Endoscopic transorbital route to the petrous apex: a feasibility anatomic study.

BACKGROUND: While the subtemporal approach represents the surgical module milestone designed to reach the petrous apex, a novel ventral route, which is the superior eyelid endoscopic transorbital approach, has been proposed to access the skull base. Accordingly, we aimed to evaluate the feasibility of this route to the petrous apex, providing a qualitative and quantitative analysis of this relatively novel pathway. METHODS: Five human cadaveric heads were dissected at the Laboratory of Surgical NeuroAnatomy of the University of Barcelona. After proper dissection planning, anterior petrosectomy via the endoscopic transorbital route was performed. Specific quantitative analysis, as well as dedicated three-dimensional reconstruction, was done. RESULTS: Using the endoscopic transorbital approach, it was possible to reach the petrous apex with an average volume bone removal of 1.33 ± 0.21 cm3. Three main intradural spaces were exposed: cerebellopontine angle, middle tentorial incisura, and ventral brainstem. The first one was bounded by the origin of the trigeminal nerve medially and the facial and vestibulocochlear nerves laterally, the second extended from the origin of the oculomotor nerve to the entrance of the trochlear nerve into the tentorium free edge while the ventral brainstem area was hardly accessible through the straight, ventral endoscopic transorbital trajectory. CONCLUSION: This is the first qualitative and quantitative anatomic study concerning details of the lateral aspect of the incisura and ventrolateral posterior fossa reached via the transorbital window. This manuscript is intended as a feasibility anatomic study, and further clinical contributions are mandatory to confirm the effectiveness of this approach, defining its possible role in the neurosurgical armamentarium.

Vasari Scoring System in Discerning between Different Degrees of Glioma and IDH Status Prediction: A Possible Machine Learning Application?

(1) The aim of our study is to evaluate the capacity of the Visually AcceSAble Rembrandt Images (VASARI) scoring system in discerning between the different degrees of glioma and Isocitrate Dehydrogenase (IDH) status predictions, with a possible application in machine learning. (2) A retrospective study was conducted on 126 patients with gliomas (M/F = 75/51; mean age: 55.30), from which we obtained their histological grade and molecular status. Each patient was analyzed with all 25 features of VASARI, blinded by two residents and three neuroradiologists. The interobserver agreement was assessed. A statistical analysis was conducted to evaluate the distribution of the observations using a box plot and a bar plot. We then performed univariate and multivariate logistic regressions and a Wald test. We also calculated the odds ratios and confidence intervals for each variable and the evaluation matrices with receiver operating characteristic (ROC) curves in order to identify cut-off values that are predictive of a diagnosis. Finally, we did the Pearson correlation test to see if the variables grade and IDH were correlated. (3) An excellent ICC estimate was obtained. For the grade and IDH status prediction, there were statistically significant results by evaluation of the degree of post-contrast impregnation (F4) and the percentage of impregnated area (F5), not impregnated area (F6), and necrotic (F7) tissue. These models showed good performances according to the area under the curve (AUC) values (>70%). (4) Specific MRI features can be used to predict the grade and IDH status of gliomas, with important prognostic implications. The standardization and improvement of these data (aim: AUC > 80%) can be used for programming machine learning software.

Predicting the early visual outcomes in sellar-suprasellar lesions compressing the chiasm: the role of SD-OCT series of 20 patients operated via endoscopic endonasal approach.

BACKGROUND: Tumors involving the sellar area often cause visual disorders due to optic nerves/chiasm compression, so that surgery is required. However, the likelihood of visual improvement/restoration is variable. Optical coherence tomography (OCT) is a valid diagnostic tool for defining pathological conditions of the optic apparatus. We herein investigated the role of the SD-OCT and the best corrected visual acuity in predicting postoperative visual recovery, in patients complaining of chiasm compression due to sellar-suprasellar lesions. METHODS: We retrospectively analyzed 20 patients (7 females and 13 males; mean age 50.8±17.87 years, range 11-83), with optic chiasm/nerve compression that underwent endoscopic endonasal approach at the Division of Neurosurgery of the University of Naples Federico II, Naples, Italy, between June 2014 and February 2015. Preoperative ophthalmological assessment focused on BCVA Snellen charts, standard automated perimetry test and SD-OCT. Test were repeated at two weeks, one and three months after surgery. RESULTS: A significant thickness reduction in all the patients, as compared to the control group was noted: GCC thickness reduction remained mostly unchanged postoperatively: 42.9% of the patients had altered visual acuity (VA), while the Perimetry revealed 90% of altered preoperative MD values (MD>-2.00): perimetry improvement was noted in 93% of cases and visual acuity in 91.3% of cases. A direct correlation between preoperative retinal status and functional recovery was identified considering the values of pRNFL and GCC. CONCLUSIONS: OCT provides valuable information regarding the entity of compression also in patients without any visual field defects. Although several factors should be taken into consideration, we retain that preoperative RNFL and GCC thickness values can be claimed as a reliable predictor of visual recovery in those patients presenting chiasm compression.

