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A 12 weeks of feeding trial was conducted to evaluate the effects of different levels of dietary yellow loess as an antibiotic (oxytetracycline) replacer in rainbow trout, Oncorhynchus mykiss. Five experimental diets were formulated to contain no antibiotics or yellow loess (control/CON), three graded levels of yellow loess 5 (YL5), 10 (YL10) and 20 g YL kg−1 diet (YL20) and oxytetracycline at 5 g OTC kg−1 diet. Forty-five fish averaging 39.4 ± 1.6 g (mean ± SD) were randomly distributed in to 15 aquaria. Triplicate groups of fish were fed one of the experimental diets at 1.5 ~ 1.9% of wet body weight per day. At the end of the feeding trial, average weight gain (WG) and specific growth rate (SGR) from fish fed CON diet were significantly lower than those from fish fed YL10, YL20 or OTC diets (P

This paper presents an overview of TRIPOLI-4®, the fourth generation of the 3D continuous-energy Monte Carlo code developed by the Service d’Etudes des Réacteurs et de Mathématiques Appliquées (SERMA) at CEA Saclay. The paper surveys the generic features: programming language, parallel operation, tracked particles, nuclear data, geometry, simulation modes, standard variance reduction techniques, sources, tracking and collision algorithms, tallies, sensitivity studies. Moreover, specific and recent features are also detailed: Doppler broadening of the elastic scattering kernel, neutron and photon material irradiation, advanced variance reduction techniques, Green’s functions, cycle correlation correction, nuclear data management and depletion capabilities. The productivity tools (T4G, SALOME TRIPOLI, T4RootTools), the Verification & Validation process and the distribution and licensing policy are finally presented.

OBJECT Posterior fossa meningiomas represent a common yet challenging clinical entity. They are often associated with neurovascular structures and adjacent to the brainstem. Resection can be undertaken for posterior fossa meningiomas, but residual or recurrent tumor is frequent. Stereotactic radiosurgery (SRS) has been used to treat meningiomas, and this study evaluates the outcome of this approach for those located in the posterior fossa. METHODS At 7 medical centers participating in the North American Gamma Knife Consortium, 675 patients undergoing SRS for a posterior fossa meningioma were identified, and clinical and radiological data were obtained for these cases. Females outnumbered males at a ratio of 3.8 to 1, and the median patient age was 57.6 years (range 12–89 years). Prior resection was performed in 43.3% of the patient sample. The mean tumor volume was 6.5 cm3, and a median margin dose of 13.6 Gy (range 8–40 Gy) was delivered to the tumor. RESULTS At a mean follow-up of 60.1 months, tumor control was achieved in 91.2% of cases. Actuarial tumor control was 95%, 92%, and 81% at 3, 5, and 10 years after radiosurgery. Factors predictive of tumor progression included age greater than 65 years (hazard ratio [HR] 2.36, 95% CI 1.30–4.29, p = 0.005), prior history of radiotherapy (HR 5.19, 95% CI 1.69–15.94, p = 0.004), and increasing tumor volume (HR 1.05, 95% CI 1.01–1.08, p = 0.005). Clinical stability or improvement was achieved in 92.3% of patients. Increasing tumor volume (odds ratio [OR] 1.06, 95% CI 1.01–1.10, p = 0.009) and clival, petrous, or cerebellopontine angle location as compared with petroclival, tentorial, and foramen magnum location (OR 1.95, 95% CI 1.05–3.65, p = 0.036) were predictive of neurological decline after radiosurgery. After radiosurgery, ventriculoperitoneal shunt placement, resection, and radiation therapy were performed in 1.6%, 3.6%, and 1.5%, respectively. CONCLUSIONS Stereotactic radiosurgery affords a high rate of tumor control and neurological preservation for patients with posterior fossa meningiomas. Those with a smaller tumor volume and no prior radiation therapy were more likely to have a favorable response after radiosurgery. Rarely, additional procedures may be required for hydrocephalus or tumor progression.

This study aims to assess the relationship of the levels of physical activities among working adults over a period of seven consecutive days, between working days and days off. This cross-sectional study used a sealed pedometer to measure the physical activity of working adults in terms of their number of daily walking steps on working days and days off. A voluntary sample of 745 working adults aged 18 – 64, who were recruited from different occupational categories in Hong Kong, had completed the study. The participants were fairly active when compared against the recommended levels of physical activity. The average daily walking steps reached 8,400 over a period of seven consecutive days. A significant difference was found between the number of walking steps on working days and that on days off. Two groups of working adults who walked less at work were plant and machine operators and assemblers, and clerks. A significant positive correlation was also found between physical activities on working days and those on days off. One's walking steps on working days were found to significantly increase one's walking steps on days off when the effect of age and gender were controlled in the analysis of multiple regressions. Physical activities on a working day are likely to determine those on a day off. Sedentary work habits may induce sedentary activities on days off. The results inform us that health promotion campaigns, for allowing exceptional levels of activities at workplaces should be undertaken to encourage working adults in Hong Kong.

Objectives/Hypothesis To determine the pediatric age groups viable for nasoseptal flap (NSF) reconstruction of endoscopic endonasal approaches (EEA) to intracranial pathology of suprasella neoplasms. Study Design Retrospective cohort study. Methods Retrospective review of 16 pediatric patients who underwent EEA with NSF reconstruction for a suprasellar defect from 2012 to 2014. Radioanatomic analysis was utilized to assess feasibility of NSF reconstruction of suprasellar neoplasms approached via EEA. Computed tomography (CT) measurements for defect size and potential flap coverage were measured by preoperative maxillofacial CT. Radiographic measurements and surgical outcomes were compared to determine if flap size would be sufficient to cover said defects in two pediatric age groups: those >10 years of age (mean age 14 years) and those 10 years of age population, and this was not due to insufficient flap coverage. Average potential flap length and width are sufficient to cover average suprasellar defect length and width in both age groups (P

Objective:We wanted to present our experience with the extended endoscopic approach to clival pathology, focusing on cerebrospinal fluid leak and reconstruction challenges.Methods:We examined a consecutive series of 37 patients undergoing the extended endoscopic approach for skull base tumours, 9 patients with clival pathology. Patients were examined for the incidence of post-operative cerebrospinal fluid leak in relation to tumour pathology, location, size, reconstruction and lumbar drain.Results:The overall incidence of post-operative cerebrospinal fluid leak was 10.8 per cent. Seventy-five per cent of patients who had a post-operative cerebrospinal fluid leak underwent a transclival approach (p < 0.05). All patients with clival pathology who underwent an intradural dissection had a post-operative cerebrospinal fluid leak (p < 0.05).Conclusion:Post-operative cerebrospinal fluid leak rates after the extended endoscopic approach have improved significantly after advancements including the vascularised nasoseptal flap. Despite this, transclival approaches continue to pose much difficulty. Further investigation is necessary to develop technical improvements that can meet the unique challenges associated with this region.

