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Purpose: Dural exposure during cholesteatoma surgery can pose a risk of cerebrospinal fluid leakage or residual disease. Therefore, delicate handling of the area surrounding the bone defect in the cranial fossa is required. However, in small-sized defects, preoperative prediction of dural exposure can be challenging. This study aimed to evaluate the diagnostic value of computed tomography (CT) for preoperative prediction of cholesteatoma-related dural exposure in bone discontinuities in the skull base., Methods: We evaluated serial high-resolution CT images showing bone density discontinuities in the middle cranial fossa (MCF) requiring mastoidectomy for cholesteatoma. The CT and intraoperative findings were analyzed retrospectively. We evaluated the length between the superior margins of the bone density discontinuities using coronal CT planes. Receiver operating characteristic (ROC) curves were constructed to determine the optimal cut-off values., Results: We extracted data from 107 bone density discontinuities, among which 54 (50.5%) showed dural exposure intraoperatively. Discontinuities with dural exposure (n = 54) had significantly greater lengths than did those without (n = 53) (p < 0.001, Wilcoxon rank-sum test). The area under the curve was 0.9780 according to the ROC analysis, and the optimal cut-off value was determined to be 2.99 mm (sensitivity 92.59%; specificity 94.34%)., Conclusion: A bone density discontinuity length of > 2.99 mm in the MCF on coronal CT plane is a reliable diagnostic marker for cholesteatoma-related dural exposure. Thus, preoperative high-resolution CT analysis can inform optimal surgical preparation and planning before manipulating the area surrounding the osteolytic lesion in the MCF., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare the incidence and the histopathological aspect of spontaneous and two induced Mongolian gerbils' models of cholesteatoma: External Auditory Canal (EAC) obliteration model and the Auditory Tube (AT) cauterization model., Methods: Fifty-four ears of 27 animals were divided into EAC obliteration, AT cauterization, and control groups and histologically assessed for cholesteatoma incidence and classification at intervals of 2, 4, 8, and 16 weeks., Results: Cholesteatoma was diagnosed in 30 of the 53 ears evaluated with a significantly higher incidence in groups that received some type of intervention (p<0.0001). It was not possible to histologically distinguish cholesteatomas of the same stage between the study groups., Conclusion: Although we observed a significant increase in cholesteatoma incidence with the two methods used when compared to the control group, all developed cholesteatomas were apparently identical from a histological point of view., (Copyright © 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Objectives: We compared the incidence of polymorphisms activating the NLRP3 inflammasome between controls and patients with cholesteatoma and its potential association with bone erosion in patients with cholesteatoma., Methods: This is a case-control study assessing the mutation rates in genes of interest in patients with and without cholesteatoma. A total of 133 saliva samples from control (n = 65) and cholesteatoma (n = 68) patients were collected for DNA extraction. Caspase recruitment domain family member 8 (CARD8) (AA: homozygous wild type, AT: heterozygous, TT: homozygous mutant polymorphism) and NLRP3 (CC: homozygous wild type, CA: heterozygous, AA: homozygous mutant) polymorphisms were analyzed with TaqMan single-nucleotide polymorphism (SNP) quantitative polymerase chain reaction (ThermoFisher Scientific, Waltham, MA). Mutation status was correlated with a novel bone erosion scoring model developed as a part of this study. Summary statistics, including frequencies (%) and median (Q1, Q3) were used to describe the sample., Results: The presence of CARD8 and NLRP3 homozygous wild-type polymorphisms were generally similar for the control and cholesteatoma patient groups. CARD8 homozygous TT polymorphisms were an exception, occurring more frequently in patients who developed a cholesteatoma compared to the control group (29% vs. 10%, P = .009). Those patients with CARD8 homozygous TT polymorphism had higher median scores of bone erosion as compared to subjects with nonhomozygous mutant genotypes (median [interquartile range]: 4.0 [3.0, 5.5] vs. 2.5 [1.0, 3.5], P = .0142)., Conclusion: Cholesteatoma patients have a significant, twofold higher incidence of CARD8 homozygous TT polymorphism. Furthermore, cholesteatoma patients with this homozygous polymorphism had greater bone erosion rates than controls. These findings suggest that genetic mutations may increase host susceptibility to cholesteatomas. Specifically, the CARD8 TT polymorphism may influence the severity of cholesteatoma-induced bone erosion., Level of Evidence: 3B., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To report our experience of a sequence of events that resulted in an iatrogenic cholesteatoma originating from the external auditory canal (EAC) years after tympanoplasty that had included a tympanomeatal flap., Methods: Data on the presentation and pathogenesis of iatrogenic cholesteatomas arising from misplaced tympanomeatal flaps during tympanoplasty without mastoidectomy were retrieved from the patients' medical records and analyzed., Results: Five patients were identified with cholesteatomas involving the EAC. They all had recurrent ear infections and varying degrees of conductive hearing loss. Each patient's past surgical history included one or more tympanoplasties in which an ipsilateral tympanomeatal flap had been raised. None had undergone a mastoidectomy. Two patients presented with small cholesteatomas that had developed over an average of 6.5 years after surgery. Three patients had large cholesteatomas that had developed over an average of 33.7 years after surgery. Clinical presentations and imaging studies suggested a misplaced tympanomeatal flap as the most likely source of cholesteatoma., Conclusion: Tympanomeatal flap misplacement may cause iatrogenic cholesteatoma formation originating from the EAC during tympanoplasty even without mastoidectomy. These cholesteatomas can grow substantially before becoming symptomatic as they extend to and through the mastoid. They may not affect the sound conduction system until late in the course of the disease. Meticulous replacement of tympanomeatal flaps and exercising a high index of suspicion postoperatively can reduce the incidence of this complication.

Purpose: To analyze the surgical management of cholesteatoma in patients with craniofacial abnormalities, cleft lip/palate by reviewing the institutional experience. The secondary aim was to identify and describe the epidemiological profile of the collected data, and to relate the cleft palate and cholesteatoma., Design and Methods: This retrospective chart review includes 97 patients with craniofacial abnormalities and acquired cholesteatoma with anatomopathological proven in 118 ears. The following data were collected from the medical records between 1994 and 2018., Results: The first surgery performed on 76 of the 118 ears (64.4%) was the wall up mastoidectomy, while 42 of the 118 ears (35.5%) received the wall down technique. During the follow-up period of these patients, which ranged from 2 to 29 years, with an average of 13.4 years (±5.88), 77 wall up (40.3%) and 114 wall down (59.6%) mastoidectomies were performed. This brought the total to 191 mastoidectomy surgeries in 118 ears of 97 patients. Of the wall up mastoidectomies, 65 of the 77 (84.4%) presented with cholesteatoma recurrence. In the wall down mastoidectomies follow up, there were new surgical approaches in 15 of the 114 procedures (13.1%), with 6 patients (5.2%) having anatomopathologically proven cholesteatoma recurrences and 9 (7.8%) having clinical instability for cavity cleaning without identification of disease recurrence., Conclusions: Early approach with wall down/modified techniques guided by specific indication criteria may be more resolute, prevent multiple procedures, and preserve the bone pathway to facilitate possible future hearing rehabilitation in these patients., (Copyright © 2020. Published by Elsevier Inc.)

Purpose of Review: Middle ear cholesteatoma is an epithelial lesion that expands into the middle ear, resulting in bone destruction. However, the pathogenesis of this has been unknown. The purpose of this review is to understand the role of keratinocyte growth factor (KGF) during epithelial stem and/or progenitor cell proliferation in middle ear cholesteatoma., Recent Findings: Many researchers have investigated the molecular mechanism of middle ear cholesteatoma to establish a conservative treatment. Recently, some studies have focused on the stem cells of middle ear cholesteatoma and their detection, but the key molecules for stem cell formation were not shown., Summary: We established an animal model for middle ear cholesteatoma and are showing the results of our studies. KGF expression accelerates the proliferation of stem/progenitor cells through the induction of transcription factor p63 expression in the epithelium of the tympanic membrane and mucosal epithelium overlying the promontory of the cochlea and within the attic. This is typical in middle ear cholesteatoma. Moreover, the partial epithelial-mesenchymal transition under the p63 signaling pathway plays an essential role in epithelial cell growth in middle ear cholesteatoma formation. Understanding p63 expression following KGF expression and associated signaling events can improve therapeutic outcomes in patients with middle ear cholesteatoma.

The aim of this study was to estimate the total number and rate of chronic otitis media (COM) operations and cholesteatoma surgeries in South Korea, using a nationwide survey which analysed a 13-year trend (2006-2018). This study also analysed the trend of COM operations and cholesteatoma surgeries according to year, sex, and age using a nationwide population-based database, and the 13-year trend was analysed according to age groups. This study used nationwide data from the National Health Information Database (NHID), which is a government-affiliated agency under the Korean Ministry of Health and Welfare that supervises all medical activities in Korea. Retrospective medical data of patients of all ages were extracted from the NHID from January 2006 to December 2018 (NHIS-2018). This study was conducted by the Research Committee of the Korean Society of Otorhinolaryngology-Head and Neck Surgery, and the Korean Audiological Society reviewed and confirmed the study. There was a 1.5 fold increase in COM operation rates in 2018, compared to 2007 figures. The annual total number of COM operations was 5,935 in 2007, 8,999 in 2012 (peak), and 8,870 in 2018 (17 in 100,000). Meanwhile, the total annual number of cholesteatoma surgeries decreased from 3,502 in 2006 to 3,199 in 2018 (6 in 100,000). The rate of COM operations was higher (1.27 fold) in the female population than in the males in 2018. However, cholesteatoma surgery rates were higher (1.2 fold) in the male population than in the females in 2018. According to the 2018 data, COM operations were most commonly performed in patients in their 50s. COM operation rates increased rapidly in patients aged 51-80. In other age groups however, rates were constant or showed a decrease in figures, especially in the 40s age group (1st rank in 2006 to 3rd rank in 2018). According to the 2018 data, cholesteatoma surgery was most commonly performed in patients in their 50s. Cholesteatoma surgery rates increased dramatically from 2006 to 2018 in patients aged 0-10 years due to congenital cholesteatoma. Cholesteatoma surgery rates also increased in patients aged 61-80 years due to ageing population. Cholesteatoma surgery rates decreased in patients aged 41-50 years, ranking 1st in 2006 and 4th in 2018. In conclusion, the annual rate of COM operations was 0.017%, and no longer increases, but stabilizes/decreased after a peak point in the advanced country. The mean rate of cholesteatoma surgery was 0.006%, and decreased annually. There was female dominance in COM operations, but male dominance in cholesteatoma surgery. Major age groups of patients who underwent COM/cholesteatoma surgery were the 50s and 60s, and congenital cholesteatoma (0-10 years) accounted for about 20% of all cholesteatoma surgery.

Acquired cholesteatoma leads to significant morbidities while current surgical options remain a challenge. The principles of surgery include complete removal of disease, prevention of recurrence, and restoration of hearing function when possible. Traditionally, this has been performed using microscopes; however, a novel technique using endoscopes offers a new perspective on our understanding of anatomy, pathogenesis and surgical approaches. In recent years, various studies have demonstrated good outcomes with transcanal endoscopic ear surgery (EES) in cholesteatoma surgery. Nevertheless, the use of EES is not universal and remains controversial due to the efficacy of microscopes, specific limitations of endoscopes and the need to learn new skills. This review focuses on recent advances in EES for the treatment of acquired cholesteatoma, benefits, current challenges, and a discussion on the indications and contraindications of EES., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Long-term transtympanic tube insertions for chronic middle ear disease are associated with high rates of complications. The objective of this study was to examine the clinical outcomes achieved with an alternate technique, the subannular tube insertion, by determining mean tube lifespan, cumulative incidence of post-operative events and complications, audiometric changes and risk factors associated with earlier tube extrusion in the pediatric population., Methods: A retrospective chart review of all patients operated for subannular tube insertion between January 2007 and 2013 was conducted in a single pediatric tertiary care center. Exploratory Cox regression analysis was performed to identify potential risk factors., Results: A total of 1014 tubes from 459 patients were included in the study. Mean subannular tube lifespan was 41.3 months with median time of 35.0 months. Cumulative incidence of post-operative events in decreasing frequency were otorrhea (21.7%), tube blockage (16.0%), tympanic membrane retraction (12.5%), otitis media with effusion (10.0%), acute otitis media (6.4%), perforation (4.6%) and cholesteatoma formation (1.1%). For patients with available pre- and post-operative audiograms, mean air-bone gap improved from 19.5 dB to 7.0 dB after subannular tube insertion (p < 0.01). Increasing age and previous subannular tube insertion carried hazard ratios of 1.029 (p < 0.01) and 1.749 (p < 0.01) for tube extrusion respectively, while craniofacial anomalies and concomitant tympanoplasty at the time of tube insertion had hazard ratios of 0.795 (p < 0.01) and 0.680 (p = 0.03)., Conclusions: Subannular tube insertion appears to be a safe and effective alternate technique for middle ear ventilation in cases of intractable disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Congenital cholesteatoma (CC) presents as a white pearl-like lesion behind a normal tympanic membrane (TM), without a history of otorrhea, infection, perforation or previous otologic surgery. Several recent studies provided new data improving this pathology characterization. The aim of this paper is to expand the knowledge about CC and to provide new insights on its pathogenesis., Methods: The study consisted of two main research parts: (1) systematic review and meta-analysis; (2) medical literature review englobing anatomy, histology, embryology and congenital pathology of the ear., Results: The search strategy identified a total of 636 papers. Seventy retrospective studies were included. A total of 1497 cases were studied and the mean age was 6.58 years, with a male-female ratio of 3:1, 34% were asymptomatic, 26% had hearing loss and 2% had facial dysfunction/paralysis. The overall estimate for antero-superior quadrant involvement was 0.70 [95% confident interval (CI) 0.64-0.76], in the postero-superior quadrant was 0.60 (95% CI 0.52-0.69), in the antero-inferior quadrant was 0.32 (95% CI 0.23-0.41), in the postero-inferior quadrant was 0.38 (95% CI 0.29-0.47), in the attic was 0.53 (95% CI 0.43-0.63) and in the mastoid was 0.33 (95% CI 0.26-0.41). More advanced Potsic stages were present in older patients. The most likely inclusion place seems to be between the pars flaccida and the upper quadrants of the pars tensa., Conclusions: During the last decades, a substantial improvement in CC diagnosis and management had been achieved. The presented mechanism seems to explain most of middle ear CC.

Körner's septum (KS) or petrosquamosal lamina is a bony lamina beginning at the articular fossa, extending above the middle ear, and running inferiorly and laterally to the facial nerve canal as it proceeds to the mastoid apex. This septum marks the junction of petrous and squamous bones. The paper presents details of the anatomical structure of KS, which is most often present at the level of the head of the malleus and/or the anterior semicircular canal. Attention is paid to embryological aspects of temporal bone development that lead to the formation of KS. Two imaging techniques most frequently used to diagnose KS are described, high resolution computed tomography (HRCT) and cone-beam computed tomography. Also presented is a case report of a 6-year-old patient suffering from chronic otitis media who developed a cholesteatoma due to presence of KS, illustrated with HRCT images and intraoperative capture. The authors describe diagnostic difficulties associated with this anatomical variant in the middle ear. The article also discusses the more frequent occurrence of this clinical problem in ears operated on due to chronic inflammation, retraction pocket or tympanosclerosis in comparison to healthy ears.

