Cholesteatoma is a destructive lesion of the temporal bone that gradually expands and causes complications by erosion of the adjacent bony structures. Bone resorption can result in destruction of the ossicular chain and otic capsule with consecutive hearing loss, vestibular dysfunction, facial paralysis and intracranial complications. Surgery is the only treatment of choice. The etiopathogenesis of cholesteatoma, however, is still controversial. This review was designed to understand the reasons for these disparities and to reduce or eliminate them. Future studies focused on developmental, epidemiological, hormonal and genetic factors as well as on treatment are likely to contribute to further understanding of cholesteatoma pathogenesis.
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.
This newly introduced method of BET was found to be a feasible and safe procedure to inflate the ET. It significantly helped to improve ET function in our study group. However, larger long-term studies are necessary to fully evaluate the clinical value of BET.
Somatic neural and neural crest stem cells are promising sources for cellular therapy of several neurodegenerative diseases. However, because of practical considerations such as inadequate accessibility of the source material, the application of neural crest stem cells is strictly limited. The secondary palate is a highly regenerative and heavily innervated tissue, which develops embryonically under direct contribution of neural crest cells. Here, we describe for the first time the presence of nestin-positive neural crest-related stem cells within Meissner corpuscles and Merkel cell-neurite complexes located in the hard palate of adult Wistar rats. After isolation, palatal neural crest-related stem cells (pNC-SCs) were cultivated in the presence of epidermal growth factor and fibroblast growth factor under serum-free conditions, resulting in large amounts of neurospheres. We used immunocytochemical techniques and reverse transcriptase-polymerase chain reaction to assess the expression profile of pNC-SCs. In addition to the expression of neural crest stem cell markers such as Nestin, Sox2, and p75, we detected the expression of Klf4, Oct4, and c-Myc. pNC-SCs differentiated efficiently into neuronal and glial cells. Finally, we investigated the potential expression of stemness markers within the human palate. We identified expression of stem cell markers nestin and CD133 and the transcription factors needed for reprogramming of somatic cells into pluripotent cells: Sox2, Oct4, Klf4, and c-Myc. These data show that cells isolated from palatal rugae form neurospheres, are highly plastic, and express neural crest stem cell markers. In addition, pNC-SCs may have the ability to differentiate into functional neurons and glial cells, serving as a starting point for therapeutic studies. Stem Cells 2009;27:1899–1910
Adult human neural crest-derived stem cells (NCSCs) are of extraordinary high plasticity and promising candidates for the use in regenerative medicine. Here we describe for the first time a novel neural crest-derived stem cell population within the respiratory epithelium of human adult inferior turbinate. In contrast to superior and middle turbinates, high amounts of source material could be isolated from human inferior turbinates. Using minimally-invasive surgery methods isolation is efficient even in older patients. Within their endogenous niche, inferior turbinate stem cells (ITSCs) expressed high levels of nestin, p75(NTR), and S100. Immunoelectron microscopy using anti-p75 antibodies displayed that ITSCs are of glial origin and closely related to nonmyelinating Schwann cells. Cultivated ITSCs were positive for nestin and S100 and the neural crest markers Slug and SOX10. Whole genome microarray analysis showed pronounced differences to human ES cells in respect to pluripotency markers OCT4, SOX2, LIN28, and NANOG, whereas expression of WDR5, KLF4, and c-MYC was nearly similar. ITSCs were able to differentiate into cells with neuro-ectodermal and mesodermal phenotype. Additionally ITSCs are able to survive and perform neural crest typical chain migration in vivo when transplanted into chicken embryos. However ITSCs do not form teratomas in severe combined immunodeficient mice. Finally, we developed a separation strategy based on magnetic cell sorting of p75(NTR) positive ITSCs that formed larger neurospheres and proliferated faster than p75(NTR) negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy.
ReviewThe aims of the European Academy of Otology and Neurootology/Japan Otological Society (EAONO/JOS) Joint Consensus Statements on Definition, Classification and Staging are as follows:1. The definitions provide terminologies in the description of cholesteatoma. 2. The classification categorized cholesteatoma into distinct categories to facilitate the comparison of surgical outcomes across reports. 3. The staging system reflects the severity of the cholesteatoma, the difficulty to achieve complete removal, and the subsequent restoration of normal function.The authors wish to present the final consensus first, followed by an explanation of the methodology on how the EAONO/JOS consensus was reached by the steering group.The clinical classification of middle ear mucosa is summarized in Figure 1. 1 EAONO/JOS Joint Consensus Statements on the Definitions, Classification and Staging of Middle Ear CholesteatomaThe 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. KEYWORDS:2 J Int Adv Otol 2017; 13(1): 1-8 Definitions and Statements on Cholesteatoma1. Cholesteatoma is a mass formed by the keratinizing squamous epithelium in the tympanic cavity and/or mastoid and subepithelial connective tissue and by the progressive accumulation of keratin debris with/without a surrounding inflammatory reaction.2. Cholesteatoma consists of matrix (keratinizing squamous epithelium), perimatrix (varying thickness of the subepithelial connective tissue), and keratin debris.3. The pathophysiology of cholesteatoma is not completel...
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