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Andrew S. Little, Daniel F. Kelly, William L. White, Paul A. Gardner, Juan C. Fernandez-Miranda, Michael R. Chicoine, Garni Barkhoudarian, James P. Chandler, Daniel M. Prevedello, Brandon D. Liebelt, John Sfondouris, Marc R. Mayberg and for the TRANSSPHER Study Group

OBJECTIVE

Many surgeons have adopted fully endoscopic over microscopic transsphenoidal surgery for nonfunctioning pituitary tumors, although no high-quality evidence demonstrates superior patient outcomes with endoscopic surgery. The goal of this analysis was to compare these techniques in a prospective multicenter controlled study.

METHODS

Extent of tumor resection was compared after endoscopic or microscopic transsphenoidal surgery in adults with nonfunctioning adenomas. The primary end point was gross-total tumor resection determined by postoperative MRI. Secondary end points included volumetric extent of tumor resection, pituitary hormone outcomes, and standard quality measures.

RESULTS

Seven pituitary centers and 15 surgeons participated in the study. Of the 530 patients screened, 260 were enrolled (82 who underwent microscopic procedures, 177 who underwent endoscopic procedures, and 1 who cancelled surgery) between February 2015 and June 2017. Surgeons who used the microscopic technique were more experienced than the surgeons who used the endoscopic technique in terms of years in practice and number of transsphenoidal surgeries performed (p < 0.001). Gross-total resection was achieved in 80.0% (60/75) of microscopic surgery patients and 83.7% (139/166) of endoscopic surgery patients (p = 0.47, OR 0.8, 95% CI 0.4–1.6). Volumetric extent of resection, length of stay, surgery-related deaths, and unplanned readmission rates were similar between groups (p > 0.2). New hormone deficiency was present at 6 months in 28.4% (19/67) of the microscopic surgery patients and 9.7% (14/145) of the endoscopic surgery patients (p < 0.001, OR 3.7, 95% CI 1.7–7.7). Microscopic surgery cases were significantly shorter in duration than endoscopic surgery cases (p < 0.001).

CONCLUSIONS

Experienced surgeons who performed microscopic surgery and less experienced surgeons who performed endoscopic surgery achieved similar extents of tumor resection and quality outcomes in patients with nonfunctioning pituitary adenomas. The endoscopic technique may be associated with lower rates of postoperative pituitary gland dysfunction. This study generally supports the transition to endoscopic pituitary surgery when the procedure is performed by proficient surgeons, although both techniques yield overall acceptable surgical outcomes.

CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: prospective cohort trial; evidence: class III.

Clinical trial registration no.: NCT02357498 (clinicaltrials.gov)

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Ali Tayebi Meybodi, Leandro Borba Moreira, Andrew S. Little, Michael T. Lawton and Mark C. Preul

OBJECTIVE

Endoscopic endonasal approaches (EEAs) are increasingly being incorporated into the neurosurgeon’s armamentarium for treatment of various pathologies, including paraclinoid aneurysms. However, few anatomical assessments have been performed on the use of EEA for this purpose. The aim of the present study was to provide a comprehensive anatomical assessment of the EEA for the treatment of paraclinoid aneurysms.

METHODS

Five cadaveric heads underwent an endonasal transplanum-transtuberculum approach to expose the paraclinoid area. The feasibility of obtaining proximal and distal internal carotid artery (ICA) control as well as the topographic location of the origin of the ophthalmic artery (OphA) relative to dural landmarks were assessed. Limitations of the EEA in exposing the supraclinoid ICA were also recorded to identify favorable paraclinoid ICA aneurysm projections for EEA.

RESULTS

The extracavernous paraclival and clinoidal ICAs were favorable segments for establishing proximal control. Clipping the extracavernous ICA risked injury to the trigeminal and abducens nerves, whereas clipping the clinoidal segment put the oculomotor nerve at risk. The OphA origin was found within 4 mm of the medial opticocarotid point on a line connecting the midtubercular recess point to the medial vertex of the lateral opticocarotid recess. An average 7.2-mm length of the supraclinoid ICA could be safely clipped for distal control. Assessments showed that small superiorly or medially projecting aneurysms were favorable candidates for clipping via EEA.

