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The existence of acquired cholesteatoma has been recognized for more than three centuries; however, the nature of the disorder has yet to be determined. Without timely detection and intervention, cholesteatomas can become dangerously large and invade intratemporal structures, resulting in numerous intra- and extracranial complications. Due to its aggressive growth, invasive nature, and the potentially fatal consequences of intracranial complications, acquired cholesteatoma remains a cause of morbidity and death for those who lack access to advanced medical care. Currently, no viable nonsurgical therapies are available. Developing an effective management strategy for this disorder will require a comprehensive understanding of past progress and recent advances. This paper presents a brief review of background issues related to acquired middle ear cholesteatoma and deals with practical considerations regarding the history and etymology of the disorder. We also consider issues related to the classification, epidemiology, histopathology, clinical presentation, and complications of acquired cholesteatoma and examine current diagnosis and management strategies in detail.

PurposeTo evaluate the appearance of mastoid and epitympanic obliteration using S53P4 bioactive glass (BG) granules in high-resolution computed tomography (HRCT) and MRI.Materials and methodsPatients undergoing mastoid and epitympanic obliteration between May 2013 and December 2015 were prospectively included in an uncontrolled clinical study. All patients underwent a temporal HRCT scan 1 year after surgery, aimed at evaluating the attenuation, homogeneity, and osseointegration of the BG granules, as well as the ventilation of the middle ear and the volume of the obliterated paratympanic spaces. If a cholesteatoma was found during surgery, additional MRI, including at least pre- and post-contrast T1-weighted, T2-weighted, and axial non-echo-planar diffusion-weighted (DW) sequences, was performed 1 year after surgery, to study the normal signal of the BG granules and the presence of residual cholesteatoma and/or other temporal bone pathologies.ResultsSeventy cases were included. On 1-year HRCT, the mean attenuation of the BG granules was 888.34 ± 166.10 HU. The obliteration was found to be mostly homogeneous with partial osseointegration. The appearance of the BG granules having a low-intensity signal in T2-weighted imaging and DW MRI was always different from the appearance of cholesteatoma. A longer follow-up has shown no attenuation or signal modification of the BG granules compared with the 1-year imaging.ConclusionRadiological follow-up of patients operated on with mastoid and epitympanic obliteration using BG granules is effective using both HRCT and MRI. A cholesteatoma and/or other potential complications could easily be detected due to the specific radiological appearance of the BG granules.Key Points• The appearance of mastoid and epitympanic obliteration by S53P4 bioactive glass (BG) granules on high-resolution computed tomography (HRCT) scans was homogeneous with an attenuation significantly higher than the attenuation of cholesteatoma and lower than mastoid bone attenuation.• The granules have a low-intensity signal on non-echo-planar diffusion-weighted sequences and on T2-weighted images and present contrast enhancement allowing the differential diagnosis with cholesteatoma and effective for the detection of other underlying temporal bone pathologies.• The volume and radiological appearance of the obliteration appear to be stable with time.

PurposeThe purpose of this study was to investigate the usefulness of temporal subtraction CT (TSCT) of temporal bone CT for the detection of postoperative recurrent/residual cholesteatoma of the middle ear.MethodsThirty-two consecutive patients with surgically proven postoperative recurrent/residual cholesteatoma and 14 consecutive patients without recurrent/residual lesion matched the selection criteria and were retrospectively evaluated. TSCT imaging was generated with the use of serial postoperative CT. Two experienced radiologists and two residents evaluated the presence of bone erosive change by comparison serial CT studies, and CT and TSCT. The detection rate of bone erosive change, sensitivity and specificity of the recurrence/residual lesions, and reading time for each reader were evaluated.ResultsTSCT + CT significantly improved the detection of bone erosive changes compared to CT-only evaluation (17.4–41.3% vs. 37.0–58.7%, p = 0.008–0.046). The mean sensitivity and specificity of TSCT + CT for experienced radiologists were 0.77 and 1.00, and 0.52 and 0.97 without TSCT. The mean sensitivity and specificity of TSCT + CT for residents were 0.64 and 1.00, and 0.41 and 1.00 without TSCT. Sensitivity showed an increase in all readers. The use of TSCT significantly reduced the reading time per case in all readers (p < 0.001).ConclusionTSCT improves the depiction of newly occurring progressive bone erosive changes, and detection sensitivity and reading time in postoperative recurrence/residual cholesteatoma of middle ear.

