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.

Topical hemostatic agents in neurosurgery, a comprehensive review: 15 years update.

Hemostasis in neurosurgery is of utmost importance. Bleeding management is one of the crucial steps of each neurosurgical procedure. Several strategies, namely thermal, mechanical, electric, and chemical, have been advocated to face blood loss within the surgical field. Over time, countless hemostatic agents and devices have been proposed. Furthermore, the ever-growing recent technological innovation has made available several novel and interesting tools. Pursuant to their impact on surgical practice, we perceived the imperative to update our previous disclosure paper. Therefore, we reviewed the literature and analyzed technical data sheets of each product in order to provide an updated and comprehensive overview in regard to chemical properties, mechanisms of action, use, complications, tricks, and pitfalls of topical hemostatic agents.

Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature.

BACKGROUND: Endocrine neoplasms are generally slow-growing tumors that can show hormonal activity and give metastases. In most cases they are benign and clearly malignant forms are easy to diagnose. However, borderline forms may occur and be, for the pathologists, very difficult to classify. In these cases, there is a strong need to identify factors that may aid. Official classification systems for endocrine neoplasms are based on the evaluation of proliferation and, in most cases, they rely on mitotic count. In support, the study of Ki67 is carried out which, however, has not yet been included in any official classification system, except for neuroendocrine neoplasms of the gastro-entero-pancreatic tract. PURPOSE: The aim of the present study was to investigate the proven or unproven role of Ki67 in endocrine neoplasms, in different districts, in order to bring to light the substantial differences, in terms of proliferation, existing between neoplasms so similar, but at the same time, so different. METHODS: A thorough search of English language literature was performed, looking for articles concerning Ki67 in five endocrine neoplasms (pituitary adenomas, thyroid neoplasms, adrenocortical neoplasms, pheochromocytomas and paragangliomas). RESULTS: From 2170, 236 articles were selected and it was seen that the endocrine neoplasm in which Ki67 was most studied was the pituitary, where it still shows a controversial role. In other neoplasms different roles were identified. CONCLUSION: The pathologist should be aware of the contribution that this proliferative marker can give to the diagnosis and, sometimes, to the therapy selection, for the clinician.

The ventral route to intracranial aneurysm: from the origin towards modern transsphenoidal surgery. An historical review and current perspective.

OBJECTIVE: A review of the main studies that have explored the use of the ventral pathway for treatment of intracranial aneurysms,including the recent reported extended transsphenoidal approaches. METHODS: A comprehensive literature review was performed using the PubMed database. We recovered 48 cases of cerebral aneurysms, approached via the transcervical-transclival, transoral-transclival, transfacial-transclival ventral pathways and the extended transsphenoidal route. The overall rates of complications and surgical success were evaluated and compared for both traditional ventral and transsphenoidal approaches. RESULTS: For traditional routes, the overall complications and surgical success rates were 74% (26/35) and 87% (13115), respectively.For extended transsphenoidal approaches were 44% (4/9) and 78% (7 /9), respectively. CONCLUSION: Our paper is a reconnaissance of what has been done via "the anterior route" and a notification of the existence of this "surgical window': Present and future of cerebral aneurysm treatment is represented by the endovascular technique. A few selected cases in specialized centers, where transsphenoidal approaches with the aid of the endoscope are routinely performed,may be treated with such techniques alone or in combination with other different procedures. Further studies in large numbers of patients will be required to validate the full benefit of this approach.

Advances in trans-sphenoidal pituitary surgery.

Pituitary surgery is a continuous evolving speciality of the neurosurgeons' armamentarium, requiring precise anatomical knowledge, technical skills and integrated appreciation of the pituitary pathophysiology. Actually, it could be considered the result of a close cooperation between different specialists, i.e. the ophthalmologist, the neuroradiologist, the endocrinologist, the neurosurgeon, the pathologist, etc. In this teamwork environment each member plays his own role, offering his contribute to the final result; every effort is performed to provide patients with the best possible procedure, individually measured. The endoscopic pituitary surgery performed by means of a transsphenoidal approach perfectly fits this scenario, being though advocated as the result of an evolutionary process rather than a revolutionary one. The "pure" endoscopic transsphenoidal surgery - consisting of a whole procedure performed with the endoscope alone and without the use of any transsphenoidal retractor - offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy, very important at the tumor/gland interface and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease and complication rate are similar to those reported in the major microsurgical series but patient compliance is by far better.

Extended endoscopic endonasal approach to the midline skull base: the evolving role of transsphenoidal surgery.

The evolution of the endoscopic endonasal transsphenoidal technique, which was initially reserved only for sellar lesions through the sphenoid sinus cavity, has lead in the last decades to a progressive possibility to access the skull base from the nose. This route allows midline access and visibility to the suprasellar, retrosellar and parasellar space while obviating brain retraction, and makes possible to treat transsphenoidally a variety of relatively small midline skull base and parasellar lesions traditionally approached transcranially. We report our current knowledge of the endoscopic anatomy of the midline skull base as seen from the endonasal perspective, in order to describe the surgical path and structures whose knowledge is useful during the operation. Besides, we describe the step-by-step surgical technique to access the different compartments, the "dangerous landmarks" to avoid in order to minimize the risks of complications and how to manage them, and our paradigm and techniques for dural and bony reconstruction. Furthermore, we report a brief description of the useful instruments and tools for the extended endoscopic approaches. Between January 2004 and April 2006 we performed 33 extended endonasal approaches for lesions arising from or involving the sellar region and the surrounding areas. The most representative pathologies of this series were the ten cranioparvngiomas, the six giant adenomas and the five meningiomas; we also used this procedure in three cases of chordomas, three of Rathke's cleft cysts and three of meningo-encephaloceles, one case of optic nerve glioma, one olfactory groove neuroendocrine tumor and one case of fibro-osseous dysplasia. Tumor removal, as assessed by post-operative MRI, revealed complete removal of the lesion in 2/6 pituitary adenomas, 7/10 craniopharyngiomas, 4/5 meningiomas, 3/3 Rathke's cleft cyst, 3/3 meningo-encephalocele. Surgical complications have been observed in 3 patients, two with a craniopharyngioma, one with a clival meningioma and one with a recurrent giant pituitary macroadenoma involving the entire left cavernous sinus, who developed a CSF leak and a second operation was necessary in order to review the cranial base reconstruction and seal the leak. One of them developed a bacterial meningitis, which resolved after a cycle of intravenous antibiotic therapy with no permanent neurological deficits. One patient with an intra-suprasellar non-functioning adenoma presented with a generalized epileptic seizure a few hours after the surgical procedure, due to the intraoperative massive CSF loss and consequent presence of intracranial air. We registered one surgical mortality. In three cases of craniopharyngioma and in one case of meningioma a new permanent diabetes insipidus was observed. One patient developed a sphenoid sinus mycosis, cured with antimycotic therapy. Epistaxis and airway difficulties were never observed. It is difficult todav to define the boundaries and the future limits of the extended approaches because the work is still in progress. Such extended endoscopic approaches, although at a first glance might be considered something that everyone can do, require an advanced and specialized training.

Remifentanil-TCI and propofol-TCI for conscious sedation during fibreoptic intubation in the acromegalic patient.

BACKGROUND AND OBJECTIVE: To evaluate the use of remifentanil-propofol administered as target-controlled infusion during awake fibreoptic intubation for anticipated difficult tracheal intubation in acromegalic patients. METHOD: In all, 20 consecutive acromegalic patients underwent elective endonasal endoscopic transsphenoidal pituitary surgery. After premedication with midazolam 0.03 mg kg(-1), initially a target-controlled infusion of remifentanil 1.0 ng mL(-1) and propofol 1.5 microg mL(-1) was started. The fibreoptic intubation was performed by the same physician experienced with the fibreoptic technique. During the fibreoptic procedure the target concentrations of remifentanil and propofol ranged between 1.0 and 5.0 ng mL(-1), and between 1.5 and 3.5 microg mL(-1), respectively. Changes in heart rate and mean arterial pressure were recorded during airway manipulation, during tracheal intubation, and at 1 and 3 min after. On the first postoperative day, patient recall and level of discomfort during fibreoptic intubation were evaluated. RESULTS: Endotracheal intubation was efficaciously and quickly secured in all patients. A significant increase in mean arterial pressure and heart rate was recorded only during tracheal intubation (P < 0.05). Oxygenation was sufficient and no bradypnea or apnoea was recorded. All patients later described their anaesthetic experience as satisfactory. During fibreoptic intubation, remifentanil (ng mL(-1)) and propofol (microg mL(-1)) mean effect-site concentrations were 3.2 +/- 0.3 and 2.0 +/- 1.0, respectively. CONCLUSION: Remifentanil and propofol target-controlled infusion provided satisfactory conscious sedation allowing for successful oral fibreoptic intubation in acromegalic patients with no recall.

The endoscopic endonasal trans-sphenoidal approach to the sellar and suprasellar area. Anatomic study.