CONCLUSIONS

When used for paraclinoid aneurysms, the EEA carries certain risks to adjacent neurovascular structures during proximal control, dural opening, and distal control. While some authors have promoted this approach as feasible, this work demonstrates that it has significant limitations and may only be appropriate in highly selected cases that are not amenable to coiling or clipping. Further clinical experience with this approach helps to delineate its risks and benefits.

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David G. Brachman, Emad Youssef, Christopher J. Dardis, Nader Sanai, Joseph M. Zabramski, Kris A. Smith, Andrew S. Little, Andrew G. Shetter, Theresa Thomas, Heyoung L. McBride, Stephen Sorensen, Robert F. Spetzler and Peter Nakaji

OBJECTIVE

Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas.

METHODS

Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression.

RESULTS

Nineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9–92.0 cm3). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically.

CONCLUSIONS

R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

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Colin J. Przybylowski, Tyler S. Cole, Jacob F. Baranoski, Andrew S. Little, Kris A. Smith and Andrew G. Shetter

OBJECTIVE

The objective of this study was to assess long-term outcomes of facial pain and numbness after radiosurgery for multiple sclerosis (MS)–related trigeminal neuralgia (MS-TN).

METHODS

The authors conducted a retrospective review of their Gamma Knife radiosurgeries (GKRSs) to identify all patients treated for MS-TN (1998–2014) with at least 3 years of follow-up. Treatment and clinical data were obtained via chart review and mailed or telephone surveys. Pain control was defined as a facial pain score of I–IIIb on the Barrow Neurological Institute (BNI) Facial Pain Intensity Scale. Kaplan-Meier analysis was performed to determine the rates of pain control after index and first salvage GKRS procedures. Patients could have had more than 1 salvage procedure. Pain control rates were based on the number of patients at risk during follow-up.

RESULTS

Of the 50 living patients who underwent GKRS, 42 responded to surveys (31 women [74%], median age 59 years, range 32–76 years). During the initial GKRS, the trigeminal nerve root entry zone was targeted with a single isocenter, using a 4-mm collimator with the 90% isodose line completely covering the trigeminal nerve and the 50% isodose line abutting the surface of the brainstem. The median maximum radiation dose was 85 Gy (range 50–85 Gy). The median follow-up period was 78 months (range 36–226 months). The rate of pain control after the index GKRS (n = 42) was 62%, 29%, 22%, and 13% at 1, 3, 5, and 7 years, respectively. Twenty-eight patients (67%) underwent salvage treatment, including 25 (60%) whose first salvage treatment was GKRS. The rate of pain control after the first salvage GKRS (n = 25) was 84%, 50%, 44%, and 17% at 1, 3, 5, and 7 years, respectively. The rate of pain control after the index GKRS with or without 1 salvage GKRS (n = 33) was 92%, 72%, 52%, 46%, and 17% at 1, 3, 5, 7, and 10 years, respectively. At last follow-up, 9 (21%) of the 42 patients had BNI grade I facial pain, 35 (83%) had achieved pain control, and 4 (10%) had BNI grade IV facial numbness (very bothersome in daily life).

CONCLUSIONS

Index GKRS offers good short-term pain control for MS-TN, but long-term pain control is uncommon. If the index GKRS fails, salvage GKRS appears to offer beneficial pain control with low rates of bothersome facial numbness.

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Ali Tayebi Meybodi, Andrew S. Little, Vera Vigo, Arnau Benet, Sofia Kakaizada and Michael T. Lawton

OBJECTIVE

The transpterygoid extension of the endoscopic endonasal approach provides exposure of the petrous apex, Meckel’s cave, paraclival area, and the infratemporal fossa. Safe and efficient localization of the lacerum segment of the internal carotid artery (ICA) is a crucial part of such exposure. The aim of this study is to introduce a novel landmark for localization of the lacerum ICA.

