Fluorescence-guided surgery in high grade gliomas using an exoscope system.

BACKGROUND: Fluorescence-guided microsurgical resections of high-grade gliomas using 5-aminolevulinic acid (5-ALA) is superior to conventional microsurgery. An optical device, usually a modified microscope, is needed for these procedures. However, an exoscope may be implemented for fluorescence techniques. We present the use of an exoscope to perform tumor resection guided by 5-ALA fluorescence in 21 consecutive patients with high-grade glioma and two neuronavigation-guided biopsies. METHODS: Twenty-three patients underwent operations. Tumor volume and localization were quantified with pre- and postoperative volumetric MRI in non-biopsy cases. RESULTS: In non-biopsy cases, the age range was 20 to 79 years, with a median of 56 (interquartile range = 45-66). Histological analysis indicated that 14 had glioblastoma multiforme, 2 grade-III oligodendrogliomas and 1 anaplastic astrocytoma, 3 metastases and 1 low-grade astrocytoma. Total resection was achieved in 15 cases; subtotal resection was performed in 5 patients. The result was partial resection in one case. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1-5, was 4.5 in the GBM group (IQR = 4-5), 3 (IQR = 2.5-3.5) in anaplastic glioma, and 2.5 (IQR = 2.25-2.75) for oligodendrogliomas. Of the three metastases, one showed fluorescence level 4. As for the two biopsy cases, one was anaplastic astrocytoma and one glioblastoma multiforme. The samples obtained were fluorescent in both cases. CONCLUSIONS: An exoscope can be also used for fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) and neuronavigation-guided biopsy. With an important advantage of low cost, this allows the surgeon to perform collaborative surgeries and adds agility to the procedure.

Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence.

Some pituitary adenomas (PA) demonstrate aggressive behavior with local invasion and recurrences. Angiogenesis is regarded as an essential step in the formation of solid tumors. The aim of this study is to find out whether angiogenic factors may have information about the aggressiveness of PA that could be useful in determining the frequency of follow-up and whether adjuvant therapy is necessary. In this retrospective descriptive study, we evaluated vascular endothelial growth factors (VEGF) and VEGF receptor (KDR) mRNA expression by RT-PCR analysis on 46 human PA samples. Clinical data, histological subtype and radiologic characteristics were studied to determine the associations between the variables and the pre-operative behavior of the tumor. In addition, we monitored 12 patients without adjuvant post-operative therapies over 46 months after surgery, determining progression of tumor remnants and its association with these markers. VEGF expression correlates with KDR expression (r = 0.40, p = 0.006). VEGF demonstrates different expression between histological subtypes (p = 0.036). The extension at magnetic resonance imaging showed that VEGF expression was related to suprasellar extension (p = 0.007), being expressed more on tumors with extrasellar growth than intrasellar ones (p = 0.008). Our results demonstrate a 27.5 times increased risk of extrasellar growth when VEGF expression exceeds 0.222 normalized copy number (NCN) (p = 0.002). Likewise, tumors with KDR greater than 0.750 NCN had less recurrence-free survival time (p = 0.032). Our results suggest that the expression of VEGF and its receptor could be a marker for poor outcome after partial tumor resection. These data should be considered in future studies evaluating angiogenic factors as therapeutic targets in patients with PA.

[Mini-open approaches in anterior lumbar spine surgery]. / Abordajes anteriores mini-open en el raquis toracolumbar.

INTRODUCTION: The anterior spine approach known as «mini-open¼ was introduced a few years ago for the surgical treatment of spine diseases. This approach allows the anterior, body and intervertebral disc structures to be exposed, as well as the anterior compression of the dural sac and the reconstruction and/or stabilisation of the levels of interest with an appropriate system. In the present article we present our experience in mini-open anterior spine surgery (MOASS) approach in the treatment of lumbar spine diseases. MATERIAL AND METHODS: We performed 74 anterior spine approaches using open surgery between the period January 2004 and July 2011. In 38 cases we used the MOASS technique at different levels: thoracic, lumbar, and infraumbilical extraperitoneal. RESULTS: There were no surgical or post-operative deaths, or further neurological deficits arising from the surgical procedure in any of the techniques (classic versus MOASS). The few complications were corrected with the appropriate treatment. CONCLUSIONS: Using the MOASS technique we have performed corrective surgery on spine injuries that could affect the thoracic spinal column, with similar results to those obtained using the classic approach and with obvious advantages.