AIM: The microscopic trans-sphenoidal approach has been the treatment of choice of different sellar lesions over the last thirty years. However, due to several advantages brought by the endoscope, which provides a panoramic and close up view of all the anatomic landmarks either in the sphenoid sinus and in the sellar region, an increasing interest for the trans-sphenoidal approach to the sellar and suprasellar region is being noticed in the recent past years. Since the endoscopic approach drives the surgeon through a corridor whose walls were previously hidden by the nasal speculum, the precise knowledge of the endoscopic anatomy and the anatomical landmarks of the surgical approach are essential to better explore the mentioned advantages. METHODS: The endoscopic endonasal approach to the sellar region was performed in 40 adult fresh cadavers, with the aim of describing the anatomical landmarks for a safe realization of the surgical approach. RESULTS: The anatomic features and the variations of the sphenoid ostia, sphenoid sinus and septae, sella turcica, optic and carotid protuberances and their relationships have been described, as well as supra and parasellar neurovascular structures. CONCLUSION: The endoscopic endonasal trans-sphenoidal approach provides a straight approach to the sellar region, where it offers a multiangled and close-up view of all the relevant neurovascular structures.

The extended endoscopic endonasal approach to the clivus and cranio-vertebral junction: anatomical study.

OBJECT: Lesions located in the retroclival area and at the level of the cranio-vertebral junction are typically approached through a variety of anterior, antero-lateral and postero-lateral skull-based approach, either alone or in combination. The aim of this anatomical study was to demonstrate the possibility of an endoscopic endonasal approach to the clivus and cranio-vertebral junction. MATERIALS AND METHODS: Five fresh cadaver heads injected with colored latex were used. A modified endonasal endoscopic approach was made through two nostrils in all cases. Endoscopic dissections were performed using rigid endoscopes, 4 mm in diameter, 18 cm in length, with 0 degrees lenses. RESULTS: Access to the clivus was possible using a lower trajectory when compared to that necessary for the sellar region. The sphenoid sinus is entered, and its inferior wall is completely removed, permitting the union of the sphenoidal and rhinopharyngeal parts of the clivus. The entire clivus can be removed, and the cranio-vertebral junction is opened, removing the anterior arch of atlas and the odontoid process. After the opening of the dura, the anterior surface of the pons and upper spinal cord with corresponding nerves and vasculature are visible. CONCLUSION: The endoscopic endonasal approach to the clivus and cranio-vertebral junction could be a valid alternative for surgical treatment of anterior lesions of these regions. Adequate endoscopic skill, lab training on cadavers and dedicated tools are required for clinical applications of the approach.

Clinical comparison of remifentanil-sevoflurane vs. remifentanil-propofol for endoscopic endonasal transphenoidal surgery.

BACKGROUND: Endoscopic endonasal transphenoidal surgery has been recently proposed as a minimally invasive procedure for the treatment of pituitary adenomas. The main objective of the anaesthesiologist is to induce sufficient haemodynamic control together with rapid recovery at the end of surgery. The aim of this study was to examine recovery profile, surgical operative conditions and haemodynamic differences using remifentanil infusion with either propofol target controlled infusion system or sevoflurane. METHOD: Forty-four adult patients were enrolled in a prospective, randomized, single-blind, two-group study: Group P received propofol target controlled infusion system and remifentanil; Group S received sevoflurane and remifentanil for maintenance of anaesthesia. RESULTS: No statistically significant differences between the two groups with regards to the haemodynamic changes, operative conditions as assessed by a four-step bleeding score (0-3), were obtained. Recovery times were considerably shorter after remifentanil-sevoflurane in comparison with remifentanil-propofol target controlled infusion system group (7.4 vs. 12.8 min, P < 0.01). CONCLUSION: This study demonstrates that sevoflurane-remifentanil gives a faster recovery and equivalent intraoperative status compared with propofol target controlled infusion system with remifentanil for the endoscopic endonasal transphenoidal approach.

B-RAF mutations are a rare event in pituitary adenomas.

Pituitary tumors are a relatively common neoplasia whose pathogenesis is still largely unknown. Recent studies have revealed frequent activating mutations of the gene for B-RAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies, including melanoma, thyroid, colorectal and ovarian cancer. However, analyses of B-RAF mutations in pituitary tumors have not been reported so far. Therefore, in the present study we have investigated the presence of the B-RAF mutations, by polymerase chain reaction (PCR) amplification of the hot spot exons 11 and 15, followed by direct sequencing, in 50 human pituitary adenomas, including 25 NFPA and 25 secreting adenomas (10 GH, 5 PRL, 6 LH and/or FSH, 4 GH/PRL). We found only one V600E mutation in a NFPA sample, suggesting that B-RAF mutations are a rare event in pituitary tumorigenesis.

Ectopic suprasellar pituitary adenoma. A case report.

The occurrence of a pituitary adenoma located entirely outside the sella turcica, so-called ectopic adenoma, is extremely rare. We report a case of a non secreting-pituitary adenoma located above the diaphragma sellae, with no invasion into the sella turcica, confirmed at surgery. The tumor was initially treated unsuccessfully by operations via the transphenoidal route. After initial negative exploration by the transphenoidal route, the patient was successfully treated by an endoscopic endonasal transphenoidal approach extended to the tuberculum sellae and the posterior planum sphenoidale to access the suprasellar supraglandular region. A brief review of ectopic adenomas and a discussion of the preoperative diagnosis are presented.