METHODS

Ten cadaveric heads were prepared for transnasal endoscopic dissection. The floor of the sphenoid sinus was drilled to expose an extension of the pharyngobasilar fascia between the sphenoid floor and the pterygoid process (the pterygoclival ligament). Several features of the pterygoclival ligament were assessed. In addition, 31 dry skulls were studied to assess features of the bony groove harboring the pterygoclival ligament.

RESULTS

The pterygoclival ligament was identified bilaterally during drilling of the sphenoid floor in all specimens. The ligament started a few millimeters posterior to the posterior end of the vomer alae and invariably extended posterolaterally and superiorly to blend into the fibrous tissue around the lacerum ICA. The mean length of the ligament was 10.5 ± 1.7 mm. The mean distance between the anterior end of the ligament and midline was 5.2 ± 1.2 mm. The mean distance between the posterior end of the ligament and midline was 12.3 ± 1.4 mm. The bony pterygoclival groove was identified at the confluence of the vomer, pterygoid process of the sphenoid, and basilar part of the occipital bone, running from posterolateral to anteromedial. The mean length of the groove was 7.7 ± 1.8 mm. Its posterolateral end faced the anteromedial aspect of the foramen lacerum medial to the posterior end of the vidian canal. A clinical case illustration is also provided.

CONCLUSIONS

The pterygoclival ligament is a consistent landmark for localization of the lacerum ICA. It may be used as an adjunct or alternative to the vidian nerve to localize the ICA during endoscopic endonasal surgery.

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Seungwon Yoon, Michael A. Mooney, Michael A. Bohl, John P. Sheehy, Peter Nakaji, Andrew S. Little and Michael T. Lawton

OBJECTIVE

With drastic changes to the health insurance market, patient cost sharing has significantly increased in recent years. However, the patient financial burden, or out-of-pocket (OOP) costs, for surgical procedures is poorly understood. The goal of this study was to analyze patient OOP spending in cranial neurosurgery and identify drivers of OOP spending growth.

METHODS

For 6569 consecutive patients who underwent cranial neurosurgery from 2013 to 2016 at the authors’ institution, the authors created univariate and multivariate mixed-effects models to investigate the effect of patient demographic and clinical factors on patient OOP spending. The authors examined OOP payments stratified into 10 subsets of case categories and created a generalized linear model to study the growth of OOP spending over time.

RESULTS

In the multivariate model, case categories (craniotomy for pain, tumor, and vascular lesions), commercial insurance, and out-of-network plans were significant predictors of higher OOP payments for patients (all p < 0.05). Patient spending varied substantially across procedure types, with patients undergoing craniotomy for pain ($1151 ± $209) having the highest mean OOP payments. On average, commercially insured patients spent nearly twice as much in OOP payments as the overall population. From 2013 to 2016, the mean patient OOP spending increased 17%, from $598 to $698 per patient encounter. Commercially insured patients experienced more significant growth in OOP spending, with a cumulative rate of growth of 42% ($991 in 2013 to $1403 in 2016).

CONCLUSIONS

Even after controlling for inflation, case-mix differences, and partial fiscal periods, OOP spending for cranial neurosurgery patients significantly increased from 2013 to 2016. The mean OOP spending for commercially insured neurosurgical patients exceeded $1400 in 2016, with an average annual growth rate of 13%. As patient cost sharing in health insurance plans becomes more prevalent, patients and providers must consider the potential financial burden for patients receiving specialized neurosurgical care.

