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Brett E. Youngerman, Matei A. Banu, Mina M. Gerges, Eseosa Odigie, Abtin Tabaee, Ashutosh Kacker, Vijay K. Anand and Theodore H. Schwartz

OBJECTIVE

The endoscopic endonasal approach (EEA) has gained increasing popularity for the resection of suprasellar meningiomas (SSMs). Appropriate case selection is critical in optimizing patient outcome. Long-term outcome data are lacking. The authors systematically identified preoperative factors associated with extent of resection (EOR) and determined the relationship between EOR and long-term recurrence after EEA for SSMs.

METHODS

In this retrospective cohort study, the authors identified preoperative clinical and imaging characteristics associated with EOR and built on the recently published University of California, San Francisco resectability score to propose a score more specific to the EEA. They then examined the relationship between gross-total resection (GTR; 100%), near-total resection (NTR; 95%–99%), and subtotal resection (STR; < 95%) and recurrence or progression with Kaplan-Meier survival analysis.

RESULTS

A total of 51 patients were identified. Radiographic GTR was achieved in 40 of 47 (85%) patients in whom it was the surgical goal. Significant independent risk factors for incomplete resection were prior surgery (OR 25.94, 95% CI < 2.00 to 336.49, p = 0.013); tumor lateral to the optic nerve (OR 13.41, 95% CI 1.82–98.99, p = 0.011); and complete internal carotid artery (ICA) encasement (OR 15.12, 95% CI 1.17–194.08, p = 0.037). Tumor size and optic canal invasion were not significant risk factors after adjustment for other variables. A resectability score based on the multivariable model successfully predicted the likelihood of GTR; a score of 0 had a positive predictive value of 97% for GTR, whereas a score of 2 had a negative predictive value of 87.5% for incomplete resection. After a mean follow-up of 40.6 ± 32.4 months (mean ± SD), recurrence was 2.7% after GTR (1 patient with atypical histology), 44.4% after NTR, and 80% after STR (p < 0.0001). Vision was stable or improved in 93.5% and improved in 67.4% of patients with a preoperative deficit. There were 5 (9.8%) postoperative CSF leaks, of which 4 were managed with lumbar drains and 1 required a reoperation.

CONCLUSIONS

The EEA is a safe and effective approach to SSMs, with favorable visual outcomes in well-selected cases. The combination of postoperative MRI-based EOR with direct endoscopic inspection can be used in lieu of Simpson grade to predict recurrence. GTR dramatically reduces recurrence and can be achieved regardless of tumor size, proximity or encasement of the anterior cerebral artery, or medial optic canal invasion. Risk factors for incomplete resection include prior surgery, tumor lateral to the optic nerve, and complete ICA encasement.

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Diana A. Julie, Stefanie P. Lazow, Daniel B. Vanderbilt, Shoshana Taube, Menachem Z. Yondorf, Albert Sabbas, Susan Pannullo, Theodore H. Schwartz and A. Gabriella Wernicke

OBJECTIVE

Adjuvant radiation therapy (RT), such as cesium-131 (Cs-131) brachytherapy or stereotactic radiosurgery (SRS), reduces local recurrence (LR) of brain metastases (BM). However, SRS is less efficacious for large cavities, and the delay between surgery and SRS may permit tumor repopulation. Cs-131 has demonstrated improved local control, with reduced radiation necrosis (RN) compared to SRS. This study represents the first comparison of outcomes between Cs-131 brachytherapy and SRS for resected BM.

METHODS

Patients with BM treated with Cs-131 and SRS following gross-total resection were retrospectively identified. Thirty patients who underwent Cs-131 brachytherapy were compared to 60 controls who received SRS. Controls were selected from a larger cohort to match the patients treated with Cs-131 in a 2:1 ratio according to tumor size, histology, performance status, and recursive partitioning analysis class. Overall survival (OS), LR, regional recurrence, distant recurrence (DR), and RN were compared.

RESULTS

With a median follow-up of 17.5 months for Cs-131–treated and 13.0 months for SRS-treated patients, the LR rate was significantly lower with brachytherapy; 10% for the Cs-131 cohort compared to 28.3% for SRS patients (OR 0.281, 95% CI 0.082–0.949; p = 0.049). Rates of regional recurrence, DR, and OS did not differ significantly between the two cohorts. Kaplan-Meier analysis with log-rank testing showed a significantly higher likelihood of freedom from LR (p = 0.027) as well as DR (p = 0.018) after Cs-131 compared to SRS treatment (p = 0.027), but no difference in likelihood of OS (p = 0.093). Six (10.0%) patients who underwent SRS experienced RN compared to 1 (3.3%) patient who received Cs-131 (p = 0.417).