Treatment following neurosurgical resection or biopsy of a central neurocytoma depends on the pathologic analysis and proliferative activity demonstrated, the extent of surgical resection, the neuroanatomic location and accessibility of residual tumor, and the patient's postoperative condition. The risks and benefits of additional surgery, radiation therapy, and/or chemotherapy should be weighed and individualized based on these factors and guided by the existing literature.

Developing a healthy lifestyle during adulthood is one of the essential factors to prepare for healthy aging. This cross-sectional descriptive study investigated the daily walking steps of 893 working adults from nine occupation categories in Hong Kong. Their daily walking steps were measured using a pedometer. Analysis of variance (ANOVA) was used to compare the difference in daily walking steps between participants in different occupation category. Chi-square test was used to compare the difference in proportion of working adults in each occupation category who walked and did not walk 10,000 steps per day. Results reveal that the participants in average walked 8661 steps per day. "Plant and machine operators and assemblers" and "clerks" were the two least active groups. Participants from the nine occupation categories demonstrated a signifi- cant difference in the number of daily walking steps. Post hoc analysis revealed a significant dif- ference between "plant and machine operators and assemblers" and "service workers and shop sales workers" (p < 0.01), as well as between "plant and machine operators and assemblers" and "craft and related workers" (p < 0.01). Participants from the nine occupation categories also demonstrated a significant difference in the proportion of those who walked and did not walk 10,000 steps per day. Owing to a large difference in number of participants in the nine occupation categories and other study limitations, further systematic investigation is indicated to confirm the study results. To summarize, working adults in Hong Kong are only somewhat active. Identifying the factors that deter the working adults from walking and the ways to promote walking among working adults is necessary to prepare a healthy older population of the future.

Fluorescence-guided surgery is a rapidly growing field that has produced some of the most important innovations in surgical oncology in the past decade. These intraoperative imaging technologies provide information distinguishing tumor tissue from normal tissue in real time as the surgery proceeds and without disruption of the workflow. Many of these fluorescent tracers target unique molecular or cellular features of tumors, which offers the opportunity for identifying pathology with high precision to help surgeons achieve their primary objective of a maximal safe resection. As novel fluorophores and fluorescent probes emerge from preclinical development, a practical understanding of the principles of fluorescence remains critical for evaluating the clinical utility of these agents and identifying opportunities for further innovation. In this review, we provide an "in-text glossary" of the fundamental principles of fluorescence with examples of direct applications to fluorescence-guided brain surgery. We offer a detailed discussion of the various advantages and limitations of the most commonly used intraoperative imaging agents, including 5-aminolevulinic acid, indocyanine green, and fluorescein, with a particular focus on the photophysical properties of these specific agents as they provide a framework through which to understand the new agents that are entering clinical trials. To this end, we conclude with a survey of the fluorescent properties of novel agents that are currently undergoing or will soon enter clinical trials for the intraoperative imaging of brain tumors.

OBJECTIVEFor some jugular foramen schwannomas (JFSs), complete resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery (SRS) is a minimally invasive alternative or adjunct to microsurgery for JFSs. The authors reviewed clinical and imaging outcomes of SRS for patients with these tumors.METHODSNine participating centers of the International Gamma Knife Research Foundation identified 92 patients who underwent SRS between 1990 and 2013. Forty-one patients had prior subtotal microsurgical resection. The median interval between previous surgery and SRS was 15 months (range 0.5–144 months). Eighty-four patients had preexisting cranial nerve (CN) symptoms and signs. The median tumor volume was 4.1 cm3 (range 0.8–22.6 cm3), and the median margin dose was 12.5 Gy (range 10–18 Gy). Patients with neurofibromatosis were excluded from this study.RESULTSThe median follow-up was 51 months (range 6–266 months). Tumors regressed in 47 patients, remained stable in 33, and progressed in 12. The progression-free survival (PFS) was 93% at 3 years, 87% at 5 years, and 82% at 10 years. In the entire series, only a dumbbell shape (extension extracranially via the jugular foramen) was significantly associated with worse PFS. In the group of patients without prior microsurgery (n = 51), factors associated with better PFS included tumor volume < 6 cm3 (p = 0.037) and non–dumbbell-shaped tumors (p = 0.015). Preexisting cranial neuropathies improved in 27 patients, remained stable in 51, and worsened in 14. The CN function improved after SRS in 12% of patients at 1 year, 24% at 2 years, 27% at 3 years, and 32% at 5 years. Symptomatic adverse radiation effects occurred in 7 patients at a median of 7 months after SRS (range 5–38 months). Six patients underwent repeat SRS at a median of 64 months (range 44–134 months). Four patients underwent resection at a median of 14 months after SRS (range 8–30 months).CONCLUSIONSStereotactic radiosurgery proved to be a safe and effective primary or adjuvant management approach for JFSs. Long-term tumor control rates and stability or improvement in CN function were confirmed.

OBJECTIVEHemifacial spasm (HFS) is characterized by involuntary tonic and/or clonic contractions of facial nerve muscles. Fully endoscopic microvascular decompression (E-MVD) for HFS has not been widely adopted. This paper aims to illustrate the safety and efficacy of the fully endoscopic technique for HFS treatment.METHODSThe authors conducted a single-center retrospective study of 27 patients (28 separate E-MVD cases; 1 patient had bilateral E-MVD) diagnosed with HFS who underwent fully E-MVD from January 2013 to October 2016. Intraoperative brainstem auditory evoked potentials and lateral spread resolution were reviewed. Outcome was based on the clinical status of the patient at the last contact point with the senior author. Complications were categorized as facial weakness, hearing loss, ataxia, dysphagia, or any adverse event able to be attributed to the surgical procedure.RESULTSHFS was relieved either completely or partially in the majority of cases (24 of 28, 85.7%). Of the 28 separate procedures, 17 (60.7%) resulted in complete resolution of symptoms, 4 (14.3%) resulted in near-complete resolution, 2 (7.1%) resulted in 50% reduction of symptoms, 1 (3.6%) resulted in minimal reduction, and 4 (14.3%) resulted in no relief. Of the 27 patients, 26 (96%) had no permanent postoperative complications. In multivariate logistic regression, the best predictor of greater than 50% resolution of spasm was resolution of intraoperative lateral spread response.CONCLUSIONSA fully E-MVD for HFS provides a safe and comprehensive view of the neurovascular conflict. Exclusive use of the endoscope in MVD is both safe and feasible in the treatment of HFS. Attention to lateral spread response monitoring remains an integral part of comprehensive neurosurgical management.

