Treatment strategies for giant pituitary adenomas in the era of endoscopic transsphenoidal surgery: a multicenter series.

OBJECTIVE: Given the anatomical complexity and frequently invasive growth of giant pituitary adenomas (GPAs), individually tailored approaches are required. The aim of this study was to assess the treatment strategies and outcomes in a large multicenter series of GPAs in the era of endoscopic transsphenoidal surgery (ETS). METHODS: This was a retrospective case-control series of 64 patients with GPAs treated at two tertiary care centers by surgeons with experience in ETS. GPAs were defined by a maximum diameter of ≥ 4 cm and a volume of ≥ 10 cm3 on preoperative isovoxel contrast-enhanced MRI. RESULTS: The primary operation was ETS in all cases. Overall gross-total resection rates were 64% in round GPAs, 46% in dumbbell-shaped GPAs, and 8% in multilobular GPAs (p < 0.001). Postoperative outcomes were further stratified into two groups based on extent of resection: group A (gross-total resection or partial resection with intracavernous remnant; 21/64, 33%) and group B (partial resection with intracranial remnant; 43/64, 67%). Growth patterns of GPAs were mostly round (11/14, 79%) in group A and multilobular (33/37, 89%) in group B. In group A, no patients required a second operation, and 2/21 (9%) were treated with adjuvant radiosurgery. In group B, early transcranial reoperation was required in 6/43 (14%) cases due to hemorrhagic transformation of remnants. For the remaining group B patients with remnants, 5/43 (12%) underwent transcranial surgery and 12/43 (28%) underwent delayed second ETS. There were no deaths in this series. Severe complications included stroke (6%), meningitis (6%), hydrocephalus requiring shunting (6%), and loss or distinct worsening of vision (3%). At follow-up (mean 3 years, range 0.5-16 years), stable disease was achieved in 91% of cases. CONCLUSIONS: ETS as a primary treatment modality to relieve mass effect in GPAs and extent of resection are dependent on GPA morphology. The pattern of residual pituitary adenoma guides further treatment strategies, including early transcranial reoperation, delayed endoscopic transsphenoidal/transcranial reoperation, and adjuvant radiosurgery.

Dumbbell-shaped pituitary adenomas: prognostic factors for prediction of tumor nondescent of the supradiaphragmal component from a multicenter series.

OBJECTIVE: Dumbbell-shaped pituitary adenomas (DSPAs) are a subgroup of macroadenomas with suprasellar extension that are characterized by a smaller diameter at the level of the diaphragma sellae opening compared with the supradiaphragmal tumor component (SDTC). Hence, DSPAs may be particularly prone to a nondescending suprasellar tumor component and risk for residual tumor or postoperative bleeding. METHODS: A multicenter retrospective cohort analysis of 99 patients with DSPA operated on via direct endoscopic endonasal transsphenoidal approach between 2011 and 2020 was conducted. Patient recruitment was performed at two tertiary care centers (Medical University of Vienna and University of Southern California) with expertise in endoscopic skull base surgery. DSPA was defined as having a smaller diameter at the level of the diaphragma sellae compared with the SDTC. RESULTS: On preoperative MRI, all DSPAs were macroadenomas (maximum diameter range 17-71 mm, volume range 2-88 cm3). Tumor descent was found in 73 (74%) of 99 patients (group A), and nondescent in 26 (26%) of 99 patients (group B) intraoperatively. DSPAs in group A had a significantly smaller diameter (30 vs 42 mm, p < 0.001) and significantly smaller volume (10 vs 22 cm3, p < 0.001) than those in group B. The ratio of the minimum area at the level of the diaphragmal opening in comparison with the maximum area of the suprasellar tumor component ("neck-to-dome area") was significantly lower in group A than in group B (1.7 vs 2.7, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.75 (95% CI 0.63-0.87). At a cutoff ratio of 1.9, the sensitivity and specificity for a nondescending suprasellar tumor component were 77% and 34%, respectively. CONCLUSIONS: In the present study, the neck-to-dome area ratio was of prognostic value for prediction of intraoperative tumor nondescent in DSPAs operated on via a direct endonasal endoscopic approach. Pituitary adenoma SDTC nondescent carried the inherent risk of hemorrhagic transformation in all cases.

Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section.

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach. The new terminology "Pituitary neuroendocrine tumors" (PitNet) that was recently proposed to replace "pituitary adenomas" reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT. We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment. Finally, whether neurosurgeons have to operate on "pituitary adenomas" or "PitNets," their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources.

Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality.

CONTEXT: Cushing syndrome (CS) results in significant morbidity and mortality. OBJECTIVE: To study acute and life-threatening complications in patients with active CS. METHODS: We performed a retrospective cohort study using inpatient and outpatient records of patients with CS in a tertiary center. A total of 242 patients with CS were included, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. We collected acute complications necessitating hospitalization, from appearance of first symptoms of hypercortisolism until 1 year after biochemical remission. Mortality data were obtained from the national registry. Baseline factors relating to and predicting acute complications were tested using uni- and multivariate analysis. RESULTS: The prevalence of acute complications was 62% in patients with benign pituitary CS, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Complications observed in patients with benign CS included infections (25%), thromboembolic events (17%), hypokalemia (13%), hypertensive crises (9%), cardiac arrhythmias (5%), and acute coronary events (3%). Among these patients, 23% had already been hospitalized for acute complications before CS was suspected, and half of complications occurred after the first surgery. Glycated hemoglobin (HbA1c) and 24-hour urinary free cortisol positively correlated with the number of acute complications per patient. Patients with malignant disease had significantly higher rates of acute complications. Mortality during the observation period was 2.8% and 59% in benign and malignant CS, respectively. CONCLUSIONS: This analysis highlights the whole spectrum of acute and life-threatening complications in CS, and their high prevalence even before disease diagnosis and after successful surgery.

High Diagnostic Accuracy of Visible 5-ALA Fluorescence in Meningioma Surgery According to Histopathological Analysis of Tumor Bulk and Peritumoral Tissue.

BACKGROUND AND OBJECTIVES: Complete neurosurgical resection of intracranial meningiomas is essential to avoid residual tumor tissue and thus minimize the risk of tumor recurrence. However, local recurrence of meningiomas is not uncommon mainly due to insufficient intraoperative detection of residual tumor tissue within the tumor bulk or peritumoral tissue such as bone and satellite lesions. Although 5-aminolevulinic acid (5-ALA) induced fluorescence was found to visualize the majority of meningiomas, no comprehensive histopathological assessment of fluorescing samples from the tumor bulk and peritumoral tissue is available. The aim of our study was thus to histopathologically analyze a large series of tissue samples derived from meningioma surgery to assess the positive predictive value (PPV) of visible 5-ALA fluorescence. STUDY DESIGN/MATERIALS AND METHODS: In this study, we retrospectively investigated a series of tissue samples with visible 5-ALA fluorescence collected during surgery of intracranial meningiomas from the tumor bulk and peritumoral tissue including the bone flap, dura/dural tail, arachnoidea, adjacent cortex, and satellite lesions. The tumor diagnosis was established according to the World Health Organization (WHO) criteria and all collected fluorescing samples were screened for presence of tumor tissue to calculate the PPV. RESULTS: Altogether, 191 tissue samples with visible 5-ALA fluorescence derived during surgery of 85 meningiomas (63 WHO grade I, 17 WHO grade II, and 5 WHO grade III) were included. In detail, 158 samples from the tumor bulk and 33 specimens from the peritumoral tissue were investigated. According to histopathological analysis, the PPV of 5-ALA fluorescence was significantly higher in samples from the tumor bulk (100%) as compared with peritumoral tissue (73%; P < 0.001). With regard to peritumoral tissue, tumor tissue was present in most fluorescing samples from the satellite lesions (100%), the bone flap (92%), arachnoidea (83%), and dura/dural tail (75%). In contrast, tumor tissue was absent in the majority of samples from fluorescing cortex (six of seven samples; 86%). However, distinct reactive tissue alterations were found in all six tumor-free fluorescing cortex samples and additional vascular proliferation in two cases. CONCLUSION: In this largest series to date, visible 5-ALA fluorescence is characterized by a high PPV detecting tumor bulk and peritumoral tissue in intracranial meningiomas. Thus, 5-ALA fluorescence supports the neurosurgeon in identifying residual tumor tissue at relevant surgical sites to optimize meningioma surgery and minimize the risk of local recurrence. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

5-ALA fluorescence for intraoperative visualization of spinal ependymal tumors and identification of unexpected residual tumor tissue: experience in 31 patients.

