Clinical application of the "sellar barrier's concept" for predicting intraoperative CSF leak in endoscopic endonasal surgery for pituitary adenomas with a machine learning analysis.

Background: Recently, it was defined that the sellar barrier entity could be identified as a predictor of cerebrospinal fluid (CSF) intraoperative leakage. The aim of this study is to validate the application of the sellar barrier concept for predicting intraoperative CSF leak in endoscopic endonasal surgery for pituitary adenomas with a machine learning approach. Methods: We conducted a prospective cohort study, from June 2019 to September 2020: data from 155 patients with pituitary subdiaphragmatic adenoma operated through endoscopic approach at the Division of Neurosurgery, Università degli Studi di Napoli "Federico II," were included. Preoperative magnetic resonance images (MRI) and intraoperative findings were analyzed. After processing patient data, the experiment was conducted as a novelty detection problem, splitting outliers (i.e., patients with intraoperative fistula, n = 11/155) and inliers into separate datasets, the latter further separated into training (n = 115/144) and inlier test (n = 29/144) datasets. The machine learning analysis was performed using different novelty detection algorithms [isolation forest, local outlier factor, one-class support vector machine (oSVM)], whose performance was assessed separately and as an ensemble on the inlier and outlier test sets. Results: According to the type of sellar barrier, patients were classified into two groups, i.e., strong and weak barrier; a third category of mixed barrier was defined when a case was neither weak nor strong. Significant differences between the three datasets were found for Knosp classification score (p = 0.0015), MRI barrier: strong (p = 1.405 × 10-6), MRI barrier: weak (p = 4.487 × 10-8), intraoperative barrier: strong (p = 2.788 × 10-7), and intraoperative barrier: weak (p = 2.191 × 10-10). We recorded 11 cases of intraoperative leakage that occurred in the majority of patients presenting a weak sellar barrier (p = 4.487 × 10-8) at preoperative MRI. Accuracy, sensitivity, and specificity for outlier detection were 0.70, 0.64, and 0.72 for IF; 0.85, 0.45, and 1.00 for LOF; 0.83, 0.64, and 0.90 for oSVM; and 0.83, 0.55, and 0.93 for the ensemble, respectively. Conclusions: There is a true correlation between the type of sellar barrier at MRI and its in vivo features as observed during endoscopic endonasal surgery. The novelty detection models highlighted differences between patients who developed an intraoperative CSF leak and those who did not.

Posterior fossa endoscopic-assisted surgery: A systematization of its surgical corridors.

INTRODUCTION: The use of endoscopic-assisted techniques in neurosurgery has been implemented to improve better visualization and predict extent of resection. We aim to systematize the posterior fossa surgical regions and the endoscopic surgical corridors providing a quick reference of the anatomy and surgical nuances. METHODS: A retrospective review of patients undergoing endoscopic-assisted surgery of the posterior fossa at a single institution between 2019 and 2020 was conducted along with a description of the microsurgical anatomy from cadaveric specimens and surgical cases. RESULTS: The posterior fossa was segmented into three topographic regions, (upper, middle and lower), with three surgical corridors within each of these. Upper region is accessed through a supracerebellar infratentorial approach and comprises the pineal and pericuadrigeminal region constituted by the median corridor, the lateral corridor, and the extreme lateral corridor. Middle region is accessed through a retrosigmoid approach and comprises the cerebellopontine angle region constituted by the supralateral corridor containing the upper neurovascular complex (NVC), the median corridor containing the median NVC, and the infralateral corridor containing the lower NVC. The lower region is accessed through a far-lateral approach and contains the craniocervical junction region constituted by the upper corridor in between the VII-VIII and IX cranial nerves (CNs), the median corridor between the X and XI CNs, and the lower corridor between the cranial and spinal rootlets of the XI CN. CONCLUSION: We propose a simple and concise systematization, dividing the area into three regions with predefined corridors.

[Pituitary carcinoma: is it too late?] / Carcinoma pituitario: es demasiado tarde?

TITLE: Carcinoma pituitario: es demasiado tarde?

[Tumor-to-tumor: a wolf in sheep's clothing]. / Tumor-to-tumor: un lobo disfrazado de cordero.

TITLE: Tumor-to-tumor: un lobo disfrazado de cordero.

Bilateral synovial cyst of the thoracic spine causing paraparesis.