Background Facial pain response (PR) to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is much less optimal. No large patient series regarding stereotactic radiosurgery (SRS) has been published. Objective To evaluate the clinical outcomes of MS-related TN treated with SRS. Methods This is a retrospective cohort study. A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study. Results The median latency period of PR after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute [BNI] Pain Scores I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%). Conclusion In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control.

OBJECTIVEPituitary 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.METHODSNineteen 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.RESULTSData 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.CONCLUSIONSPituitary 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.

Context Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge. Objective To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management. Design International, multicenter, retrospective cohort analysis. Setting Ten medical centers participating in the International Gamma Knife Research Foundation. Patients Patients with CD with >6 months endocrine follow-up. Intervention SRS using Gamma Knife radiosurgery. Main Outcome Measures The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded. Results In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation. Conclusions SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS.

OBJECTIVEThe role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.METHODSThe authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988–2000) or modern (2001–2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).RESULTSThe study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.CONCLUSIONSDespite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.

Introduction Fluorescence-guided surgery has emerged as a powerful tool to detect, localize and resect tumors in the operative setting. Our laboratory has pioneered a novel way to administer an FDA-approved near-infrared (NIR) contrast agent to help surgeons with this task. This technique, coined Second Window ICG, exploits the natural permeability of tumor vasculature and its poor clearance to deliver high doses of indocyanine green (ICG) to tumors. This technique differs substantially from established ICG video angiography techniques that visualize ICG within minutes of injection. We hypothesized that Second Window ICG can provide NIR optical contrast with good signal characteristics in intracranial brain tumors over a longer period of time than previously appreciated with ICG video angiography alone. We tested this hypothesis in an intracranial mouse glioblastoma model, and corroborated this in a human clinical trial. Methods Intracranial tumors were established in 20 mice using the U251-Luc-GFP cell line. Successful grafts were confirmed with bioluminescence. Intravenous tail vein injections of 5.0 mg/kg (high dose) or 2.5 mg/kg (low dose) ICG were performed. The Perkin Elmer IVIS Spectrum (closed field) was used to visualize NIR fluorescence signal at seven delayed time points following ICG injection. NIR signals were quantified using LivingImage software. Based on the success of our results, human subjects were recruited to a clinical trial and intravenously injected with high dose 5.0 mg/kg. Imaging was performed with the VisionSense Iridium (open field) during surgery one day after ICG injection. Results In the murine model, the NIR signal-to-background ratio (SBR) in gliomas peaks at one hour after infusion, then plateaus and remains strong and stable for at least 48 hours. Higher dose 5.0 mg/kg improves NIR signal as compared to lower dose at 2.5 mg/kg (SBR = 3.5 vs. 2.8; P = 0.0624). Although early (≤ 6 hrs) visualization of the Second Window ICG accumulation in gliomas is stronger than late (≥24 hrs) visualization (SBR = 3.94 vs. 2.32; p

Introduction Approximately 100,000 brain metastases are diagnosed annually in the United States. Our laboratory has pioneered a novel technique, second window indocyanine green (SWIG), which allows for real-time intraoperative visualization of brain metastasis through normal brain parenchyma and intact dura. Methods Thirteen patients with intraparenchymal brain metastases were administered indocyanine green (ICG) at 5 mg/kg the day before surgery. A near-infrared (NIR)– capable camera was used intraoperatively to identify the tumor and to inspect surgical margins. Neuropathology was used to assess the accuracy and precision of the fluorescent dye for identifying tumor. Results ICG was infused at 24.7 ± 3.45 hours before visualization. All 13 metastases fluoresced with an average signal-to-background ratio (SBR) of 6.62. The SBR with the dura intact was 67.2% of the mean SBR once the dura was opened. The NIR signal could be visualized through normal brain parenchyma up to 7 mm. For the 39 total specimens, the mean SBR for tumor specimens ( n = 28) was 6.9, whereas the SBR for nontumor specimens ( n = 11) was 3.7. The sensitivity, specificity, positive predictive value, and negative predictive value of NIR imaging for tumor was 96.4%, 27.3%, 77.1%, and 75.0%. Discussion SWIG relies on the passive accumulation of dye in abnormal tumor tissue via the enhanced permeability and retention effect. It provides strong NIR optical contrast, which can be used to localize tumors before dural opening. The use of SWIG for margin assessment remains limited by its lack of specificity (high false-positive rate); however, ongoing improvements in imaging parameters show great potential to reduce false-positive results.

Introduction: Both microvascular decompression (MVD) and stereotactic radiosurgery (SRS) have been demonstrated to be effective in treating medically refractory trigeminal neuralgia. However, there is controversy over which one offers more durable pain relief and the patient selection for each treatment. We used a decision analysis model to calculate the health-related quality of life (QOL) for each treatment. Methods: We searched PubMed and the Cochrane Database of Systematic Reviews for relevant articles on MVD or SRS for trigeminal neuralgia published between 2000 and 2015. Using data from these studies, we modeled pain relief and complication outcomes and assigned QOL values. A sensitivity analysis using a Monte Carlo simulation determined which procedure led to the greatest QOL. Results: MVD produced a significantly higher QOL than SRS at a seven-year follow-up. Additionally, MVD patients had a significantly higher rate of complete pain relief and a significantly lower rate of complications and recurrence. Conclusions: With a decision-analytic model, we calculated that MVD provides more favorable outcomes than SRS for the treatment of trigeminal neuralgia.

To evaluate the prevalence of affective disorders and identify their associated factors among Chinese mothers of preschool children diagnosed with autism spectrum disorders.This cross-sectional study was conducted at the Autism Spectrum Disorders Multidisciplinary Clinic of the United Christian Hospital from August 2012 to June 2013. All mothers of a consecutive series of preschool children diagnosed with autism spectrum disorders at their first visit to the clinic were recruited. Information regarding the child-related, maternal, and environmental factors was collected. Psychiatric diagnoses were made according to the Chinese-Bilingual Structured Clinical Interview for DSM-IV Axis I Disorders. Independent factors associated with maternal affective disorders were determined by univariate and multivariate analyses.Of the 121 subjects, the point prevalence of affective disorders as a group was 29.8%. The point prevalence of major depressive disorders, adjustment disorders, anxiety disorders, and bipolar affective disorders was 14.9%, 10.7%, 3.3% and 0.8%, respectively. A higher level of disruptive and self-absorbed behaviours in the children (as assessed by the Developmental Behaviour Checklist), a higher level of affiliate stigma (as assessed by 22-item Affiliate Stigma Scale), and a history of psychiatric disorders were independently associated with current affective disorders.Psychiatric disorders, predominantly affective disorders, are common among Chinese mothers of preschool children with autism spectrum disorders. Identification of independent factors associated with maternal affective disorders can aid in the early detection of cases and planning of early intervention programmes to address both child and maternal psychological needs.

