Ultrastructural and Molecular Evidence of Macroautophagy in Functioning PitNETs and Experimental Pituitary Tumors.

INTRODUCTION: Macroautophagy is a lysosome-mediated degradation process that controls the quality of cytoplasmic components and organelles, with its regulation depending on autophagy-related proteins (Atg) and with Beclin1/Atg6 and microtubule-associated protein light chain 3 (LC3/Atg8) being key players in the mammalian autophagy. As reports on this mechanism in the field of pituitary neuropathology and neuroendocrinology are scarce, our study analyzed the ultrastructural signs of macroautophagy and the expression of Beclin1 and LC3 proteins in human functioning PitNETs and in experimental pituitary tumors. METHODS: A group of humans functioning PitNETs and an experimental lactotroph model in rats of the F344 strain stimulated with estradiol benzoate (BE) were used. Ultrastructural and molecular evidence of the macroautophagic process was evaluated using different techniques. RESULTS: In functioning PitNETs cohort, 60% exhibited evidence of macroautophagy, with a significant difference found for Beclin1 and LC3 between macro- and micro-PitNETs (p < 0.05). In the experimental model, the expression of both Beclin1 and LC3 proteins was immunopositive in normal and tumoral glands when analyzed by immunofluorescence, Western blot, and immunohistochemistry. In the experimental model, protein expression was associated with increased glandular size and weight. CONCLUSIONS: Our study revealed evidence of macroautophagy at the pituitary level and the important role of Beclin1 and LC3 in the progression of functioning PitNETs, implying that this mechanism participate in regulating pituitary cell growth.

[Microscopic excision of a colloyd cyst of the third ventricle assisted by endoscopy. Case report and literature analysis.] / Exéresis microquirúrgica de quiste coloide del tercer ventrículo asistido por endoscopía. Presentación de un caso y revisión bibliográfica.

Introduction: Colloid cysts are histologically benign lesions, probably derived from the endoderm, which represent 0.3-2% of brain tumors. They are usually attached to the roof of the third ventricle in direct relation to the foramen of Monro, which can cause a blockage to the circulation of cerebrospinal fluid, determining hydrocephalus and in some cases sudden death. Other more common symptoms are headache, nausea and vomiting, blurred vision, gait ataxia, and cognitive impairment. Treatment options include microsurgery, endoscopy, stereotaxic casting, or cerebrospinal fluid shunts for the treatment of hydrocephalus. The objective of surgery is the total excision of the lesion. It should be noted that the microsurgical technique allows total excision more frequently, but at the cost of greater manipulation and tissue trauma; on the contrary, endoscopic being minimally invasive, allows better tissue preservation, although the rates of complete tumor excision are usually lower due to the difficulties in dissecting the lesions densely adhered to the roof of the third ventricle. Method: We present a clinical case of a patient with a third ventricle tumor compatible with a colloid cyst, with progressive hydrocephalus, operated with microsurgical technique and endoscopic assistance. Result: Total excision of the colloid cyst with improvement of the symptoms. Antegrade memory disorder that resolved completely after 3 months. Conclusion: The endoscopy-assisted microsurgical technique is safe for the management of this pathology and provides intraoperative benefits.

Introducción: Los quistes coloides son lesiones histológicamente benignas, probablemente derivadas del endodermo, que representan el 0,3-2% de los tumores cerebrales. Habitualmente se encuentran adheridas al techo del tercer ventrículo en relación directa con el foramen de Monro, lo que puede provocar un bloqueo a la circulación del líquido cefalorraquídeo determinando hidrocefalia y en algunos casos muerte súbita. Otros síntomas más habituales son cefalea, náuseas y vómitos, visión borrosa, ataxia de la marcha y deterioro cognitivo. Las opciones terapéuticas incluyen la microcirugía, endoscopia, vaciamiento estereotáxico o derivaciones de líquido cefalorraquídeo para el tratamiento de la hidrocefalia. El objetivo de la cirugía es la exéresis total de la lesión. Se destaca que la técnica microquirúrgica permite exéresis totales con más frecuencia, pero a costa de mayor manipulación y traumatismo tisular; por el contrario la endoscópica al ser mínimamente invasiva permite mejor preservación tisular, aunque los índices de exéresis completa del tumor suelen ser menores debido a las dificultades para disecar a las lesiones densamente adheridas al techo del tercer ventrículo. Método: Se presenta un caso clínico de un paciente con un tumor del tercer ventrículo compatible con quiste coloide, con hidrocefalia evolutiva, operado con técnica microquirúrgica y asistencia endoscópica. Resultado: Exéresis total del quiste coloide con mejoría de la sintomatología. Trastorno mnésico anterógrado que resolvió a los 3 meses completamente. Conclusión: La técnica microquirúrgica asistida por endoscopia es segura para el manejo de esta patología y aporta beneficios intraoperatorios.

