Patricia Zadnik Sullivan, Ahmed Albayar, Ashwin G. Ramayya, Brendan McShane, Paul Marcotte, Neil R. Malhotra, Zarina S. Ali, H. Isaac Chen, M. Burhan Janjua, Comron Saifi, James Schuster, M. Sean Grady, Joshua Jones and Ali K. Ozturk
Multidisciplinary treatment including medical oncology, radiation oncology, and surgical consultation is necessary to provide comprehensive therapy for patients with spinal metastases. The goal of this study was to review the use of radiation therapy and/or surgical intervention and their impact on patient outcomes.
In this retrospective series, the authors identified at their institution those patients with spinal metastases who had received radiation therapy alone or had undergone surgery with or without radiation therapy within a 6-year period. Data on patient age, chemotherapy, surgical procedure, radiation therapy, Karnofsky Performance Status (KPS), primary tumor pathology, Spinal Instability Neoplastic Score (SINS), and survival after treatment were collected from the patient electronic medical records. N − 1 chi-square testing was used for comparisons of proportions. The Student t-test was used for comparisons of means. A p value < 0.05 was considered statistically significant. A survival analysis was completed using a multivariate Cox proportional hazards model.
Two hundred thirty patients with spinal metastases were identified, 109 of whom had undergone surgery with or without radiation therapy. Among the 104 patients for whom the surgical details were reviewed, 34 (33%) had a history of preoperative radiation to the surgical site but ultimately required surgical intervention. In this surgical group, a significantly increased frequency of death within 30 days was noted for the SINS unstable patients (23.5%) as compared to that for the SINS stable patients (2.3%; p < 0.001). The SINS was a significant predictor of time to death among surgical patients (HR 1.11, p = 0.037). Preoperative KPS was not independently associated with decreased survival (p > 0.5) on univariate analysis. One hundred twenty-six patients met the criteria for inclusion in the radiation-only analysis. Ninety-eight of these patients (78%) met the criteria for potential instability (PI) at the time of treatment, according to the SINS system. Five patients (5%) with PI in the radiation therapy group had a documented neurosurgical or orthopedic surgery consultation prior to radiation therapy.
At the authors’ institution, patients with gross mechanical instability per the SINS system had an increased rate of 30-day postoperative mortality, which remained significant when controlling for other factors. Surgical consultation for metastatic spine patients receiving radiation oncology consultation with PI is low. The authors describe an institutional pathway to encourage multidisciplinary treatment from the initial encounter in the emergency department to expedite surgical evaluation and collaboration.
Steve S. Cho, Jun Jeon, Love Buch, Shayoni Nag, MacLean Nasrallah, Philip S. Low, M. Sean Grady, Sunil Singhal and John Y. K. Lee
Intraoperative molecular imaging with tumor-targeted fluorescent dyes can enhance resection rates. In contrast to visible-light fluorophores (e.g., 5-aminolevulinic-acid), near-infrared (NIR) fluorophores have increased photon tissue penetration and less contamination from tissue autofluorescence. The second-window ICG (SWIG) technique relies on passive accumulation of indocyanine green (ICG) in neoplastic tissues. OTL38, conversely, targets folate receptor overexpression in nonfunctioning pituitary adenomas. In this study, we compare the properties of these 2 modalities for NIR imaging of pituitary adenomas to better understand the potential for NIR imaging in neurosurgery.
A total of 39 patients with pituitary adenomas were enrolled between June 2015 and January 2018 in 2, sequential, IRB-approved studies. Sixteen patients received systemic ICG infusions 24 hours prior to surgery, and another 23 patients received OTL38 infusions 2–3 hours prior to surgery. NIR fluorescence signal-to-background ratio (SBR) was recorded during and after resection. Immunohistochemistry was performed on the 23 adenomas resected from patients who received OTL38 to assess expression of folate receptor–alpha (FRα).
All 16 adenomas operated on after ICG administration demonstrated strong NIR fluorescence (mean SBR 4.1 ± 0.69 [SD]). There was no statistically significant difference between the 9 functioning and 7 nonfunctioning adenomas (p = 0.9). After administration of OTL38, the mean SBR was 1.7 ± 0.47 for functioning adenomas, 2.6 ± 0.91 for all nonfunctioning adenomas, and 3.2 ± 0.53 for the subset of FRα-overexpressing adenomas. Tissue identification with white light alone for all adenomas demonstrated 88% sensitivity and 90% specificity. SWIG demonstrated 100% sensitivity but only 29% specificity for both functioning and nonfunctioning adenomas. OTL38 was 75% sensitive and 100% specific for all nonfunctioning adenomas, but when assessment was limited to the 9 FRα-overexpressing adenomas, the sensitivity and specificity of OTL38 were both 100%.
