Anatomical Risk Factors for Intraoperative Cerebrospinal Fluid Leaks During Transsphenoidal Surgery for Pituitary Adenomas.

BACKGROUND: Cerebrospinal fluid (CSF) fistulas are among the most clinically important and frequent complications of transsphenoidal surgery for pituitary adenomas. Between the adenoma and the CSF, a "barrier" exists that consists of ≤3 elements. These, from cephalad to caudad, are the arachnoid, dura mater (sellar diaphragm), and pituitary glandular tissue. The objective of the present study was to determine whether the presence or absence of any of these 3 anatomical elements would be associated with the development of an intraoperative CSF fistula. METHODS: From November 2016 to June 2018, 40 patients with pituitary adenomas underwent surgery, by transsphenoidal endonasal access, under a microscope. All procedures were filmed in 3 dimensions. The intraoperative findings and preoperative magnetic resonance images were analyzed and compared. The patients who had developed a fistula were compared against those who had not. RESULTS: In 20 patients, glandular tissue was identified between the tumor and subarachnoid space. In 13, dura mater was evident, and in 7, only the arachnoid was noted. An intraoperative CSF fistula occurred in 6 patients, all of whom had the arachnoid as the only barrier. The presence of a fistula was significantly more likely statistically for patients with an arachnoid-only barrier than for those with any other barrier composition (P < 0.001). CONCLUSIONS: The anatomical architecture forming the roof of the pituitary fossa is an important determinant of intraoperative CSF fistula risk. When the barrier consists of only the arachnoid, the risk will be significantly greater than when the barrier contains additional elements. Preoperative magnetic resonance imaging would be useful to determine the type of the existing barrier.

Macroprolactinoma appearing after resolution of hydrocephalus.

SUMMARY: The role of mechanical forces influencing the growth of a pituitary adenoma is poorly understood. In this paper we report the case of a young man with hyperprolactinaemia and an empty sella secondary to hydrocephalia, who developed a macroprolactinoma following the relief of high intraventricular pressure. LEARNING POINTS: The volume of a pituitary tumour may be influenced not only by molecular but also by local mechanical factors.Intratumoural pressure, resistance of the sellar diaphragm and intracranial liquid pressure may play a role in the final size of a pituitary adenoma.The presence of hydrocephalus may hide a pituitary macroadenoma.

Abordaje extremolateral transcondilar: práctica de laboratorio, técnica quirúrgica y reporte de casos / Far lateral transcondilar approach: laboratory practice, surgical technique and case reports

Objetivo: describir el abordaje extremo lateral y su uso en la resección tumoral de una lesión de clivus y en el clipado de un aneurisma vertebro-PICA derecho. Material y método: se estudió la región occipito-cervical de dos cabezas de cadáveres adultos (cuatro arterias vertebrales), fijadas en formol e inyectadas con silicona coloreada. Se revisaron las historias clínicas y el archivo de imágenes de dos pacientes, con patología tumoral y vascular respectivamente, evaluados y tratados en el Hospital de Clínicas ôJosé de San Martínö y en el ôCentro Médicoö de la Universidad de Nueva York, durante el año 2009. Descripción: se valoró el estudio anatómico de piezas cadavéricas del área occipitocervical en conjunto con las distintas estrategias de abordaje quirúrgico, describiendo tanto las estructuras anatómicas de interés, como las ventajas y desventajas de cada técnica. Conclusión: el abordaje extremo lateral es una herramienta efectiva para acceder a lesiones vasculares y neoplásicas del área anterolateral de la unión craneovertebral. Requiere una completa preparación prequirúrgica del paciente, un minucioso conocimiento anatómico de la región, el estricto monitoreo neurofisiológico y anestésico durante el acto quirúrgico y un oportuno examen y control postoperatorio que incluya la evaluación precoz del impacto sobre los pares bajos

Abordaje extremolateral transcondilar: práctica de laboratorio, técnica quirúrgica y reporte de casos / Far lateral transcondilar approach: laboratory practice, surgical technique and case reports