To broaden the ethnic groups in which tapentadol IR is evaluated for treating acute postoperative pain to include Asians.In this phase 3, multicenter, double-blind, randomized study, 352 Korean adults with moderate-to-severe pain following hallux valgus surgery received tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours for 72 hours. Patients requesting other (rescue) analgesics during this period were discontinued for lack of efficacy. The primary endpoint, sum of pain intensity difference (SPID) over 48 hours, was evaluated based on the difference between tapentadol IR and placebo in least squares (LS) mean change from baseline using analysis of covariance (ANCOVA). Secondary endpoints included the time to first rescue medication use and the distribution of responder rates.A treatment effect, favoring tapentadol IR, was observed for SPID48 (p0.001 for both doses vs. placebo, ANCOVA). The between-group difference (vs. placebo) in LS means of SPID48 was 76.4 (95% CI: 51.0, 101.7) for tapentadol IR 50 mg and 90.6 (95% CI: 65.1, 116.1) for tapentadol IR 75 mg. Time to first rescue medication use was delayed for tapentadol IR (p0.001 for both doses vs. placebo; log-rank test). The distribution of responders at 12, 24, 48, and 72 hours favored tapentadol IR (p ≤ 0.001 for both doses vs. placebo; Cochran-Mantel-Haenszel test). Dizziness, nausea, and vomiting were each reported in ≥ 10% tapentadol-treated patients and at an incidence ≥ 2-fold higher vs. placebo. The study findings may be limited by study drug dosing every 4 to 6 hours and frequent monitoring during treatment, neither of which mimic pain treatment in clinical practice. However, any potential bias based on this systematic monitoring of patients would be mitigated by the randomized, double-blind nature of the study, with all treatment groups similarly affected by such biases, if any.Tapentadol IR reduced acute pain intensity, significantly more than placebo, after orthopedic surgery in Korean patients.NCT01516008.

Object Parasellar and sellar meningiomas are challenging tumors owing in part to their proximity to important neurovascular and endocrine structures. Complete resection can be associated with significant morbidity, and incomplete resections are common. In this study, the authors evaluated the outcomes of parasellar and sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an adjunct to microsurgical removal or conventional radiation therapy and as a primary treatment modality. Methods A multicenter study of patients with benign sellar and parasellar meningiomas was conducted through the North American Gamma Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors identified all patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were also required to have a minimum of 6 months of imaging and clinical follow-up after GKRS. Factors predictive of new neurological deficits following GKRS were assessed via univariate and multivariate analyses. Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. Results The authors identified 763 patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were assessed clinically and with neuroimaging at routine intervals following GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of 56 years (range 8–90 years). Three hundred fifty-five patients (50.7%) had undergone at least one resection before GKRS, and 3.8% had undergone prior radiation therapy. The median follow-up after GKRS was 66.7 months (range 6–216 months). At the last follow-up, tumor volumes remained stable or decreased in 90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10 years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery, prior radiation therapy, or a tumor margin dose < 13 Gy significantly increased the likelihood of tumor progression after GKRS. At the last clinical follow-up, 86.2% of patients demonstrated no change or improvement in their neurological condition, whereas 13.8% of patients experienced symptom progression. New or worsening cranial nerve deficits were seen in 9.6% of patients, with cranial nerve (CN) V being the most adversely affected nerve. Functional improvements in CNs, especially in CNs V and VI, were observed in 34% of patients with preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6% of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome with tumor growth and accompanying neurological decline was statistically more likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior surgery (p = 0.021). Conclusions Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients.

This paper intends to establish the possibility on the application of a hybrid (CO2 laser+GMA) welding process to austenite stainless steel (STS304L) by clarifying the bead profiles and mechanical characteristics of the hybrid welded joints. Moreover, the residual stress, plastic strain characteristics and their production mechanism of the welded joints were examined by thermal elastic-plastic analysis. The visual test of the welds was classified as quite stringent (Quality B′) in quality for weld imperfections in terms of four items (reinforcement, backbead, undercut and bead uniformity of the weld). The tensile strength of the hybrid welded joints was approximately 546 MPa, which satisfied the classification requirements. The hardness of the hybrid welded joints was within the acceptable range (the maximum value 340–360 HV).

Data on stereotactic radiosurgery (SRS) for four or more metastases are limited. Existing studies are confounded by significant proportions of patients receiving prior whole-brain radiation therapy (WBRT) or concurrent WBRT with SRS. Furthermore, published results disagree about the impact of tumor volume on overall survival. A retrospective review identified 38 patients without prior intracranial radiation or surgery who received Gamma Knife (GK) as sole treatment to ≥4 brain metastases in a single session. Twenty-eight cases with follow-up imaging were analyzed for intracranial progression. Prognostic factors were examined by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses. Common primary tumors were non-small cell lung (45%), melanoma (37%), and breast (8%). Cases were recursive partitioning analysis class II (94%) or III (6%). Patients harbored a median five tumors (range 4-12) with median total tumor volume of 1.2 cc. A median dose of 21 Gy was prescribed to the 50% isodose line. Patients survived a median 6.7 months from GK. Local treatment failure occurred in one case (4%) and distant failure in 22 (79%). On multivariate analysis, total tumor volume ≥3 cc was significantly associated with distant failure and worsened overall survival (P = 0.042 and 0.040). Fourteen patients (37%) underwent salvage WBRT at a median 10.3 months from GK and seven patients received repeat GK. GK as sole initial treatment for four or more simultaneous metastases spares some patients WBRT and delays it for others. Increased total tumor volume (≥3 cc) is significantly associated with worsened overall survival.

Object No clear treatment guidelines for pediatric craniopharyngiomas exist. The authors developed a decision analytical model to evaluate outcomes of 4 surgical approaches for craniopharyngiomas in children, including attempted gross-total resection (GTR), planned subtotal removal plus radiotherapy, biopsy plus radiotherapy, and endoscopic resections of all kinds. Methods Pooled data, including the authors' own experience, were used to create evidence tables, from which incidence, relative risks, and summary outcomes in quality-adjusted life years (QALYs) were calculated for the 4 management strategies. Results Quality-adjusted life years at the 5-year follow-up were 2.3 ± 0.1 for attempted GTR, 2.9 ± 0.2 for planned subtotal removal plus radiotherapy, 3.9 ± 0.2 for biopsy plus radiotherapy, and 3.7 ± 0.2 for endoscopic resection (F = 17,150, p < 0.001). Similarly, QALYs at 10-year follow-up were 4.5 ± 0.2 for attempted GTR, 5.7 ± 0.5 for planned subtotal removal plus radiotherapy, and 7.8 ± 0.5 for biopsy plus radiotherapy (F = 6,173, p < 0.001). On post hoc pairwise comparisons, the differences between all pairs compared were also highly significant (p < 0.001). Since follow-up data at 10 years are lacking for endoscopic cases, this category was excluded from 10-year comparisons. Conclusions Biopsy with subsequent radiotherapy is the preferred approach with respect to improved overall quality of life. While endoscopic approaches also show promise in preserving quality of life at five-year follow-up, there are not sufficient data to draw conclusions about this comparison at 10 years.