Recommendations for the diagnosis and radiological follow-up of pituitary neuroendocrine tumours.

Pituitary neuroendocrine tumours (PitNETs) constitute a heterogeneous group of tumours with a gradually increasing incidence, partly accounted for by more sensitive imaging techniques and more extensive experience in neuroradiology in this regard. Although most PitNETs are indolent, some exhibit aggressive behaviour, and recurrence may be seen after surgical removal. The changes introduced in the WHO classification in 2017 and terminological debates in relation to neuroendocrine tumours warrant an update of the guidelines for the diagnosis, preoperative and postoperative management, and follow-up of response to treatment of PitNETs. This multidisciplinary document, an initiative of the Neuroendocrinology area of the Sociedad Española de Endocrinología y Nutrición [Spanish Society of Endocrinology and Nutrition] (SEEN), focuses on neuroimaging studies for the diagnosis, prognosis and follow-up of PitNETs. The basic requirements and elements that should be covered by magnetic resonance imaging are described, and a minimum radiology report to aid clinicians in treatment decision-making is proposed. This work supplements the consensus between the Neuroendocrinology area of the SEEN and the Sociedad Española de Anatomía Patológica [Spanish Society of Pathology] (SEAP) for the pathological study of PitNETs.

Postoperative CSF leakages after transsphenoidal surgery for pituitary adenomas: Analysis of a series of 302 surgical procedures. / Fístulas posquirúrgicas de líquido cefalorraquídeo tras cirugía transesfenoidal de adenomas hipofisarios: análisis de una serie de 302 intervenciones.

INTRODUCTION: Transsphenoidal surgical removal is the preferred treatment of most pituitary adenomas. Postoperative cerebrospinal fluid (CSF) leakage is the leading cause of morbidity after this procedure, with an incidence rate that varies from 0,5-15% in the main published series. OBJECTIVES: The primary objective of this study was to establish the incidence of postoperative CSF leakage in a sample of surgeries performed at the University Hospital of La Ribera by the same surgical team. The secondary objectives were to: ascertain the distinctive features between patients with and without postoperative CSF leakage, identify risk factors for their development, evaluate the relationship between the surgical technique for closing the sella turcica and the onset of postoperative CSF leakage and evaluate different treatment regimens for this complication. METHODS: The data of 302 consecutive transsphenoidal surgical procedures for pituitary adenoma removal which were performed between 1999 and 2017 were retrospectively reviewed. RESULTS AND CONCLUSIONS: The incidence of postoperative CSF leakage in our series was 2,3% (in accordance with similar published studies). It was possible to correlate intraoperative CSF leakage with two variables: pituitary macroadenoma and tumors with suprasellar extension (P<.005). This correlation did not exist for postoperative CSF leakage. We found a statistically significant correlation between intraoperative and postoperative CSF leakage (P<.005). Due to the low incidence of postoperative CSF leakage in our series, it was not possible to identify risk factors for its development.

Is it time to consider the expression of specific-pituitary hormone genes when typifying pituitary tumours?

The aim of the present study is to check whether we can replicate, in an independent series, previous results showing that the molecular study of pituitary-specific gene expression complements the inmunohistochemical identification of pituitary neuroendocrine tumours. We selected 112 patients (51 (46.4%) women; mean age 51.4±16 years; 102 macroadenomas (91.9%), 9 microadenomas (8.1%)) with complete clinical, radiological, immunohistochemical and molecular data from our data set of pituitary neuroendocrine tumours. Patients were different from those previously studied. We measured the expression of the pituitary-specific hormone genes and type 1 corticotrophin-releasing hormone and arginine vasopressin 1b receptors, by quantitative real-time polymerase chain reaction using TaqMan probes. Afterwards, we identified the different pituitary neuroendocrine tumour subtypes following the 2017 World Health Organization classification of pituitary tumours, calculating the concordance between their molecular and immuhistochemical identification. The concordance between molecular and immunohistochemical identification of functioning pituitary neuroendocrine tumours with the clinical diagnosis was globally similar to the previous series, where the SYBR Green technique was used instead of TaqMan probes. Our results also corroborated the poor correlation between molecular and immunohistochemical detection of the silent pituitary neuroendocrine tumour variants. This discrepancy was more remarkable in lactotroph, null-cell and plurihormonal pituitary neuroendocrine tumours. In conclusion, this study validates the results previously published by our group, highlighting a complementary role for the molecular study of the pituitary-specific hormone genes in the typification of pituitary neuroendocrine tumours subtypes.

Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas.

AIM: The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling. METHODS: Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard. RESULTS: Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes. CONCLUSIONS: According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.

Fluorescence-guided surgery and biopsy in gliomas with an exoscope system.

BACKGROUND: The introduction of fluorescence-guided resection allows a better identification of tumor tissue and its more radical resection. We describe our experience with a modified exoscope to detect 5 ALA-induced fluorescence in neuronavigation-guided brain surgery or biopsy of malignant brain tumors. METHODS: Thirty-eight patients with a suspected preoperative diagnosis of high-grade astrocytoma were included. We used a neuronavigation device and a high-definition exoscope system with a built-in filter to detect 5-ALA fluorescence in all cases. Thirty patients underwent craniotomy with tumor resection and 8 underwent frameless stereotactic brain biopsy. RESULTS: Histopathological diagnosis confirmed the presence of high-grade gliomas in 34 patients. Total resection was achieved in 23 cases and subtotal in 7. No relevant complications related to the administration of 5-ALA were detected. CONCLUSIONS: The use of the exoscope in 5-ALA fluorescence-guided tumor surgery has twofold implications: during brain tumor surgery it can be considered a valuable tool to achieve a more radical resection of the lesion, and when applied to a biopsy of a suspected brain high-grade glioma, it decreases the possibility of a negative biopsy.

Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid ultrasound evaluation advisable?

Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59±13 years; disease duration 6.7±7.2 years) and 50 controls (51% males, mean age 58±15 years) were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma). These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening.

Fístulas posquirúrgicas de líquido cefalorraquídeo tras cirugía transesfenoidal de adenomas hipofisarios: análisis de una serie de 302 intervenciones / Postoperative CSF leakages after transsphenoidal surgery for pituitary adenomas: Analysis of a series of 302 surgical procedures

Introducción: El tratamiento de elección para la mayor parte de los adenomas hipofisarios es su resección quirúrgica por vía transesfenoidal. Las fístulas posquirúrgicas de líquido cefalorraquídeo (LCR) constituyen una de las complicaciones más características y potencialmente graves de este tratamiento. Su incidencia es variable para las principales series publicadas en la literatura, con un rango del 0,5 al 15%. Objetivos: El objetivo principal de nuestro trabajo fue establecer la incidencia de fístulas de LCR tras cirugía transesfenoidal en una muestra de 302 intervenciones realizadas en pacientes afectos de adenomas hipofisarios en el Hospital Universitario de la Ribera y por un mismo equipo quirúrgico. Como objetivos secundarios se plantearon: conocer las características diferenciales entre pacientes con y sin fístulas posquirúrgicas de LCR, detectar factores de riesgo para su desarrollo, valorar la relación entre la técnica de cierre de la silla turca y la aparición de fístulas posquirúrgicas de LCR y valorar las diferentes pautas de tratamiento de la complicación. Métodos: Se realizó un estudio descriptivo retrospectivo basado en una revisión sistemática de 302 casos de adenomas hipofisarios intervenidos en nuestro centro a través de una vía de abordaje transesfenoidal entre los años 1999 y 2017. Resultados y conclusiones: La incidencia de fístulas posquirúrgicas de LCR en nuestra serie fue del 2,3% (concordante con la descrita en series amplias previamente publicadas). La aparición de una fístula intraoperatoria de LCR se correlacionó con dos variables del estudio: macroadenomas y tumores con extensión supraselar (p<0,005). Esta correlación no existió para fístulas posquirúrgicas. Sí fue posible establecer una relación estadísticamente significativa entre la aparición de fístulas intraoperatorias y posquirúrgicas de LCR (p<0,005). La baja incidencia de fístulas posquirúrgicas de LCR tras cirugía transesfenoidal de adenomas hipofisarios en nuestra casuística no permitió identificar factores de riesgo para su desarrollo