OBJECTIVE: Gross-total resection (GTR) is the treatment of choice in the majority of patients suffering from spinal ependymal tumors. In such tumors, the extent of resection (EOR) is considered the key factor for tumor recurrence and thus patient prognosis. However, incomplete resection is not uncommon and leads to increased risk of tumor recurrence. One important cause of incomplete resection is insufficient intraoperative visualization of tumor tissue as well as residual tumor tissue. Therefore, the authors investigated the value of 5-aminolevulinic acid (5-ALA)-induced fluorescence in a series of spinal ependymal tumors for improved tumor visualization. METHODS: Adult patients who underwent preoperative 5-ALA administration and surgery for a spinal ependymal tumor were included in this study. For each tumor, a conventional white-light microsurgical resection was performed. Additionally, the fluorescence status (strong, vague, or no fluorescence) and fluorescence homogeneity (homogenous or inhomogeneous) of the spinal ependymal tumors were evaluated during surgery using a modified neurosurgical microscope. In intramedullary tumor cases with assumed GTR, the resection cavity was investigated for potential residual fluorescing foci under white-light microscopy. In cases with residual fluorescing foci, these areas were safely resected and the corresponding samples were histopathologically screened for the presence of tumor tissue. RESULTS: In total, 31 spinal ependymal tumors, including 27 intramedullary tumors and 4 intradural extramedullary tumors, were included in this study. Visible fluorescence was observed in the majority of spinal ependymal tumors (n = 25, 81%). Of those, strong fluorescence was noted in 23 of these cases (92%), whereas vague fluorescence was present in 2 cases (8%). In contrast, no fluorescence was observed in the remaining 6 tumors (19%). Most ependymal tumors demonstrated an inhomogeneous fluorescence effect (17 of 25 cases, 68%). After assumed GTR in intramedullary tumors (n = 15), unexpected residual fluorescing foci within the resection cavity could be detected in 5 tumors (33%). These residual fluorescing foci histopathologically corresponded to residual tumor tissue in all cases. CONCLUSIONS: This study indicates that 5-ALA fluorescence makes it possible to visualize the majority of spinal ependymal tumors during surgery. Unexpected residual tumor tissue could be detected with the assistance of 5-ALA fluorescence in approximately one-third of analyzed intramedullary tumors. Thus, 5-ALA fluorescence might be useful to increase the EOR, particularly in intramedullary ependymal tumors, in order to reduce the risk of tumor recurrence.

Expression of additional transcription factors is of prognostic value for aggressive behavior of pituitary adenomas.

OBJECTIVE: According to the latest WHO classification of tumors of endocrine organs in 2017, plurihormonal adenomas are subclassified by their transcription factor (TF) expression. In the group of plurihormonal adenomas with unusual immunohistochemical combinations (PAWUC), the authors identified a large fraction of adenomas expressing TFs for gonadotroph adenoma (TFGA) cells in addition to other TFs. The aim of this study was to compare clinicopathological parameters of PAWUC with TFGA expression to gonadotroph adenomas that only express TFGA. METHODS: This retrospective single-center series comprises 73 patients with TFGA-positive pituitary adenomas (SF1, GATA3, estrogen receptor α): 22 PAWUC with TFGA (TFGA-plus group) and 51 with TFGA expression only (TFGA-only group). Patient characteristics, outcome parameters, rate of invasiveness (assessed by direct endoscopic inspection), and MIB1 and MGMT status were compared between groups. RESULTS: Patients in the TFGA-plus group were significantly younger than patients in the TFGA-only group (age 46 vs 56 years, respectively; p = 0.007). In the TFGA-only group, pituitary adenomas were significantly larger (diameter 25 vs 18.3 mm, p = 0.002). Intraoperatively, signs of invasiveness were significantly more common in the TFGA-plus group than in the TFGA-only group (50% vs 16%, p = 0.002). Gross-total resection was significantly lower in the nonfunctioning TFGA-plus group than in the TFGA-only group (44% vs 86%, p = 0.004). MIB1 and MGMT status showed no significant difference between groups. CONCLUSIONS: These data suggest a more aggressive behavior of TFGA-positive adenomas if an additional TF is expressed within the tumor cells. Shorter radiographic surveillance and earlier consideration for retreatment should be recommended in these adenoma types.

High Interobserver Agreement in the Subjective Classification of 5-Aminolevulinic Acid Fluorescence Levels in Newly Diagnosed Glioblastomas.