[Surgical treatment in acromegaly: experience in Córdoba]. / Tratamiento quirúrgico en acromegalia: experiencia en Córdoba

Introduction: Acromegaly prevalence is 35-70 / million. Transsphenoidal surgery is the first-line treatment, with a remission rate of 80% for microadenomas and 50% for macroadenomas. Our aim was to evaluate the surgical results in Córdoba and determine predictive remission factors due to the lack of records. Methods: Retrospective-descriptive study of patients with surgery as the first therapeutic line. Remission criteria: IGF1 normalization for age/sex, with GH ≤1.0 g/L. Test X2 and Fisher's exact test with p<0.05. Results: 38 patients were included: 61% women and 39% men; Average age 45 years. Most frequent chief complaint: headache and acral growth (26%), visual disturbances (20%). Macroadenomas were the 84% of the tumors. Of 37 patients, 54% underwent microscopic surgery, 38% endoscopic and 8% transcranial. The 29% of patients showed post-operative complications and diabetes insipidus was the most frequent (10%). The percentage of them was: 33% transcranial surgery, 29% endoscopic and 25% microscopic (p = 0.557). The biochemical remission at 6 months was 34% and at 12 months 55% (p= 0.0001). No significant differences between the endoscopic and microscopic approach (p = 0.071). Of 36 patients, 31% showed complete tumor resection. The subjective clinical improvement was 88%. There weren´t predictive remission factors with significant differences. Conclusion: The surgical biochemical remission was similar to the bibliography. We didn´t find predictive remission factors but a larger number of patients could modify these results.

Introducción: La acromegalia tiene una prevalencia de 35-70/millón. La cirugía transesfenoidal es el tratamiento de elección, siendo la tasa de remisión del 80% en microadenomas y 50% en macroadenomas. Debido a la falta de registros, nos propusimos evaluar los resultados quirúrgicos en Córdoba y determinar factores predictivos de remisión. Métodos: Estudio retrospectivo-descriptivo de pacientes con cirugía como primera línea terapéutica. Criterios de remisión: normalización de IGF1 para edad/sexo, con GH ≤1,0 g/L.Test X2 y test exacto de Fisher y p<0,05. Resultados: Se incluyeron 38 pacientes: 61% mujeres y 39% hombres; edad promedio 45 años. Motivos de consulta más frecuentes: cefalea y crecimiento acral (26%), alteraciones visuales (20%). El 84% de los tumores fueron macroadenomas. De 37 pacientes, 54% se sometieron a cirugía microscópica, 38% endoscópica y 8% transcraneal. El 29% evidenció complicaciones postquirúrgicas, siendo la diabetes insípida la más frecuente (10%). El porcentaje de las mismas fue: cirugía transcraneal el 33%, endoscópica 29% y microscópica 25% (p= 0,557). La remisión bioquímica a los 6 meses fue de 34% y a los 12 meses 55% (p=0,0001). Sin diferencias significativas entre la vía endoscópica y microscópica (p=0,071). De 36 pacientes el 31% evidenció resección tumoral completa. La mejoría clínica subjetiva fue del 88%. No hubo factores predictivos de remisión bioquímica estadísticamente significativos. Conclusión: La remisión bioquímica con la cirugía fue similar a la bibliografía. No encontramos factores predictivos de remisión pero un número mayor de casos podría modificar estos resultados.

[Endoscopic Anatomy of the Inferior Orbital Fissure-Müller's Muscle Structural Unit at the Medial Sellar Orbital Junction and its surgical relevance] / Anatomía endoscópica de la unidad estructural Fisura orbitaria inferior - Músculo de Müller en la Junción órbito selar medial y su importancia quirúrgica.

