TGF-ß1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells.

Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF-ß1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF-ß1 in WT and SSTR2-overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFßR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF-ß1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH- and PRL-secretion and proliferation were improved in the presence of TGF-ß1, as well as by SSTR2 overexpression. The OCT/TGF-ß1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF-ß1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF-ß1/TGFßR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.

Cirugía endoscópica endonasal extendida a la región Petro-Clival / Ápex Petroso. Reporte de un caso y revisión de la literatura / Endonasal endoscopic surgery extended to the Petro-Clival / Petrópe region. Case report and literature review

INTRODUCCIÓN: las indicaciones de la cirugía endoscópica endonasal en el tratamiento de tumores de base de cráneo continúan expandiéndose, sobre todo para los tumores extradurales, como son los cordomas. A partir de un caso, nuestro objetivo fue revisar la literatura relevante de estos desafiantes tumores operados bajo esta técnica. CASO CLÍNICO: paciente de 59 de edad con antecedentes de depresión mayor, que comenzó con un cuadro de diplopía por compromiso del VI par izquierdo. Los estudios (CT y RM) mostraron un proceso expansivo en la región del ápex petroso. Se realizó un abordaje endoscópico extendido a la región petro-clival con resección tumoral subtotal. Buena evolución postquirúrgica con desaparición de su diplopía. El diagnóstico histológico fue de Cordoma Condroide. Se indicó radioterapia adyuvante. DISCUSIÓN: a partir del conocimiento y la experiencia en el manejo endoscópico de la patología intraselar se desarrollaron abordajes para el tratamiento de patologías que comprometen la fosa anterior, media e inclusive la fosa posterior. Actualmente, los abordajes endoscópicos, se han extendido a otras áreas de la base de cráneo que de otro modo presentan un reto técnico para la exposición a través de los abordajes transcraneales habituales. El abordaje endoscópico endonasal ofrece una ruta quirúrgica adecuada para la resección del tumor que se presenta en este caso. Las vías que pueden ser utilizados para llegar a la región petroclival a través de la acceso endonasal incluyen la medial (con o sin la movilización de ACI) y la infrapetrosa transterigoidea. En este reporte de caso se analizan las indicaciones del abordaje endoscópico endonasal basado en una revisión de la literatura. CONCLUSIÓN: el abordaje endoscópico endonasal extendido se presenta como una alternativa segura para el tratamiento de determinadas lesiones petro-clivales. Se requieren más estudios anatómicos y clínicos para establecer mejor el rol de este tipo de técnicas en el manejo de las lesiones localizadas en esta región

INTRODUCTION: indications for endoscopic endonasal surgery for the treatment of skull base tumors continue to expand, particularly for extradural tumors, such as chordomas. Based on this case report presentation, we aim to review the literature on the endoscopic technique relevant to the management of these challenging tumors. CASE REPORT: a 59 year-old woman who presented with diplopia due to left sixth nerve palsy underwent imaging studies (CT, MRI) that revealed a mainly intra-osseous expansive process of the left petrous apex. An expanded endoscopic endonasal approach to the petroclival region was performed and the tumor was subtotally resected. The patient recovered from surgery with resolved diplopia. Histopathology was compatible with chondroid chordoma. The radiation therapy was indicated after surgery. DISCUSSION: built upon the bulk experience on the treatment of intrasellar pathology, endonasal endoscopic approaches have been developed for the treatment of skull base lesions involving the anterior, middle and even posterior cranial fossae. Nowadays, the use of these techniques has spread to other areas of the skull base, which otherwise present as a formidable technical challenge for exposure through transcranial approaches. The endonasal endoscopic approach provides an adequate surgical corridor for the resection of the tumor presented in this case report. The alternative corridors that can be utilized to reach the petroclival region through the endonasal endoscopic route include the medial corridor (with or without ICA mobilization) and the transpterygoid infrapetrous corridor. In this article, we discuss the indications for the endoscopic endonasal approach for the case presented, and discuss our choice of approach based on our review of the literature. CONCLUSION: the extended endoscopic endonasal approach presents as a safe alternative for the treatment of select petroclival lesions. Further anatomical and clinical studies are required to better establish the role of the endoscopic endonasal approach for lesions located in this region