BACKGROUND AND OBJECTIVES: Fluorescence-guided resection of glioblastomas (GBM) using 5-aminolevulinic acid (5-ALA) improves intraoperative tumor visualization and is thus widely used nowadays. During resection, different fluorescence levels can usually be distinguished within the same tumor. Recently, we demonstrated that strong, vague, and no fluorescence correspond to distinct histopathological characteristics in newly diagnosed GBM. However, the qualitative fluorescence classification by the neurosurgeon is subjective and currently no comprehensive data on interobserver variability is available. The aim of this study was thus to investigate the interobserver variability in the classification of 5-ALA fluorescence levels in newly diagnosed GBM. STUDY DESIGN/MATERIALS AND METHODS: A questionnaire investigating the interobserver variability in 5-ALA fluorescence quantification was performed at a nation-wide neurosurgical oncology meeting. The participants involved in the neurosurgical/neurooncological field were asked to categorize 30 cases of 5-ALA fluorescence images derived from GBM resection on a lecture hall screen according to the widely used three-tier fluorescence classification scheme (negative, vague, or strong fluorescence). Additionally, participants were asked for information on their medical background such as specialty, level of training, and experience with 5-ALA fluorescence-guided procedures. Interobserver agreement was defined as the calculated mean κ values for each observer. RESULTS: A total of 36 questionnaires were included in the final analysis. The mean average κ value in fluorescence classification within the entire cohort was 0.71 ± 0.12 and 29 (81%) participants had a substantial or almost perfect interobserver agreement (κ values 0.6-1.0). Interobserver agreement was significantly higher in neurosurgeons (mean κ: 0.83) as compared with non-neurosurgeons involved in the neurooncological field (mean κ: 0.52; P < 0.001). Furthermore, interobserver agreement was significantly higher in participants who had experience with at least 25 5-ALA fluorescence-guided surgeries (mean κ: 0.87) compared with less experienced colleagues (mean κ: 0.82; P = 0.039). CONCLUSION: Our study found a high interobserver agreement in the qualitative classification of different 5-ALA fluorescence levels in newly diagnosed GBM. Interobserver agreement increases significantly in more experienced participants and therefore a high level of experience is crucial for reliable intraoperative fluorescence classification. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Optimizing MR imaging for intraoperative image guidance in sellar pathologies.

PURPOSE: With the advancement of extended endonasal approaches, the ability to surgically reach parasellar tumor extensions increase. The aim of the study was to propose an optimized imaging protocol for surgical guidance in the cavernous sinus (CS) for proper visualization structures at risk. METHODS: Prospective case control analysis of 20 consecutive pituitary adenoma patients scheduled for endoscopic transnasal surgery. Assessment of the capability of three different MRI sequences (MPRAGE, VIBE, CISS) by 4 investigators to correctly visualize sellar and parasellar structures. Invasiveness and position of the normal pituitary gland were compared with the intraoperative findings. RESULTS: The consensus between the 4 examiners to achieve the same results for all modalities was 40% for MPRAGE, 70% for VIBE and 60% for CISS sequences (p = 0.155). A consensus of Knosp Grade per patient was 80% for MPRAGE, 100% for VIBE and 90% for CISS (overall kappa 0.60). A higher Knosp Grade was found in MPRAGE sequences compared to the other sequences. Intraoperative status of invasiveness was correctly identified in 12/20 (60%) with MPRAGE, 19/20 (95%) with VIBE and 11/20 (55%) with CISS sequences. The position of the normal pituitary gland was most frequent evaluable in 15/20 (75%) and correctly identified in 12/15 (80%) cases. CONCLUSION: Our data showed that VIBE sequences obtain the highest degree of consensus with intraoperative findings of invasiveness and position of the normal pituitary gland. VIBE sequences, due to their high spatial resolution and at the same time fast image acquisition could provide improved imaging for neuronavigation.

Ectopic Cushing's syndrome in a patient with inferior petrosal sinus sampling indicating pituitary-dependent ACTH secretion.

In an unclear case of Cushing's syndrome, IPSS identifies the origin of ACTH secretion, and together with MRI enables the localization of an ectopic corticotroph adenoma in the parasellar or cavernous sinuses region.

Is Intraoperative Pathology Needed if 5-Aminolevulinic-Acid-Induced Tissue Fluorescence Is Found in Stereotactic Brain Tumor Biopsy?