Objectives: This study aimed to investigate the effect of canal wall up with bony obliteration tympanoplasty (CWU-BOT) on the health-related quality of life (HRQOL) in patients with chronic otitis media with cholesteatoma by using the chronic otitis media questionnaire 12 (COMQ-12)., Materials and Methods: This study is a retrospective analysis of the COMQ-12 of 26 patients who completed the COMQ-12 before and after a CWU-BOT with eradication of cholesteatoma followed by obliteration of the mastoid and paratympanic space with bone chips and bone pâté and reconstruction of the tympanic membrane and ossicular chain., Results: All patients were operated upon in our institute between 2014 and 2017. The median score of the 12 questions was preoperatively and postoperatively calculated, and then compared. A large effect was observed in the total score and the questions about running ear, discharge, and visits to the general practitioner. A medium positive size effect was observed in the questions about hearing in noisy surroundings, discomfort, dizziness, tinnitus, medication use, and the mental aspect of the patient. In the questions about the hearing at home and quality of life and impact on work, we noted a small positive size effect. In 50% of patients, the HRQOL became normal; the remaining 50% improved to a level very close to normal., Conclusion: Canal wall up with bony obliteration tympanoplasty (CWU-BOT) showed a clear decrease in the severity of the symptoms, life and work impact, and health care after surgery.

Objectives: To characterize blast-induced cholesteatomas (BIC) in terms of symptoms, presentation, and location within the middle ear cleft (MEC)., Design: A search for all English language articles in "MEDLINE" via "PubMed" and "Google Scholar" was conducted., Results: A total of 67 ears with BIC were included. Fifty-eight ears in which the traumatic perforation failed to spontaneously close were excluded, leaving seven case reports (eight patients, nine ears) for statistical analysis. Time between blast exposure to spontaneous tympanic membrane (TM) closure was 16 days to 10 months. Time between blast exposure and cholesteatoma diagnosis was 5 months to 4 years. The cholesteatomas were diagnosed due to symptoms in two ears, as asymptomatic finding on physical examination in one ear and as asymptomatic finding in axial imaging in three ears., Conclusions: BICs can develop behind intact tympanic membrane or along with TM perforation. Based on the current review, when a TM perforation and spontaneous healing were documented, after blast exposure, MRI scan is an integral component of the follow-up. The optimal timing for MRI performance after blast exposure, is yet to be identified.

Keratin (K) is the main component of the epithelial cell mesenchymal cytoskeleton, which protects the integrity of epithelial cells and maintains the function of normal epithelial cells. The expression of keratin affects epidermal proliferation and differentiation, and so as to be used as a marker for proliferation, differentiation and migration of keratinocytes. Middle ear cholesteatoma is one of the common ear diseases. In the middle ear cholesteatoma, keratinocytes over-proliferate and keratin debris accumulates. In this paper, we reviewed the recent studies on middle ear cholesteatoma and explained the possible mechanisms of keratin in the pathogenesis of middle ear cholesteatoma from the aspects of "proliferation" and " bone resorption ". At the same time, the existing problems as well as the prospect of the future research were discussed.

Intracranial complications secondary to chronic otitis media (COM) include otogenic brain abscess and sinus thrombosis. Intravenous antibiotics and imaging have significantly reduced the incidence of intracranial complications secondary to COM. However, the same does not apply to a developing country like Malaysia, which still experiences persisting otogenic complications. This case series describes 3 patients with COM and intracranial complications. All 3 patients had COM with mastoiditis, with 1 of the 3 having a cholesteatoma. Postulated reasons for the continued occurrence include poor access to health care, poor compliance with medication, and the lack of pneumococcal vaccination during childhood. In conclusion, public awareness and a timely specialty referral can reduce the incidence of intracranial complications of COM.

Objective: To evaluate the effectiveness of the chemically assisted dissection with sodium 2-mercaptoethanesulfonate (MESNA), in the reduction of residual and recurrent cholesteatoma after mastoidectomy in children with chronic cholesteatomatous otitis media (CCOM)., Study Design: Retrospective case-control study., Setting: Tertiary referral center., Population: One hundred forty mastoidectomies performed in patients under 18 years of age for the treatment of CCOM., Interventions: Chemically assisted dissection (CAD) with MESNA compared with surgical dissection without MESNA., Main Outcome Measures: Recidivism of cholesteatoma (recurrence and residual disease), variations in the average of bone conduction threshold after treatment, and complications., Results: Recidivism of cholesteatoma was significantly lower when CAD with MESNA was used (p < 0.0001). No difference was found in the mean variation of the average of bone conduction thresholds between the groups, confirming its safety profile regarding auditory function. Meatoplasty stenosis after surgery was more prevalent within CAD with MESNA group (p: 0.049)., Conclusion: Recurrent and residual cholesteatoma remains a problem, especially in children and despite surgical techniques such as canal wall down mastoidectomy and endoscopic ear surgery. CAD with MESNA can be safe and effective to reduce recurrence rates. Multicenter and prospective studies with larger number of patients are needed to validate these findings. The higher rate of meatoplasty stenosis after CAD with MESNA merits additional clinical research to confirm these findings, as well as in vitro studies evaluating the effect of the drug on the activity of fibroblasts and other growth factors that may be involved.

This study was performed to investigate whether miniature pigs are a suitable animal model for studies of the Eustachian tube (ET). Sixteen Chinese experimental miniature pigs were used in this investigation. Ten animals were used for anatomical and morphometric analyses to obtain qualitative and quantitative information regarding the ET. Three animals were used for histological analysis to determine the fine structure of ET cross-sections. Three animals were used to investigate the feasibility of balloon dilation of the Eustachian tube (BDET). The anatomical study indicated that the pharyngeal orifice and tympanic orifice of the miniature pig ET are located at the posterior end of the nasal lateral wall and anterior wall of the middle ear cavity, respectively. The cartilaginous tube was seen to pass through the whole length of the ET, the length of the cartilaginous part of the ET and the diameter of the isthmus were similar between humans and miniature pigs. The inclination of the ET in miniature pigs was larger than that in humans. The gross histology seemed to be slightly different between miniature pig and human, but the fine structures were essentially the same in both species. BDET experiments verified that the miniature pig model is suitable as a model for clinical operations. The miniature pig ET corresponds very well to that of humans. In addition, the miniature pig ET is suitable as a model for clinical operations. Therefore, the miniature pig is a valid animal model for ET study. Anat Rec, 302:1024-1038, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Disfunction of Eustachian tube will cause negative pressure of middle ear, which may result in tympanic membrane retraction pocket. Severe pocket can consequently cause cholesteatoma. In clinical practice it is not uncommon to find a cholesteatoma limited to epitympanum, with an otherwise normal pars tensa and mesotympanum. This review explains the theory of "selective epitympanic dysventilation syndrome" developed by endoscopic technique. In the majority of the patients, the only ventilation pathway to the epitympanum is through the tympanic isthmus. Even if Eustachian tube function has recovered, an isthmus blockage with selective epitympanic dysventilation may lead to common attic cholesteatoma.

Background and Aim: As in other syndromes characterized by craniofacial anomalies, middle ear cholesteatoma is known to have a high prevalence in Turner syndrome. The aim of this study was to review a multicenter experience with the surgical management of middle ear cholesteatoma in children with Turner syndrome., Methods: We retrospectively analyzed sixteen girls with Turner syndrome who underwent otologic surgery for middle ear cholesteatoma between January 2000 and December 2012. Surgery was performed in 3 tertiary care otologic centers. Four patients had bilateral disease, resulting in a total of 20 ears treated. The following data were recorded: age, history of ventilation tube insertion, status of the controlateral ear, cholesteatoma location and extension, and surgical technique involved. Cholesteatoma recidivism, stable mastoid cavity and hearing levels were the main outcomes measured., Results: Follow-up ranged from 3 to 15 years (mean 7 years). Fourteen ears underwent canal wall down mastoidectomy: no cases of recurrent cholesteatoma were observed in these cases; revision mastoidectomy with cavity obliteration was needed in 2 ears (14.3%) for recurrent otorrhea. In the remaining 6 ears a staged canal wall up mastoidectomy was performed: 1 child showed a recurrent cholesteatoma and required conversion to canal wall down mastoidectomy. A postoperative air-bone gap result of 0 to 20 dB was achieved in 6 ears (30%); in 9 ears (45%) postoperative air-bone gap was between 21 and 30 dB, while in 5 (25%) was >30 dB. Bone conduction thresholds remained unaffected in all cases., Conclusions: Cholesteatoma in children with Turner syndrome is a challenging entity for the otologic surgeon. Although not mandatory, canal wall down mastoidectomy should be regarded as the technique of choice to achieve a safe and dry ear in TS children with middle ear cholesteatoma. Intact canal wall mastoidectomy should be adopted only in appropriately selected patients such as those with limited attic cholesteatoma that can be regularly followed-up.