BACKGROUND AND PURPOSE: Endoscopic endonasal approach is the procedure of choice for the resection of ventral skull base neoplasms, with defect closure requiring multilayer reconstruction. This study evaluates the temporal MR imaging evolution of nasoseptal flaps and free grafts used in endoscopic skull base reconstruction. MATERIALS AND METHODS: Sixty-nine follow-up brain MRIs of 22 patients who had endoscopic skull base reconstruction using 26 nasoseptal flaps combined with 8 collagen-matrix dural grafts, 10 fascia lata grafts, and 10 intracranial fat grafts were retrospectively reviewed. Temporal changes in signal intensity, enhancement, thickness, and the configuration of reconstructive layers were evaluated. Tissue with signal intensity or enhancement different from that of normal evolving reconstructive layers at the surgical bed was evaluated, and its association with clinically confirmed tumor was assessed with the Fisher exact test. RESULTS: All normal reconstructive layers were retracted to cranial defects and showed maturation of imaging features within 2–6 months. The immediate postoperative T2-isointensity to brain and enhancement of nasoseptal flaps persisted, but the flap thickness was reduced by 20%–30% (average thickness, 4.5 ± 1.3 mm); additionally, the C shape and vascular pedicle of the nasoseptal flaps became indistinct, but the flap location remained unchanged. The initial appearance of the nonenhancing fascia lata with variable T2 signal intensity became enhancing with increasing T2-hypointensity and a graft-thickness reduction of ≥50% (average thickness, 3.5 ± 1.6 mm). All fat grafts showed progressive resorption. In 6 patients, abnormal tissue represented residual or recurrent tumor (P = .0001). CONCLUSIONS: Maturation and stability of multilayer endoscopic skull base reconstructions on MR imaging occurs within 2–6 months postoperatively. Understanding of the normal imaging evolution of endoscopic skull base reconstructions is essential to distinguish them from neoplasms.

Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (β-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms.

Most solid cancers are treated by surgical resections to reduce the burden of disease. Surgeons often face the challenge of detecting small areas of residual neoplasm after resection or finding small primary tumors for the initial resection. Intraoperative molecular imaging (IMI) is an emerging technology with the potential to dramatically improve cancer surgery operations by allowing surgeons to better visualize areas of neoplasm using fluorescence imaging. Over the last two years, two molecular optical contrast agents received U.S. Food and Drug Administration approval, and several more drugs are now on the horizon. Thus a conference was organized at the University of Pennsylvania to bring together oncologic surgeons from different specialties to discuss the current clinical status of IMI trials with a specific focus on phase 2 and phase 3 studies. In addition, phase 1 and experimental trials were also discussed briefly, to highlight other novel techniques. Our review summarizes the discussions from the conference and delves into the types of cancers discussed, different contrast agents in human trials, and the clinical value being studied. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

INTRODUCTION: To improve surgical resection of brain tumors, our lab has pioneered a novel fluorescent dye technique, Second-Window Indocyanine-Green (SWIG), that relies on passive delivery and accumulation of indocyanine-green (ICG) in neoplastic tissue via the enhanced permeability and retention effect. We hypothesize that SWIG can provide early localization of brain metastasis prior to dural opening and can improve identification of surgical margins. METHODS: Subjects were prospectively enrolled in clinical trial after informed consent. Approximately 24 hours prior surgery, subjects were infused intravenously with 2.5mg/kg or 5mg/kg of ICG. Intraoperatively, a dedicated near-infrared (NIR) camera was used to detect ICG signal. After bone flap removal, the NIR imaging system was positioned above the presumed location of tumor. Additional NIR images were obtained after dural opening, corticectomy, and after conventional white-light surgical resection. RESULTS: We enrolled 50 patients with 51 total intraparenchymal brain metastases (23 lung, 7 breast, 8 GU/GI, 4 melanoma, and 7 others). Prior to dural opening, NIR signal was identified in 35 patients at an average depth of 4.3mm with SBR = 5.3 + 3.7. In the seven patients where NIR signal could not be identified prior to dural opening, tumor depth was an average of 8.4mm from cortical surface. Upon dural opening and tumor identification, all 51 tumors demonstrated strong NIR signal with SBR = 6.2 + 2.8. With white light alone, sensitivity/specificity/PPV/NPV for tumor detection was 83%, 94%, 98%, 57%. With NIR, sensitivity/specificity/PPV/NPV for tumor detection was 100%, 29%, 85%, 100%. DISCUSSION: NIR fluorophores are superior to visible light fluorophores in their depth of penetration. All contrast-enhancing brain metastasis accumulate ICG using our SWIG technique, and NIR fluorescence could be used to localize brain metastasis prior to dural opening. NIR fluorophores are likely to represent the next phase in tumor visualization given the rapid growth of fluorophores targeted to systemic cancers.