To evaluate if fusion computed tomography-diffusion-weighted magnetic resonance imaging may have a role in the pre-operative assessment of congenital middle-ear cholesteatoma. A retrospective chart review of surgically treated congenital middle-ear cholesteatoma patients over a 2-year timespan was conducted. Pre-operative staging was performed on computed tomography and fusion computed tomography-diffusion-weighted magnetic resonance imaging based on extension of the disease according to the ChOLE classification system and the Potsic classification system. Intra-operative staging was compared to imaging findings to evaluate accuracy of the two imaging modalities in predicting congenital middle-ear cholesteatoma extent. Computed tomography was able to correctly predict congenital middle-ear cholesteatoma extent in three out of six cases according to the ChOLE classification system, all of which were staged as Ch1a and Ch1b on pre-operative computed tomography. Cases in which computed tomography was not able correctly to determine congenital middle-ear cholesteatoma extent were staged as Ch3 on pre-operative computed tomography. Fusion scans correctly determined congenital middle-ear cholesteatoma extent in all cases according to the ChOLE classification. Fusion computed tomography-diffusion-weighted magnetic resonance imaging may be helpful in cases of congenital middle-ear cholesteatoma where pre-operative computed tomography shows mastoid and antrum opacification, in which computed tomography alone may overestimate cholesteatoma extension beyond the level of the lateral semi-circular canal.

This study aimed to evaluate the clinical features and outcomes of patients with middle-ear granulation pathologies associated with attic retractions. The clinical records of adult patients with middle-ear granulation pathologies and attic retractions confirmed via computed tomography and surgical exploration between January 2012 and January 2019 were retrospectively reviewed. A total of 59 patients were included. Endoscopic examination showed a normal pars tensa but retraction of the pars flaccida in all patients. No granulation tissue or debris were observed. Low-pitched tinnitus was the principal complaint of 55 patients (100 per cent), followed by ear fullness (14 patients, 23.7 per cent). Of the 59 patients, 52 patients (88.1 per cent) underwent canal wall up mastoidectomy and 7 patients (11.9 per cent) underwent endoscopic endaural atticoantrotomy. No ossicular chain destruction was evident. All patients were followed up for 12 months. Tinnitus disappeared completely in 48 patients (81.4 per cent), improved significantly in 9 patients (15.3 per cent) and improved mildly in 2 patients (3.3 per cent). A granulation tissue pathology should be considered when a patient complains of low-pitched tinnitus and exhibits retraction of the pars flaccida. Computed tomography and surgical exploration should be scheduled.

Cholesteatoma is an expansile destructive lesion of the middle ear and mastoid, which can result in significant complications by eroding adjacent bony structures. Currently, there is an inability to accurately distinguish cholesteatoma tissue margins from middle ear mucosa tissue, causing a high recidivism rate. Accurately differentiating cholesteatoma and mucosa will enable a more complete removal of the tissue. Develop an imaging system to enhance the visibility of cholesteatoma tissue and margins during surgery. Cholesteatoma and mucosa tissue samples were excised from the inner ear of patients and illuminated with 405, 450, and 520 nm narrowband lights. Measurements were made with a spectroradiometer equipped with a series of different longpass filters. Images were obtained using a red-green-blue (RGB) digital camera equipped with a long pass filter to block reflected light. Cholesteatoma tissue fluoresced under 405 and 450 nm illumination. Middle ear mucosa tissue did not fluoresce under the same illumination and measurement conditions. All measurements were negligible under 520 nm illumination conditions. All spectroradiometric measurements of cholesteatoma tissue fluorescence can be predicted by a linear combination of emissions from keratin and flavin adenine dinucleotide. We built a prototype of a fluorescence imaging system using a 495 nm longpass filter in combination with an RGB camera. The system was used to capture calibrated digital camera images of cholesteatoma and mucosa tissue samples. The results confirm that cholesteatoma emits light when it is illuminated with 405 and 450 nm, whereas mucosa tissue does not. We prototyped an imaging system that is capable of measuring cholesteatoma tissue autofluorescence.

The European Academy of Otology and Neurotology (EAONO) has previously published a consensus document on the definitions and classification of cholesteatoma. It was based on the Delphi consensus methodology involving the broad EAONO membership. At the same time, the Japanese Otological Society (JOS) had been working independently on the \"Classification and Staging of Cholesteatoma.\" EAONO and JOS then decided to collaborate and produce a joint consensus document. The EAONO/JOS joint consensus on \"Definitions, Classification and Staging of Middle Ear Cholesteatoma\" was formally presented at the 10th International Conference on Cholesteatoma and Ear Surgery in Edinburgh, June 5-8, 2016. The international otology community who attended the consensus session was given the chance to debate and give their support or disapproval. The statements on the \"Definitions of Cholesteatoma\" received 89% approval. The \"Classification of Cholesteatoma\" received almost universal approval (98%). The \"EAONO/JOS Staging System on Middle Ear Cholesteatoma\" had a majority of approval (75%). Some international otologists wanted to see more prognostic factors being incorporated in the staging system. In response to this, the EAONO/JOS steering group plans to set up an \"International Otology Outcome Working Group\" to work on a minimum common otology data set that the international otology community can use to evaluate their surgical outcome. This will generate a large database and help identify relevant prognostic factors that can be incorporated into the staging system in future revisions.