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Michael A. Mooney, Joseph Georges, Mohammedhassan Izady Yazdanabadi, Katherine Y. Goehring, William L. White, Andrew S. Little, Mark C. Preul, Stephen W. Coons, Peter Nakaji and Jennifer M. Eschbacher

OBJECTIVE

The objective of this study was to evaluate the feasibility of using confocal reflectance microscopy (CRM) ex vivo to differentiate adenoma from normal pituitary gland in surgical biopsy specimens. CRM allows for rapid, label-free evaluation of biopsy specimens with cellular resolution while avoiding some limitations of frozen section analysis.

METHODS

Biopsy specimens from 11 patients with suspected pituitary adenomas were transported directly to the pathology department. Samples were immediately positioned and visualized with CRM using a confocal microscope located in the same area of the pathology department where frozen sections are prepared. An H & E–stained slide was subsequently prepared from imaged tissue. A neuropathologist compared the histopathological characteristics of the H & E–stained slide and the matched CRM images. A second neuropathologist reviewed images in a blinded fashion and assigned diagnoses of adenoma or normal gland.

RESULTS

For all specimens, CRM contrasted cellularity, tissue architecture, nuclear pleomorphism, vascularity, and stroma. Pituitary adenomas demonstrated sheets and large lobules of cells, similar to the matched H & E–stained slides. CRM images of normal tissue showed scattered small lobules of pituitary epithelial cells, consistent with matched H & E–stained images of normal gland. Blinded review by a neuropathologist confirmed the diagnosis in 15 (94%) of 16 images of adenoma versus normal gland.

CONCLUSIONS

CRM is a simple, reliable approach for rapidly evaluating pituitary adenoma specimens ex vivo. This technique can be used to accurately differentiate between pituitary adenoma and normal gland while preserving biopsy tissue for future permanent analysis, immunohistochemical studies, and molecular studies.

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Michael A. Mooney, Douglas A. Hardesty, John P. Sheehy, Robert Bird, Kristina Chapple, William L. White and Andrew S. Little

OBJECTIVE

The goal of this study was to determine the interrater and intrarater reliability of the Knosp grading scale for predicting pituitary adenoma cavernous sinus (CS) involvement.

METHODS

Six independent raters (3 neurosurgery residents, 2 pituitary surgeons, and 1 neuroradiologist) participated in the study. Each rater scored 50 unique pituitary MRI scans (with contrast) of biopsy-proven pituitary adenoma. Reliabilities for the full scale were determined 3 ways: 1) using all 50 scans, 2) using scans with midrange scores versus end scores, and 3) using a dichotomized scale that reflects common clinical practice. The performance of resident raters was compared with that of faculty raters to assess the influence of training level on reliability.

RESULTS

Overall, the interrater reliability of the Knosp scale was “strong” (0.73, 95% CI 0.56–0.84). However, the percent agreement for all 6 reviewers was only 10% (26% for faculty members, 30% for residents). The reliability of the middle scores (i.e., average rated Knosp Grades 1 and 2) was “very weak” (0.18, 95% CI −0.27 to 0.56) and the percent agreement for all reviewers was only 5%. When the scale was dichotomized into tumors unlikely to have intraoperative CS involvement (Grades 0, 1, and 2) and those likely to have CS involvement (Grades 3 and 4), the reliability was “strong” (0.60, 95% CI 0.39–0.75) and the percent agreement for all raters improved to 60%. There was no significant difference in reliability between residents and faculty (residents 0.72, 95% CI 0.55–0.83 vs faculty 0.73, 95% CI 0.56–0.84). Intrarater reliability was moderate to strong and increased with the level of experience.

CONCLUSIONS

Although these findings suggest that the Knosp grading scale has acceptable interrater reliability overall, it raises important questions about the “very weak” reliability of the scale's middle grades. By dichotomizing the scale into clinically useful groups, the authors were able to address the poor reliability and percent agreement of the intermediate grades and to isolate the most important grades for use in surgical decision making (Grades 3 and 4). Authors of future pituitary surgery studies should consider reporting Knosp grades as dichotomized results rather than as the full scale to optimize the reliability of the scale.