e18307 Background: Metastatic spinal cord compression (MSCC) and symptomatic brain metastases (mets) are potential emergencies that demand coordinated multidisciplinary management. Patients (pts) with concerning symptoms are often referred to the Emergency Department (ED) for expedited imaging, but most do not require subsequent ED or inpatient management. Unnecessary ED visits incur substantial cost to the health system and patients, and cause psychosocial stress for patients often near the end-of-life. To improve access to expedited outpatient imaging for high-risk pts and reduce unnecessary ED visits, we developed outpatient rapid MRI protocols and pathways to rule out MSCC and brain mets. Methods: Tailored abbreviated MRI protocols were developed to allow rapid acquisition of brain ( < 13 minutes) and full spine ( < 25 minutes) exams. Dedicated appointments were reserved on the daily MRI schedule. Exams were immediately interpreted and reported by Radiology to the ordering clinician. This pathway was piloted within the Thoracic Oncology group beginning in 10/2018. Results: Referring specialties included Radiation Oncology (50%), Medical Oncology (36%), Pulmonology (7%), and Surgery (7%). For 6 pts who had outpatient rapid brain imaging, median time from order to exam start was 4.3 h (1.8-31) and order to final report 6.8 h (3.2-34.1). Brain mets were found in 4/6 patients. Only 1/4 positive studies required subsequent ED management. For 8 pts referred for rapid spine imaging, median time from order to exam start was 14.4 h (2.2-72.5) and order to final report 16.7 h (4.0-74.4). Only 1 patient was found to have cord compression and required ED/inpatient management. Overall, 86% of patients did not require ED or inpatient admission. 3 pts (all with negative imaging) died a median 13.4 d (1.4-28.3) after order placement. Conclusions: Outpatient rapid MRI protocols facilitate same-day imaging, interpretation, and management, improving care for thoracic oncology pts with new concerning neurologic symptoms and reducing unnecessary ED visits. Future work will expand access beyond Thoracic Oncology and further quantify improvements in cost savings and patient quality of life.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the utility of 5-ALA and SWIG in detecting areas of neoplasm in a murine model of GBM. Primary outcome is the distribution of the two dyes in comparison to the true tumor extent; the sensitivity, specificity, PPV, and NPV of both dyes will be calculated. The secondary outcome is the suitability of existing cell-lines used for GBM research for studies in fluorescence-guided surgery. METHODS/STUDY POPULATION: Two cell lines are used for this research: U87, derived from human GBM; and GL261, derived from rodent stem cells. U87 are implanted intracranially into 6-week old athymic, nude, female mice, while GL261 are implanted intracranially into 10-week old female C57BL/6 mice. The mice are weighed every 3 days to monitor health and bioluminescence imaging is performed between 7-10 days after implantation to confirm tumor implantation and monitor tumor growth. The mice are sacrificed between 10-21 days after implantation. 5mg/kg of intravenous ICG is administered 24-hours prior to harvest and 250mg/kg of intraperitoneal 5-ALA is administered 3-hours prior to harvest. Once the mice are sacrificed, their brains are quickly harvested and placed in cold formalin. Using a high-resolution Odyssey CLx scanner, near-infrared fluorescence from ICG is captured in coronal cross sections of the brains through the tumor. Similarly, 5-ALA fluorescence is imaged using a 405nm LED excitation source and 610-690nm bandpass filter. Afterwards, slices of the brain are stained with H&E, which serves as the gold-standard of the extent of tumor. Images from ICG, 5-ALA, and H&E can then be compared using ImageJ to compare the extent of tumor to the distribution of the dyes. RESULTS/ANTICIPATED RESULTS: In separate, previous studies in humans, both 5-ALA and SWIG have demonstrated utility in detecting residual neoplasm in HGG resections. In general, 5-ALA is more specific for areas of neoplasm, while SWIG is more sensitive. Thus, I anticipate that in this study, SWIG will show a greater distribution than 5-ALA, with SWIG distributing to areas beyond the tumor and 5-ALA distributing within, but not completely covering, the tumor. SWIG’s sensitivity and NPV for detecting tumor should be >90%, while its specificity and PPV may be closer to 50%. For 5-ALA, specificity and PPV should be close to 80-90%, but its sensitivity and NPV may be

A variety of lesions may arise within the cerebellopontine angle (CPA). Schwannomas and meningiomas are most commonly found in this location. Imaging characteristics of meningiomas include hyperdensity on head computed tomography (CT) and avid contrast enhancement on T1-weighted postcontrast magnetic resonance imaging (MRI). Here, we present the case of a 49-year-old woman with enlarging right CPA meningioma. The patient reported mild hearing loss on the right but her neurological exam was otherwise benign. Since the lesion was enlarging and symptomatic, the patient was offered resection of the mass for diagnosis and treatment via an endoscopic retrosigmoid approach. We provide a video that illustrates the steps taken to resect this mass endoscopically. After cerebrospinal fluid (CSF) was drained to achieve brain relaxation, the tumor was visualized. The tumor had a rich vascular supply and had the appearance of a typical meningioma. The bipolar was used to cauterize the tumor's vascular supply. The tumor capsule was then opened with the microscissors. The round knife, suction, and ultrasonic tissue debrider were used to debulk the tumor. After internal debulking of the tumor, the capsule was dissected off the cerebellum and mobilized. A combination of blunt and sharp dissection was done to free the tumor capsule from the adjacent structures. Inferiorly, the lower cranial nerves were visualized. Tissue pathology confirmed a diagnosis of grade I meningioma. A gross total resection was achieved and the patient remained neurologically stable, postoperatively. Furthermore, T1-weighted postcontrast brain MRI, 1 year after surgery, showed no residual.The link to the video can be found at: https://youtu.be/X9c_inLp-So.

Background: Although the Leap Frog intensivist staffing model has been shown to improve outcomes in the intensive care unit (ICU), to date, no one has examined the effect of an intensivist model in a dedicated trauma ICU. With stricter adherence to evidence-based protocols and 24-hour availability, we hypothesized that a mature intensivist model in a trauma ICU would decrease mortality. Methods: Level II trauma center trauma ICU admissions 2006 to 2011. The ICU care provided by 6 trauma intensivists. Two periods were compared: early (2006-2008) and mature (2009-2011). Patients matched on age, Injury Severity Score (ISS), preexisting conditions, and so on in a univariate analysis, with significant variables placed in a logistic regression model, with mortality as the outcome. Results: A total of 3527 patients (2999 excluding do not resuscitate status) were reviewed. Age ≥65 (odds ratio [OR] 2.38, P < .001), ISS ≥17 (OR 3.3, P < .001), coagulopathy (OR 1.64, P = .004), and anemia (OR 1.73, P = .02) were independent predictors of mortality. Multivariate logistic model encompassing these factors found no statistically significant differences in mortality across the 6-year period. The ICU efficiency showed significant improvements in terms of ventilator days (30.1% EARLY vs 24.4% MATURE; P < .001), decreases in mean consultant use per patient (0.55 ± 0.85 EARLY vs 0.40 ± 0.74 MATURE; P < .001), and increase in number of bedside procedures per patient (0.09 ± 0.48 EARLY vs 0.40 ± 0.74 MATURE; P < .001 Conclusions: Our mature intensivists staffing model shows improvement in ICU throughput (ventilator days, ICU days, decreased consultant use, and increased bedside procedures) but no survival benefit. Further improvements in overall trauma mortality may lie in the resuscitative and operative phase of patient care.