IV and V grade arteriovenous Malformations: A multicenter surgical experience. Use of multiple grading system to predict surgical risk.

OBJECTIVE: The aim of our study is to report a multicenter experience in the treatment of IV and V grade arteriovenous malformations (AVMs) and to apply commonly used grading scales for surgical risk assessment for these vascular high-grade lesions. METHODS: Between January 2015 and December 2019, a retrospective study was conducted to identify patients undergoing microsurgical intervention for cAVMs at two Italian centers specialized in the treatment of vascular pathologies. Data on patients with Spetzler-Martin IV and V and with a score equal or more than 7 according to Lawton-Young classification were collected. Ruptured AVMs at admission were subsequently classified according to the new proposed AVICH classification. RESULTS: A total of 20 patients with high grade (IV and V) cAVMs were enrolled in the study and the average follow-up was 36.45 months. The outcome based on mRS was favorable in 65 % of cases. The pre-operative mRS was a factor influencing clinical outcome, as well as the number of bleedings preceding the treatment, age, and nidus characteristics. S-M IV, L-Y 3 and S-M supp 7 scores were associated with good outcome. Based on the AVICH classification, for ruptured cAVMs, having a score of 9 ore less was correlated to a postoperative mRS fewer or equal than 2. CONCLUSIONS: Surgical management for high-grade AVMs should be considered in highly selected patients with repeated bleeding or disabling symptoms. Classification systems provide an aid in selecting patients for surgery, also in grade IV and V. It is essential to establish common registers for the management of these complex vascular malformations.

The Impact of Intraoperative Monitoring on Extent of Resection and Long-Term Neurological Outcomes: A Series of 39 Intramedullary Ependimomas.

AIM: To analyze the impact of intraoperative neurophysiological monitoring (IONM) on the extent of removal and long-term neurological outcomes in a series of grade II ependymomas. MATERIAL AND METHODS: We retrospectively reviewed 88 consecutive patients who underwent surgical resection of an intramedullary spinal cord tumor (IMSCT) at the Clinic of Neurosurgery of the Clinical Center of Serbia in Belgrade between January 2012 and December 2017. In all, 39 patients (25 males and 14 females; mean age 46.16 years) with grade II ependymomas were enrolled in this study; the mean follow-up time was 49.84 months. The modified McCormick Scale (mMCS) was used to assess the short- and long-term outcomes, and the patients were divided into two groups based on whether they underwent IONM. RESULTS: The gross-total removal rate was 89.7%, and it was not influenced by use of IONM, location or tumor size. Upon admission,43.2% of the patients were dependent (grades IV and V), while 56.8% were independent (grades I, II and III), according to the mMCS. After 3 months of follow-up, 76.9% of the patients maintained or improved their neurological status, but this percentage was reduced after long-term follow-up. CONCLUSION: Total surgical resection with good neurological outcomes can be achieved in the vast majority of patients with grade II ependymomas; it is important to emphasize that the use of IONM allows acceptable extent of resection and provides better results in terms of functional outcomes, with lower morbidity rates. Therefore, no correlation was demonstrated between the decrease in the basal amplitudes of IONM and D-waves and poor neurological outcomes.

Ommaya Reservoir System for the Treatment of Cystic Craniopharyngiomas: Surgical Results in a Series of 11 Adult Patients and Review of the Literature.

