Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution.

INTRODUCTION: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution's experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children's National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. CONCLUSION: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

Conditioned recurrence-free survival following gross-total resection of nonfunctioning pituitary adenoma: a single-surgeon, single-center retrospective study.

OBJECTIVE: The authors sought to determine the time to recurrence after achieving gross-total resection of nonfunctioning pituitary adenoma (NFPA) in adult patients. The authors also sought to determine the rate of recurrence after increasing years of recurrence-free imaging. METHODS: The authors performed a retrospective chart review of all adult patients who underwent gross-total resection of NFPA between September 2004 and January 2018 by the senior surgeon. The primary outcome of the study was time to recurrence, defined by imaging and/or clinical criteria. RESULTS: The median follow-up time of the 148 patients who met the inclusion criteria was 91 months; 12 of these patients (8.1%) had recurrence. The median time to recurrence was 80 months. The range of time for these recurrences was 36-156 months. The probabilities of remaining recurrence free at 180 months after gross-total resection of NFPA and 12, 36, 60, 84, or 120 months of recurrence-free imaging were 82%, 84%, 86%, 88%, and 93%, respectively. The year-over-year odds of a recurrence increased linearly by 1.07%. There was no difference in recurrence-free imaging when patients were stratified by Knosp grade or tumor subtype. None of the patients with recurrence underwent repeat resection. When identified, patients were managed either conservatively or with radiosurgery. CONCLUSIONS: Increased intervals of recurrence-free imaging were not associated with a decrease in risk of recurrence, which suggests that patients require life-long periodic imaging. If followed with periodic imaging, recurrence can be discovered before clinically symptomatic and successfully treated without repeat surgery.

A phase II randomized controlled trial of tiopronin for aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH. METHODS: In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH. RESULTS: Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm. CONCLUSIONS: The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov).

Easily Screenable Characteristics Associated with Cognitive Improvement and Dysfunction After Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is an effective treatment for the prevention of stroke in patients with carotid artery stenosis. We aimed to clarify the incidence and risk factors for early cognitive dysfunction (eCD) and early cognitive improvement (eCI), defined as change in cognitive performance ≤24 hours after surgery, using a battery of neuropsychometric tests. METHODS: In total, 585 patients undergoing CEA were tested with neuropsychometric tests before and after surgery; 155 patients undergoing "simple" spine surgery were the reference group. Patient performance for each test was evaluated by z scores. Cognitive change was defined as eCD (or eCI) if: 1) patients had a z score ≤-2 (or ≥2) in ≥2 cognitive domains or 2) patients had mean z scores across all domains ≤-1.5 (or ≥1.5). Associations between the categorical cognitive outcomes and variables of interest were modeled using the proportional odds model. RESULTS: Of the 585 subjects, 24% had eCD, 6% had eCI, and 70% had "no change." Patients who had eCD were more likely to be statin naïve (odds ratio [OR] 1.23 [1.03-1.48], P = 0.02) or women (OR 1.27 [1.06-1.53], P = 0.02). Those with eCI were less likely to have less formal education (OR 0.95 [0.90-1.00], P = 0.04) and less likely to have diabetes mellitus (OR 0.8 [0.65-0.99], P = 0.04). CONCLUSIONS: Patients having CEA may develop eCD or eCI postoperatively. Medications likely to be associated with less eCD are statins and aspirin, which correlate most strongly in asymptomatic patients. In addition to confirming previous findings, we found that women were more likely than men to develop eCD. More sex-specific studies and analysis are needed to better explore these findings.

Systematic review and meta-analysis of perioperative and long-term outcomes in patients receiving statin therapy before carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is associated with perioperative stroke and mortality in a minority of cases. The aim of this systematic review and meta-analysis was to investigate the effect of pre-operative statins on perioperative outcomes in patients undergoing CEA for internal carotid artery (ICA) stenosis. METHODS: A systematic review of PubMed, Medline, and the Cochrane Database of Systematic Reviews was performed. Studies were included which reported perioperative stroke and/or survival outcomes following CEA for ICA stenosis and compared patients who were and were not taking pre-operative statins. Relevant data were extracted and pooled using meta-analysis. RESULTS: Seven studies met the inclusion criteria, comprising 21,387 patients. A total of 68.9% (14,976) were administered statins and 31.1% (6657) were statin-free. Pre-operative statin use was higher in patients with a history of cardiac disease (12.2 vs. 23.6% in the statin-free group), diabetes (31.6 vs. 25.1% in the statin-free group), and hypertension (83.5 vs. 72.2% in the statin-free group), while a greater proportion of statin-free patients had symptomatic disease (44.9 vs. 55.5% in the statin-free group). Statins were associated with reduced perioperative stroke in all patients (OR 0.57; 95% CI 0.34-0.95; p = 0.03) and in symptomatic patients (OR 0.57; 95% CI 0.35-0.93; p = 0.03). A trend towards lower perioperative mortality (OR 0.54; 95% CI 0.29, 1.03; p = 0.06) and significantly improved overall survival was observed in the statin group (HR 0.69; 95% CI 0.59-0.81; p < 0.001) at a mean follow-up of 62 months (range 27-76 months). CONCLUSIONS: Administration of statins before CEA is associated with lower rates of perioperative stroke and improved overall survival. Compliance with optimal medical treatment associated with the use of pre-operative statins may limit the clinical significance of these findings. Future investigation to characterize the potential benefit of statin therapy in patients undergoing CEA for ICA stenosis is warranted.

Topical vancomycin to reduce surgical-site infections in neurosurgery: Study protocol for a multi-center, randomized controlled trial.

Surgical-site infections (SSIs) account for 20% of all healthcare-associated infections, are the most common nosocomial infection among surgical patients, and are a focus of quality improvement initiatives. Despite implementation of many quality care measures (e.g. prophylactic antibiotics), SSIs remain a significant cause of morbidity, mortality, and economic burden, particularly in the field of neurosurgery. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. However, a randomized controlled trial assessing its efficacy in the general neurosurgical population has yet to be done. The principle aim of "Topical Vancomycin for Neurosurgery Wound Prophylaxis" (NCT02284126) is to determine whether prophylactic, topical vancomycin reduces the risk of SSIs in the adult neurosurgical population. This prospective, multicenter, patient-blinded, randomized controlled trial will enroll patients to receive the standard of care plus topical vancomycin, or the standard of care alone. The primary endpoint of this study is a SSI by postoperative day (POD) 30. Patients must be over 18years of age. Patients are excluded for renal insufficiency, vancomycin allergy, and some ineligible procedures. Univariate analysis and logistic regression will determine the effect of topical vancomycin on SSIs at 30days. A randomized controlled trial is needed to determine the efficacy of this treatment. Results of this trial are expected to directly influence the standard of care and prevention of SSIs in neurosurgical patients.