BACKGROUND AND PURPOSE: Absorbable gelatin-thrombin matrix is increasingly being used in neurosurgical procedures; unlike other hemostats, the stable matrix is left undisturbed and fills the surgical bed after achieving hemostasis. We investigated the immediate postoperative radiographic imaging appearance of the gelatin-thrombin matrix in intracranial operative beds. MATERIALS AND METHODS: Thirty-one consecutive patients (18 men, 13 women; mean age, 59 years) with 34 surgical cavities, had 31 brain MRIs and 9 head CTs performed ≤ 48 hours postoperatively. They were retrospectively reviewed. Images were evaluated independently by 2 neuroradiologists blinded to the surgical techniques. Surgical beds were evaluated for the presence of the gelatin-thrombin matrix, which appeared as pseudoair material (Hounsfield units ≤ −100) on CT, had characteristic T2-hypointense speckles in a T2-hyperintense background, and demonstrated complete gradient-recalled echo hypointensity on MR imaging. To determine the diagnostic performance of imaging features for the detection of the gelatin-thrombin matrix, the Fisher exact test for the association between imaging features and the presence of the gelatin-thrombin matrix and κ analysis for interobserver agreement were performed. RESULTS: Hemostasis was achieved with standard methods in 12 surgical beds and with the gelatin-thrombin matrix in 22 beds. Interobserver agreement was substantial. The gelatin-thrombin matrix demonstrated pseudoair hypoattenuation (88% sensitivity, 100% specificity, 90% accuracy; P = .067, κ = 0.74) and distinctive T2-hypointense speckles in a background of T2-hyperintensity (81% sensitivity, 85% specificity, 82% accuracy; P =

Object Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1–223 months). Results Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02–1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96–4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Conclusions Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

This study was carried out to investigate the physicochemical and sensory properties of milk with added powdered peanut sprout extract microcapsules (PPSEM) during the storage at 4°C for 16 d. The size of PPSEM varies from 3 to 10 μm as observed by the scanning electron microscopy (SEM). The pH values of all samples ranged from 6.8 to 6.6 during the storage. Release of resveratrol for 0.5 and 1% PPSEM addition was about 0.89 μl/ml and TBARS value found to lower during storage of 16 d. The a* and b* color values of high concentrations (1.5, 2.0, 2.5 and 3.0%) of PPSEM-added milk samples were significantly increased during the storage (p

Purely endoscopic endonasal approaches to surgical resection of pediatric suprasellar craniopharyngiomas are uncommonly performed. The aim of the study is to assess the feasibility and to describe the short-term outcomes of endonasal endoscopic approaches for the gross total resection of suprasellar craniopharyngiomas in the pediatric population.A combined neurosurgical-otolaryngologic team performed gross total resection of craniopharyngiomas in seven pediatric patients (mean age 9.6 years) at The Children's Hospital of Philadelphia over 2011-2012. Short-term outcomes were analyzed over a mean follow-up period of 6.3 months.All tumors involved the sellar and/or suprasellar space and contained some cystic component. The mean maximal tumor diameter was 31.5 mm (range 18.5-62.0 mm). Using a binostril approach, gross total tumor resection was obtained in all patients (100 %). All patients with preoperative visual dysfunction demonstrated improvement in visual acuity. New or stable panhypopituitarism was observed in all cases. All patients developed postoperative diabetes insipidus, and cerebrospinal fluid leak occurred in one patient (15 %).Complete radiographic resection of pediatric craniopharyngioma can be achieved via a purely endoscopic endonasal approach. In particular, this approach can be performed safely using the "two-nostrils-four-hands" technique with intraoperative neuronavigation. This approach should be highly considered in patients with progressive visual dysfunction. Further studies are needed to characterize the long-term surgical and clinical outcome of pediatric patients treated with this surgical approach.

Introduction Postoperative CSF leak is the most common complication of endoscopic endonasal approach (EEA) to skull base lesions. Endoscopic multilayer closure of skull base defect using pedicled nasoseptal flaps (NSF) based off the sphenopalatine artery reduces CSF leaks. EEA robustly expands in surgical arena, yet postoperative imaging evaluation remains poorly studied. This work illustrates normal MR imaging appearance of skull base reconstruction utilizing NSFs during immediate postoperative period. Methods We retrospectively identified patients who had skull base reconstructions utilizing NSFs following EEAs and immediate postoperative-enhanced brain MRI. NSFs and free grafts were evaluated for signal intensity, thickness, configuration, enhancement, vascular pedicle of NSF, relationship in multilayer reconstruction, and defect coverage. Imaging findings were correlated with surgical technique and CSF leaks. Results Twenty-eight patients had 26 multilayer reconstructions and 34 NSFs. Twenty-nine NSFs showed enhancing C-shaped arc at the skull base. Of those, 26 flaps (90%) were confidently identified by visualization of their vascular pedicles, 3 were not distinguishable from adjacent mucosa and pedicles were not identified. Five NSFs showed no enhancement (1 CSF leak). Twenty-seven enhancing NSFs approximated defects with close abutment to free grafts. One flap was displaced; one incompletely covered the defect (2 CSF leaks). Fisher exact test demonstrated an association between incomplete defect coverage and displacement of NSFs with CSF leak ( P = 0.05). Conclusion Endoscopic skull base reconstruction utilizing NSF has characteristic MR imaging appearance. Non-enhancing mucosal gap or displacement of NSF may indicate incomplete defect coverage, identifying patients at risk for CSF leak.

Background Minimally invasive techniques in spine surgery have gained significant popularity due to decreased tissue dissection and destruction, postoperative pain, and hospital stay. The laparoscopic anterior lumbar interbody fusion (ALIF), an innovation in minimally invasive spine surgery, is rarely done because it has marginal benefit over the mini-open ALIF technique in rates of retrograde ejaculation and vascular complications. We propose these outcomes can be improved with enhanced robotic-assisted dissection and exposure for ALIF. Patients Two patients with single-level degenerative spine disease at L5-S1, associated with mechanical back pain, underwent anterior spinal exposure using the da Vinci S Surgical Robot during ALIF. Results In this report, we provide the first description of the use of a surgical robot in the dissection and exposure for ALIF in patients with degenerative spine disease. We demonstrate successful use of the da Vinci Surgical Robot in separating the presacral nervous plexus from retroperitoneal structures without postoperative vascular or urological complications over a 1-year follow-up period. Conclusion Use of the robotic assistance in the performance of ALIF is possible without significant operative complications. This technique may provide added benefit over conventional laparoscopic approaches to the spine.

Introduction We sought to identify factors associated with increased length of stay (LOS) and morbidity in patients undergoing resection of pituitary macroadenomas. Methods We reviewed records of 203 consecutive patients who underwent endoscopic endonasal resection of a pituitary macroadenoma (mean age = 55.7 [16-88]) years, volume = 11.3 (1.0-134.3) cm3. Complete resection was possible in 60/29.6% patients. Mean follow-up was 575 days. Multivariate logistic regression was performed using MATLAB. Results Mean LOS was 4.67 (1-66) days and was associated with CSF leak (p = 0.025), lumbar drain placement (p = 0.041; n = 8/3.9% intraoperative, n = 20/9.9% postoperative), and any infection (p = 0.066). Age, diabetes insipidus (n = 17/8.37%), and syndrome of inappropriate antidiuretic hormone secretion (n = 12/5.9%) were not associated with increased LOS (p > 0.2). Postoperative CSF leak in the hospital (n = 21/10.3%) was associated with intraoperative CSF leak (p = 0.002; n = 82/40.4%) and complete resection (p = 0.012). There was no significant association (p > 0.1) between postoperative CSF leak in the hospital following surgery and the use of a fat graft (n = 61/30.1%), nasoseptal flap (155/76.4%), or perioperative lumbar drain placement (n = 8/3.94%). Conclusion Complete resection is associated with increased risk of CSF leak and LOS. Operative strategies including placement of fat graft, nasoseptal flap, or intraoperative lumbar drain placement may have limited value in reducing the risk of postoperative CSF leak.