Intraoperative imaging with NIR fluorophores demonstrates highly sensitive detection of pituitary adenomas. OTL38, a folate-receptor–targeted fluorophore, is highly specific for nonfunctioning adenomas but has no utility in functioning adenomas. SWIG, which relies on passive diffusion into neoplastic tissue, is applicable to both functioning and nonfunctioning pituitary adenomas, but it is less specific than targeted fluorophores. Thus, targeted and nontargeted NIR fluorophores play important, yet distinct, roles in intraoperative imaging. Selectively and intelligently using either agent has the potential to greatly improve resection rates and outcomes for patients with intracranial tumors.
Susan R. Durham, Katelyn Donaldson, M. Sean Grady and Deborah L. Benzil
With nearly half of graduating US medical students being female, it is imperative to understand why females typically make up less than 20% of the neurosurgery applicant pool, a number that has changed very slowly over the past several decades. Organized neurosurgery has strongly indicated the desire to overcome the underrepresentation of women, and it is critical to explore whether females are at a disadvantage during the residency application process, one of the first steps in a neurosurgical career. To date, there are no published studies on specific applicant characteristics, including gender, that are associated with match outcome among neurosurgery resident applicants. The purpose of this study is to determine which characteristics of neurosurgery residency applicants, including gender, are associated with a successful match outcome.
De-identified neurosurgical resident applicant data obtained from the San Francisco Fellowship and Residency Matching Service for the years 1990–2007 were analyzed. Applicant characteristics including gender, medical school attended, year of application, United States Medical Licensing Exam (USMLE) Step 1 score, Alpha Omega Alpha (AOA) status, and match outcome were available for study.
Of the total 3426 applicants studied, 473 (13.8%) applicants were female and 2953 (86.2%) were male. Two thousand four hundred forty-eight (71.5%) applicants successfully matched. USMLE Step 1 score was the strongest predictor of match outcome with scores > 245 having an OR of 20.84 (95% CI 10.31–42.12) compared with those scoring < 215. The mean USMLE Step 1 score for applicants who successfully matched was 233.2 and was 210.8 for those applicants who did not match (p < 0.001). Medical school rank was also associated with match outcome (p < 0.001). AOA status was not significantly associated with match outcome. Female gender was associated with significantly lower odds of matching in both simple (OR 0.59, 95% CI 0.48–0.72) and multivariate analyses (OR 0.57, 95% CI 0.34–0.94 CI). USMLE Step 1 scores were significantly lower for females compared to males with a mean score of 230.1 for males and 221.5 for females (p < 0.001). There was no significant difference in medical school ranking or AOA status when stratified by applicant gender.
The limited historical applicant data from 1990–2007 suggests that USMLE Step 1 score is the best predictor of match outcome, although applicant gender may also play a role.
Ralph G. Dacey, Oliver E. Flouty, M. Sean Grady, Matthew A. Howard III and Marc R. Mayberg
When performing ventriculoperitoneal shunt surgery it is necessary to create a subgaleal pocket that is of sufficient size to accommodate a shunt valve. In most cases the valve is placed over the posterior skull where the galea begins to transition to suboccipital neck fascia. Dense fibrous attachments in this region of the skull make it technically awkward to develop the subgaleal valve pocket using standard scissors and a blunt dissection technique. In this report the authors describe a new device that enables surgeons to create the shunt valve pocket by using a simple semi-sharp dissection technique.
The authors analyzed the deficiencies of the standard valve pocket dissection technique and designed shunt scissors that address the identified shortcomings. These new scissors allow the surgeon to sharply dissect the subgaleal space by using an efficient hand-closing maneuver.
Standard surgical scissors were modified to create shunt scissors that were tested on the benchtop and used in the operating room. In all cases the shunt scissors proved easy to use and allowed the efficient and reliable creation of a subgaleal valve pocket in a technically pleasing manner.
Shunt scissors represent an incremental technical advance in the field of neurosurgical shunt operations.
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.
Gabrielle Lynch, Karina Nieto, Saumya Puthenveettil, Marleen Reyes, Michael Jureller, Jason H. Huang, M. Sean Grady, Odette A. Harris, Aruna Ganju, Isabelle M. Germano, Julie G. Pilitsis, Susan C. Pannullo, Deborah L. Benzil, Aviva Abosch, Sarah J. Fouke and Uzma Samadani
The objective of this study is to determine neurosurgery residency attrition rates by sex of matched applicant and by type and rank of medical school attended.