Objective Chronic otitis media can cause cholesteatomas or tympanosclerosis; however, the pathophysiology of such conditions is not completely known. The aim was to identify a bacterial genome that might be present in tympanosclerotic plaques and cholesteatomas using sequence analysis of the gene responsible for the transcription of 16 ribosomal RNA (rRNA). Study Design Metagenomics analysis of the samples. Setting Samples were collected and evaluated at tertiary care centers. Subjects and Methods Sixty-five tympanosclerotic plaques and 37 cholesteatomas were evaluated. The polymerase chain reaction (PCR) was performed using primers designed for the amplification of the gene responsible for the transcription of bacterial 16 rRNA. The PCR-positive samples were sequenced via Sanger method, and 46 selected samples were analyzed with next-generation sequencing (NGS). Results Sanger sequencing revealed the presence of bacterial genomes in a total of 18 of the 102 samples tested. Sequencing of these genomes indicated the presence of Alloiococcus otitis, Staphylococcus aureus, Achromobacter xylosoxidans, Escherichia coli, Staphylococcus sciuri, Staphylococcus caprae, Parvimonas spp., and Bacillus sp. in the tested samples. The NGS showed 1 or more different bacterial genomes in 44 (95.7%) of the 46 samples tested. Predominately, genome of Clostridiales (27 samples), Staphylococcaceae (24 samples), Peptoniphilaceae (12 samples), and Turicella otitidis (9 samples) were identified. Conclusion The middle ear is inhabited by a diverse microbial community than that previously known. With the use of molecular biology, it has become easier to identify the bacterial genomes and improve our understanding of the role of middle ear microbiota in the pathogenesis of chronic inflammatory ear diseases.

Cholesteatoma is an abnormal formation of benign cystic lesions from the squamous epithelium of the temporal bone, and the local invasive growth could damage the structures of middle ear. Cholesteatoma has been the research focus in otorhinolaryngology, however the pathogenesis of it is still unclear. From the previous studies we found that the epidermal proliferation was one of the important factors in the pathogenesis of the cholesteatoma, which was also involved in multiple proliferation pathways. In this paper, we briefly reviewed the progress and the mechanisms of the actions of cholesteatoma in these pathways.

Objectives: To investigate the distribution of ciliated epithelium in the human middle ear and its potential role in the formation of cholesteatoma., Study Design: Comparative human temporal bone study., Methods: We selected temporal bones from 14 donors with a diagnosis of cholesteatoma, 15 with chronic otitis media without retraction pockets, 14 with chronic otitis media with retraction pockets, 14 with cystic fibrosis (CF), and 16 controls. We mapped the distribution of the ciliated cells in the mucosal lining of the middle ear and tympanic membrane using three-dimensional reconstruction analysis, and counted the number of ciliated cells in the middle ear mucosa., Results: Ciliated cells are extremely sparse in the epithelial lining of the lateral surface of the ossicles in the epitympanum and the medial surface of the tympanic membrane. Furthermore, there is a significant decrease in the number of ciliated cells in these areas in temporal bones with cholesteatoma, chronic otitis media, chronic otitis media with retraction pockets, and CF compared to controls. Ciliated cells most commonly are located at the hypotympanum and the Eustachian tube opening but not the tympanic membrane or epitympanum., Conclusion: The paucity of ciliated epithelial cells on the medial side of the tympanic membrane and the lateral surface of the ossicles in the epitympanum in cases with cholesteatoma and/or chronic otitis media do not support the mucosal migration theory of cholesteatoma formation., Level of Evidence: NA. Laryngoscope, 128:1663-1667, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

The basal stem/progenitor cell maintains homeostasis of the epidermis. Progressive disturbance of this homeostasis has been implicated as a possible cause in the pathogenesis of epithelial disease, such as middle ear cholesteatoma. In many cases of stem/progenitor cell regulation, the importance of extracellular signals provided by the surrounding cells is well-recognized. Keratinocyte growth factor (KGF) is a mesenchymal-cell-derived paracrine growth factor that specifically participates in skin homeostasis; however, the overexpression of KGF induces middle ear cholesteatoma. In this study, two kinds of thymidine analogs were transferred at different time points and we investigated the effects of overexpressed KGF on the cell kinetics of stem/progenitor cells in vivo. As a result, BrdU(+)EdU(+) cells (stem/progenitor cells) were detected in the thickened epithelium of KGF-transfected specimens. The use of a high-resolution microscope enabled us to analyze the phosphorylated level of p63 in individual nuclei, and the results clearly demonstrated that BrdU(+)EdU(+) cells are regarded as progenitor cells. In the overexpression of KGF, the stimulation of progenitor cell proliferation was inhibited by SU5402, an inhibitor for tyrosine kinase of KGFR. These findings indicate that KGF overexpression may increase stem/progenitor cell proliferation and block terminal differentiation, resulting in epithelial hyperplasia, which is typical in middle ear cholesteatoma.

Cholesteatoma is a potentially life-threatening middle ear lesion due to the formation of an inflamed ectopic mass of keratinizing squamous epithelium. Surgical removal remains the only treatment option, emphasizing the need to gain a better understanding of this severe disease. We show for the first time that stem cells residing in cholesteatoma tissue contribute to disease progression. Cells expressing the "stemness" markers Nestin and S100B were detected in middle ear cholesteatoma and auditory canal skin. Isolated Nestin + /S100B + -cells showed the capability for self-renewal, neurosphere formation and differentiation into mesodermal and ectodermal cell types. Compared to auditory canal skin stem cells middle ear cholesteatoma-derived stem cells displayed an enhanced susceptibility to inflammatory stimuli, and this suggested a possible contribution to the inflammatory environment in cholesteatoma tissue. Cholesteatoma derived stem cells were able to differentiate into keratinocyte-like cells using factors mimicking the microenvironment of cholesteatoma. Our findings demonstrate a new perspective on the pathogenesis of cholesteatoma and may lead to new treatment strategies for this severe middle ear lesion.

Objectives: The aim of this study was to quantify the natural behavior of asymptomatic deep pars tensa retraction in both adults and children., Materials and Methods: Asymptomatic pars tensa retraction pockets that contacted the promontory were included. Persistently symptomatic pars tensa retraction, pars tensa retraction that did not contact the promontory, patients with attic retraction pockets and patients with cholesteatoma were excluded. Patients were followed up annually and were eliminated from the study if they required active intervention or recovered so that their ears were persistently ventilated with no contact of the tympanic membrane to the promontory. Outcome variables included surgical intervention, surgical intervention for cholesteatoma, and spontaneous improvement and were studied using the life table method., Results: In total, 64 children and 25 adults were enrolled, of whom 19 children and five adults required intervention and five children and two adults developed pars tensa cholesteatomas. No significant difference was observed between children and adults. In total, three children, but no adults, developed attic cholesteatomas without progression of the pars tensa disease. Furthermore, the ears of 20 children, but not even one adult ear, returned to normal over the 10-year study period., Discussion: Most retracted adult ears did not change. Over 10 years, the most common finding in children was the return of their ears to normal. Ear of all children recovered during the second decade. Deterioration to form cholesteatoma was not influenced by age. Attic cholesteatoma without the progression of pars tensa disease was observed in children, but not in adults.