Objetivo: describir el abordaje extremo lateral y su uso en la resección tumoral de una lesión de clivus y en el clipado de un aneurisma vertebro-PICA derecho. Material y método: se estudió la región occipito-cervical de dos cabezas de cadáveres adultos (cuatro arterias vertebrales), fijadas en formol e inyectadas con silicona coloreada. Se revisaron las historias clínicas y el archivo de imágenes de dos pacientes, con patología tumoral y vascular respectivamente, evaluados y tratados en el Hospital de Clínicas “José de San Martín” y en el “Centro Médico” de la Universidad de Nueva York, durante el año 2009. Descripción: se valoró el estudio anatómico de piezas cadavéricas del área occipitocervical en conjunto con las distintas estrategias de abordaje quirúrgico, describiendo tanto las estructuras anatómicas de interés, como las ventajas y desventajas de cada técnica. Conclusión: el abordaje extremo lateral es una herramienta efectiva para acceder a lesiones vasculares y neoplásicas del área anterolateral de la unión craneovertebral. Requiere una completa preparación prequirúrgica del paciente, un minucioso conocimiento anatómico de la región, el estricto monitoreo neurofisiológico y anestésico durante el acto quirúrgico y un oportuno examen y control postoperatorio que incluya la evaluación precoz del impacto sobre los pares bajos

Schwannoma vestibular: abordaje y fresado del polo acústico / Vestibular schwanoma: surgical approaches & internal acoustic canal drilling

Objetivo: describir los abordajes al ángulo pontocerebeloso y los reparos anatómicos para el fresado del poro acústico. Descripción: el acceso a la región se puede llevar a cabo a través de un abordaje translaberíntico, retrosigmoideo o subtemporal. La decisión depende del examen clínico del paciente y sus estudios por imágenes. El fresado del poro acústico es utilizado para la remoción del componente intracanalicular del tumor y para la identificación y preservación del nervio facial. El bulbo yugular y el canalículo coclear por debajo, el seno petroso superior y la arteria subarcuata por arriba y los conductos semicirculares posterior, superior, la crus que los intersecta, el conducto endolinfático y el saco endolinfático hacia lateral son estructuras en estrecha relación anatómica con la región. El conocimiento de su localización es esencial para la preservación funcional del nervio facial y la audición. Conclusión: el conocimiento anatómico del área a fresar es elemental para alcanzar el resultado más cercano al standard contemporáneo de remoción total del tumor con preservación funcional del nervio facial y la audición, con la ayuda de una experimentada técnica microquirúrgica y monitoreo neurofisiológico intraoperatorio.

Exposure of the sciatic nerve in the gluteal region without sectioning the gluteus maximus: an anatomical and microsurgical study.

BACKGROUND: Complete sectioning of the gluteus maximus muscle is an extensive procedure when approaching the sciatic nerve in the buttock, resulting in significant morbidity and a prolonged postoperative recovery period. By contrast, dissecting through the muscle by splitting its fibers is faster, involves less damage to tissues and diminishes recovery time. The objective of the present work was to perform a cadaveric study to obtain measurements of the maximum, minimum and mean exposure that this minimally invasive approach can offer. METHODS: Both gluteal regions from each of ten fresh cadavers were dissected via a transgluteal approach, using a transverse curvilinear incision. After exposure of the sciatic nerve, the maximum length of exposed nerve was measured. As a final step, a 6 cm long sural graft reconstruction was performed, aided by a surgical microscope and microscopic techniques. FINDINGS: The mean sciatic nerve exposure obtained was 115.4 ± 17.9 mm, ranging from a maximum of 152 mm to a minimum of 90 mm. In all 20 cases, it was possible to perform microsurgical reconstruction under the microscope. We further illustrate these findings with three live patients in whom the transgluteal approach was employed to successfully expose and repair the sciatic nerve. CONCLUSIONS: The transgluteal approach is useful in the operative repair of lesions of the proximal sciatic nerve. It is a less invasive technique than classical complete sectioning of the gluteus maximus muscle, and yields better aesthetic results and a faster return to normal daily activities. Complex lesions, like nerve trauma requiring grafts and nerve tumours, can be treated with minimal risk. Nevertheless, it is less comfortable for the surgeon, and the entire extent of the exposed nerve might not be visualized simultaneously during surgery.

The transzygomatic approach.