Spinal synovial cysts are degenerative extradural lesions mostly found in the lumbar region, and more rarely at cervical or thoracic levels and in a bilateral presentation. We report a patient with a history of progressive paraparesis associated with bilateral cervicothoracic synovial cysts, causing spinal canal narrowing and cord compression, ultimately resulting in myelopathy. A review of the literature summarizes previous reports on this topic. Surgical excision of the extradural mass, decompression of the spinal canal and instrumented fusion were performed, improving lower limb deficit and gait. Post-surgical MRI showed evidence of complete cyst resection, and good arthrodesis consolidation with adequate sagittal balance. Surgical excision is indicated in case of medical treatment failure or increasing symptom severity. Given the strong pathophysiological link between synovial cysts and spinal instability, concomitant instrumented fusion may help improve outcome.

Adenomas no funcionantes: análisis retrospectivo de 202 pacientes / Non-functional adenomas: retrospective analysis of 202 patients

RESUMEN Los pacientes con adenomas hipofisarios constituyen una población heterogénea y requieren un enfoque individualizado. El objetivo de nuestro trabajo fue analizar nuestra población con adenomas hipofisarios no funcionantes (ACNF) y evaluar factores pronóstico de crecimiento (como el Ki-67) que ayuden en la toma de decisiones. Se realizó un análisis retrospectivo de 202 pacientes, incluyendo evaluación basal, enfoque terapéutico y evolución tumoral en 2 grupos: pacientes con conducta expectante (n = 69) y pacientes con cirugía (n = 133). La serie tuvo 55% de pacientes mujeres y la edad media al diagnóstico fue de 49 años. Los motivos de consulta más frecuentes fueron incidentaloma hipofisario y alteraciones visuales. Radiológicamente, 83% fueron macroadenomas, 77% invasivos y 55% mostraron compromiso visual. Entre los adenomas invasores, el 53% tenían disfunción hipofisaria, siendo el hipogonadismo el hallazgo más frecuente. El tratamiento inicial fue la cirugía en el 65,8% realizándose por vía transnasal en el 79% de los casos. Las complicaciones más frecuentes fueron diabetes insípida transitoria e hiponatremia, con mayor incidencia de diabetes insípida permanente en la cirugía transcraneal. La inmunohistoquímica mostró gonatropinomas en el 43,4% de los casos y fue negativa en el 37,7%. Doce adenomas tuvieron índice de proliferación Ki-67 ≥3%. Luego de la cirugía 56,8% de los pacientes mejoraron el campo visual, 22,6% recuperó alguna función endocrina y 18,8% agregó un nuevo déficit. En pacientes no operados, se observó crecimiento tumoral en 5,6% de los adenomas Hardy 1-2 y en el 21% de los Hardy 3-4. Entre los adenomas operados, aquellos sin resto tumoral postoperatorio no presentaron recurrencia. De los tumores con remanente postoperatorio (78,6%) no irradiados, el 41,5% mostró recrecimiento lesional al seguimiento. Este porcentaje se eleva a 66,6% en aquellos con Ki-67 ≥3% y disminuye a 12% en los que recibieron radioterapia.

ABSTRACT Patients with pituitary adenomas are a heterogeneous population and require an individualized approach. The aim of our study was to analyze our population of patients with nonfunctioning pituitary adenomas (NFA) and to evaluate prognostic growth factors (such as Ki-67) that help in decision making. A retrospective analysis of 202 patients, including baseline assessment, therapeutic approach and tumor evolution was performed in 2 groups: expectant management (n = 69) and surgery (n = 133). The mean age at diagnosis was 49 years, 55% women. The most frequent reasons for consultation were pituitary incidentaloma and visual impairment. Eighty three percent were macroadenomas, 77% invasive, and 55% with visual impairment. Among the invasive adenomas, 53% had pituitary dysfunction, with hypogonadism being the most frequent finding. The initial treatment was surgery in 65.8%, 79% of them through transnasal approach. The most frequent complications were transient diabetes insipidus and hyponatremia, with a higher incidence of permanent diabetes insipidus in transcranial surgery. The immunohistochemistry showed: 43.4% gonadotropinomas, 37.7% negative. Twelve adenomas had proliferation index Ki-67 ≥3%. After surgery, 56.8% improved the visual fields, 22.6% recovered some endocrine function and 18.8% added a new deficit. In non-operated patients, tumor growth was observed in 5.6% of the Hardy 1-2 adenomas and 21% of the Hardy 3-4 adenomas. Among the operated adenomas, those without postoperative tumor residue did not present recurrence. In tumors with non-irradiated postoperative remnant (78.6%), 41.5% increased. This percentage rises to 66.6% in those with Ki-67 ≥3%, and decreases to 12% in those who received radiotherapy.

Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity.

Increased levels of the proto-oncogene pituitary tumor-transforming gene 1 (PTTG) have been repeatedly reported in several human solid tumors, especially in endocrine-related tumors such as pituitary adenomas. Securin PTTG has a critical role in pituitary tumorigenesis. However, the cause of upregulation has not been found yet, despite analyses made at the gene, promoter and mRNA level that show that no mutations, epigenetic modifications or other mechanisms that deregulate its expression may explain its overexpression and action as an oncogene. We describe that high PTTG protein levels are induced by the RWD-containing sumoylation enhancer (RWDD3 or RSUME), a protein originally identified in the same pituitary tumor cell line in which PTTG was also cloned. We demonstrate that PTTG and RSUME have a positive expression correlation in human pituitary adenomas. RSUME increases PTTG protein in pituitary tumor cell lines, prolongs the half-life of PTTG protein and regulates the PTTG induction by estradiol. As a consequence, RSUME enhances PTTG transcription factor and securin activities. PTTG hyperactivity on the cell cycle resulted in recurrent and unequal divisions without cytokinesis, and the consequential appearance of aneuploidies and multinucleated cells in the tumor. RSUME knockdown diminishes securin PTTG and reduces its tumorigenic potential in a xenograft mouse model. Taken together, our findings show that PTTG high protein steady state levels account for PTTG tumor abundance and demonstrate a critical role of RSUME in this process in pituitary tumor cells.

Surgical treatment of cerebellar hemangioblastomas.

BACKGROUND: Hemangioblastomas (HBL) are uncommon tumors of the central nervous system (CNS), corresponding to 1-2.5% of all intracranial tumors. They can present sporadically or in patients with von Hippel-Lindau (VHL) disease and are most often located in the cerebellum, brainstem, and spinal cord. VHL disease is a multiple neoplasia syndrome inherited in an autosomal dominant fashion and caused by a VHL suppressor gene deletion. We present our experience in the management of patients with cerebellar HBL. METHODS: Thirty consecutive patients with cerebellar HBL were included in this study. Hospital charts, radiological images, and operative records were reviewed. Modified Rankin scores were used to evaluate the clinical course. RESULTS: Thirty patients diagnosed with cerebellar HBL were operated. Complete total resection was achieved in 93% of the cases. Postoperatively, 83% of the patients showed good functional recovery. CONCLUSIONS: HBL of the cerebellum should be resected when symptomatic or when the tumor (or a tumor-associated cyst) shows signs of enlargement. Surgical intent should seek en bloc resection to minimize intraoperative bleeding. Patients with HBLs must be tested for VHL gene mutations, and in confirmed cases, relatives should be offered genetic counseling.

[Supratentorial cavernous malformations in an Argentinian institution: experience with surgical treatment]. / Malformaciones cavernosas supratentoriales en una institucion argentina: experiencia del tratamiento quirurgico.

INTRODUCTION: Cavernous malformations are vascular malformations of the central nervous system formed by a group of capillaries not covered by pia mater and communicated to the vascular system at very low pressure with very slow flow. Surgery or radiosurgery are the treatment modalities. AIMS: To analyze our results after surgical treatment of supratentorial cavernous malformations, reviewing clinical presentation, surgical indications and postoperative complications. PATIENTS AND METHODS: Analytical retrospective study of medical records and images of patients who underwent resection of supratentorial cavernomas at FLENI from January 1996 until December 2013. RESULTS: We evaluated 51 patients, mean age 34 years, followed for an average of 30 months. In 1.96% of patients diagnosis was incidental, the rest all presented symptoms. Bleeding at diagnosis was observed in 23.52%. Total excision of supratentorial cavernous malformations was possible in all cases. The only postoperative complication was one case of meningitis. CONCLUSIONS: The bleeding rate of supratentorial cavernous malformations in our series was 1.38% per patient per year. Surgical treatment effectively eliminated, or at least reduced symptoms, prevented rebleeding, and decreased need for antiepileptic drug therapy. Surgery have a low complication rate and good outcome.