To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Specific DNA or RNA of 9 respiratory viruses (rhinovirus, influenza virus, picornavirus, syncytial respiratory virus, metapneumovirus, coronavirus, enterovirus, adenovirus and bocavirus) and 5 bacteria (S. pneumoniae, H. influenzae, M. catarrhalis, P. aeruginosa and S. aureus) were extracted and quantified by real-time PCR. 37 OME and 14 cochlear implant children were included in the study. At the adenoid, virus and bacteria were similarly detected in both OME and control patients. At the middle ear washes, however, a higher prevalence of bacteria was observed in patients with OME (p = 0.01). S. pneumoniae (p = 0.01) and M. catarrhalis (p = 0.022) were the bacteria responsible for this difference. Although total virus detection was not statistically different from controls at the middle ear washes (p = 0.065), adenovirus was detected in higher proportions in adenoid samples of OME patients than controls (p = 0.019). Despite both OME and control patients presented similar rates of viruses and bacteria at the adenoid, children with OME presented higher prevalence of S. pneumonia, M. catarrhalis in middle ear and adenovirus in adenoids when compared to controls. These findings could suggest that these pathogens could contribute to the fluid persistence in the middle ear.

Objectives To compare MR imaging features in patients with incidental mastoid T2-hyperintensity with those of clinical acute mastoiditis, to ascertain characteristic differences between them. Methods MR images of 35 adult and paediatric patients with clinical acute mastoiditis and 34 consecutive age-matched controls without relevant middle ear pathology and with incidental T2-hyperintensity that covered ≥ 50 % of the mastoid were retrospectively analysed with regard to signal, diffusion, and enhancement characteristics, and presence of complications. Results Incidental mastoid T2-hyperintensity that covered ≥ 50 % of the mastoid volume was found in 4.6 % of reviewed MR scans (n = 2341), and associated significantly ( p  < 0.05) less with the involvement of the tympanic cavity (38 % vs. 74 %) and mastoid antrum (56 % vs. 80 %), hypointense-to-CSF signal intensity on T2 FSE (6 % vs. 86 %), intramastoid diffusion restriction (0 % vs. 62 %), intense intramastoid enhancement (0 % vs. 51 %), periosteal enhancement (3 % vs. 69 %), perimastoid dural enhancement 3 % vs. 43 %), bone destruction (0 % vs 49 %), intratemporal abscess or cholesteatoma (0 % vs. 24 %), labyrinth involvement (0 % vs. 14 %), and extracranial abscesses (0 % vs. 20 %). Conclusion Hypointense-to-CSF signal intensity on T2WI, restricted diffusion, intense intramastoid enhancement among other MR imaging characteristics favoured an acute mastoiditis diagnosis over clinically non-relevant incidental mastoid pathology. Key Points • Intramastoid T2-hyperintensity alone is not a reliable sign for acute mastoiditis. • In acute mastoiditis, intramastoid T2-weighted signal intensity is usually hypointense to CSF. • Diffusion restriction and intense intramastoid enhancement are absent in incidental mastoid effusion. • An ADC value ≥ 1.72 × 10 -3 mm 2 /s contradicts the AM diagnosis.

Middle ear cholesteatoma (cholesteatoma), also known as a cholesteatomatous chronic otitis media, is concerning because it expands into the middle ear with bone destruction and causes irreversible hearing loss. Surgical resection is currently the only curative treatment, but the high recurrence rate remains a major problem, necessitating the development of novel therapies. In our previous study, we demonstrated that histone modifications are involved in the pathogenesis of cholesteatoma and that keratinocyte growth factor (KGF)-induced murine cholesteatoma is suppressed by administration of MI-503, a menin-MLL inhibitor. This study was designed to assess the therapeutic potential of menin-MLL inhibitors for the non-surgical management of cholesteatoma and to elucidate their mechanism of action. For the in vitro study, a growth inhibition assay was performed by administering menin-MLL inhibitors to mouse-derived primary tympanic membrane epithelial cells. For the in vivo study, menin-MLL inhibitors were topically administered into a KGF-induced murine cholesteatoma for seven consecutive days. The therapeutic effects on cholesteatoma were analyzed using micro-computed tomography imaging. The menin-MLL inhibitors reduced KGF-induced cholesteatoma in vivo (3/3, 100%). Among the menin-MLL inhibitors, BMF-219 (50 µM), a covalent menin inhibitor, showed the strongest inhibitory effect against cholesteatoma, with a 70.75 ± 8.92% rate of residual lesion. These findings show promising results for the therapeutic use of menin-MLL inhibitors in the non-surgical management of cholesteatoma.