We aim to describe the technical details of the transzygomatic approach to intracranial surgery. The incision begins at the level of the inferior border of the zygomatic arch, anterior to the tragus, and extends towards the contralateral pupillary line. A subgaleal and interfascial dissection is performed. Then, the zygomatic arch is vertically sectioned twice and mobilized downwards, together with the masseter muscle. Next, a fronto-temporo-sphenoidal craniotomy is performed and complete exposure of the anterior temporal dura achieved. Thus, the surgical possibilities are: (i) intradural access to the middle fossa; (ii) intradural pretemporal access to the basal cisterns; (iii) intradural transtemporal access to the insular region; and (iv) extradural access to the middle fossa. The transzygomatic approach offers excellent exposure to the floor of the middle fossa and the lateral wall of the cavernous sinus (both intradurally and extradurally). Also, combined with a pretemporal approach, it affords a good view of the interpeduncular cistern; and using a transtemporal approach, it provides good access to the insular region.

Serum insulin-like growth factor-1 measurement in the diagnosis and follow-up of patients with acromegaly: preliminary data.

Measurement of serum insulin-like growth factor-1 (IGF-I) is the current method for diagnosing and monitoring acromegaly. However, the use of commercially available kits needs to be validated. In our study, we have investigated the use of two different IGF-I immunoassays in patients already diagnosed with acromegaly. We compared a two-site immunoradiometric assay with ethanol-acid extraction (IRMA-DSL) and a solid-phase chemiluminescent immunometric assay (ICMA-IMMULITE), correlating the clinical finding with the biochemical results. A total of 102 samples (77 women and 25 men aged 18-79 years) were analyzed with the two different IGF-I assays. Sixty-four of samples had been taken from patients with acromegaly in different stages. Pearson regression showed a high correlation coefficient; otherwise, Bland and Altman analyses showed a mean difference of 177.6 ng/ml, with upper and lower limits of -183.5 and 538.7 ng/ml in the 102 samples studied. Normal serum IGF-I was found in 64 and 41.5% of patients with treated acromegaly when measured by ICMA and IRMA, respectively. In our study, IGF-I-ICMA had a better clinical correlation in patients with treated acromegaly. The reevaluation of current IGF-I immunoassays is necessary to correctly interpret treatment response in acromegalic patients and thus achieve a better correlation between clinical and biochemical results.

Neurofibromatosis type 2: molecular and clinical analyses in Argentine sporadic and familial cases.

Neurofibromatosis 2 is a familial syndrome characterized by the development of schwannomas, meningiomas and ependymomas. Most of them are benign however, their location in the nervous system has harmful effects on important cranial and spinal structures. These tumors are developed as the outcome of NF2 gene (22q12) inactivation. The NF2 protein, merlin or schwannomin belongs to the Ezrin, Radixin, Moesin (ERM) family involved in the cytoskeletal network and has a tumor suppressor function. Inactivating mutations occur as "de novo" (more frequently) or as inherited, and most of them are frameshift or nonsense. Our aim is to study NF2 gene alterations in Argentine patients and relate them to clinical features. 10 families and 29 single patients were analyzed for: 1) at-risk haplotype by STR-segregation analysis and 2) NF2 gene mutations by SSCP/heteroduplex/sequencing. The at-risk haplotype was uncovered in 8 families and mutations were identified in 5 patients. The molecular data are in full agreement with the clinical features supporting previous reports. The obtained results were important for the detection of mutation-carrying relatives and exclusion of other individuals from risk.

Gene expression profiling of the hedgehog signaling pathway in human meningiomas.