Introduction: The high incidence of chronic otitis media with effusion and Eustachian tube dysfunction in children with Down syndrome (DS) may predispose them to cholesteatoma formation. Establishing the diagnosis, choosing the appropriate operative intervention, and post-operative care can be challenging., Objective: To describe management strategies for cholesteatoma diagnosis, surgical treatment, and post-operative management in children with Down syndrome., Methods: Retrospective case series of 14 patients (17 total ears) with Down syndrome diagnosed with cholesteatoma over a 9-year period., Results: A total of 14 patients with cholesteatoma (3 with bilateral disease) were analyzed. Thirteen ears (76.5%) had ≥2 tympanostomy tubes insertions prior to cholesteatoma diagnosis, and otorrhea and hearing loss were the most common presenting symptoms. Common pre-operative CT scan findings included mastoid sclerosis and ossicular erosion. The average age at first surgery was 9.8 years, and the average follow-up was 4.3 years. For acquired cholesteatoma, most ears were managed with canal wall up (CWU) approaches, but ultimately 6/15 (40.0%) required canal wall down (CWD) approaches. Postoperatively, 3 (20.0%) ears developed new tympanic membrane retraction pockets, but no recurrent cholesteatoma. Four (26.7%) ears developed recurrent disease, and 3 (20.0%) had residual disease at secondary procedures. Ossiculoplasty was performed in 4 ears. Twelve (70.6%) ears were rehabilitated with hearing aids or FM systems., Conclusions: The diagnosis of cholesteatoma in Down syndrome was associated with otorrhea, hearing loss, and CT scan findings of ossicular erosion and mastoid sclerosis. Most cases were managed with CWU surgical approaches. Hearing aid use was common post-operatively., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: By comparing the clinical characteristics of patulous Eustachian tube with habitual nasal extraction and those of non-Eustachian tube abnormalities, we aimed to investigate the relationship between patulous Eustachian tube and acquired cholesteatoma of middle ear. Methods: A total of 218 patients in Affiliated Hospital of Qingdao University from November 2011 to November 2016 who underwent surgical treatment and with complete data of acquired cholesteatoma of middle ear were enrolled. The patients were divided into two groups: patulous Eustachian tube with habitual nasal extraction and non-Patulous Eustachian tube. Their ages of onset , sides, characteristics of acoustic immitance, clinical manifestations, prognosis and complications were compared. The statistical analysis was carried out with SPSS 19.0 software. Results: Among the 218 cases of acquired cholesteatoma of the middle ear, 22 cases were diagnosed as patulous Eustachian tube with habitual nasal extraction [with average age of (35.7±7.5) years]; 196 cases were diagnosed as non-patulous Eustachian tube [with average age of (47.8±20.1) years]. The average age of the patulous Eustachian tube with habitual nasal extraction was significantly lower than that of the non-patulous Eustachian tube group ( t =4.25, P <0.01). Ratio of bilateral middle ear cholesteatoma in patulous Eustachian tube [68.2%(15/22)] was significantly higher than that of the non-patulous Eustachian tube group [18.9%(37/196)] (χ(2)=26.47, P <0.01). Conclusions: Some acquired cholesteatoma patients are associated with the patulous Eustachian tube with habitual nasal extraction. The patients have a lower age, and are susceptible for bilateral middle ear cholesteatoma.

We have undertaken the analysis of the specific clinical manifestations of acquired cholesteatoma of the middle ear in 437 chronic patients suffering from this pathology. 96.1% of them presented with primarily acquired cholesteatoma of the middle ear (including 53.3% having attic cholesteatoma, 22.8% with sinus cholesteatoma, and 19.9% of tensa retraction cholesteatoma). 3.9% of the patients exhibited a different mechanism of development of cholesteatoma. The secondary acquired mesotympanic cholesteatoma formed in association with the long-term chronic inflammation of the middle ear, concomitant perforation of the tympanic membrane and epithelial invasion from the edge of the tympanic membrane perforation and middle ear cavity. Typmanosclerosis of different degree and localization played an important role in the enhancement of the prevalence of this condition. All types of acquired cholesteatoma were found to extend beyond the point of origin of the disorder. The maximum destruction of the ossicular chain was documented in the patients presenting with sinus cholesteatoma. Those with secondary acquired cholesteatoma showed the worst functional capacity as a result of rigid fixation of the auditory ossicles. The overall cholesteatoma relapse rate (including both residual and recurrent cholesteatoma) was estimated to be 15.6%. It is concluded that the surgical strategy should be chosen on an individual basis for each concrete patient. The long-term observation of the treated patients with the application of the up-to-date radiological techniques is believed to be the indispensable prerequisite for the successful management of the complicated pathology under consideration.

Objective: We have recently proposed a hypothesis that acid leakage through the cholesteatoma epithelium mediates bone resorption in middle ear cholesteatoma. In the present study, we investigated the expressions of transient receptor potential vanilloid (TRPV) channels, which have been shown to play roles in the regulation of epidermal barrier function, in the cholesteatoma epithelium in comparison with the normal skin., Methods: Cholesteatoma epithelium and postauricular skin were collected from 17 patients with primary acquired middle ear cholesteatoma who underwent tympanomastoidectomy. Expressions of TRPV1, TRPV3, TRPV4, and TRPV6 were explored by fluorescence immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)., Results: TRPV1, TRPV3, TRPV4, and TRPV6 mRNAs were all detected by qRT-PCR both in the skin and cholesteatoma tissue. Immunohistochemical staining showed that TRPV1 and TRPV3 were positive in the viable cell layers of the epidermis of the skin, and only TRPV3 was positive in those of the cholesteatoma epithelium. The immunoreactivity for TRPV3 was significantly weaker in cholesteatoma than in the skin., Conclusions: The lower expression of TRPV3 in cholesteatoma may be one of the mechanisms underlying the increased permeability of this tissue. On the other hand, TRPV1, TRPV4, and TRPV6 are unlikely to be involved in the regulation of epithelial permeability in cholesteatoma.

Objective: To investigate the efficacy of the application of tragus cartilage-perichondrium in open method tympanoplasty. Method: Thirty patients with middle ear cholesteatoma were treated with open method tympanoplasty and titanium ossicular prosthesis replacement surgery utilized the tragus cartilage-perichondrium, the air-bone gap and the recovery of tympanic membrane were observed before and after operation. Result: Thirty ears achieved primary healing. After a follow-up of 12 months, no prosthesis extrusion and atticus lateral wall collapse were observed. The average air-bone gaps reduced by 13 dB in average. Conclusion: The tragus cartilage-perichondrium is an appropriate material in open method tympanoplasty., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Importance: Chronic rhinosinusitis (CRS) can cause an obstruction of the tubal orifice and thereby compromise ventilation of the middle ear. The resulting negative pressure in the middle ear may, in turn, lead to the formation of an eardrum retraction pocket and subsequent acquired cholesteatoma. This study hypothesizes that CRS may increase the risk of cholesteatoma., Objective: To evaluate the risk of cholesteatoma in patients with CRS., Design, Setting, and Participants: This study used a nationwide, population-based claims database to test the hypothesis that CRS may increase the risk of cholesteatoma. The Longitudinal Health Insurance Database of Taiwan was used to compile data from (1) 12 670 patients with newly diagnosed CRS between January 1, 1997, and December 31, 2002, and (2) a comparison cohort of 63 350 matched individuals without CRS, resulting in a CRS vs control ratio of 1:5. Data analysis was performed from June 1 to October 27, 2015. Each patient was followed up for 8 years to identify those in whom cholesteatoma subsequently developed. The Kaplan-Meier method was used to determine the cholesteatoma-free survival rate, and the log-rank test was used to compare survival curves. Cox proportional hazards regression models were used to compute the 8-year hazard ratios (HRs)., Main Outcomes and Measures: Diagnosis of cholesteatoma., Results: Among the 76 020 patients enrolled in this study, 35 220 (46.3%) were female; mean (SD) age was 27.57 (22.03) years. A total of 209 patients developed cholesteatoma, 66 (101 084 person-years) individuals from the CRS cohort and 143 (506 540 person-years) from the comparison cohort were diagnosed with cholesteatoma during the 8-year follow-up period. The incidence of cholesteatoma per 1000 person-years was more than twice as high among patients with CRS (0.65; 95% CI, 0.50-0.81 person-years) than among those without CRS (0.28; 95% CI, 0.24-0.33). The absolute difference in the incidence density between CRS and non-CRS group was 0.37 (95% CI, 0.21-0.53) per 1000 patient-years. After adjusting for potential confounders, patients with CRS had a 69% increased risk of cholesteatoma within 8 years, compared with those without CRS (HR, 1.69; 95% CI, 1.23-2.32). Patients with CRS presented a significantly lower 8-year cholesteatoma-free survival rate than did those in the comparison group. The absolute difference in the 8-year cholesteatoma-free survival rate between the CRS and non-CRS groups was 0.0029 (95% CI, 0.0016-0.0043)., Conclusions and Relevance: This is the first large-scale study, to date, to demonstrate a prospective link between CRS and the subsequent development of cholesteatoma within a follow-up period of 8 years. The purpose of the study was to draw attention to the possibility of development of cholesteatoma among patients with CRS. Because that possibility exists, clinicians should keep this association in mind as well as the importance of a thorough head and neck examination.