Background: Diseases of the orbit represent a surgical challenge, particularly those compromising the orbital apex. Optimal surgical access should provide the best possible exposure, allowing to identify certain key anatomical structures, called landmarks. Objective: Describe the endoscopic anatomy of the structural unit formed by the Inferior Orbital Fissure (IOF) and the Müller's muscle (MM) at the orbital apex (OA), thus generating a new endoscopic anatomical landmark. Materials and methods: A bone-descriptive analysis of the IOF in dry craniums, was followed by dissection and endoscopic study of six heads (twelve sides), colored and fixed in formaldehyde. In ten dry craniums (twenty sides), distances and angles of OA foramina were measured (optic foramen [OF] and foramen rotundum [FR]). Statistical analysis was performed with SPSS 17.0 statistical software (SPSS, Inc. Chicago, IL). Results: The structural unit IOF-MM was identified in all endoscopic dissections, verifying its intimate relationship with the OA. From the morpho-metric standpoint, OF and FR were found at an average distance of 65.19 mm and 60.16 mm, respectively. The average angle of the OF was 13.32 degrees, whereas the one for FR was 19.31 degrees. We found a significant correlation between OF and FR only on the left side (left hemi-crane) (Kendall Tau b 0.69, p=0.006). There were no anatomical or morphological differences between both sides. Conclusion: The unit IOF-MM is a constant anatomical landmark, useful and safe under endoscopic technique, which allows the recognition of the OA and its contiguous areas.

Antecedentes: Las enfermedades que afectan la órbita representan un desafío quirúrgico, en particular las que comprometen el ápex orbitario. Una vía óptima de acceso quirúrgico proporciona la mejor exposición permitiendo identificar ciertas estructuras anatómicas claves llamadas reparos anatómicos Objetivo: Describir la anatomía endoscópica de la unidad estructural Fisura Orbitaria Inferior / Músculo de Müller a nivel del ápex orbitario generando así un nuevo reparo anatómico endoscópico. Material y método: Análisis descriptivo óseo de la fisura orbitaria inferior (FOI) en cráneos secos, disección y estudio bajo técnica endoscópica de 6 cabezas fijadas en formol y coloreadas; finalmente se tomaron distancias y ángulos a forámenes relacionados con el ápex orbitario a 10 cráneos secos. El análisis estadístico se realizó con el programa estadístico SPSS 17,0 (SPSS, Inc., Chicago, IL). Resultado: En todas las disecciones endoscópicas se pudo identificar la unidad fisura orbitaria inferior-músculo de Müller y también verificar su íntima relación con el ápex orbitario. Morfométricamente el foramen óptico y el foramen redondo mayor están a una distancia promedio de 65.19mm y 60.16mm respectivamente. Los ángulos promedio del FO fue de 13.32 grados y del FRM de19.31 grados. Hallamos correlación significativa entre CO. y el FRM sólo en el hemicráneo izquierdo, (Tau b de Kendall 0.69, P=0.006). No se encontraron diferencias anatómicas (o morfológicas) significativas entre lados. Conclusión: bajo técnica endoscópica la unidad Fisura Orbitaria Inferior-Músculo de Müller (FOI-MM) es un reparo anatómico constante, útil y seguro que permite el reconocimiento del ápex orbitario y sus áreas contiguas.

Endoscopic, endonasal variability in the anatomy of the internal carotid artery.

BACKGROUND: Classic three-dimensional schemas of the internal carotid artery (ICA) for transcranial approaches do not necessarily apply to two-dimensional endoscopic views. Modifying an existing ICA segment classification, we define endoscopic orientation for the lacerum (C3) to clinoid (C5) segments through an endonasal approach. METHODS: In 20 cadaveric heads, we classified endoscopic appearance based on shape and angulation of C3 to C5 segments. Distances were measured between both arteries, and between the ICA and pituitary gland. RESULTS: We identified 4 common ICA patterns: types I through III matched side-to-side, whereas type IV was asymmetric. In 80% of specimens, the pituitary gland had direct contact with the ICA. In 20% of specimens, a space existed between the pituitary gland and the cavernous segment. Access to the posterior aspect of the cavernous sinus medial to the cavernous segment was possible without retraction of the artery or pituitary gland. Spaces between the lacerum and cavernous segments were trapezoid (80%) and hourglass (20%). CONCLUSIONS: Distinguishing which ICA type courses between the lacerum and clinoid segments can help clarify the relationships between the artery and its surrounding structures during endoscopic approaches. Adapting the classic terminology of ICA segments provided consistency of endoscopic relevance, defined potential endoscopic corridors, and highlighted the critical step of arterial contact.

Anatomy of the inferior orbital fissure: implications for endoscopic cranial base surgery.