Introduction: Transsphenoidal surgical removal is the preferred treatment of most pituitary adenomas. Postoperative cerebrospinal fluid (CSF) leakage is the leading cause of morbidity after this procedure, with an incidence rate that varies from 0,5-15% in the main published series. Objectives: The primary objective of this study was to establish the incidence of postoperative CSF leakage in a sample of surgeries performed at the University Hospital of La Ribera by the same surgical team. The secondary objectives were to: ascertain the distinctive features between patients with and without postoperative CSF leakage, identify risk factors for their development, evaluate the relationship between the surgical technique for closing the sella turcica and the onset of postoperative CSF leakage and evaluate different treatment regimens for this complication. Methods: The data of 302 consecutive transsphenoidal surgical procedures for pituitary adenoma removal which were performed between 1999 and 2017 were retrospectively reviewed. Results and conclusions: The incidence of postoperative CSF leakage in our series was 2,3% (in accordance with similar published studies). It was possible to correlate intraoperative CSF leakage with two variables: pituitary macroadenoma and tumors with suprasellar extension (P<.005). This correlation did not exist for postoperative CSF leakage. We found a statistically significant correlation between intraoperative and postoperative CSF leakage (P<.005). Due to the low incidence of postoperative CSF leakage in our series, it was not possible to identify risk factors for its development

Abordajes anteriores mini-open en el raquis toracolumbar / Mini-open approaches in anterior lumbar spine surgery

Introducción El abordaje anterior vertebral conocido como mini-open fue introducido hace unos años para el tratamiento quirúrgico de la patología del raquis. Dicho abordaje permite la exposición directa de las estructuras anteriores, cuerpo y disco intervertebral, la descompresión anterior del saco dural y la reconstrucción y/o estabilización de los niveles de interés con un sistema adecuado. En el presente trabajo presentamos nuestra experiencia en mini-open anterior spine surgery (MOASS) en el abordaje anterior del raquis para tratamiento de patología del raquis toracolumbar. Material y métodos En el periodo entre enero de 2004 y julio de 2011 hemos realizado 74 abordajes anteriores de columna mediante cirugía abierta. En 38 casos utilizamos la técnica MOASS a distintos niveles: torácico, lumbar e infraumbilical extraperitoneal. Resultados No tuvimos mortalidad quirúrgica ni postoperatoria, ni déficits neurológicos añadidos derivados del acto quirúrgico, en ninguna de las técnicas (clásica versus MOASS). Las complicaciones fueron escasas y corregidas con el adecuado tratamiento. Conclusiones Mediante la técnica MOASS hemos realizado la corrección quirúrgica de lesiones vertebrales que pueden afectar al raquis toracolumbar, con resultados similares a los obtenidos mediante el abordaje clásico y ventajas reseñables (AU)

Introduction The anterior spine approach known as «mini-open» was introduced a few years ago for the surgical treatment of spine diseases. This approach allows the anterior, body and intervertebral disc structures to be exposed, as well as the anterior compression of the dural sac and the reconstruction and/or stabilisation of the levels of interest with an appropriate system. In the present article we present our experience in mini-open anterior spine surgery (MOASS) approach in the treatment of lumbar spine diseases. Material and methods We performed 74 anterior spine approaches using open surgery between the period January 2004 and July 2011. In 38 cases we used the MOASS technique at different levels: thoracic, lumbar, and infraumbilical extraperitoneal. Results There were no surgical or post-operative deaths, or further neurological deficits arising from the surgical procedure in any of the techniques (classic versus MOASS). The few complications were corrected with the appropriate treatment. Conclusions Using the MOASS technique we have performed corrective surgery on spine injuries that could affect the thoracic spinal column, with similar results to those obtained using the classic approach and with obvious advantages (AU)