Objective: Analyze the presentation and evolution of chronic suppurative otitis media (CSOM) in children with cochlear implants (CI) and explore the merit of early intervention., Study Design: Retrospective patient review., Setting: Tertiary referral hospital and cochlear implant programme., Patients: Children with a CI who developed CSOM., Intervention: Tympanoplasty., Main Outcome Measures: Disease control, recurrence of cholesteatoma, cochlear implant preservation., Results: Eight children fit our inclusion criteria with a mean follow up of 8 years. Onset of CSOM symptoms was observed on an average of 5 years after implantation (range, 2-13 yr) and led to surgical intervention in an average of 15.6 months following symptom onset. Cholesteatoma was found in four of the eight patients. Of these, one patient underwent a subtotal petrosectomy and explantation with reimplantation at the same stage but the reimplant failed to function and was explanted subsequently. One patient was initially managed by a canal wall up mastoidectomy and explantation but went on to require subtotal petrosectomy and labyrinthectomy for recurrent disease. One patient underwent a subtotal petrosectomy with explantation and is awaiting a reimplantation. The fourth patient had limited disease around the electrodes that was excised without compromising the implant. In the group of patients with CSOM without cholesteatoma, one underwent an explantation due to recurrent ear infections and a subsequent cartilage tympanoplasty for a retracted eardrum. The remaining three patients underwent successful excision of retraction pockets and repair of eardrums using cartilage with the implant in situ. A mean follow up of 2 years after the implant preservation surgeries shows good functioning of the CI., Conclusion: Early recognition of CSOM is paramount in patients with CI as delay in treatment can result in the infection spreading via the cochleostomy resulting in loss of the cochlea. Recurrent ear infections in an implanted ear should prompt early examination to exclude the presence of middle ear disease, which may require anesthesia in a young child.

Objective: To assess the role of Rho/Rho-kinase pathway in the pathogenesis of cholesteatoma., Materials and Methods: Thirty-eight patients with cholesteatoma, who had gone mastoidectomies were enrolled in this prospective study. Cholesteatomas matrix (CM) and a piece of the external ear canal skin (EECS as control) were taken and transferred to the liquid nitrogen and kept at -86 °C for Rho A and Rho-kinase (ROCK) analysis with Western blotting and commercial ELISA kits (Cell Biolabs Inc., San Diego, CA). The tissues were homogenized by an appropriate ice-cold lysis buffer. Following centrifugation, the supernatant was taken and total protein amount was detected by the Bradford method. Thereafter, tissue homogenates were subjected to sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis electrophoresis then transferred to nitrocellulose membrane where it was treated with specific monoclonal primary antibody against to ROCK-2 and HRP-conjugated seconder antibody, respectively. The protein blots were visualized with commercial x-ray film and dansitometrically analyzed by the Scion Image Program (Cell Biolabs Inc., San Diego, CA). In another series of experiments, Rho-kinase activities were assessed by ROCK-2 ELISA kits., Results: There were no statistical differences in Rho A translocation between CM and EECS. However, ROCK activity was found to be lower in CM than EECS as detected by ELISA kits. Furthermore, ROCK protein expression was also significantly lower in CM than EECS as demonstrated by Western blotting., Conclusion: Given Rho-kinase could take essential roles in cell differentiation, the results of this study implicate that down-regulated Rho-kinase could be responsible for the keratinocyte undifferentiation seen in cholesteatoma pathogenesis.

Objectives/hypothesis: To highlight the phenomenon of cholesteatoma arising from the vascular strip following tympanoplasty and tympanomastoidectomy., Study Design: Multi-institutional retrospective chart review., Methods: Consecutive adult and pediatric patients evaluated between 2000 and 2015 with acquired cholesteatoma arising from the skin of a prior vascular strip were identified. Patients with evidence of residual or recurrent cholesteatoma elsewhere in the middle ear, mastoid, or ear canal were excluded., Results: Seventeen cases (71% female, 53% right-sided) were identified, and the mean age at presentation was 39.2 years. Patients presented on average 12.9 years following prior otologic surgery, which was most commonly tympanoplasty without mastoidectomy (59%). However, younger patients presented with symptoms sooner following prior surgery (r = 0.61, r 2 = 0.37, P = 0.0095). The most common presenting symptom was otorrhea (76%). All patients were found to have mastoid cholesteatoma with bony erosion, and three patients exhibited additional tegmen or posterior fossa bone defects. The middle ear was not involved with cholesteatoma in any case. A canal wall down procedure was performed due to extensive bony canal erosion in 29% of cases., Conclusion: The vascular strip is an uncommon source of iatrogenic cholesteatoma that can present years following an otherwise uncomplicated otologic surgery. The findings presented herein highlight the importance of careful vascular strip orientation at the conclusion of otologic surgery., Level of Evidence: 4. Laryngoscope, 127:698-701, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Cholesteatoma is a common clinical picture seen by otolaryngologists. The disease is characterised by an abnormal grow "of skin in the wrong place". Specifically, in acquired cholesteatoma, the main causative issue is associated with ventilatory deficits within the middle ear and results in chronic infection. Molecular science has associated the presence of specific molecules with its development, and moreover recent research suggests that deregulated angiogenesis is a crucial process in the development of cholesteatoma and its recurrence. Further, haematologists have linked von Willebrand factor and its defects (both quantitative and qualitative) to augmented angiogenesis through upregulation of the vascular endothelial growth factor and angiogenic cytokines. Thus, herewith we probed whether a relationship between von Willebrand disease and the etiopathogenesis of cholesteatoma, plays a potential role for anti-angiogenic molecules for the advent of cholesteatoma surgery adjuvant treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Cholesteatoma is a destructive lesion that can result in life-threatening complications. Typically, it presents with hypoacusis and continuous otorrhea as symptoms. Because it is a rare disease, there are few studies in Brazil describing the characteristics of patients with the disease., Objective: This study aimed to determine the prevalence of cholesteatoma in patients with chronic otitis media and describe clinical, audiological and surgical characteristics of patients with acquired middle ear cholesteatoma treated at a referral hospital in the public health system., Methods: Cross-sectional and prospective cohort study, including 1710 patients with chronic otitis media, treated between August 2000 and June 2015, without prior surgery. Detailed clinical history, videotoscopy, and audiometry were performed, in addition to review of medical records to search for surgical data. Cholesteatomas were classified according to their route of formation., Results: Of the patients with chronic otitis media, 419 (24.5%) had cholesteatoma; mean age of 34.49 years; 53.5% female and 63.8% adults. Bilateral cholesteatoma was observed in 17.1%. Anterior epitympanic cholesteatoma corresponded to 1.9%; posterior epitympanic, 32.9%; posterior mesotympanic, 33.7%; two routes, 14.8%; and indeterminate, 16.7%. The mean air-bone gap was 29.84dB and did not differ between routes of formation. There were no correlations between gap size and patient age or duration of symptoms. Of the surgical cases, 16.8% underwent closed tympanomastoidectomy and 75.2% open tympanomastoidectomy., Conclusion: The prevalence of cholesteatoma in patients with chronic otitis media was 24.5% and it was more common in adults than in children. Posterior mesotympanic cholesteatoma was more frequent, with no difference in mean air-bone gap between the different routes of formation. In patients undergoing surgery, open tympanomastoidectomy was the procedure most frequently chosen., (Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Conclusions: The present study revealed that miR-21 promotes the proliferation and invasion of cholesteatoma keratinocytes. These results provide a partial explanation for the more aggressive clinical behavior observed in cholesteatoma., Objective: This study aims to investigate the post-transcriptional regulatory effects that control proliferation, apoptosis, and invasion in cholesteatoma keratinocytes. In particular, the potential role of miR-21 was focused on in this study., Methods: Thirty cholesteatoma tissues were processed for RNA and cell culture. Cholesteatoma keratinocytes were transfected with miR-21 mimics, miR-21 inhibitors, or negative control miRNAs; and growth curves were drawn. RT-PCR was used to assess the expression levels of miR-21. EdU incorporation assay and TUNEL staining were used to assess the proliferation and apoptosis of cholesteatoma keratinocytes, respectively. The invasive abilities of cholesteatoma keratinocytes were examined using 6-well Transwell plates., Results: MiRNA-21 was upregulated when cholesteatoma keratinocytes were transfected with miR-21 mimics. Furthermore, the number of proliferative EdU + cells increased in cholesteatoma keratinocytes transfected with miR-21 mimics; and the number of TUNEL-positive cells also increased in cells transfected with miR-21 mimics. In addition, the number of migrated cells transfected with miR-21 mimics was higher, compared with migrated cells transfected miR-21 inhibitors or control miRNA.

