A Foreign Body Lodged in the Glottis of a Toddler for a Prolonged Time: Anatomical Considerations and Review of the Literature.

Our scope is to present the unusual case of an impacted foreign body in a child's larynx for a prolonged period due to recurrent misdiagnosis and review the literature emphasizing the laryngeal foreign body. A toddler girl from a rural region was initially referred to a primary pediatric care center due to a sudden choking episode. The mother made an unsuccessful attempt to pull out a possible foreign body by blind finger sweeping. After 22 days of recurrent misdiagnosis and unsuccessful conservative therapies, the child developed hoarseness of voice and dyspnea during physical exertion. The patient underwent a flexible nasopharyngolaryngeal endoscopy, which observed a foreign body in the glottis, and an emergency microlaryngoscopy. Persistence of laryngeal symptoms in a child with a sudden choking episode should always raise the suspicion of a respiratory tract foreign body impaction. The most appropriate therapeutical approach is rigid bronchoscopy under general anesthesia.

Pathogenesis of Nasal Polyposis: Current Trends.

Chronic Rhinosinusitis (CRS) is characterized by edema of the sub-epithelial layers, but, only specific types of CRS are developing polyps. Nasal polyposis may develop under different pathogenetic mechanisms rendering the typical macroscopic classification of CRS, with or without nasal polyps, rather deficient. Currently, we approach nasal polyposis, in terms of diagnosis and treatment, according to its endotype, which means that we focus on the specific cells and cytokines that are participating in its pathogenesis. It appears that the molecular procedures that contribute to polyp formation, initiating with a Th-2 response of the adaptive immune system, are local phenomena occurring in the sub-epithelial layers of the mucosa. Several hypotheses are trying to approach the etiology that drives the immune response towards Th-2 type. Extrinsic factors, like fungi, Staphylococcus superantigens, biofilms, and altered microbiome can contribute to a modified and intense local reaction of the immune system. Some hypotheses based on intrinsic factors like the elimination of Treg lymphocytes, low local vitamin-D levels, high levels of leukotrienes, epithelial to mesenchymal transition (EMT) induced by hypoxia, and altered levels of NO, add pieces to the puzzle of the pathogenesis of nasal polyposis. Currently, the most complete theory is that of epithelial immune barrier dysfunction. Intrinsic and extrinsic conditions can damage the epithelial barrier rendering sub-epithelial layers more vulnerable to invasion by pathogens that trigger a Th-2 response of the adaptive immune system. Th2 cytokines, subsequently, induce the accumulation of eosinophils and IgE together with the remodeling of the stroma in the sub-epithelial layers leading, eventually, to the formation of nasal polyps.

The Eustachian Tube Dysfunction in Children: Anatomical Considerations and Current Trends in Invasive Therapeutic Approaches.

The eustachian tube (ET) has a crucial role in the physiology of the middle ear. Thus, any condition that renders the tube dysfunctional is directly implicated with middle ear pathophysiology, like in the case of acute otitis media and otitis media with effusion. Children are more vulnerable to pathologies of the middle ear, primarily due to the immature development of their eustachian tubes. Otitis media with effusion, apart from being a burden for hearing, with direct consequences for speech development, may also be implicated in cholesteatoma formation. Medical therapy is not practically effective for the treatment of effusion. Moreover, the established surgical approaches, like grommets and adenoidectomy, deal only indirectly with the problem since they are not addressing the dysfunctional ET itself. An emerging interventional approach that intends to restore the function of the tube is the transnasal balloon dilation of the cartilaginous part of the ET. Growing international experience indicates that this promising technique is safe and effective. In the current review, we aim to provide background information on the anatomy, physiology, and pathophysiology of the ET and to present the progress of the balloon dilation technique with emphasis on pediatric patients.

Androgen receptor in laryngeal carcinoma: could there be an androgen-refractory tumor?

Androgen receptors (ARs) which are implicated in the pathogenesis of several malignancies can also be a possible downstream effector in laryngeal cancer. In the present study, 97 invasive squamous laryngeal carcinomas were studied by immunohistochemistry for protein expression of AR. Androgen receptors were expressed in 52.6% of tumor specimens, suggesting their implication in the pathogenesis of this tumor. Our study's aim was to investigate the hypothetical scenario of an androgen refractory laryngeal carcinoma where androgen receptors can be activated by nodal molecules in the course of an Epithelial-to-mesenchymal transition (EMT) phenomenon. In line with this we correlated AR expression with the expression of ILK, p-Akt, E-cadherin, ß-catenin in our sample as well as with tumor grade and TNM stage. A reverse correlation between nuclear AR and cytoplasmic ILK expression was evidenced, indicating an interaction of those molecules in laryngeal carcinoma. Finally in our material, in those carcinomas that were expressing ARs, stronger nuclear expression of the receptor was characterized by poorer cell differentiation and correlated with the acquisition of EMT features like E-cadherin loss and ß-catenin translocation raising a question whether activated ARs can drive an EMT procedure.