Arachnoid cyst with intracystic haemorrhage and subdural haematoma: case report and literature review.

Arachnoid cysts (AC) are usually asymptomatic. However, very rarely they can become symptomatic due to cyst enlargement or haemorrhage, often after head trauma. In such cases bleeding is often confined to the subdural space, but intracystic haemorrhage has rarely been observed. We report a case of a child who had intracranial hypertension syndrome due to a right middle cranial fossa AC with intracystic bleeding and subdural haematoma.

Simultaneous presentation of meningiomas with other intracranial tumours.

Fifteen patients with simultaneous presentation of meningiomas with other intracranial tumours are reviewed. The associated tumours included a brain metastasis in six cases, glioma in three, pituitary adenoma in two, craniopharyngioma in one,acoustic schwannoma in two and brain lymphoma in one. A correct preoperative radiological diagnosis was made in 12 patients; in three others the associated tumour was discovered at operation and by histological studies. A one-stage removal of both tumours through the same approach was performed in nine patients, whereas six others underwent two-stage operations with an interval of 1 - 13 months. The literature relating to meningiomas associated with other intracranial tumours is reviewed and the possible pathogenetic correlations are discussed. A diagnostic pitfall may occur for metastasis into a meningioma, glioma surrounding a meningioma and different suprasellar lesions. The surgical indication and management of meningiomas may be significantly influenced by the presence of another different intracranial tumour.

Endoscopic endonasal transsphenoidal removal of an intra-suprasellar schwannoma mimicking a pituitary adenoma.

Intracranial schwannomas, accounting for 8 to 10 % of all primary brain neoplasms, are relatively frequent intracranial tumors, but a "pure" intrasellar localization is exceptional. We report the case of an intra-suprasellar schwannoma mimicking a non-functioning pituitary macroadenoma both radiographically and clinically. A 73-year-old man presented with an episode of lipothymia followed by episodes of mental confusion. The neurological investigations revealed a bitemporal hemianopia and a hypopituitaric status. The neuroradiological investigations showed an intra-suprasellar mass resembling a pituitary adenoma. The patient underwent surgery performed by means of an endoscopic endonasal transsphenoidal approach, with a subtotal excision of the tumor. The histopathological studies revealed a cellular schwannoma. The review of the literature disclosed another 8 cases of intrasellar schwannomas. The possibility of an intrasellar schwannoma has to be considered in the differential diagnoses of neoplastic and non-neoplastic lesions of the sellar area.

Hemorrhagic vascular complications of endoscopic transsphenoidal surgery.

Two hundred and fifty consecutive patients operated on by an endoscopic endonasal transsphenoidal approach were retrospectively analyzed in order to evaluate hemorrhagic vascular complications occurring during or after the surgical procedure and their appropriate management. Vascular complications of endoscopic transsphenoidal surgery are identical to those of a microsurgical transsphenoidal approach. Damage to the sphenopalatine artery and to the internal carotid artery (ICA), which are the most frequent vascular troubles, may require technical tricks because of some aspects connected to the approach itself and of the physical properties of the endoscope. Furthermore, the progress in interventional neuroradiology in the last decades offers new solutions in respect to the past, where the use of the surgical microscope was already a tremendous progress. The anatomic substrate of each complication is discussed, along with the peculiar surgical details related to it.

Primary cerebellar germinomas of the posterior fossa.

Primary cerebellar germinomas, in the absence of germ-cell tumours outside the nervous system or elsewhere in the cranial cavity and CSF pathways, are exceptional; only two previous cases have been reported in the literature. Two personal observations are described from our 20-year records of intra-axial posterior fossa tumours. The patients were a 32-year-old man and a 17-year-old woman with a clinical history of posterior fossa tumour, studied by computed tomography. The first patient with slight cerebellar signs had a small right hemispheric cerebellar tumour, and the other had a left cerebellar mass with hydrocephalus and progressive intracranial hypertension. Both were treated by tumour removal and irradiation to the whole posterior fossa. The survival times were 58 and 49 months, respectively. The diagnosis of primary cerebellar germinoma cannot be suspected before pathological confirmation. The clinical, neuroradiological and surgical findings are non-specific and quite similar to those of other malignant cerebellar tumours, such as anaplastic gliomas or metastases. Surgery and radiotherapy ensure adequate tumour control in the early stages; cases of recurrence or disseminated disease may be treated by irradiation and chemotherapy.

Expression and function of somatostatin receptor subtype 1 in human growth hormone secreting pituitary tumors deriving from patients partially responsive or resistant to long-term treatment with somatostatin analogs.

The role of somatostatin (SS) receptor subtype 1 (SSTR(1)) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR(1) agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR(1) mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR(1) receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR(1), BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR(1) subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR(1) may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo.