Impact of histopathological classification of non-functioning adenomas on long term outcomes: comparison of the 2004 and 2017 WHO classifications.

PURPOSE: Outcomes of patients with non-functioning pituitary adenomas categorized using the 2004 and 2017 WHO classification systems are understudied. We report outcomes from the University of Virginia of patients with non-functioning pituitary adenomas categorized using both systems. METHODS: We constructed a database from all 239 patients who underwent resection of a non-functioning pituitary adenoma between 2003 and 2015 and had at least 5 years of follow-up. Pathologic diagnosis was determined under both the 2004 and 2017 WHO classification systems. We compared the rates of recurrence and progression between subtypes using univariate and multivariate Cox regression analyses. RESULTS: Nearly 30% of the tumors in our database were classified as null cell adenomas under the 2004 classification system, whereas only 10% of the tumors were classified as null cell adenomas using the 2017 classification system. Most of these tumors were reclassified as either corticotroph or gonadotroph adenomas. Despite our relatively large cohort and average follow-up of nearly 9 years, we did not detect a significant difference in recurrence and progression between subtypes. CONCLUSIONS: The majority of null cell adenomas diagnosed under the 2004 WHO classification system are reclassified as gonadotroph or corticotroph adenomas under the 2017 WHO classification system. Rates of progression and recurrence between subtypes are not as different as previously believed at our institution and require a larger cohort to further investigate.

Ventilator Mode Does Not Influence Blood Loss or Transfusion Requirements During Major Spine Surgery: A Retrospective Study.

BACKGROUND: Blood loss during adult spinal deformity surgery is multifactorial. Anesthetic-related factors, such as mode of mechanical ventilation, may contribute to intraoperative blood loss. The aim of this study was to determine the influence of ventilator mode and ventilator parameters on intraoperative blood loss and transfusion requirements in patients undergoing prone position spine surgery. METHODS: This single-center retrospective study examined electronic medical records of patients ≥18 years of age who underwent elective prone position spine surgery between May 2015 and June 2016. Associations between ventilator mode and ventilator parameters with intraoperative estimated blood loss (EBL), packed red blood cells (PRBCs), fresh-frozen plasma (FFP), cryoprecipitate and platelet transfusions, and subfascial drain output were examined using multiple linear regression models controlling for age, sex, American Society of Anesthesiologist (ASA) physical status score, body mass index (BMI), preoperative blood coagulation parameters and laboratory values, operative levels, cage constructs, osteotomies, transforaminal lumbar interbody fusions, laminectomies, reoperation, spine surgery invasiveness index, and operative time. In a secondary analysis, EBL, blood product transfusions, and postoperative drain output were compared between pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) propensity score-matched cohorts. RESULTS: Nine hundred forty-six records were reviewed, and 822 were included in the analysis. After adjusting for confounding, no statistically significant associations were observed between mode of ventilation and intraoperative EBL (estimate, -2; 95% confidence interval [CI], -248 to 245; P = .99) or blood product transfusions (PRBC: estimate, -9; 95% CI, -154 to 135; P = .90; FFP: estimate, -3; 95% CI, -59 to 54; P = .93; cryoprecipitate: estimate, -14; 95% CI, -70 to 43; P = .63; platelets: -7; 95% CI, -39 to 24; P = .64). After propensity score matching (n = 27 per group), no significant differences were observed in EBL (mean difference, 525 mL; 95% CI, -15 to 1065; P = .056) or blood transfusions (PRBC: mean difference, 208 mL; 95% CI, -23 to 439; P = .077; FFP (mean difference, 34 mL; 95% CI, -17 to 84; P = .19); cryoprecipitate (mean difference, 55 mL; 95% CI, -24 to 133; P = .17); or platelets (mean difference, 26 mL; 95% CI, -12 to 64; P = .18) between PCV and VCV groups. CONCLUSIONS: In prone position spine surgery, neither mode of mechanical ventilation nor airway pressure is associated with intraoperative blood loss or need for allogeneic transfusion. Use of modern ventilation strategies using lung protective techniques may mitigate differences in blood loss previously observed between PCV and VCV modes.

Genomic and molecular characterization of pituitary adenoma pathogenesis: review and translational opportunities.

OBJECTIVE: Innovations in genomics, epigenomics, and transcriptomics now lay the groundwork for therapeutic interventions against neoplastic disease. In the past 30 years, the molecular pathogenesis of pituitary adenomas has been characterized. This enhanced understanding of the biology of pituitary tumors has potential to impact current treatment paradigms, and there exists significant translational potential for these results. In this review the authors summarize the results of genomics and molecular biology investigations into pituitary adenoma pathogenesis and behavior and discuss opportunities to translate basic science findings into clinical benefit. METHODS: The authors searched the PubMed and MEDLINE databases by using combinations of the keywords "pituitary adenoma," "genomics," "pathogenesis," and "epigenomics." From the initial search, additional articles were individually evaluated and selected. RESULTS: Pituitary adenoma growth is primarily driven by unrestrained cell cycle progression, deregulation of growth and proliferation pathways, and abnormal epigenetic regulation of gene expression. These pathways may be amenable to therapeutic intervention. A significant number of studies have attempted to establish links between gene mutations and tumor progression, but a thorough mechanistic understanding remains elusive. CONCLUSIONS: Although not currently a prominent aspect in the clinical management of pituitary adenomas, genomics and epigenomic studies may become essential in refining patient care and developing novel pharmacological agents. Future basic science investigations should aim at elucidating mechanistic understandings unique to each pituitary adenoma subtype, which will facilitate rational drug design.

Endoscopic endonasal surgery outcomes for pediatric craniopharyngioma: a systematic review.

OBJECTIVE: The goal of this study was to systematically review the outcomes of endoscopic endonasal surgery (EES) for pediatric craniopharyngiomas so as to assess its safety and efficacy. METHODS: A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2019. All studies assessing outcomes following EES for pediatric craniopharyngiomas were included. RESULTS: Of the total 48 articles identified in the original literature search, 13 studies were ultimately selected. This includes comparative studies with other surgical approaches, retrospective cohort studies, and case series. CONCLUSIONS: EES for pediatric craniopharyngiomas is a safe and efficacious alternative to other surgical approaches. Achieving gross-total resection with minimal complications is feasible with EES and is comparable, if not superior in some cases, to traditional means of resection. Ideally, a randomized controlled trial might be implemented in the future to further elucidate the effectiveness of EES for resection of craniopharyngiomas.

Chiari I malformation in children-the natural history.

PURPOSE: To review the natural history of asymptomatic and symptomatic pediatric Chiari I malformations with and without syringomyelia. MATERIALS AND METHODS: We reviewed the literature for case reports and case series describing the natural history of asymptomatic and symptomatic children with Chiari I malformations with and without syringomyelia. Our review included approximately 700 asymptomatic children without syringomyelia, 100 symptomatic children without syringomyelia, 22 asymptomatic children with syringomyelia, and 11 symptomatic children with syringomyelia. Symptomatic and imaging outcomes at the point of last reported follow-up were noted to describe the natural history of Chiari I malformations in children. RESULTS: Our review of about 700 asymptomatic children with CM-I without syrinx revealed that most children do not exhibit new-onset symptoms (5-6%) or syrinx (2-3%). The nearly 100 published cases of symptomatic CM-I without syrinx suggest that about half of children report symptomatic improvement (48%) and few report symptomatic worsening (7%). New-onset syrinx is rarely observed (2%). Few cases have been published about asymptomatic and symptomatic CM-I with syrinx as syringomyelia are generally regarded to be an indication for surgical intervention. Nevertheless, all 22 children with asymptomatic CM-I with syringomyelia included in this study were asymptomatic at follow-up, with syrinx resolution observed in 18 children and tonsillar herniation improvement observed in 16 children. Overall, our review of asymptomatic pediatric CM-I with or without syringomyelia suggests that its natural history is much more favorable than previously acknowledged and that the literature generally favors conservative management of these cases. CONCLUSION: Our review of asymptomatic pediatric CM-I with or without syringomyelia suggests that its natural history is much more favorable than previously acknowledged and that the literature generally favors conservative management of these cases. Further study of symptomatic pediatric CM-I is necessary to better understand its natural history.

Characteristics of traumatic brain injury during Operation Enduring Freedom-Afghanistan: a retrospective case series.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality, especially among members of the armed services. Injuries sustained in the battlefield are subject to different mechanisms than those sustained in civilian life, particularly blast and high-velocity injury. Due to the unique nature of these injuries and the challenges associated with battlefield medicine, surgical interventions play a key role in acute management of TBI. However, the burden of chronic disease posed by TBI is poorly understood and difficult to investigate, especially in the military setting. The authors report the case logs of a United States Navy neurosurgeon, detailing the acute management and outcomes of 156 patients sustaining TBI between November 2010 and May 2011 during the war in Afghanistan. By demographics, more than half of the patients treated were local nationals. By mechanism of injury, blunt trauma (40.4%) and explosive injury (37.2%) were the most common contributors to TBI. Decompressive craniectomies (24.0%) and clot evacuations (14.7%) were the procedures most commonly performed. Nearly one-quarter of patients were transferred to receive further care, yet only 3 patients were referred for rehabilitative services. Furthermore, the data suggest that patients sustaining comorbid injuries in addition to TBI may be predisposed to worse outcomes. Improvements in documentation of military patients may improve knowledge of TBI and further identify potential variables or treatments that may affect prognosis. The increased survivability from TBI also highlights the need for additional research expenditure in the field of neurorehabilitation specifically.

Rotational thromboelastometry-guided transfusion during lumbar pedicle subtraction osteotomy for adult spinal deformity: preliminary findings from a matched cohort study.

OBJECTIVESignificant blood loss and coagulopathy are often encountered during adult spinal deformity (ASD) surgery, and the optimal intraoperative transfusion algorithm is debatable. Rotational thromboelastometry (ROTEM), a functional viscoelastometric method for real-time hemostasis testing, may allow early identification of coagulopathy and improve transfusion practices. The objective of this study was to investigate the effect of ROTEM-guided blood product management on perioperative blood loss and transfusion requirements in ASD patients undergoing correction with pedicle subtraction osteotomy (PSO).METHODSThe authors retrospectively reviewed patients with ASD who underwent single-level lumbar PSO at the University of Virginia Health System. All patients who received ROTEM-guided blood product transfusion between 2015 and 2017 were matched in a 1:1 ratio to a historical cohort treated using conventional laboratory testing (control group). Co-primary outcomes were intraoperative estimated blood loss (EBL) and total blood product transfusion volume. Secondary outcomes were perioperative transfusion requirements and postoperative subfascial drain output.RESULTSThe matched groups (ROTEM and control) comprised 17 patients each. Comparison of matched group baseline characteristics demonstrated differences in female sex and total intraoperative dose of intravenous tranexamic acid (TXA). Although EBL was comparable between ROTEM versus control (3200.00 ± 2106.24 ml vs 3874.12 ± 2224.22 ml, p = 0.36), there was a small to medium effect size (Cohen's d = 0.31) on EBL reduction with ROTEM. The ROTEM group had less total blood product transfusion volume (1624.18 ± 1774.79 ml vs 2810.88 ± 1847.46 ml, p = 0.02), and the effect size was medium to large (Cohen's d = 0.66). This difference was no longer significant after adjusting for TXA (ß = -0.18, 95% confidence interval [CI] -1995.78 to 671.64, p = 0.32). More cryoprecipitate and less fresh frozen plasma (FFP) were transfused in the ROTEM group patients (cryoprecipitate units: 1.24 ± 1.20 vs 0.53 ± 1.01, p = 0.03; FFP volume: 119.76 ± 230.82 ml vs 673.06 ± 627.08 ml, p < 0.01), and this remained significant after adjusting for TXA (cryoprecipitate units: ß = 0.39, 95% CI 0.05 to 1.73, p = 0.04; FFP volume: ß = -0.41, 95% CI -772.55 to -76.30, p = 0.02). Drain output was lower in the ROTEM group and remained significant after adjusting for TXA.CONCLUSIONSFor ASD patients treated using lumbar PSO, more cryoprecipitate and less FFP were transfused in the ROTEM group compared to the control group. These preliminary findings suggest ROTEM-guided therapy may allow early identification of hypofibrinogenemia, and aggressive management of this may reduce blood loss and total blood product transfusion volume. Additional prospective studies of larger cohorts are warranted to identify the appropriate subset of ASD patients who may benefit from intraoperative ROTEM analysis.