The study follows a cohort of 1361 individuals who matched into a neurosurgery residency program through the SF Match Fellowship and Residency Matching Service from 1990 to 1999. The main outcome measure was achievement of board certification as documented in the American Board of Neurological Surgery Directory of Diplomats. A secondary outcome measure was documentation of practicing medicine as verified by the American Medical Association DoctorFinder and National Provider Identifier websites. Overall, 10.7% (n = 146) of these individuals were women. Twenty percent (n = 266) graduated from a top 10 medical school (24% of women [35/146] and 19% of men [232/1215], p = 0.19). Forty-five percent (n = 618) were graduates of a public medical school, 50% (n = 680) of a private medical school, and 5% (n = 63) of an international medical school. At the end of the study, 0.2% of subjects (n = 3) were deceased and 0.3% (n = 4) were lost to follow-up.
The total residency completion rate was 86.0% (n = 1171) overall, with 76.0% (n = 111/146) of women and 87.2% (n = 1059/1215) of men completing residency. Board certification was obtained by 79.4% (n = 1081) of all individuals matching into residency between 1990 and 1999. Overall, 63.0% (92/146) of women and 81.3% (989/1215) of men were board certified. Women were found to be significantly more at risk (p < 0.005) of not completing residency or becoming board certified than men. Public medical school alumni had significantly higher board certification rates than private and international alumni (82.2% for public [508/618]; 77.1% for private [524/680]; 77.8% for international [49/63]; p < 0.05). There was no significant difference in attrition for graduates of top 10–ranked institutions versus other institutions. There was no difference in number of years to achieve neurosurgical board certification for men versus women.
Overall, neurosurgery training attrition rates are low. Women have had greater attrition than men during and after neurosurgery residency training. International and private medical school alumni had higher attrition than public medical school alumni.
Michael D. Cusimano, Katrina Zanetti and Conor Sheridan
Concussion: pathophysiology and sequelae
Paul S. Echlin, M. Sean Grady and Shelly D. Timmons
Bert W. O'Malley Jr., M. Sean Grady, Brandon C. Gabel, Marc A. Cohen, Gregory G. Heuer, Jared Pisapia, Leif-Erik Bohman and Jason M. Leibowitz
The endoscopic endonasal approach for resection of pituitary lesions is an effective surgical option for tumors of the sella turcica. In this study the authors compared outcomes after either purely endoscopic resection or traditional microscope-aided resection. They also attempted to determine the learning curve associated with a surgical team converting to endoscopic techniques.
Retrospective data were collected on patients who were surgically treated for a pituitary lesion at the Hospital of the University of Pennsylvania between July 2003 and May 2008. Age, sex, race, presenting symptoms, length of hospital stay, surgical approach, duration of surgery, tumor pathological features, gross-total resection (GTR) of tumor, recurrence of the lesion, and intraoperative and postoperative complications were noted. All procedures were performed by the same senior neurosurgeon, who was initially unfamiliar with the endoscopic endonasal approach.
A total of 25 patients underwent microscopic resection and 25 patients underwent endoscopic resection performed by a single skull base team consisting of the same senior neurosurgeon and otorhinolaryngologist (M.S.G. and B.W.O.). In the microscopically treated cohort, there were 8 intra- or postoperative complications, 6 intraoperative CSF leaks, 17 (77%) of 22 patients had GTR on postoperative imaging, 5 patients underwent ≥ 2 operations, and 10 (59%) of 17 patients reported total symptom resolution at follow-up. The endoscopically treated group had 7 intraor postoperative complications and 7 intraoperative CSF leaks. Of the patients who had pre- and postoperative imaging studies, 14 (66%) of 21 endoscopically treated patients had GTR; 4 patients had ≥ 2 operations, and 10 (66%) of 15 patients reported complete symptom resolution at follow-up. The first 9 patients who were treated endoscopically had a mean surgical time of 3.42 hours and a mean hospital stay of 4.67 days. The next 8 patients treated had a mean surgical time of 3.11 hours and a mean hospital stay of 3.13 days. The final 8 patients treated endoscopically had a mean surgical time of 2.22 hours and a mean hospital stay of 3.88 days. The difference in length of operation between the first 9 and the last 8 patients treated endoscopically was significantly different. There was a trend toward decreased CSF leaks and other complications from the first 2 groups compared with the third group.
In this subset of patients, the use of endoscopic endonasal resection results in a similar complication and symptom resolution rate compared with traditional techniques. The authors postulate that the learning curve for endoscopic resection can be ≤ 17 procedures.