Naturally occurring myringostapediopexy frequently results in minimal hearing loss and is asymptomatic. Management decisions in such ears, however, often hinge on an appraisal of evolution toward cholesteatoma. The study of the contralateral ear has been used by our research team to infer the progression of chronic otitis media. This cross-sectional, comparative study describes the clinical findings of the contralateral ear in a series of patients with myringostapediopexy. This study included a historical and current sample of 46 patients divided into a pediatric (≤18 years) and an adult group. Patient distribution according to sex was similar (52.2% male), and 56.5% were adults. Mean conductive hearing loss ranged from 14.1 to 21.2 dB in ears with myringostapediopexy and from 16.0 to 26.6 dB in the contralateral ears according to the frequency assessed. The contralateral ear was normal in only 19.6% of the cases of myringostapediopexy. Central tympanic membrane perforation was found in 6.5% of the cases; perforation-retraction, in 17.4%; moderate or severe retraction, in 28.3%; and cholesteatoma, in 28.3%. The prevalence of cholesteatoma in the contralateral ear in the pediatric and adult groups was not significantly different (p = 0.5; χ(2) test). The presence of significant abnormalities, particularly cholesteatoma, in the contralateral ears suggests a probable unfavorable progression in cases of myringostapediopexy and may influence management decisions.

Objectives/hypothesis: To review the recent cell proliferation signal pathways in the etiopathogenesis of acquired middle ear cholesteatoma., Data Sources: PubMed (to September 2015)., Review Methods: Articles about cell proliferation signal pathways in the etiopathogenesis of acquired cholesteatoma and treatment advances were searched in the PubMed database, from which 73 were included in this review., Results: The exact underlying cellular and molecular mechanism of acquired cholesteatoma still remains unknown. Recent research tends to regard the proliferation of cholesteatoma epithelial cells as the mechanism of cholesteatoma pathogenesis. Cell proliferation signal pathways including epidermal growth factor receptor/phosphoinositide 3-kinase/protein kinase B signal pathway, mitogen-activated protein kinase signal pathway, interleukin-6/signal transducer and activator of transcription 3 signal pathway, inhibitor of DNA binding/differentiation-1/nuclear factor-κB/cyclinD1 signal pathway, microRNA-mediated proliferation signal pathway, and keratinocyte growth factor/keratinocyte growth factor receptor signal pathway have been proven to play important roles in acquired middle ear cholesteatoma., Conclusions: This review outlines the main biological properties of certain cell proliferation signal pathways, aiming to facilitate the development of potential therapeutic targets for intratympanic drug therapy for the nonsurgical or complementary treatment of cholesteatoma., Level of Evidence: NA Laryngoscope, 126:1923-1930, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

The aim of the present study was to comprehensively evaluate the clinical features and long-term outcomes of congenital aural stenosis (CAS). This study presents a retrospective review of patients who underwent meatoplasty for CAS at a tertiary referral hospital from 2008 to 2015. A total of 246 meatoplasty procedures were performed on 232 patients in the present study. We performed multivariate regression analysis. Except in the age < 6 years group, no significant difference was observed among different age groups for cholesteatoma formation, p > 0.05. Except for the stenosis of the external auditory canal (EAC) (>4 mm) group, the other stenosis of EAC groups were not associated with cholesteatoma formation, p > 0.05. Postoperative air-bone gaps (ABG) less than 30 dB occurred in 77.3% (99/128) of the patients, and the Jahrsdoerfer score was associated with postoperative ABG, p < 0.001. The complication rate of CAS was 13.8% (20/144), and males showed a higher risk for postoperative complications (OR, 6.563; 95% CI, 1.268-33.966, p = 0.025). These results indicate that meatoplasty was an effective surgical intervention for CAS, showing a stable hearing outcome with prolonged follow-up. There was no significant difference between the cholesteatoma and no cholesteatoma groups for hearing outcomes, p > 0.05.

This study examined the differences between congenital cholesteatoma (CC) and acquired cholesteatomas (AC) in children by comparing clinical features and treatment courses. This was a retrospective study which retrospectively evaluated 127 children with middle ear cholesteatomas using medical records from January 1999 to December 2012 in the Department of Otolaryngology, Niigata University Hospital. The study comprised 69 and 58 cases of CC and AC, respectively. The main outcome measures include patient backgrounds, the opportunities for consultations, mastoid cell development, intraoperative finding of stapes, surgical procedure and number of surgeries. The average age at operation was 6.4 and 9.8 years in CC and AC, respectively. AC was more prevalent in boys. Mastoid development was better in CC than in AC. We adopted a two-stage operation in 17 cases (25 %) of CC and in 22 cases (38 %) of AC. The repeat surgery rate was 11.6 % in CC and 27.6 % in AC. Three times as many operations were required for three cases (4.3 %) of CC and 10 cases (17.2 %) of AC. The lesions in AC were more difficult to control. In the treatment of pediatric middle ear cholesteatoma, we had to keep the outcome in mind.

Objective: The aim of this study was to investigate the proliferative and apoptotic activity of middle ear cholesteatoma in pediatric and adult patients, in addition to comparing its histopathological aspects and the severity of advanced bone destruction., Materials and Methods: Medical records of 223 patients treated for chronic otitis media with cholesteatoma at the Otolaryngology Department of Dokuz Eylul University between January 1992 and December 2013 were retrospectively evaluated. Sixty-one patients subjected to tympanomastoidectomy due to middle ear cholesteatoma, with sufficient specimens for histopathological examination, were included in the study. Sections of archived tissues in paraffin blocks were subjected to new histopathological examinations. The proliferative and apoptotic activities of cholesteatoma were determined by immunohistochemical staining for epithelial thickness (ET), and Ki-67 and caspase-3 expression. A novel scoring system, the Bone Erosion Score (BES), was developed to estimate the severity of bone destruction. The Austin-Kartush classification score (AKCS) was also calculated., Results: ET and Ki-67 expression was higher in adult patients than in the pediatric patients (p=0.009 and 0.01, respectively); however, caspase-3 immunopositivity did not show any significant intergroup differences (p=0.106). The differences in AKCS and BES between pediatric and adult patients were not statistically significant. According to the correlation analysis, a significant positive correlation was observed between AKCS and BES (p=0.001), and between ET and Ki-67 expression (when histopathological data were compared) (p=0.001)., Conclusion: The proliferative activity of cholesteatoma was higher in adult patients. Therefore, these findings do not support the theory that the aggressive clinical course of cholesteatoma in pediatric patients is correlated with its histopathological characteristics., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study aimed to evaluate the relationship between cholesteatoma formation and the degree of mastoid pneumatisation, and to assess the relationship between the location of cholesteatoma and the degree of mastoid pneumatisation., Methods: Data on all patients undergoing mastoid exploration for cholesteatoma between 1993 and 2011 were collected prospectively. Basic demographics, the degree of mastoid pneumatisation and cholesteatoma site were recorded., Results: A total of 393 patients (222 males and 171 females) underwent surgery for cholesteatoma. Patients' mean age was 37 years (range, 6-79 years). Pneumatisation of the mastoid was sclerotic in 23 per cent (n = 90), diploic in 16.7 per cent (n = 66) and cellular in 60.3 per cent of cases (n = 237) (p < 0.001). Atticoantral disease was present in 88.9 per cent of sclerotic, 95.4 per cent of diploic and 91.1 per cent of cellular mastoids. Middle-ear cholesteatoma was present in 54.4 per cent of sclerotic, 56 per cent of diploic and 51.9 per cent of cellular mastoids., Conclusion: The findings demonstrate the presence of cholesteatoma in well-pneumatised mastoids. It is hypothesised that a well-pneumatised mastoid may lead to cholesteatoma formation.