BACKGROUND: Intraoperative histopathology and acquisition of multiple tissue samples in stereotactic biopsies results in a prolonged length of surgery and potentially increased complication rate. OBJECTIVE: To investigate the clinical benefits of a novel strategy for stereotactic brain tumor biopsies with the assistance of 5-aminolevulinic acid (5-ALA) induced fluorescence. METHODS: Patients that received 5-ALA prior to stereotactic biopsy of a suspected brain tumor were included. According to our strategy, the procedure was terminated in the case of strong fluorescence of the biopsy samples. In contrast, intraoperative histology was demanded in the case of vague/no fluorescence. Length of surgery, number of biopsy samples, diagnostic rate, and periprocedural complications were compared between these 2 groups. RESULTS: Altogether, 79 patients were included, and strong fluorescence was present in 62 cases (79%), vague fluorescence was in 4 cases (5%), and no fluorescence was in 13 cases (16%). The diagnostic rate was comparable in biopsies with strong fluorescence without intraoperative histopathology and cases with vague/no fluorescence with intraoperative histopathology (98% vs 100%; P = 1.000). A significantly shorter length of surgery (41 vs 77 min; P < .001) and reduced average number of biopsy samples (3.6 vs 4.9; P = .011) was found in patients with strong compared to vague/no fluorescence. However, no statically significant difference in periprocedural complications between cases with strong and vague/no fluorescence was found (7% vs 18%; P = .166). CONCLUSION: Our data demonstrate the clinical benefits of a novel strategy for stereotactic brain tumor biopsies with assistance of 5-ALA. Thus, this biopsy strategy will increase the efficiency of this standard neurosurgical procedure in the future.

Focal irregularities in 7-Tesla MRI of unruptured intracranial aneurysms as an indicator for areas of altered blood-flow parameters.

OBJECTIVE: In the last several decades, various factors have been studied for a better evaluation of the risk of rupture in incidentally discovered intracranial aneurysms (IAs). With advanced MRI, attempts were made to delineate the wall of IAs to identify weak areas prone to rupture. However, the field strength of the MRI investigations was insufficient for reasonable image resolution in many of these studies. Therefore, the aim of this study was to analyze findings of IAs in ultra-high field MRI at 7 Tesla (7 T). METHODS: Patients with incidentally found IAs of at least 5 mm in diameter were included in this study and underwent MRI investigations at 7 T. At this field strength a hyperintense intravascular signal can be observed on nonenhanced images with a brighter "rim effect" along the vessel wall. Properties of this rim effect were evaluated and compared with computational fluid dynamics (CFD) analyses. RESULTS: Overall, 23 aneurysms showed sufficient image quality for further evaluation. In 22 aneurysms focal irregularities were identified within this rim effect. Areas of such irregularities showed significantly higher values in wall shear stress and vorticity compared to areas with a clearly visible rim effect (p = 0.043 in both). CONCLUSIONS: A hyperintense rim effect along the vessel wall was observed in most cases. Focal irregularities within this rim effect showed higher values of the mean wall shear stress and vorticity when compared by CFD analyses. Therefore, these findings indicate alterations in blood flow in IAs within these areas.

Detailed analysis of 5-aminolevulinic acid induced fluorescence in different brain metastases at two specialized neurosurgical centers: experience in 157 cases.

OBJECTIVE: Incomplete neurosurgical resection of brain metastases (BM) due to insufficient intraoperative visualization of tumor tissue is a major clinical challenge and might result in local recurrence. Recently, visible 5-aminolevulinic acid (5-ALA) induced fluorescence was first reported in patients with BM. The aim of this study was thus to investigate, for the first time systematically, the value of 5-ALA fluorescence for intraoperative visualization of BM in a large patient cohort. METHODS: Adult patients (≥ 18 years) with resection of suspected BM after preoperative 5-ALA administration were prospectively recruited at two specialized neurosurgical centers. During surgery, the fluorescence status (visible or no fluorescence); fluorescence quality (strong, vague, or none); and fluorescence homogeneity (homogeneous or heterogeneous) of each BM was investigated. Additionally, these specific fluorescence characteristics of BM were correlated with the primary tumor type and the histopathological subtype. Tumor diagnosis was established according to the current WHO 2016 criteria. RESULTS: Altogether, 157 BM were surgically treated in 154 patients. Visible fluorescence was observed in 104 BM (66%), whereas fluorescence was absent in the remaining 53 cases (34%). In detail, 53 tumors (34%) showed strong fluorescence, 51 tumors (32%) showed vague fluorescence, and 53 tumors (34%) had no fluorescence. The majority of BM (84% of cases) demonstrated a heterogeneous fluorescence pattern. According to primary tumor, visible fluorescence was less frequent in BM of melanomas compared to all other tumors (p = 0.037). According to histopathological subtype, visible fluorescence was more common in BM of ductal breast cancer than all other subtypes (p = 0.008). It is of note that visible fluorescence was observed in the surrounding brain tissue after the resection of BM in 74 (67%) of 111 investigated cases as well. CONCLUSIONS: In this largest series to date, visible 5-ALA fluorescence was detected in two-thirds of BM. However, the characteristic heterogeneous fluorescence pattern and frequent lack of strong fluorescence limits the use of 5-ALA in BM and thus this technique needs further improvements.

Challenging the osseous component of sphenoorbital meningiomas.

BACKGROUND: Intraosseous growth is a unique feature of sphenoorbital meningiomas (SOM). Its close relation to neurovascular structures limits complete surgical resection and possibly contributes to the high recurrence rate. OBJECTIVE: To evaluate the growth behavior of intraosseous remnants and develop a protocol for precise intraoperative visualization of intraosseous SOM. METHODS: We included 31 patients operated for SOM from 2004 to 2017. The growth velocity of the intraosseous tumor component was volumetrically calculated in 20 cases. To improve accuracy of image guidance, we implemented a specialized bone surface-based registration algorithm. For intraoperative bone visualization, we included CT in multimodality continuous image guidance in 23 patients. The extent of resection (EOR) was compared with a standard MR-only navigation group (n = 8). RESULTS: In 11/20 cases (55%), a progressive regrowth of the intraosseous SOM remnant was noted during a mean follow-up of 52 months (range 20-132 months). We observed a mean increase of 6.2 cm3 (range 0.2-23.7 cm3) per patient and side during the follow-up period. Bone surface-based registration was significantly more accurate than skin surface-based registration (mean 0.7 ± 0.4 mm and 1.9 ± 0.7 mm, p < 0.001). The EOR of the intraosseous component was significantly higher using CT + MRI navigation compared with controls (96% vs. 81%, p = 0.044). CONCLUSION: Quantitative assessment of the biological behavior of intraosseous remnants revealed a continuous slow growth rate independent of the soft tumor component of more than half of SOM. According to our data, application of a multimodal image guidance provided high accuracy and significantly increased the resection rate of the intraosseous component of SOM.

ICAR: endoscopic skull-base surgery.

BACKGROUND: Endoscopic skull-base surgery (ESBS) is employed in the management of diverse skull-base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature. To consolidate and critically appraise the available literature, experts in skull-base surgery have produced the International Consensus Statement on Endoscopic Skull-Base Surgery (ICAR:ESBS). METHODS: Using previously described methodology, topics spanning the breadth of ESBS were identified and assigned a literature review, evidence-based review or evidence-based review with recommendations format. Subsequently, each topic was written and then reviewed by skull-base surgeons in both neurosurgery and otolaryngology. Following this iterative review process, the ICAR:ESBS document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:ESBS document addresses the role of ESBS in primary cerebrospinal fluid (CSF) rhinorrhea, intradural tumors, benign skull-base and orbital pathology, sinonasal malignancies, and clival lesions. Additionally, specific challenges in ESBS including endoscopic reconstruction and complication management were evaluated. CONCLUSION: A critical review of the literature in ESBS demonstrates at least the equivalency of ESBS with alternative approaches in pathologies such as CSF rhinorrhea and pituitary adenoma as well as improved reconstructive techniques in reducing CSF leaks. Evidence-based recommendations are limited in other pathologies and these significant knowledge gaps call upon the skull-base community to embrace these opportunities and collaboratively address these shortcomings.

An advanced protocol for intraoperative visualization of sinunasal structures: experiences from pituitary surgery.

OBJECTIVE: The transsphenoidal route to pituitary adenomas challenges surgeons because of the highly variable sinunasal anatomy. Orientation may be improved if the appropriate information is provided intraoperatively by image guidance. The authors developed an advanced image guidance protocol dedicated to sinunasal surgery that extracts information from multiple modalities and forms it into a single image that includes fine sinunasal structures and arteries.The aim of this study was to compare the advantages of this novel image guidance protocol with the authors' previous series, with emphasis on anatomical structures visualized and complication rate. METHODS: This retrospective analysis comprised 200 patients who underwent surgery for pituitary adenoma via a transnasal transsphenoidal endoscopic approach. The authors' standard image guidance protocol consisting of CT for solid bone, T1CEMRI for soft tissues, and MRA for the carotid artery was applied in 100 consecutive cases. The advanced image guidance protocol added a first-hit ray casting of the CT scan for visualization of fine sinunasal structures, and adjustments to the MRA to visualize the sphenopalatine artery (SPA) were applied in a subsequent 100 consecutive cases. RESULTS: A patent sphenoid ostium-i.e., an ostium not covered by a mucosal layer-was visualized significantly more often by the advanced protocol than the standard protocol (89% vs 40%, p < 0.001) in primary surgeries. The SPA and its branches were only visualized by the advanced protocol (87% and 91% of cases in primary surgeries and reoperations, respectively) and not once by the standard protocol. The number of visualized complete and incomplete sphenoid septations matched significantly more commonly with the surgical view when using the advanced protocol than the standard protocol at primary operation (mean 1.9 vs 1.6, p < 0.001). However, in 25% of all cases a complex and not a simple sinus anatomy was present. In comparison with the intraoperative results, a complex sphenoid sinus anatomy was always detected by the advanced but not by the standard protocol (25% vs 8.5%, p = 0.001).Furthermore, application of the advanced protocol reduced the cumulative rate of complications (25% vs 18% [standard vs advanced group]). Although an overall significant difference could not be determined (p = 0.228), a subgroup analysis of reoperations (35/200) revealed a significantly lower rate of complications in the advanced group (5% vs 30%, p = 0.028). CONCLUSIONS: The data show that the advanced image guidance protocol could intraoperatively visualize the fine sinunasal sinus structures and small arteries with a high degree of detail. By improving intraoperative orientation, this may help to reduce the rate of complications in endoscopic transsphenoidal surgery, especially in reoperations.

Challenging Knosp high-grade pituitary adenomas.

OBJECTIVE: Parasellar growth is one of the most important prognostic variables of pituitary adenoma surgery, with adenomas regarded as not completely resectable if they invade the cavernous sinus (CS) but potentially curable if they displace CS structures. This study was conducted to correlate surgical treatment options and outcomes to the different biological behaviors (invasion vs displacement) of adenomas with parasellar extension into the superior or inferior CS compartments or completely encasing the carotid artery (Knosp high grades 3A, 3B, and 4). METHODS: This was a retrospective cohort analysis of 106 consecutive patients with Knosp high-grade pituitary adenomas with parasellar extension who underwent surgery via a primary endoscopic transsphenoidal approach between 2003 and 2017. Biological tumor characteristics (surgical status of invasiveness and tumor texture, 2017 WHO classification, proliferation rate), extent of resection, and complication rate were correlated with parasellar extension grades 3A, 3B, and 4 on preoperative MRI studies. RESULTS: Invasiveness was significantly less common in grade 3A (44%) than in grade 3B (72%, p = 0.037) and grade 4 (100%, p < 0.001) adenomas. Fibrous tumor texture was significantly more common in grade 4 (52%) compared to grade 3A (20%, p = 0.002), but not compared to grade 3B (28%) adenomas. Functioning macroadenomas had a significantly higher rate of invasiveness than nonfunctioning adenomas (91% vs 55%, p = 0.002). Mean proliferation rate assessed by MIB-1 was > 3% in all groups but without significant difference between the groups (grade 3A, 3.2%; 3B, 3.9%; 4, 3.7%). Rates of endocrine remission/gross-total resection were significantly higher in grade 3A (64%) than in grade 3B (33%, p = 0.021) and grade 4 (0%, p < 0.001) adenomas. In terms of complication rates, no significant difference was observed between grades. CONCLUSIONS: According to the authors' data, the biological behavior of pituitary adenomas varies significantly between parasellar extension patterns. Adenomas with extension into the superior CS compartment have a lower rate of invasive growth than adenomas extending into the inferior CS compartment or encasing the carotid artery. Consequently, a significantly higher rate of remission can be achieved in grade 3A than in grade 3B and grade 4 adenomas. Therefore, the distinction into grades 3A, 3B, and 4 is of importance for prediction of adenoma invasion and surgical treatment considerations.

A New Clip Generation for Microsurgical Treatment of Intracranial Aneurysms-The First Case Series.

OBJECTIVE: Considerable effort has been made in order to reduce surgical invasiveness while maintaining optimal exploiting of the operative space in aneurysm surgery. One aspect of this evolution is represented by the Lazic (Peter Lazic GmbH, Tuttlingen, Germany) aneurysm clip system. The purpose of this study was to illustrate the new generation clip system in practiced aneurysm surgery. METHODS: A retrospective analysis of all aneurysm surgeries in our departments between December 2015 and January 2018 using the new D-Clip system was performed. Evaluation included standardized retrospective review of the main surgeon, the nursing staff, as well as an analysis of surgical video documentation by objective reviewers. RESULTS: Forty-five patients with 50 intracranial aneurysms underwent surgical clipping using the D-Clip system. A total of 64 permanent and 19 temporary D-Clips were applied. Nine clips needed to be replaced. All aneurysms could be occluded totally. Surgeons considered handling and manoeuvrability of clip application as feasible and good in all cases (100%), even under impaired visibility circumstances (14%). Objective video analysis revealed comparable results. Nursing staff scored handling and practicability of D-Clips equivalent to the preceding L-Clip generation. There were no intraoperative complications. Surgery-related postoperative morbidity was 6.7%. CONCLUSIONS: The new D-Clip system combines an attenuated design for minimally invasive clipping procedures with traditional mechanisms of common clip systems. It therefore appears to be highly versatile in the context of variable different aneurysm morphologies and locations while maintaining high standard surgical safety and efficacy.

Ex-vivo analysis of quantitative 5-ALA fluorescence intensity in diffusely infiltrating gliomas using a handheld spectroscopic probe: Correlation with histopathology, proliferation and microvascular density.

BACKGROUND: Intraoperative semiquantitative classification of different visible 5-aminolevulinic acid (5-ALA) fluorescence levels by the neurosurgeon is subjective. Recently, handheld spectroscopic probes were introduced enabling quantitative analysis of 5-ALA induced fluorescence intensity (FI). The aim of this ex-vivo study was to correlate the FI in gliomas of different grades with histopathology, proliferation and microvasular density (MVD). PATIENTS AND METHODS: Patients with suspected World Health Organization (WHO) grade II-IV gliomas were included and tissue samples from different visible fluorescence levels (strong, vague or none) were intraoperatively collected. After resection, the FI of each sample was investigated ex-vivo by a handheld spectroscopic probe. The FI values were correlated with visible fluorescence, histopathology (WHO grade, quality of tissue, histopathological parameters of anaplasia), proliferation (MIB-1) and MVD. RESULTS: Altogether, 143 tumor samples with strong (n = 61), vague (n = 21) and no fluorescence (n = 61) were collected in 68 patients. We found significantly different median FI values between all three visible fluorescence levels. Moreover, the median FI value was significantly higher in WHO grade III/IV samples and compact tumor tissue compared to WHO grade II samples and infiltrated tumor tissue. Further, significant differences in median FI values were observed in specific histopathological parameters of anaplasia (mitotic rate, cell density, nuclear pleomorphism and microvascular proliferation) in multivariable analysis. Finally, a significant correlation between the proliferation rate and FI, but not between MVD and FI was noted. CONCLUSION: Our data indicate that handheld spectroscopic probes are capable of visualizing intratumoral glioma heterogeneity by objective assessment of fluorescence and may thus optimize future glioma surgery.

Multiple Pituitary Apoplexy-Cavernous Sinus Invasion as Major Risk Factor for Recurrent Hemorrhage.

OBJECTIVE: Pituitary apoplexy is a rare but potentially life-threatening disorder that occurs in up to 10% of adenomas. Whereas risk factors for the initial hemorrhagic event are well described, there is minor knowledge on clinical symptomatic recurrent pituitary apoplexies. METHODS: At the Medical University of Vienna, 76 patients were surgically treated for clinical symptomatic pituitary apoplexy between 1990 and 2017. Four patients (5.3%) suffered multiple pituitary apoplexies after initial surgery. In this retrospective study, neuroradiologic images, clinical data, and intraoperative findings were reviewed for potential risk factors of multiple apoplexies in pituitary adenomas. RESULTS: Patients with multiple apoplexies had significantly higher Knosp grading on preoperative imaging (median grade 4), and more frequently observed cavernous sinus invasion intraoperatively (P = 0.01). Consequently, all cases with multiple pituitary apoplexies remained with residual adenoma postoperatively. In cases of residual tumor within the cavernous sinus, recurrent apoplexy occurred in 23.5% of patients. A tumor recurrence/residual was resected significantly earlier in patients with single apoplexy (median 2.2 years) than in patients with multiple apoplexies (median 5.4 years; P = 0.05). Multiple pituitary apoplexies caused significantly greater rates of ophthalmoplegia (75% vs. 14.1%; P = 0.01) and long-term hormone-replacement therapy was necessary in all cases. CONCLUSIONS: Cavernous sinus invasion and subtotal resection are high risk factors for multiple apoplexies in pituitary adenomas. Early treatment is recommended for residual tumor in the cavernous sinus to minimize the risk of recurrent apoplexy with subsequent worse clinical outcome.