Differential beta-catenin expression between glottic and supraglottic laryngeal carcinoma.

Glottic carcinomas present with a favorable prognosis comparing to supraglottic. This fact is mainly attributed to differences in anatomical, histological and embryological aspects. It is possible that differential molecular anatomy between the two distinct anatomical entities contributes to this clinical observation as well. The current study intended to evaluate, by immunohistochemistry in paraffin-embedded tissue samples from 97 invasive squamous laryngeal carcinomas, the possible differential expression of crucial molecules for malignant cell's function such as integrin-linked kinase, phosphorylated Akt, E-cadherin, beta-catenin, androgen receptor, estrogen receptor-beta and vimentin between glottic and supraglottic laryngeal carcinomas. We documented a correlation of supraglottic laryngeal carcinomas with high grade (p = 0.001) and enhanced tumor TNM stage (p < 0.001). The supraglottic location was correlated with the abolishment of beta-catenin from the membrane (p = 0.025). However, the diverse anatomical locations are not characterized by statistically significant differential expression of ILK, p-Akt, AR, ER-beta, E-cadherin and vimentin. Our results show that it is possible that molecular factors, such as beta-catenin, are differently expressed in glottic and supraglottic carcinomas, leading to the distinct clinical behavior of those tumors.

Estrogen receptor-beta expression in human laryngeal carcinoma: correlation with the expression of epithelial-mesenchymal transition specific biomarkers.

Laryngeal carcinoma is a malignancy of the respiratory tract with a significantly higher male to female ratio, suggesting involvement of gender-depended factors in the pathogenesis. Estrogen influences the pathological processes of hormone-dependent cancers, such as breast, prostate and ovarian cancers, through its receptors, estrogen receptor-alpha (ER-alpha) and -beta (ER-beta). While ER-alpha promotes cell proliferation, recent studies indicate that ER-beta is protective against carcinoma progression into an invasive state. However, it is unclear whether ER-beta plays a role in laryngeal cancer. In the present study we examined the expression of ER-beta in 80 invasive human squamous laryngeal carcinomas by immunohistochemistry and correlated ER-beta expression with markers of epithelial-mesenchymal transition (EMT). ER-beta was expressed in 83% of tumour specimens where it was localized in the nuclei of tumour cells. The expression of ER-beta correlated positively with the maintenance of E-cadherin and beta-catenin at cell junctions and negatively with the loss of E-cadherin, nuclear translocation of beta-catenin and increased TNM stage. We concluded that estrogen receptor-beta expression is documented in laryngeal cancer indicating a possible role in the pathogenesis of this malignancy. It is suggested that ER-beta could protect tumour cells from acquiring aggressive EMT features such as E-cadherin downregulation and nuclear beta-catenin activation.

Integrin-linked kinase cytoplasmic and nuclear expression in laryngeal carcinomas.

Integrin-linked kinase (ILK) has been implicated in the development and progression of several human malignancies. Previous in vitro studies also implicate ILK in the activation of Akt and beta-catenin as well as in the regulation of E-cadherin expression. However, the role of ILK in human laryngeal cancer and its possible in vivo downstream effectors in the disease are currently unknown. We examined by immunohistochemistry the protein expression of ILK, phosphorylated-Akt (p-Akt), E-cadherin, and beta-catenin in 97 invasive squamous laryngeal carcinomas. Increased cytoplasmic and nuclear expression of ILK and p-Akt decreased membranous expression of E-cadherin and nuclear accumulation of beta-catenin was found in 87.6%, 85.6%, 71.1%, and 43.3% of cases, respectively. Our results suggest that ILK expression may be implicated in human laryngeal carcinoma and its localization in the nucleus possibly proposes novel nuclear functions of this molecule. In addition, enhanced ILK expression correlates with activation of Akt but not with downregulation of E-cadherin and activation of beta-catenin. Finally, in our material while activated Akt seems to characterize well-differentiated tumors, loss of E-cadherin and activation of beta-catenin correlated with high grade carcinomas.