The Hedgehog (Hh) signaling pathway has an important role during embryogenesis and in adult life, regulating proliferation, angiogenesis, matrix remodeling and stem-cell renewal. Deregulation of the Hh pathway is involved in tumor development, since mutations in several components of this pathway were found in patients with basal cell carcinoma, medulloblastoma and other tumors; however, the role of Hh in meningiomas has not been studied yet. Meningiomas represent 30% of primary cranial tumors, are mostly benign and prevail in the second half of life. Novel therapies for meningiomas such as targeted molecular agents could use Hh pathway components. To provide information concerning molecular alterations, by use of real-time RT-PCR, we studied expression at the mRNA level of 32 Hh pathway and target genes in 36 meningioma specimens of different grades. mRNA levels of 16 genes, involved mainly in Hh pathway activation and cell proliferation, increased in meningiomas in comparison with normal tissue, whereas those of 7 genes, mainly related to Hh pathway repression, decreased. The most significant changes occurred in signal transduction (SMO) and GLI-transcription factor genes, and the target FOXM1 mRNA attained the highest values; their over-expression was found in aggressive and in benign tumors. Some proliferation-related genes (SPP1, IGF2) were overexpressed in higher meningioma grades. A correlation in expression between genes with a similar function was also found. Our results show a marked activation of the Hh pathway in meningiomas, which may be important for their biological and clinical characterization and would be useful for gene therapy.

Gene expression profiling of ErbB receptors and ligands in human meningiomas.

ErbB family receptors mediate major cellular functions implied in tumorigenesis, though their role in meningiomas was not thoroughly studied. Meningiomas represent 30% of primary cranial tumors, are mostly benign, and prevail in the second half of life. Tumor therapy requires information about molecular alterations, thus we studied expression of ErbB receptor and ligand genes by real-time RT-PCR in different meningioma grades. Receptors were overexpressed (ErbB1, ErbB2) or underexpressed (ErbB3, ErbB4). Ligands EGF, TGFA, AREG, DTR, BTD were underexpressed and the neuregulins were overexpressed or underexpressed. A strong ErbB1-ErbB2 correlation was found. These data might be useful for gene therapy.

T3 receptors in human pituitary tumors.

OBJECTIVE: The purpose of this work was to investigate the synthesis of T3 receptors in human tumors of the anterior pituitary gland, its relationship with the hormone synthesized and/or secreted by the tumor and the post-surgical evolution of the patient. METHODS: Patients were evaluated clinically and by magnetic nuclear resonance to classify the adenoma according to their size. Hormonal concentrations in sera were determined by radioimmunoassay. Immunohistochemistry of the pituitary hormones was performed in the tumors. Tumors were obtained at surgery and immediately frozen in ice, transported to the laboratory and stored at -70 degrees C. Reverse transcription was performed with purified RNA from the tumors. RESULTS: Out of 33 pituitary tumors, 29 had RNA for T3 receptors synthesis (88%). They were present in different histological specimens, the tumors were grades 1-4 according to their size, and there was no relationship between the size of the tumor and the presence of T3 receptor RNAs. The post-surgical evolution of the patient was mostly dependent on the size and not on the presence of T3 receptors. DISCUSSION: The presence of thyroid hormone receptors in pituitary tumors is in line with two important characteristics of these tumors: they are histologically benign and well differentiated.

Conceptos actuales en la cirugía de los nervios periféricos: ¿Cuándo se debe operar un nervio lesionado? / Current concepts in surgery of peripheral nerves: when to operate a damaged nerve?

OBJETIVO: Uno de los factores más importantes en cuanto al pronóstico de recuperación de una lesión de un nervio periférico es el momento en el cual es reparado. El objetivo de este artículo es hacer hincapié en las indicaciones reales de la cirugía del trauma a los nervios periféricos en los miembros. ESTUDIOS SELECCIONADOS: Son los citados en las referencias. SÍNTESIS DE LOS DATOS: Se analizan las clasificaciones actualmente empleadas, y se citan los diferentes mecanismos fisiopatológicos que provocan las lesiones. En base ellos, se establecen dos grandes grupos: lesiones cerradas y abiertas. Las primeras son las que generalmente requieren una conducta inicial expectante y una cirugía en diferido no antes de los tres meses de transcurrido el trauma. En cambio, las lesiones abiertas, cortantes o contuso-cortantes, se deben explorar en forma rápida para efectuar una reconstrucción cuando es factible, o limpiar y reparar los bordes del nervio seccionado cuando no es posible efectuar una reparación en forma directa. Las excepciones a estos principios de manejo, que son casos especiales, son citadas en este trabajo. CONCLUSIONES: La indicación precisa del momento adecuado para reparar un nervio lesionado se basa en algunos simples principios de clasificación y fisiopatología del trauma a los nervios periféricos.