CONCLUSIONS

Postresection patients with BM treated with Cs-131 brachytherapy were more likely to achieve local control compared to SRS-treated patients. This study provides preliminary evidence of the potential of Cs-131 to reduce LR following gross-total resection of single BM, with minimal toxicity, and suggests the need for a prospective study to address this question.

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Mina M. Gerges, Brett Youngerman, Vijay K. Anand, Jeffrey P. Greenfield and Theodore H. Schwartz

An 8-year-old child presented with fatigue, weight loss, and visual deterioration. MRI demonstrated a craniopharyngioma with compression of the optic chiasm and extensive edema on the hypothalamus and optic radiations. The tumor was completely removed via an endoscopic endonasal approach. Postoperatively, vision improved and hypothalamic edema completely resolved within 5 days. This video demonstrates the technical nuances of the surgery and discusses the impact of surgery on the hypothalamic nuclei in pediatric patients.

The video can be found here: https://youtu.be/wxkBmhTPi6c.

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Iyan Younus, Mina Gerges, Theodore H. Schwartz and Rohan Ramakrishna

OBJECTIVE

Despite the rise of studies in the neurosurgical literature suggesting that patients with Medicaid insurance have inferior outcomes, there remains a paucity of data on the impact of insurance on outcomes after endonasal endoscopic transsphenoidal surgery (EETS). Given the increasing importance of complications in quality-based healthcare metrics, the objective of this study was to assess whether Medicaid insurance type influences outcomes in EETS for pituitary adenoma.

METHODS

The authors analyzed a prospectively acquired database of EETS for pituitary adenoma from 2005 to 2018 at NewYork-Presbyterian Hospital, Weill Cornell Medicine. All patients with Medicaid insurance were identified. As a control group, the clinical, socioeconomic, and radiographic data of all other patients in the series with non-Medicaid insurance were reviewed. Statistical significance was determined with an alpha < 0.05 using Pearson chi-square and Fisher’s exact tests for categorical variables and the independent-samples t-test for continuous variables.

RESULTS

Of 584 patients undergoing EETS for pituitary adenoma, 57 (10%) had Medicaid insurance. The maximum tumor diameter was significantly larger for Medicaid patients (26.1 ± 12 vs 23.1 ± 11 mm for controls, p < 0.05). Baseline comorbidities including diabetes mellitus, hypertension, smoking history, and BMI were not significantly different between Medicaid patients and controls. Patients with Medicaid insurance had a significantly higher rate of any complication (14% vs 7% for controls, p < 0.05) and long-term cranial neuropathy (5% vs 1% for controls, p < 0.05). There were no statistically significant differences in endocrine outcome or vision outcome. The mean postoperative length of stay was significantly longer for Medicaid patients compared to the controls (9.4 ± 31 vs 3.6 ± 3 days, p < 0.05). This difference remained significant even when accounting for outliers (5.6 ± 2.5 vs 3.0 ± 2.7 days for controls, p < 0.05). The most common causes of extended length of stay greater than 1 standard deviation for Medicaid patients were management of perioperative complications and disposition challenges. The rate of 30-day readmission was 7% for Medicaid patients and 4.4% for controls, which was not a statistically significant difference.

CONCLUSIONS

The authors found that larger tumor diameter, longer postoperative length of stay, higher rate of complications, and long-term cranial neuropathy were significantly associated with Medicaid insurance. There were no statistically significant differences in baseline comorbidities, apoplexy, endocrine outcome, vision outcome, or 30-day readmission.

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Danielle Golub, Jonathan Hyde, Siddhant Dogra, Joseph Nicholson, Katherine A. Kirkwood, Paulomi Gohel, Stephen Loftus and Theodore H. Schwartz

OBJECTIVE

High-grade gliomas (HGGs) continue to carry poor prognoses, and patient outcomes depend heavily on the extent of resection (EOR). The utility of conventional image-guided surgery is limited by intraoperative brain shift. More recent techniques to maximize EOR, including intraoperative imaging and the use of fluorescent dyes, combat these limitations. However, the relative efficacy of these two techniques has never been systematically compared. Thus, the authors performed an exhaustive systematic review in conjunction with quantitative network meta-analyses to evaluate the comparative effectiveness of 5-aminolevulinic acid (5-ALA) and intraoperative MRI (IMRI) in optimizing EOR in HGG. They secondarily analyzed associated progression-free and overall survival and performed subgroup analyses by level of evidence.