OBJECTIVE: Treatment of cystic craniopharyngiomas can be challenging and recurrences are frequent, even after total resection. In selected cases, less-aggressive surgery with the sole drainage of the cyst reliefs symptoms caused by mass effect and represents a valid alternative option, notably in pediatric population. We herein analyze a series of adult cystic craniopharyngiomas, managed with Ommaya Reservoir implant, focusing on local tumor control and eventual complications. METHODS: In total, 11 nonconsecutive adult cystic craniopharyngiomas (7 recurrent lesions) were treated with Ommaya Reservoir System (ORS), in 2 neurosurgical centers. ORS was placed in 9 cases using minimally invasive procedures: 6 burr-hole endoscopic insertion and 3 navigated electromagnetic placement; in the remaining 2 patients, the Ommaya reservoir was used as a shunt to prevent cyst recollection during a transcranial approach. RESULTS: The main presenting symptoms were visual impairment (75%), cognitive and behavioral disorders (66.7%), hypopituitarism (38%), headache (30.8%), and hypothalamic obesity (8%). The median follow-up period was 41.4 months. In all patients, the visual function and intracranial hypertension improved after decompression. Local tumor control was accomplished in 8 patients (72.7%), without the need of adjuvant treatments. The endoscopic vision carried similar rates of tumor control than stereotaxy (75% vs. 66.7%). CONCLUSIONS: In selected patients, tailored procedures are required to achieve long-term tumor control and as well limit surgery-related morbidity. ORS could represent a safe and effective treatment option for cystic craniopharyngiomas, providing also reduced surgical-related morbidity, especially in recurrent lesions and in patients not suitable for radical surgery.

Endoscopic Endonasal Transsphenoidal Surgery: History and Evolution.

In previous decades, extensive and disfiguring transfacial and/or transcranial approaches were used to reach the sellar and parasellar areas. However, these surgical routes were burdened by severe complications and high mortality rates. Recently, the development of endoscopic endonasal techniques has revolutionized the surgical strategies for approaching the sella and adjacent areas and increased the development of transsphenoidal surgery. With these techniques, surgeons have been able to overcome the visual limitations of the open surgical approaches and access areas previously hidden from view. After the contributions of the Pittsburgh duo, Carrau and Jho, pioneers of pure endoscopic surgery, our school began to implement this technique, introducing technical innovations and variations, describing the anatomical details and defining new routes, and playing a key role in its widespread clinical application.

Defining the lateral limits of the endoscopic endonasal transtuberculum transplanum approach: anatomical study with pertinent quantitative analysis.

OBJECTIVE: The extended endoscopic endonasal transtuberculum transplanum approach is currently used for the surgical treatment of selected midline anterior skull base lesions. Nevertheless, the possibility of accessing the lateral aspects of the planum sphenoidale could represent a limitation for such an approach. To the authors' knowledge, a clear definition of the eventual anatomical boundaries has not been delineated. Hence, the present study aimed to detail and quantify the maximum amount of bone removal over the planum sphenoidale required via the endonasal pathway to achieve the most lateral extension of such a corridor and to evaluate the relative surgical freedom. METHODS: Six human cadaveric heads were dissected at the Laboratory of Surgical NeuroAnatomy of the University of Barcelona. The laboratory rehearsals were run as follows: 1) preliminary predissection CT scans, 2) the endoscopic endonasal transtuberculum transplanum approach (lateral limit: medial optocarotid recess) followed by postdissection CT scans, 3) maximum lateral extension of the transtuberculum transplanum approach followed by postdissection CT scans, and 4) bone removal and surgical freedom analysis (a nonpaired Student t-test). A conventional subfrontal bilateral approach was used to evaluate, from above, the bone removal from the planum sphenoidale and the lateral limit of the endonasal route. RESULTS: The endoscopic endonasal transtuberculum transplanum approach was extended at its maximum lateral aspect in the lateral portion of the anterior skull base, removing the bone above the optic prominence, that is, the medial portion of the lesser sphenoid wing, including the anterior clinoid process. As expected, a greater bone removal volume was obtained compared with the approach when bone removal is limited to the medial optocarotid recess (average 533.45 vs 296.07 mm2; p < 0.01). The anteroposterior diameter was an average of 8.1 vs 15.78 mm, and the laterolateral diameter was an average of 18.77 vs 44.54 mm (p < 0.01). The neurovascular contents of this area were exposed up to the insular segment of the middle cerebral artery. The surgical freedom analysis revealed a possible increased lateral maneuverability of instruments inserted in the contralateral nostril compared with a midline target (average 384.11 vs 235.31 mm2; p < 0.05). CONCLUSIONS: Bone removal from the medial aspect of the lesser sphenoid wing, including the anterior clinoid process, may increase the exposure and surgical freedom of the extended endoscopic endonasal transtuberculum transplanum approach over the lateral segment of the anterior skull base. Although this study represents a preliminary anatomical investigation, it could be useful to refine the indications and limitations of the endoscopic endonasal corridor for the surgical management of skull base lesions involving the lateral portion of the planum sphenoidale.