OBJECTIVE: One of the most critical factors related to the neurological deficit associated with peripheral nerve lesions is surgical timing. The purpose of the present work in to determine actual indications of peripheral nerve trauma exploration and repair. SELECTED ARTICLES: Are quoted at references. OBTAINED DATA: Peripheral nerve lesions classification and physiopathology are throughoutly analyzed. Two groups of injuries were established: open and closed peripheral nerve trauma. In the latter, conservative inicial management and surgery y after three or more months is the rule. Meanwhile, open lesions preclude acute exploration and reparation of the nerve gap when a direct suture is possible. If not, reparation of the nerve endings and clening of the injury site should be done. Exceptions to this principles are mentioned.

Expression of p16(INK4A) gene in human pituitary tumours.

Pituitary adenomas comprise 10-15% of primary intracranial tumours but the mechanisms leading to tumour development are yet to be clearly established. The retinoblastoma pathway, which regulates the progression through the cell cycle, is often deregulated in different types of tumours. We studied the cyclin-dependent kinase inhibitor p16(INK4A) gene expression at mRNA level in human pituitary adenomas. Forty-six tumour specimens of different subtypes, 21 clinically non-functioning, 12 growth hormone-secreting, 6 prolactin-secreting, 6 adrenocorticotropin-secreting, and 1 thyrotropin-secreting tumours were studied. All clinically non-functioning and most of the hormone-secreting tumours were macroadenomas (38/46). The RT-PCR assay and electrophoresis of the PCR-products showed that p16(INK4A) mRNA was undetectable in: 62% of non-functioning, 8% of growth hormone-secreting, 17% of prolactin-secreting and 17% of adrenocorticotropin-secreting adenomas. Forty percent of all macroadenomas and 25% of microadenomas had negative p16(INK4A) mRNA, the latter results suggest that the absence of p16(INK4A) product might be an early event in tumours with no expression of this suppressor gene. Within the non-functioning adenomas 63% were "null cell" and 37% were positive for some hormone, both subgroups showed similar percentage of cases with absence of p16(INK4A) mRNA. Our results show that clinically non-functioning macroadenomas have impaired p16(INK4A) expression in a clearly higher proportion than any other pituitary tumour subtype investigated. Other regulatory pathways may be implicated in the development of tumours with positive p16(INK4A) expression.

Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.

CONTEXT: An association between germline aryl hydrocarbon receptor-interacting protein (AIP) gene mutations and pituitary adenomas was recently shown. OBJECTIVE: The objective of the study was to assess the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA). DESIGN: This was a multicenter, international, collaborative study. SETTING: The study was conducted in 34 university endocrinology and genetics departments in nine countries. PATIENTS: Affected members from each FIPA family were studied. Relatives of patients with AIP mutations underwent AIP sequence analysis. MAIN OUTCOME MEASURES: Presence/absence and description of AIP gene mutations were the main outcome measures. INTERVENTION: There was no intervention. RESULTS: Seventy-three FIPA families were identified, with 156 patients with pituitary adenomas; the FIPA cohort was evenly divided between families with homogeneous and heterogeneous tumor expression. Eleven FIPA families had 10 germline AIP mutations. Nine mutations, R16H, G47_R54del, Q142X, E174frameshift, Q217X, Q239X, K241E, R271W, and Q285frameshift, have not been described previously. Tumors were significantly larger (P = 0.0005) and diagnosed at a younger age (P = 0.0006) in AIP mutation-positive vs. mutation-negative subjects. Somatotropinomas predominated among FIPA families with AIP mutations, but mixed GH/prolactin-secreting tumors, prolactinomas, and nonsecreting adenomas were also noted. Approximately 85% of the FIPA cohort and 50% of those with familial somatotropinomas were negative for AIP mutations. CONCLUSIONS: AIP mutations, of which nine new mutations have been described here, occur in approximately 15% of FIPA families. Although pituitary tumors occurring in association with AIP mutations are predominantly somatotropinomas, other tumor types are also seen. Further study of the impact of AIP mutations on protein expression and activity is necessary to elucidate their role in pituitary tumorigenesis in FIPA.