METHODS

PubMed, Embase, Cochrane Central, and Web of Science were searched for studies evaluating conventional neuronavigation, IMRI, and 5-ALA in HGG resection. The primary study endpoint was the proportion of patients attaining gross-total resection (GTR), defined as 100% elimination of contrast-enhancing lesion on postoperative MRI. Secondary endpoints included overall and progression-free survival and subgroup analyses for level of evidence. Comparative efficacy analysis of IMRI and 5-ALA was performed using Bayesian network meta-analysis models.

RESULTS

This analysis included 11 studies. In a classic meta-analysis, both IMRI (OR 4.99, 95% CI 2.65–9.39, p < 0.001) and 5-ALA (OR 2.866, 95% CI 2.127–3.863, p < 0.001) were superior to conventional navigation in achieving GTR. Bayesian network analysis was employed to indirectly compare IMRI to 5-ALA, and no significant difference in GTR was found between the two (OR 1.9 favoring IMRI, 95% CI 0.905–3.989, p = 0.090). A handful of studies additionally suggested that the use of either IMRI (2 and 4 studies, respectively) or 5-ALA (2 and 2 studies, respectively) improves progression-free and overall survival.

CONCLUSIONS

IMRI and 5-ALA are individually superior to conventional neuronavigation for achieving GTR of HGG. Between IMRI and 5-ALA, neither method is clearly more effective. Future studies evaluating the comparative cost and surgical time associated with IMRI and 5-ALA will better inform any cost-benefit analysis.

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Iyan Younus, Mina M. Gerges, Rafael Uribe-Cardenas, Peter F. Morgenstern, Mahmoud Eljalby, Abtin Tabaee, Jeffrey P. Greenfield, Ashutosh Kacker, Vijay K. Anand and Theodore H. Schwartz

OBJECTIVE

Endoscopic endonasal approaches (EEAs) to the skull base have evolved over the last 20 years to become an essential component of a comprehensive skull base practice. Many case series show a learning curve from the earliest cases, in which the authors were inexperienced or were not using advanced closure techniques. It is generally accepted that once this learning curve is achieved, a plateau is reached with little incremental improvement. Cases performed during the early steep learning curve were eliminated to examine whether the continued improvement exists over the “tail end” of the curve.

METHODS

A prospectively acquired database of all EEA cases performed by the senior authors at Weill Cornell Medicine/NewYork-Presbyterian Hospital was reviewed. The first 200 cases were eliminated and the next 1000 consecutive cases were examined to avoid the bias created by the early learning curve.

RESULTS

Of the 1000 cases, the most common pathologies included pituitary adenoma (51%), meningoencephalocele or CSF leak repair (8.6%), meningioma (8.4%), craniopharyngioma (7.3%), basilar invagination (3.1%), Rathke’s cleft cyst (2.8%), and chordoma (2.4%). Use of lumbar drains decreased from the first half to the second half of our series (p <0.05) as did the authors’ use of fat alone (p <0.005) or gasket alone (p <0.005) for dural closure, while the use of a nasoseptal flap increased (p <0.005). Although mean tumor diameter was constant (on average), gross-total resection (GTR) increased from 60% in the first half to 73% in the second half (p <0.005). GTR increased for all pathologies but most significantly for chordoma (56% vs 100%, p <0.05), craniopharyngioma (47% vs 0.71%, p <0.05) and pituitary adenoma (67% vs 75%, p <0.05). Hormonal cure for secreting adenomas also increased from 83% in the first half to 89% in the second half (p <0.05). The rate of any complication was unchanged at 6.4% in the first half and 6.2% in the latter half of cases, and vascular injury occurred in only 0.6% of cases. Postoperative CSF leak occurred in 2% of cases and was unchanged between the first and second half of the series.

CONCLUSIONS

This study demonstrates that contrary to popular belief, the surgical learning curve does not plateau but can continue for several years depending on the complexity of the endpoints considered. These findings may have implications for clinical trial design, surgical education, and patient safety measures.

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Mina M. Gerges, Kavelin Rumalla, Saniya S. Godil, Iyan Younus, Walid Elshamy, Georgiana A. Dobri, Ashutosh Kacker, Abtin Tabaee, Viay K. Anand and Theodore H. Schwartz

OBJECTIVE

Nonfunctioning pituitary adenomas are benign, slow-growing tumors. After gross-total resection (GTR) or subtotal resection (STR), tumors can recur or progress and may ultimately require additional intervention. A greater understanding of long-term recurrence and progression rates following complete or partial resection and the need for further intervention will help clinicians provide meaningful counsel for their patients and assist data-driven decision-making.