Purpose: This study aims to report the postoperative complications and management of cochlear implantation in pediatric patients at our institution. All procedures were carried out by a single surgeon utilizing minimally invasive techniques. The impact of past surgical history of tympanostomy tubes was also reviewed to access association with postoperative complications., Materials and Methods: All children receiving cochlear implants at our institution between April 2003 and October 2014 were reviewed. Complications were grouped into "major" and "minor" depending on degree of management and "immediate," "early," and "delayed" depending on time of presentation., Results: In our series, 248 cochlear implants were placed into 141 children. The mean age at time of surgery was 4.8 years. The overall complication rate per ear was 16.5%, 5.2% being major and 11.3% being minor complications. Complications arose in the first 30 days following surgery in 8.4% of patients, with acute otitis media being the most common. A history of tympanostomy tubes did not impact complication rate. Excluding device failures, major complication rate was 2.4%. Hematoma was not encountered, and delayed seroma occurred in one patient., Conclusion: Minimally invasive cochlear implantation carries a low complication rate. The most common major complication was intrinsic device failure, and the most common minor complication was acute otitis media. Past medical history of chronic otitis media with tympanostomy tube placement prior to cochlear implantation did not have a statistically significant impact on postoperative complication rates. Given the rarity of hematomas and seromas, pressure dressings appear to be unnecessary with this approach., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Importance: Surgeons should understand the potential long-term complications in patients who undergo cochlear implantation (CI) and should be able to facilitate counseling., Objectives: To review the delayed complications after CI and some of the management plans used to treat these complications., Evidence Acquisition: The PubMed and OVID databases were searched for articles published from January 1, 2003, through December 31, 2013, using the search terms cochlear implant and complications. Seven hundred sixty-six articles were identified and searched for reports of delayed complications (>3 days after surgery). Exclusion criteria consisted of a language other than English, no long-term follow-up or report of delayed complications, small case series with fewer than 10 patients, and CI in patients with cochlear malformations. Additional articles were identified with specific search criteria consisting of cochlear implant combined with mastoiditis, meningitis complication, otitis media, hematoma, cholesteatoma, and facial nerve injury. Data were collected from January 1 through April 1, 2014, and analyzed from April 30 to May 1, 2014., Findings: A total of 88 individual articles were analyzed for this study. These articles included a total of 22 842 patients. Of 8519 patients with data in regard to sex, 4319 (50.7%) were male. The patients' ages ranged from 0.2 to 94.9 years, with a mean age of 19.0 years. The duration of follow-up ranged from 1 month to 17 years. The total number of delayed complications was 1302 (5.7%), with vestibular complications (181 of 4655 patients [3.9%]) being the most common; device failure (507 of 14 704 patients [3.4%]), the second most common; and taste problems (22 of 776 patients [2.8%]), the third most common. Less common complications included cholesteatoma (40 of 8579 patients [0.5%]) and facial nerve palsy (31 of 4785 patients [0.6%])., Conclusions and Relevance: Cochlear implantation continues to be a reliable and safe procedure, with a low percentage of severe complications when performed by experienced surgeons. The patients should receive lifetime follow-up. These patients need lifetime follow-up to monitor for potential complications and to facilitate their care if complications occur.

Conclusion: Overexpression of receptor activator of nuclear factor-κB ligand (RANKL) and low expression of osteoprotegerin (OPG) are typical features in middle ear cholesteatoma patients. The altered RANKL/OPG protein ratio suggests that alterations in the RANKL-OPG pathway may be major factors in the pathogenesis of middle ear cholesteatoma., Objective: Our meta-analysis explored the contribution of one important cytokine pathway, the RANKL and OPG pathway, in the development of middle ear cholesteatoma., Methods: We screened Embase, the Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine, China National Knowledge Infrastructure, PubMed, and Web of Science for relevant articles. RANKL expression and ratio of RANKL/OPG were analyzed using Comprehensive Meta-Analysis Version 2 software., Results: The electronic literature search identified five studies that contained information on the correlation of RANKL and OPG expression with middle ear cholesteatoma. Increased RANKL expression positively correlated with middle ear cholesteatoma, while OPG expression showed an inverse association (p < 0.05). The ratio of RANKL/OPG in middle ear cholesteatoma cases was higher than in healthy controls, indicating that our observations are applicable to each individual case. Subgroup analysis based on country of study revealed that OPG levels decreased in China and Korea, and high RANKL expression was found in Poland, China, and Korea (all p < 0.05).

Introduction: The treatment for head and neck cancer with radiotherapy can cause different alterations of the auditory system. We report two cases of chronic otitis of the external and middle ear secondary to osteoradionecrosis of the temporal bone. This article aims to report the experience of the surgical approach in such condition., Cases Report: The first patient was treated with radiotherapy in his childhood for a cerebellar tumor. He developed years later a cholesteatoma which invaded the mastoid cavities through a destruction of the external auditory canal. The second was treated for a malignant parotid tumour 15 years before by surgery and radiotherapy. She developed a chronic otorrhea with a partial destruction of the bony external auditory canal. Both patients were treated by surgery with reconstruction including bone, cartilage, fascia and skin grafts. The outcome was good in both cases. Osteo­radio­necrosis of the temporal bone is a rare but serious complication of radiotherapy for head and neck cancer. This complication can occur even many years after the treatment. Our two cases demonstrate a way to solve this pathology. A long term supervision with regular cares is essential in order to get a good healing. Due to the improvement of the radiation therapy we could expect less complications of this type in the future.

Objective: To review recent biomolecular advances in etiopathogenesis of acquired cholesteatoma., Data Sources: MEDLINE via OVID (to March 2014) and PubMed (to March 2014)., Review Methods: All articles referring to etiopathogenesis of acquired cholesteatoma were identified in the above databases, from which 89 articles were included in this review., Results: The mechanisms underlying the etiopathogenesis of acquired cholesteatoma remain a subject of competing hypotheses. Four theories dominate the debate, including theories of invagination, immigration, squamous metaplasia, and basal cell hyperplasia. However, no single theory has been able to explain the clinical characteristics of all cholesteatoma types: uncoordinated hyperproliferation, invasion, migration, altered differentiation, aggressiveness, and recidivism. Modern technologies have prompted a number of researchers to seek explanations at the molecular level. First, cholesteatomas could be considered an example of uncontrolled cell growth, capable of altering the balance toward cellular hyperproliferation and enhancing the capacity for invasion and osteolysis. Second, the dysregulation of cell growth control involves internal genomic or epigenetic alterations and external stimuli, which induce excessive host immune response to inflammatory and infectious processes. This comprises several complex and dynamic pathophysiologic changes that involve extracellular and intracellular signal transduction cascades., Conclusions: This article summarizes the existing theories and provides conceptual insights into the etiopathogenesis of acquired cholesteatoma, with the aim of stimulating continued efforts to develop a nonsurgical means of treating the disorder., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)