTRACT

PURPOSE: To evaluate the effectiveness and safety of surgery for chronic otitis media in elderly patients, compared to younger adults and children. METHODS: Patients with chronic otitis media with and without cholesteatoma formation were assessed. Patients aged 65 years and older were included and compared to adults aged 35-55 and to children. Effectiveness was evaluated by comparing postoperative dry and safe ears in ages groups, safety was assessed by comparing postoperative adverse events. RESULTS: Postoperative success and adverse events did not differ between age groups. Children had more recurrent cholesteatoma than adults. No difference in recurrent cholesteatoma between adults was observed. CONCLUSION: Surgical treatment for chronic otitis media with and without cholesteatoma in elderly patients is safe and effective. Age has no influence on postoperative adverse events and treatment outcomes in chronic otitis media. Cholesteatoma recurrence was not different between adult age groups.


Subject(s)
Cholesteatoma, Middle Ear , Otitis Media, Suppurative , Otitis Media , Adult , Aged , Child , Humans , Cholesteatoma, Middle Ear/surgery , Otitis Media, Suppurative/surgery , Otitis Media/complications , Otitis Media/surgery , Treatment Outcome , Chronic Disease
20.
Eur Arch Otorhinolaryngol ; 280(11): 4845-4850, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37149831

ABSTRACT

PURPOSE: To investigate the role of non-echo planar diffusion weighted imaging (DWI) using "periodically rotated overlapping parallel lines with enhanced reconstruction" (PROPELLER) sequence for the diagnosis of cholesteatoma compared to surgical and histopathological results in an attempt to determine the factors causing false negative and false positive diagnoses. METHODS: Patients who had PROPELLER DWI before ear surgery were retrospectively reviewed. The presence of a lesion with diffusion restriction on PROPELLER DWI was accepted as positive for cholesteatoma, and the results were compared to the intraoperative and histopathological findings. RESULTS: A total of 112 ears in 109 patients were reviewed. On PROPELLER DWI, a lesion with diffusion restriction was found in 101 (90.2%) ears, while in 11 (9.8%) of the patients, no diffusion restriction was found. Surgery and histopathological analysis revealed a cholesteatoma in 100 (89.3%) ears, while in 12 (10.7%) ears, no cholesteatoma was found surgically. There were 96 (85.7%) true positives, 7 (6.2%) true negatives, 5 (4.5%) false positives and 4 (3.6%) false negatives. The accuracy, sensitivity, specificity, positive predictive and negative predictive values of non-echo planar DWI were calculated to be 91.96%, 96%, 58.33%, 95.05%, and 63.64%, respectively. CONCLUSION: Non-echo planar DWI using PROPELLER sequence has high accuracy, sensitivity and positive predictive value and can be used for the detection of cholesteatoma. The external auditory canal, postoperative ears and small lesions should be evaluated with caution to avoid false results.


Subject(s)
Cholesteatoma, Middle Ear , Humans , Cholesteatoma, Middle Ear/diagnostic imaging , Cholesteatoma, Middle Ear/surgery , Retrospective Studies , Sensitivity and Specificity , Diffusion Magnetic Resonance Imaging/methods , Predictive Value of Tests
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