Effect of combined treatment with a pan-PI3K inhibitor or an isoform-specific PI3K inhibitor and everolimus on cell proliferation in GH-secreting pituitary tumour in an experimental setting.

PURPOSE: PI3K/Akt/mTOR pathway activation is common in GH-secreting pituitary tumours, and a target for treatment with mTOR inhibitors, including everolimus (EVE). The current study aimed to evaluate the efficacy of two PI3K inhibitors (PI3Ki), NVP-BKM120 and NVP-BYL719, alone and in combination with EVE in rat GH-secreting pituitary tumour cell line (GH3) and human GH-secreting pituitary tumour cell cultures. METHODS: In GH3 cell line and in six GH-secreting tumour cell cultures, the effects of PI3Ki and EVE, as single agents and in combination, were tested on cell viability and colony survival, by MTT and clonogenic assay, respectively, whereas western blot was performed to evaluate the underlying intracellular signalling pathways. RESULTS: PI3Ki and EVE showed a dose-dependent inhibition of cell viability in GH3 cell line, with PI3Ki displaying a synergistic effect when combined with EVE. PI3Ki and EVE inhibited colony survival in GH3 cell line with no further improvement in combination. In GH-secreting pituitary tumour cell cultures PI3Ki are effective in inhibiting cell viability increasing the slight and non significant inhibition induced by EVE as single agent, generally showing a synergistic effect. Despite in both GH3 cell line and GH-secreting pituitary tumour cell cultures combination of PI3Ki enhanced EVE effect, the study of intracellular signalling pathways revealed a different regulation of PI3K/Akt/mTOR and MAPK between the two models. CONCLUSIONS: The results of the current study demonstrated that PI3Ki, especially in combination with EVE, are effective in inhibiting cell proliferation, therefore representing a promising therapeutic tool for the treatment of aggressive GH-secreting pituitary tumours, not responsive to standard medical therapies.

A Survival Analysis with Identification of Prognostic Factors in a Series of 110 Patients with Newly Diagnosed Glioblastoma Before and After Introduction of the Stupp Regimen: A Single-Center Observational Study.

BACKGROUND: Current treatment protocol for glioblastoma multiforme (GBM) is based on maximal safe resection followed by the Stupp protocol. In Serbia, temozolomide was introduced as adjuvant therapy in 2011. The aims of this study were to confirm the safety and efficacy on overall and progression-free survival of the Stupp protocol and evaluate the influence of prognostic factors in one of the largest series of patients with GBM treated over a 2-year period. METHODS: Between January 2010 and December 2012, 110 patients with newly diagnosed GBM underwent surgical removal at the Neurooncology Department of the Clinic Center of Serbia. Patients were divided into 2 groups according to postoperative treatment. Group A (n = 24 patients), treated before January 2011, received adjuvant standard radiation therapy and carmustine (bis-chloroethyl-nitrosourea), and group B (n = 86 patients), treated after January 2011, received postoperative treatment according to the Stupp protocol. RESULTS: The Stupp protocol had a significant favorable impact on overall survival at 1-year follow-up (79.1% in group B vs. 62.5% in group A; P = 0.016); no differences were noted in regard to progression-free survival. Multivariate analysis identified younger age and gross total resection of tumor as positive prognostic factors. CONCLUSIONS: Adoption of the Stupp protocol had a favorable impact on overall, but not on progression-free, survival rate. Wider surgical resection involving the peritumoral brain zone, as confirmed by univariate and multivariate analysis, represents the most favorable prognostic factor.