METHODS

The authors retrospectively analyzed their institutional database for patients undergoing endoscopic endonasal surgery (EES) for nonfunctioning pituitary macroadenomas (2003–2014). Only patients with follow-up of at least 5 years after surgery were included. Tumor volumes were measured on pre- and postoperative MRI. Tumor recurrence was defined as the presence of a 0.1-cm3 tumor volume after GTR, and tumor progression was defined as a 25.0% increase in residual tumor after STR.

RESULTS

A total of 190 patients were included, with a mean age of 63.8 ± 13.2 years; 79 (41.6%) were female. The mean follow-up was 75.0 ± 18.0 months. GTR was achieved in 127 (66.8%) patients. In multivariate analysis, age (p = 0.04), preoperative tumor volume (p = 0.03), Knosp score (p < 0.001), and Ki-67 (p = 0.03) were significant predictors of STR. In patients with GTR, the probability of recurrence at 5 and 10 years was 3.9% and 4.7%, and the probability of requiring treatment for recurrence was 0.79% and 1.6%, respectively. In 63 patients who underwent STR, 6 (9.5%) received early postoperative radiation and did not experience progression, while the remaining 57 (90.5%) were observed. Of these, the probability of disease progression at 5 and 10 years was 21% and 24.5%, respectively, and the probability of requiring additional treatment for progression was 17.5% and 21%. Predictors of recurrence or progression in the entire group were Knosp score (p < 0.001) and elevated Ki-67 (p = 0.03). Significant predictors of progression after STR in those who did not receive early radiotherapy were cavernous sinus location (p < 0.05) and tumor size > 1.0 cm3 (p = 0.005).

CONCLUSIONS

Following GTR for nonfunctioning pituitary adenomas, the 10-year chance of recurrence is low and the need for treatment even lower. After STR, although upfront radiation therapy may prevent progression, even without radiotherapy, the need for intervention at 10 years is only approximately 20% and a period of observation may be warranted to prevent unnecessary prophylactic radiation therapy. Tumor volume > 1 cm3, Knosp score ≥ 3, and Ki-67 ≥ 3% may be useful metrics to prompt closer follow-up or justify early prophylactic radiation therapy.

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Swathi Chidambaram, Susan C. Pannullo, Michelle Roytman, David J. Pisapia, Benjamin Liechty, Rajiv S. Magge, Rohan Ramakrishna, Philip E. Stieg, Theodore H. Schwartz and Jana Ivanidze

OBJECTIVE

There is a need for advanced imaging biomarkers to improve radiation treatment planning and response assessment. T1-weighted dynamic contrast-enhanced perfusion MRI (DCE MRI) allows quantitative assessment of tissue perfusion and blood-brain barrier dysfunction and has entered clinical practice in the management of primary and secondary brain neoplasms. The authors sought to retrospectively investigate DCE MRI parameters in meningiomas treated with resection and adjuvant radiation therapy using volumetric segmentation.

METHODS

A retrospective review of more than 300 patients with meningiomas resected between January 2015 and December 2018 identified 14 eligible patients with 18 meningiomas who underwent resection and adjuvant radiotherapy. Patients were excluded if they did not undergo adjuvant radiation therapy or DCE MRI. Demographic and clinical characteristics were obtained and compared to DCE perfusion metrics, including mean plasma volume (v p), extracellular volume (v e), volume transfer constant (K trans), rate constant (k ep), and wash-in rate of contrast into the tissue, which were derived from volumetric analysis of the enhancing volumes of interest.

RESULTS

The mean patient age was 64 years (range 49–86 years), and 50% of patients (7/14) were female. The average tumor volume was 8.07 cm3 (range 0.21–27.89 cm3). The median Ki-67 in the cohort was 15%. When stratified by median Ki-67, patients with Ki-67 greater than 15% had lower median v p (0.02 vs 0.10, p = 0.002), and lower median wash-in rate (1.27 vs 4.08 sec−1, p = 0.04) than patients with Ki-67 of 15% or below. Logistic regression analysis demonstrated a statistically significant, moderate positive correlation between v e and time to progression (r = 0.49, p < 0.05). Furthermore, there was a moderate positive correlation between K trans and time to progression, which approached, but did not reach, statistical significance (r = 0.48, p = 0.05).

CONCLUSIONS

This study demonstrates a potential role for DCE MRI in the preoperative characterization and stratification of meningiomas, laying the foundation for future prospective studies incorporating DCE as a biomarker in meningioma diagnosis and treatment planning.

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Lessons learned in the evolution of endoscopic skull base surgery

JNSPG 75th Anniversary Invited Review Article

Theodore H. Schwartz, Peter F. Morgenstern and Vijay K. Anand

OBJECTIVE

Endoscopic skull base surgery (ESBS) is a relatively recent addition to the neurosurgical armamentarium. As with many new approaches, there has been significant controversy regarding its value compared with more traditional approaches to ventral skull base pathology. Although early enthusiasm for new approaches that appear less invasive is usually high, these new techniques require rigorous study to ensure that widespread implementation is in the best interest of patients.

METHODS

The authors compared surgical results for ESBS with transcranial surgery (TCS) for several different pathologies over two different time periods (prior to 2012 and 2012–2017) to see how results have evolved over time. Pathologies examined were craniopharyngioma, anterior skull base meningioma, esthesioneuroblastoma, chordoma, and chondrosarcoma.

RESULTS

ESBS offers clear advantages over TCS for most craniopharyngiomas and chordomas. For well-selected cases of planum sphenoidale and tuberculum sellae meningiomas, ESBS has similar rates of resection with higher rates of visual improvement, and more recent results with lower CSF leaks make the complication rates similar between the two approaches. TCS offers a higher rate of resection with fewer complications for olfactory groove meningiomas. ESBS is preferred for lower-grade esthesioneuroblastomas, but higher-grade tumors often still require a craniofacial approach. There are few data on chondrosarcomas, but early results show that ESBS appears to offer clear advantages for minimizing morbidity with similar rates of resection, as long as surgeons are familiar with more complex inferolateral approaches.

CONCLUSIONS

ESBS is maturing into a well-established approach that is clearly in the patients’ best interest when applied by experienced surgeons for appropriate pathology. Ongoing critical reevaluation of outcomes is essential for ensuring optimal results.

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Edgar G. Ordóñez-Rubiano, Jonathan A. Forbes, Peter F. Morgenstern, Leopold Arko, Georgiana A. Dobri, Jeffrey P. Greenfield, Mark M. Souweidane, Apostolos John Tsiouris, Vijay K. Anand, Ashutosh Kacker and Theodore H. Schwartz

OBJECTIVE

Gross-total resection (GTR) of craniopharyngiomas (CPs) is potentially curative and is often the goal of surgery, but endocrinopathy generally results if the stalk is sacrificed. In some cases, GTR can be attempted while still preserving the stalk; however, stalk manipulation or devascularization may cause endocrinopathy and this strategy risks leaving behind small tumor remnants that can recur.

METHODS

A retrospective review of a prospective cohort of patients who underwent initial resection of CP using the endoscopic endonasal approach over a period of 12 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, was performed. Postresection integrity of the stalk was retrospectively assessed using operative notes, videos, and postoperative MRI. Tumors were classified based on location into type I (sellar), type II (sellar-suprasellar), and type III (purely suprasellar). Pre- and postoperative endocrine function, tumor location, body mass index, rate of GTR, radiation therapy, and complications were reviewed.

RESULTS

A total of 54 patients who had undergone endoscopic endonasal procedures for first-time resection of CP were identified. The stalk was preserved in 33 (61%) and sacrificed in 21 (39%) patients. GTR was achieved in 24 patients (73%) with stalk preservation and 21 patients (100%) with stalk sacrifice (p = 0.007). Stalk-preservation surgery achieved GTR and maintained completely normal pituitary function in only 4 (12%) of 33 patients. Permanent postoperative diabetes insipidus was present in 16 patients (49%) with stalk preservation and in 20 patients (95%) following stalk sacrifice (p = 0.002). In the stalk-preservation group, rates of progression and radiation were higher with intentional subtotal resection or near-total resection compared to GTR (67% vs 0%, p < 0.001, and 100% vs 12.5%, p < 0.001, respectively). However, for the subgroup of patients in whom GTR was achieved, stalk preservation did not lead to significantly higher rates of recurrence (12.5%) compared with those in whom it was sacrificed (5%, p = 0.61), and stalk preservation prevented anterior pituitary insufficiency in 33% and diabetes insipidus in 50%.

CONCLUSIONS

While the decision to preserve the stalk reduces the rate of postoperative endocrinopathy by roughly 50%, nevertheless significant dysfunction of the anterior and posterior pituitary often ensues. The decision to preserve the stalk does not guarantee preserved endocrine function and comes with a higher risk of progression and need for adjuvant therapy. Nevertheless, to reduce postoperative endocrinopathy attempts should be made to preserve the stalk if GTR can be achieved.