TITLE: Malformaciones cavernosas supratentoriales en una institucion argentina: experiencia del tratamiento quirurgico.Introduccion. Las malformaciones cavernosas son lesiones vasculares del sistema nervioso central constituidas por endotelio sinusoidal que forma capilares agrupados o cavernas que carecen de los elementos tipicos de una pared arterial madura y ausencia de tejido neural interpuesto. El endotelio esta rodeado por una densa capa de fibras colagenas que dejan pequeñas hendiduras por las que se extravasa hemosiderina. Se comunican con el sistema vascular a muy baja presion y su tratamiento puede ser por microcirugia o radiocirugia. Objetivos. Analizar las malformaciones cavernosas supratentoriales tratadas quirurgicamente en nuestra institucion (FLENI), determinar la epidemiologia y las caracteristicas intrinsecas, estudiar la clinica de presentacion, determinar las indicaciones quirurgicas y complicaciones, y establecer el pronostico. Pacientes y metodos. Estudio retrospectivo analitico de historias clinicas e imagenes de pacientes operados de malformaciones cavernosas supratentoriales en la FLENI desde enero de 1996 hasta diciembre de 2013. Resultados. Evaluamos a 51 pacientes, de 34 años de media, seguidos durante una media de 30 meses. El 1,96% de los pacientes presento diagnostico incidental y el resto mostro sintomas. El 23,52% presento hemorragia en el momento del diagnostico. En todas las cirugias se logro una exeresis total de las malformaciones cavernosas supratentoriales. Se observo un caso de meningitis postoperatoria. Conclusiones. La tasa de sangrado de las malformaciones cavernosas supratentoriales en nuestro medio es del 1,38% por paciente por año. El tratamiento quirurgico es eficaz para erradicar o disminuir los sintomas y para evitar un posible resangrado. Presenta una tasa muy baja de complicaciones y un pronostico neurologico favorable.

Bone metastases from secondary glioblastoma multiforme: a case report.

Extraneural metastases of glioblastoma multiforme (GBM) are a relatively rare occurrence which usually manifest after de novo GBM. We report a case of a patient with an oligodendroastrocytoma who developed over a period of 12 years malignant progression to glioblastoma followed by multiple cytologically confirmed bone metastases. No 1p deletions were detected in the original tumour. GBM cells disclosed the EGFr(+) and p53(-) immunophenotype more characteristic of a primary GBM.

Subarachnoid fat dissemination after resection of a cerebellopontine angle dysontogenic cyst: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: This case report illustrates the clinical and radiological relevance of extensive intracranial subarachnoid and ventricular dissemination in dysontogenic (dermoid) tumors. CLINICAL PRESENTATION: We describe a patient with a cerebellopontine angle dysontogenic tumor. Postoperatively, the cyst disseminated fat particles extensively into the subarachnoid space. Magnetic resonance imaging (MRI) studies revealed continuous dispersion of the fat particles into the cerebral cisterns, subarachnoid space, and ventricles. INTERVENTION: Eight years of clinical and MRI follow-up demonstrated neither neurological deterioration in the patient nor growth of the multiple lesions. CONCLUSION: Intracranial subarachnoid dissemination of fat material may occur during the preoperative or postoperative course of dermoid and epidermoid cysts. Aseptic meningitis or other complications such as hydrocephalus, seizures, or cranial nerve deficits also may occur owing to spillage of intracranial cyst contents into the subarachnoid space. MRI can detect the presence of fat drops that may adhere to the surrounding structures or migrate with the cerebrospinal fluid flow. Intracranial disseminated fat particles can remain silent without radiological or neurological change, justifying a wait-and-see approach. During long-term postoperative follow-up, however, regular MRI studies and clinical examinations are necessary to avoid potential complications.

Use of antiepileptic drugs in nontraumatic neurosurgical procedures. Is there any best route and time of administration?

We assessed in 15 consecutive patients the best route and time of administration for phenytoin (PHT) prophylaxis in neurosurgical procedures. We also correlated PHT levels in serum and cerebrospinal fluid after oral and parenteral loading doses. The mean PHT level was 13.9 micrograms/ml in serum and 2.03 micrograms/ml in cerebrospinal fluid (CSF), with a significant correlation between levels in both compartments (r = 0.73, p < 0.01). Mean PHT levels among the different groups were not statistically significant. We conclude that therapeutic levels of PHT in CSF can be achieved independently of the route of administration, as long as accepted loading doses are used.