Background Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. Objective To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Methods Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue. Results NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). Conclusion With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. Abbreviations 5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.

Introduction The gold standard for the determination of the erythrocyte sedimentation rate (ESR) is the Westergren method. Other methods to measure the ESR have become available. They range from modest modifications of the Westergren method to very different methodologies. The ICSH therefore established a Working Group to investigate these new approaches and compile recommendations for their validation and verification. Methods A panel of six experts in laboratory hematology examined the peer-reviewed literature and EQA surveys from over 6000 laboratories on four continents performing ESR testing. This information was used to create lists of ESR instrument manufacturers and their methods. Results Only 28% of laboratories surveyed used the unmodified Westergren method, while 72% of sites used modified or alternate methods. Results obtained with the new instruments could differ from results obtained with the Westergren method by up to 142%. Different non-Westergren methods showed differences from each other of up to 42%. The new methods were often significantly faster, safer, and less labor-intensive. They reduced costs and often used standard EDTA tubes, eliminating the need for a dedicated ESR tube. Conclusion Based on the consensus of the Working Group, recommendations for manufacturers for the validation of new ESR methods were developed. In addition, a list of recommendations for laboratories that are moving to modified or alternate methods was compiled, addressing instrument performance verification and communications of results to clinical users.

Background Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the “oncometabolite” 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly-sensitive non-invasive technique for assessing brain metabolism. This study aims to assess tumor metabolism using 2D L-COSY at 7T for the detection of 2HG in IDH-mutant gliomas. Methods Nine treatment-naïve patients with suspected intracranial neoplasms were scanned at 7T MRI/MRS scanner using the 2D L-COSY technique. 2D-spectral processing and analyses were performed using a MATLAB-based reconstruction algorithm. Cross and diagonal peak volumes were quantified in the 2D L-COSY spectra and normalized with respect to the creatine peak at 3.0 ppm and quantified data were compared with previously-published data from six normal subjects. Detection of 2HG was validated using findings from immunohistochemical (IHC) staining in patients who subsequently underwent surgical resection. Results 2HG was detected in both of the IDH-mutated gliomas (grade III Anaplastic Astrocytoma and grade II Diffuse Astrocytoma) and was absent in IDH wild-type gliomas and in a patient with breast cancer metastases. 2D L-COSY was also able to resolve complex and overlapping resonances including phosphocholine (PC) from glycerophosphocholine (GPC), lactate (Lac) from lipids and glutamate (Glu) from glutamine (Gln). Conclusions This study demonstrates the ability of 2D L-COSY to unambiguously detect 2HG in addition to other neuro metabolites. These findings may aid in establishing 2HG as a biomarker of malignant progression as well as for disease monitoring in IDH-mutated gliomas.

Schwannomas are benign nerve sheath tumors that may arise along the complex course of the cranial nerves (CNs), anywhere in the head and neck. Sound knowledge of the CN anatomy and imaging features of schwannomas is paramount for making the correct diagnosis. In this article, we review approaches to diagnosing CN schwannomas by describing their imaging characteristics and the associated clinical presentations. Relevant anatomic considerations are highlighted by using illustrative examples and key differential diagnoses categorized according to regions, which include the anterior skull base, orbit, cavernous sinus, basal cisterns, and neck. The clinical presentations associated with CN schwannomas vary and range from no symptoms to symptoms caused by mass effect or CN deficits. Individuals with the inherited disorder neurofibromatosis type 2 are predisposed to multiple schwannomas. When a lesion follows the course of a CN, the radiologist's roles are to confirm the imaging features of schwannoma and exclude appropriate differential considerations. The characteristic imaging features of CN schwannomas reflect their slow growth as benign neoplasms and include circumscribed margins, displacement of local structures, and smooth expansion of osseous foramina. These neoplasms exhibit various degrees of solid enhancement, often with internal cystic spaces on magnetic resonance (MR) and computed tomographic (CT) images and heterogeneous high signal intensity specifically on T2-weighted MR images. Clinical and/or imaging evidence of end-organ compromise of the involved CN may exist and aid in the identification of the nerve of origin. With a detailed understanding of the course of the CNs, the diagnostic features of CN schwannomas, and the correlation between these data and the associated clinical presentations of these tumors, the radiologist can have a key role in the diagnosis of CN schwannomas and the treatment planning for affected patients. (©)RSNA, 2016.

OBJECTIVE As odontoid process fractures become increasingly common in the aging population, a technical understanding of treatment approaches is critical. 3D image guidance can improve the safety of posterior cervical hardware placement, but few studies have explored its utility in anterior approaches. The authors present in a stepwise fashion the technique of odontoid screw placement using the Medtronic O-arm navigation system and describe their initial institutional experience with this surgical approach. METHODS The authors retrospectively reviewed all cases of anterior odontoid screw fixation for Type II fractures at an academic medical center between 2006 and 2015. Patients were identified from a prospectively collected institutional database of patients who had suffered spine trauma. A standardized protocol for navigated odontoid screw placement was generated from the collective experience at the authors' institution. Secondarily, the authors compared collected variables, including presenting symptoms, injury mechanism, surgical complications, blood loss, operative time, radiographically demonstrated nonunion rate, and clinical outcome at most recent follow-up, between navigated and nonnavigated cases. RESULTS Ten patients (three female; mean age 61) underwent odontoid screw placement. Most patients presented with neck pain without a neurological deficit after a fall. O-arm navigation was used in 8 patients. An acute neck hematoma and screw retraction, each requiring surgery, occurred in 2 patients in whom navigation was used. Partial vocal cord paralysis occurred after surgery in one patient in whom no navigation was used. There was no difference in blood loss or operative time with or without navigation. One patient from each group had radiographic nonunion. No patient reported a worsening of symptoms at follow-up (mean duration 9 months). CONCLUSIONS The authors provide a detailed step-by-step guide to the navigated placement of an odontoid screw. Their surgical experience suggests that O-arm–assisted odontoid screw fixation is a viable approach. Future studies will be needed to rigorously compare the accuracy and efficiency of navigated versus nonnavigated odontoid screw placement.