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Emerging Paradigms in Cholesteatoma: From a Traditional Approach to Personalized Therapy
by
Zamfir-Chiru-Anton, Adina
,
Manda, Dana
,
Gheorghe, Dan-Cristian
in
Animals
,
Biological markers
,
Care and treatment
2025
Cholesteatoma is a prevalent disease affecting both children and adults. In this review, we present the recent findings related to the molecular mechanisms involved in cholesteatoma and discuss how researchers can target new molecules to treat this disease. These new approaches illustrate the paradigm shift from a primarily surgical solution to a biological “control and prevent” strategy.
Journal Article
Middle ear congenital cholesteatoma: systematic review, meta-analysis and insights on its pathogenesis
by
Santos, Ricardo
,
Escada, Pedro
,
Gilberto, Nelson
in
Cholesteatoma, Middle Ear - congenital
,
Cholesteatoma, Middle Ear - epidemiology
,
Cholesteatoma, Middle Ear - etiology
2020
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.
Journal Article
Open- and closed-type congenital cholesteatomas of the middle ear: computed tomography differentiation and correlation with surgical staging
2025
To investigate the differences in computed tomography (CT) features between closed-type congenital cholesteatoma (CCC) and open-type congenital cholesteatoma (OCC) of the middle ear and to evaluate the usefulness of preoperative CT examination for staging workup of congenital cholesteatoma (CC) in correlation with the surgical findings.
We retrospectively reviewed the preoperative CT scans of the temporal bone obtained from 80 patients with surgically confirmed CC of the middle ear. All patients had a solitary lesion, except for one patient with two lesions, resulting in 81 CCs, which formed the basis of this study. We compared the CT features between CCCs and OCCs, focusing on their morphological characteristics, such as size, shape, location, and bone change. Based on the Potsic classification, the stage of CCs was determined at CT and surgery, and the results were compared between CCCs and OCCs.
Of the 81 CCs, surgery revealed 43 CCCs and 38 OCCs. On CT scans, CCC was frequently seen as a small (median: 3.15 mm), round to oval (65.1%) mass, most commonly located in the anterosuperior quadrant (74.4%) of the middle ear with less frequent ossicular erosion (14.0%). In contrast, OCC was frequently seen as a large (median: 6.70 mm), irregular (94.7%) mass, most commonly located in the posterosuperior quadrant (68.4%) of the middle ear with frequent ossicular erosion (55.3%). The size, shape, location, and presence of ossicular erosion were significantly different between the two types. Overall, the CT and surgical stages of CCs demonstrated good agreement (kappa value: 0.77) and the CT and surgical stages of OCCs were statistically significantly higher than those of CCCs (
< 0.001 in both).
CT is useful for preoperative determination of the types and staging of CC of the middle ear.
Preoperative differentiation between CCC and OCC is important to avoid reoperation and prevent an extensive surgery. By providing valuable information on the morphology and extent of the lesions, CT is useful for not only the accurate preoperative determination of the type of CCs but also the accurate prediction of staging of the lesion, which should be important to preparing optimal treatment plans.
Journal Article
Updates and Knowledge Gaps in Cholesteatoma Research
2015
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.
Journal Article
Bioactive glass granules for mastoid and epitympanic surgical obliteration: CT and MRI appearance
by
Pyatigorskaya, Nadya
,
Sterkers, Olivier
,
Bielle, Franck
in
Attenuation
,
Bioglass
,
Biological activity
2019
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.
Journal Article
Acoustical Effects of Tympanostomy Tube Attachment to Human Tympanic Membrane
2025
Purpose
Several therapeutic approaches for hearing disorders involve attaching medical devices to the tympanic membrane. The attachment of these devices can change the mechanical and acoustical properties of the middle ear, affecting the middle-ear vibrations. The alteration of passive mechanical properties results from the mass, stiffness, and geometry of the attached device. Additionally, procedures like tympanostomy tube attachment create perforations on the tympanic membrane, altering both the mechanical and acoustical properties of the middle ear. This study examined the acoustical effects of these as well as the combination of acoustical and mechanical effects of the attached devices on middle-ear vibrations.
Methods
A finite-element model of the middle ear, including the middle-ear cavity, was used to systematically study the effects of perforation size and location on vibration outputs. Experimental data from the literature were used to tune the model. This model was then employed to investigate the combined mechanical and acoustical effects of tympanostomy tubes on vibration outputs.
Results
In presence of both the mechanical effects of the device (due to its mass and stiffness) and the acoustical effects of it (due to perforations), the reduction in the motion of the stapes footplate resulting from the acoustical effects is more remarkable at low frequencies (below about 1 kHz). However, at higher frequencies, the mechanical effects of the device are dominant.
Conclusion
The findings of this study provide insights into the optimal design of the shape, location, and other characteristics of medical devices implanted on the tympanic membrane.
Journal Article
Improved assessment of middle ear recurrent/residual cholesteatomas using temporal subtraction CT
2022
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.
Journal Article
Menin-MLL inhibitors as a new therapeutic target for middle ear cholesteatoma
2026
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.
Journal Article
Computational fluid dynamics analysis of middle ear pressure dynamics: Evidence for efficient pressure equalization during partial eustachian tube opening
2026
Eustachian tube (ET) dysfunction is associated with middle ear pathologies; however, the quantitative relationship between ET opening and pressure equalization remains insufficiently characterized. Computational fluid dynamics (CFD) offers a robust tool for analyzing middle ear pressure dynamics, particularly in elucidating pressure equilibrium mechanisms under partial ET opening conditions.
This study aimed to investigate pressure dynamics in the tympanic cavity, mastoid antrum, and air cells during ET opening using CFD, to compare pressure distributions between full and partial openings, and to determine whether partial opening can achieve equilibration equivalent to full opening.
Eight normal temporal bones were reconstructed from high-resolution computed tomography scans of four healthy adults. ET openings were simulated at 10%, 30%, 50%, and 100% patency using CFD, and results were validated against in vivo Tubomanometry data. Pressure variations in the tympanic cavity, mastoid antrum, and air cells were monitored throughout the process. Mesh independence was verified to ensure reliability, and statistical analyses were conducted using SPSS 27.0, with P < 0.05 considered significant.
CFD simulations revealed distinct pressure dynamics within the ET-middle ear system. Airflow velocity peaked at the narrow isthmus, generating a localized pressure drop. Effective middle ear pressure equilibration-across the tympanic cavity, antrum, and mastoid air cells-was achieved with partial ET opening in most cases: 30% opening sufficed for full equilibration in two ears, while 50% opening achieved complete equilibration in six. This equivalence to full patency was consistently observed during pressurization, stabilization, and depressurization phases.
Effective middle ear pressure equilibration can be achieved with partial ET opening (50%) in most cases (75% of ears). These findings provide valuable insight into middle ear physiology and its response under pathological conditions, offering a theoretical basis for optimizing the management of ET dysfunction.
Journal Article
Imaging guidance for cholesteatoma surgery using tissue autofluorescence
2023
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.
Journal Article