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Vijay R. Ramakrishnan, Jeffrey D. Suh, Jennifer Y. Lee, Bert W. O'Malley Jr., M. Sean Grady and James N. Palmer


As tumors enlarge, they generally grow along paths of least resistance. For pituitary macroadenomas, extrasellar extension into the suprasellar region, cavernous sinus, or sphenoid sinus may occur. The sphenoid sinus is known to have a variable anatomical configuration, and the authors hypothesize that certain anatomical factors may resist tumor expansion into the sphenoid sinus, thereby directing tumor growth into the suprasellar space. In this paper the authors' goal was to determine if sphenoid anatomy influences pituitary tumor growth.


The authors conducted a retrospective analysis of 106 consecutive surgical cases of pituitary macroadenoma. Patient demographics, suprasellar extension, sellar width, and features of the sphenoid intersinus septum were recorded on radiographic review. The chi-square test, t-test, logistic regression, and classification and regression tree analysis were used for statistical analysis.


Of the 106 patients included in the study, 71 (67%) demonstrated suprasellar extension of their tumor. Patients with suprasellar tumor extension had significantly greater intersinus septum width (width > 1.27 mm: OR = 14.32; p = 0.0012) and were significantly older (age > 54 yrs: OR = 3.33; p = 0.0176). They also tended to be male and to have two or more sphenoid partitions (OR = 6.58; p = 0.0306). While patients with suprasellar extension tended to be more likely to have a midline partition and a larger sellar width than their counterparts, these differences did not reach statistical significance.


Certain aspects of the sphenoid sinus anatomy may function to resist pituitary tumor growth into the sphenoid sinus. Progressive enlargement of pituitary macroadenomas may extend in a suprasellar direction, in part, as a consequence of the sphenoid sinus anatomy.

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John Y. K. Lee, Steve S. Cho, Ryan Zeh, John T. Pierce, Maria Martinez-Lage, Nithin D. Adappa, James N. Palmer, Jason G. Newman, Kim O. Learned, Caitlin White, Julia Kharlip, Peter Snyder, Philip S. Low, Sunil Singhal and M. Sean Grady


Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%–20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented.


Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2–4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression.


Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance.


Pituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

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Peter J. Madsen, Vivek P. Buch, Jennifer E. Douglas, Arjun K. Parasher, David K. Lerner, Erin Alexander, Alan D. Workman, James N. Palmer, Shih-Shan Lang, Benjamin C. Kennedy, Arastoo Vossough, Nithin D. Adappa and Phillip B. Storm


Craniopharyngioma represents up to 10% of pediatric brain tumors. Although these lesions are benign, attempts at gross-total resection (GTR) can lead to serious complications. More conservative approaches have emerged but require adjuvant radiation. Endoscopic endonasal surgery (EES) aimed at GTR has the potential to result in fewer complications, but there has been limited comparison to open surgery. The authors performed a review of these two approaches within their institution to elucidate potential benefits and complication differences.


The authors performed a retrospective review of pediatric patients undergoing resection of craniopharyngioma at their institution between 2001 and 2017. Volumetric analysis of tumor size and postoperative ischemic injury was performed. Charts were reviewed for a number of outcome measures.


A total of 43 patients with an average age of 8.2 years were identified. Open surgery was the initial intervention in 15 and EES in 28. EES was performed in patients 3–17 years of age. EES has been the only approach used since 2011. In the entire cohort, GTR was more common in the EES group (85.7% vs 53.3%, p = 0.03). Recurrence rate (40% vs 14.2%, p = 0.13) and need for adjuvant radiation (20.0% vs 10.7%, p = 0.71) were higher in the open surgical group, although not statistically significant. Pseudoaneurysm development was only observed in the open surgical group. Volumetric imaging analysis showed a trend toward larger preoperative tumor volumes in the open surgical group, so a matched cohort analysis was performed with the largest tumors from the EES group. This revealed no difference in residual tumor volume (p = 0.28), but the volume of postoperative ischemia was still significantly larger in the open group (p = 0.004). Postoperative weight gain was more common in the open surgical group, a statistically significant finding in the complete patient group that trended toward significance in the matched cohort groups. Body mass index at follow-up correlated with volume of ischemic injury in regression analysis of the complete patient cohort (p = 0.05).


EES was associated with similar, if not better, extent of resection and significantly less ischemic injury than open surgery. Pseudoaneurysms were only seen in the open surgical group. Weight gain was also less prevalent in the EES cohort and appears be correlated with extent of ischemic injury at time of surgery.