Considering many approaches to the skull base confront the inferior orbital fissure (IOF) or sphenomaxillary fissure, the authors examine this anatomy as an important endoscopic surgical landmark. In morphometric analyses of 50 adult human dry skulls from both sexes, we divided the length of the IOF into three segments (anterolateral, middle, posteromedial). Hemotoxylin- and eosin-stained sections were analyzed. Dissections were performed using transnasal endoscopy in four formalin-fixed cadaveric cranial specimens (eight sides); three endoscopic approaches to the IOF were performed. IOF length ranged from 25 to 35 mm (mean 29 mm). Length/width of the individual anterolateral, middle, and posteromedial segments averaged 6.46/5, 4.95/3.2, and 17.6/ 2.4 mm, respectively. Smooth muscle within the IOF had a consistent relationship with several important anatomical landmarks. The maxillary antrostomy, total ethmoidectomy approach allowed access to the posteromedial segment of the fissure. The endoscopic modified, medial maxillectomy approach allowed access to the middle and posterior-medial segment. The Caldwell-Luc approach allowed complete exposure of the IOF. The IOF serves as an important anatomic landmark during endonasal endoscopic approaches to the skull base and orbit. Each of the three segments provides a characteristic endoscopic corridor, unique to the orbit and different fossas surrounding the fissure.

Muller's muscle, no longer vestigial in endoscopic surgery.

BACKGROUND: As a thin filmy covering overlaying the inferior orbital fissure (IOF), Muller's muscle was considered a vestigial structure in humans, and for this reason, its anatomical significance was neglected. Because of increasing interest in endonasal approaches to the skull base that encompasses this region, we re-examined this structure's role as an anatomical landmark from an endoscopic perspective. METHODS: In 10 cadaveric specimens, microanatomical dissections were performed (n = 5); endoscopic dissections were performed (n = 5) via approaches of the middle turbinate or inferior turbinate, and via the Caldwell-Luc approach through the maxillary sinus. Histological examinations were performed in 20 human fetuses (Embryology Institute, Universidad Complutense de Madrid, Madrid, Spain). RESULTS: In cadaveric dissections, Muller's muscle was demonstrated in all specimens, serving as a bridge-like structure that spanned the entire IOF and separated the orbit from the temporal, infratemporal, and pterygopalatine fossas. Depending on which endoscopic corridor was used, a different aspect of the IOF and Muller's muscle was identified. In our endoscopic and microscopic observations, Muller's muscle was extensive, not only spanning the IOF but also extending posteriorly to reach the superior orbital fissure (SOF) and anterior confluence of the cavernous sinus. Histological analysis identified many anastomotic connections between the ophthalmic venous system and pterygoid plexus that may explain how infection or tumor spreads between these regions. CONCLUSIONS: Muller's muscle serves as an anatomical landmark in the IOF and facilitates anatomical orientation in this region for endoscopic skull base approaches. Its recognition during endoscopic approaches allows for a better three-dimensional understanding of this anterior cranial base region.

Evidence of improved surgical outcome following endoscopy for nonfunctioning pituitary adenoma removal.

OBJECT: Because of their size and lateral extension, total removal of nonfunctioning pituitary adenomas (NFPAs) remains a challenge and postoperative tumor remnants are frequent. Endoscopy has improved the surgeon's view; however, its superiority in terms of surgical outcome remains undetermined. The authors' aim in this study was to compare the clinical results and morbidity between microscopic and endoscopic techniques in 164 patients with NFPAs. METHODS: Tumoral (3D MR imaging), endocrinological, and ophthalmological results and morbidity were compared between 2 groups of 82 patients with newly diagnosed NFPAs surgically treated via either a sublabial microscopic approach (Group B) or a fully endonasal endoscopic technique (Group A). RESULTS: The groups showed no difference in terms of clinical features, tumor size, or cavernous sinus invasion (p > 0.05). One year postoperatively, the quality of resection was significantly improved in Group A (gross-total removal [GTR]: 74% vs 50% in Group B, p = 0.002) with greater control of lateral extension (Knosp Grade 2: GTR 88.2% vs 47.8% in Group B, p = 0.02; Knosp Grade 3: 67.9% vs 16.7% in Group B, p < 0.001) and suprasellar extension (tumor height 20-30 mm: GTR 76% vs 53% in Group B, p = 0.01). Endocrinological outcome in patients with a partial deficiency in anterior pituitary function preoperatively was significantly better in Group A (improvement 56% vs 25% in Group B, stabilization 22% vs 46%, and aggravation 22% vs 29%; p = 0.01). Among the ophthalmologically symptomatic patients, 100% from Group A improved compared with 93% in Group B (p = 0.35). Lastly, no significant difference was found regarding morbidity. These data were supported by the literature in which the GTR rate is consistently higher for endoscopy compared with microscopy. CONCLUSIONS: In this large series of patients with NFPAs, endoscopy improved the quality of resection and endocrinological outcome. Larger studies focusing on the impact of these promising results on the long-term recurrence of NFPAs are warranted.