Effectiveness and Safety of Attic Exposition-Antrum Exclusion versus Canal Wall-Up in Patients with Acquired Stage Ib and II Cholesteatoma Affecting the Attic and Tympanic Cavity.

This study aims to test the effectiveness and safety of exteriorization surgery comprising atticotomy and obliteration of the additus ad antrum, also referred to as attic exposition-antrum exclusion (AE-AE) surgery. This surgery combines otoendoscopy with surgical microscopy for the treatment of acquired pars flaccida cholesteatoma in stages Ib and II (according to the classification of the Japan Otological Society) present in the attic and the tympanic cavity. We reviewed a historical cohort of 65 patients. Of the total, 21 were treated with canal wall-up tympanomastoidectomy (CWU). Patients in whom the AE-AE technique was performed had residual and recurrence rates of 0% and 9.1%, respectively, compared with 28.6% and 9.5%, respectively, for those treated with CWU. In the AE-AE procedure, surgery is performed in one stage compared with the two stages in CWU, to address the risk of residual cholesteatoma. Auditory thresholds were higher in the CWU group compared with the AE-AE group in the pre-surgery (53 ± 16 vs. 44 ± 15 dB; p = 0.039) and post-surgery (52 ± 18 vs. 42 ± 16 dB; p = 0.042) evaluations but not in pre-post-surgery comparisons for either the AE-AE technique (p = 0.89) or the CWU technique (p = 0.96). We conclude that AE-AE is an effective and safe technique for the treatment of acquired stage Ib and II cholesteatoma present in the attic and tympanic cavities.

Valor pronóstico de la ruta de EGFR-PI3K-pAKT-mTOR-pS6 en los carcinomas epidermoides nasosinusales / Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell carcinomas

Antecedentes y objetivos: En estudios previos hemos indicado que EGFR tiene un papel en la carcinogénesis en un subgrupo de carcinomas epidermoides nasosinusales (CENS). Además, EGFR activa a 2 de las más importantes vías de señalización intracelular como son la PI3K/pAKT/mTOR/pS6 y la vía MAP-cinasas. El objetivo de este estudio fue evaluar la participación de la ruta de EGFR/PI3K/pAKT/mTOR/pS6 y su relación con parámetros clínico-patológicos y de seguimiento de los CENS. Material y métodos: La expresión proteica de PTEN, pAKT, mTOR y pS6 fue analizada mediante inmunohistoquímica en 54 CENS. Los resultados fueron relacionados con diversos parámetros clínico-patológicos y la supervivencia. Resultados: La pérdida de expresión de PTEN se observó en 33/54 casos (61%) y la sobreexpresión de pAKT, mTOR y pS6 se observó en 19/54 casos (35%), 8/54 casos (15%) y 47/54 casos (87%), respectivamente. La pérdida de expresión de PTEN se relacionó con la invasión intracraneal y el desarrollo de metástasis regionales (p = 0,005). La ausencia de sobreexpresión de pS6 se relacionó con una supervivencia específica (p = 0,008) y global (p = 0,007) más favorables y la ausencia de recidivas locales (p = 0,055). No se observaron relaciones significativas entre la expresión de pAKT y mTOR y los parámetros clínico-patológicos estudiados. Conclusiones: Las alteraciones en la expresión de los componentes de la vía EGFR/PI3K/pAKT/mTOR/pS6 son frecuentes en un subgrupo de CENS. Este estudio revela que la ausencia de sobreexpresión de pS6 se relaciona con mejores resultados clínicos, por lo que la expresión pS6 podría considerarse como un marcador pronóstico

Background and objectives: We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma. Material and methods: The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC. Results: Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied. Conclusions: Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker

Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell carcinomas. / Valor pronóstico de la ruta de EGFR-PI3K-pAKT-mTOR-pS6 en los carcinomas epidermoides nasosinusales.

BACKGROUND AND OBJECTIVES: We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma. MATERIAL AND METHODS: The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC. RESULTS: Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied. CONCLUSIONS: Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker.