abbreviatioNs CS = cavernous sinus; ER = endocrinological remission; GTR = gross-total resection; ICA = internal carotid artery. submitted May 22, 2014. accepted December 2, 2014. iNclude wheN citiNg Published online February 6, 2015; DOI: 10.3171/2014.12.JNS141083. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. obJect An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade. methods The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas. results The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas. coNclusioNs The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previousl...

This survey confirms that TMZ is established as first-line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low MGMT and concurrent radiotherapy were associated with a better response. The limited long-term effect of TMZ and the poor efficacy of other drugs highlight the need to identify additional effective therapies.

OBJECTIVE Robotic devices have recently been introduced in stereotactic neurosurgery in order to overcome the limitations of frame-based and frameless techniques in terms of accuracy and safety. The aim of this study is to evaluate the feasibility and accuracy of the novel, miniature, iSYS1 robotic guidance device in stereotactic neurosurgery. METHODS A preclinical phantom trial was conducted to compare the accuracy and duration of needle positioning between the robotic and manual technique in 162 cadaver biopsies. Second, 25 consecutive cases of tumor biopsies and intracranial catheter placements were performed with robotic guidance to evaluate the feasibility, accuracy, and duration of system setup and application in a clinical setting. RESULTS The preclinical phantom trial revealed a mean target error of 0.6 mm (range 0.1-0.9 mm) for robotic guidance versus 1.2 mm (range 0.1-2.6 mm) for manual positioning of the biopsy needle (p < 0.001). The mean duration was 2.6 minutes (range 1.3-5.5 minutes) with robotic guidance versus 3.7 minutes (range 2.0-10.5 minutes) with manual positioning (p < 0.001). Clinical application of the iSYS1 robotic guidance device was feasible in all but 1 case. The median real target error was 1.3 mm (range 0.2-2.6 mm) at entry and 0.9 mm (range 0.0-3.1 mm) at the target point. The median setup and instrument positioning times were 11.8 minutes (range 4.2-26.7 minutes) and 4.9 minutes (range 3.1-14.0 minutes), respectively. CONCLUSIONS According to the preclinical data, application of the iSYS1 robot can significantly improve accuracy and reduce instrument positioning time. During clinical application, the robot proved its high accuracy, short setup time, and short instrument positioning time, as well as demonstrating a short learning curve.

OBJECTIVEParasellar 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).METHODSThis 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.RESULTSInvasiveness 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.CONCLUSIONSAccording 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.

Context Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging. Objective We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness. Design and subjects Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients. Results Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated. Conclusion We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.

OBJECTIVE Internal carotid artery injury (ICAI) is a rare, life-threatening complication of endoscopic endonasal approaches that will be encountered by most skull base neurosurgeons and otolaryngologists. Rates of surgical proficiency for managing ICAI are not known, and the role of simulation to improve performance has not been studied on a nationwide scale. METHODS Attending and resident neurosurgery and otorhinolaryngology surgeons (n = 177) were recruited from multicenter regional and national training courses to assess training outcomes and validity at scale of a prospective educational intervention to improve surgeon technical skills using a previously validated, perfused human cadaveric simulator. Participants attempted an initial trial (T1) of simulated ICAI control using their preferred technique. An educational intervention including personalized instruction was performed. Participants attempted a second trial (T2). Task success (dichotomous), time to hemostasis (TTH), estimated blood loss (EBL), and surgeon heart rate were measured. RESULTS Participant rating scales confirmed that the simulation retained face and construct validity across eight instructional settings. Trial success (ICAI control) improved from 56% in T1 to 90% in T2 (p < 0.0001). EBL and TTH decreased by 37% and 38%, respectively (p < 0.0001). Postintervention resident surgeon performance (TTH, EBL, and success rate) was superior to preintervention attending surgeon performance. The most improved quartile of participants achieved 62% improvement in TTH and 73% improvement in EBL, with trial success improvement from 25.6% in T1 to 100% in T2 (p < 0.0001). Baseline surgeon confidence was uncorrelated with T1 success, while posttraining confidence correlated with T2 success. Tachycardia was measured in 57% of surgeon participants, but was attenuated during T2, consistent with development of resiliency. CONCLUSIONS Prior to training, many attending and most resident surgeons could not manage the rare, life-threatening intraoperative complication of ICAI. A simulated educational intervention significantly improved surgeon performance and remained valid when deployed at scale. Simulation also promoted the development of favorable cognitive skills (accurate perception of skill and resiliency). Rare, life-threatening intraoperative complications may be optimal targets for educational interventions using surgical simulation.

Context Cushing’s syndrome (CS) results in significant morbidity and mortality. Objective To study acute and life-threatening complications in patients with active CS. Design Retrospective cohort study. Setting In- and outpatient records of patients with CS in a tertiary center. Patients 242 patients with CS, including 213 with benign CS (pituitary n=101, adrenal n=99, ectopic n=13), and 29 with malignant disease. Main outcome measures We collected acute complications necessitating hospitalization, from appearance of first symptoms of hypercortisolism until one 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%). 23% of these patients were hospitalized for acute complications before CS was suspected, and half of complications occurred after the first surgery. HbA1c and 24-hour urinary free cortisol (UFC) 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.

OBJECTIVEPituitary adenoma (PA) consistency, or texture, is an important intraoperative characteristic that may dictate operative dissection techniques and/or instruments used for tumor removal during endoscopic endonasal approaches (EEAs). The impact of PA consistency on surgical outcomes has yet to be elucidated.METHODSThe authors developed an objective 5-point grading scale for PA consistency based on intraoperative characteristics, including ease of tumor debulking, manipulation, and instrument selection, ranging from cystic/hemorrhagic tumors (grade 1) to calcified tumors (grade 5). The proposed grading system was prospectively assessed in 306 consecutive patients who underwent an EEA for PAs, and who were subsequently analyzed for associations with surgical outcomes, including extent of resection (EOR) and complication profiles.RESULTSInstitutional database review identified 306 patients who underwent intraoperative assessment of PA consistency, of which 96% were macroadenomas, 70% had suprasellar extension, and 44% had cavernous sinus invasion (CSI). There were 214 (69.9%) nonfunctional PAs and 92 functional PAs (31.1%). Distribution of scores included 15 grade 1 tumors (4.9%), 112 grade 2 tumors (36.6%), 125 grade 3 tumors (40.8%), 52 grade 4 tumors (17%), and 2 grade 5 tumors (0.7%). Compared to grade 1/2 and grade 3 PAs, grade 4/5 PAs were significantly larger (22.5 vs 26.6 vs 27.4 mm, p < 0.01), more likely to exhibit CSI (39% vs 42% vs 59%, p < 0.05), and trended toward nonfunctionality (67% vs 68% vs 82%, p = 0.086). Although there was no association between PA consistency and preoperative headaches or visual dysfunction, grade 4/5 PAs trended toward preoperative (p = 0.058) and postoperative panhypopituitarism (p = 0.066). Patients with preoperative visual dysfunction experienced greater improvement if they had a grade 1/2 PA (p < 0.05). Intraoperative CSF leaks were noted in 32% of cases and were more common with higher-consistency-grade tumors (p = 0.048), although this difference did not translate to postoperative CSF leaks. Gross-total resection (%) was more likely with lower PA consistency score as follows: grade 1/2 (60%), grade 3 (50%), grade 4/5 (44%; p = 0.045). Extracapsular techniques were almost exclusively performed in grade 4/5 PAs. Assignment of scores showed low variance and high reproducibility, with an intraclass correlation coefficient of 0.905 (95% CI 0.815–0.958), indicating excellent interrater reliability.CONCLUSIONSThese findings demonstrate clinical validity of the proposed intraoperative grading scale with respect to PA subtype, neuroimaging features, EOR, and endocrine complications. Future studies will assess the relation of PA consistency to preoperative MRI findings to accurately predict consistency, thereby allowing the surgeon to tailor the exposure and prepare for varying resection strategies.