Microsurgical versus endoscopic transsphenoidal resection for acromegaly: a systematic review of outcomes and complications.

PURPOSE: The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal resection (TSR) for the treatment of acromegaly. METHODS: A literature review was performed, and studies with at least five patients who underwent TSR for acromegaly, reporting biochemical remission criteria and long-term remission outcomes were included. Data extracted from each study included surgical technique, perioperative complications, biochemical remission criteria, and long-term remission outcomes. RESULTS: Fifty-two case series from 1976 to 2016 met the inclusion criteria, comprising 4375 patients. Thirty-six reports were microsurgical (n = 3144) and 13 were endoscopic (n = 940). Three studies compared microsurgical (n = 111) to endoscopic TSR outcomes (n = 180). The overall initial and long-term remission rates were 58.2 vs. 57.4% and 69.2 vs. 70.2% for the microsurgical and endoscopic groups, respectively. For microadenomas, the initial and long-term remission rates were 77.6 vs. 82.2% and 76.9 vs. 73.5% for microsurgical and endoscopic approaches, respectively. For macroadenomas, the initial and long-term remission rates were 46.9 vs. 60.0% and 40.2 vs. 61.5% for microsurgical and endoscopic approaches, respectively. The rates of postoperative CSF leak were 3.0 vs. 2.3% for the microscopic and endoscopic groups, respectively. The rates of hypopituitarism and transient diabetes insipidus were 6.7 vs. 6.4% and 9.0 vs. 7.8% for the microscopic and endoscopic groups, respectively. CONCLUSIONS: Both endoscopic and microsurgical approaches for TSR of growth hormone-secreting adenomas are viable treatment options for patients with acromegaly, and yield similarly high rates of remission under the most current consensus criteria.

Perivascular space burden interacts with APOE-ε4 status on cognition in older adults.

Enlarged perivascular spaces (ePVS) may adversely affect cognition. Little is known about how basal ganglia ePVS interact with apolipoprotein (APOE)-ε4 status. Vanderbilt Memory and Aging Project participants (n = 326, 73 ± 7, 59% male) underwent 3 T brain MRI at baseline to assess ePVS and longitudinal neuropsychological assessments. The interaction between ePVS volume and APOE-ε4 carrier status was related to baseline outcomes using ordinary least squares regressions and longitudinal cognition using linear mixed-effects regressions. ePVS volume interacted with APOE-ε4 status on cross-sectional naming performance (ß = -0.002, p = 0.002), and executive function excluding outliers (ß = 0.001, p = 0.009). There were no significant longitudinal interactions (p-values>0.10) except for Coding excluding outliers (ß = 0.002, p = 0.05). While cross-sectional models stratified by APOE-ε4 status indicated greater ePVS related to worse cognition mostly in APOE-ε4 carriers, longitudinal models stratified by APOE-ε4 status showed greater ePVS volume related to worse cognition among APOE-ε4 non-carriers only. Results indicated that greater ePVS volume interacts with APOE-ε4 status on cognition cross-sectionally. Longitudinally, the association of greater ePVS volume and worse cognition appears stronger in APOE-ε4 non-carriers, possibly due to the deleterious effects of APOE-ε4 on cognition across the lifespan.

Baseline grey matter volumes and white matter hyperintensities predict decline in functional activities in older adults over a 5-year follow-up period.

INTRODUCTION: Functional independence is an essential predictor of quality of life in aging, yet few accessible predictors of functional decline have been identified. This study examined associations between baseline structural neuroimaging markers and longitudinal functional status. METHODS: Linear mixed effects models with follow-up time interaction terms related baseline grey matter volume and white matter hyperintensities (WMHs) to functional trajectory, adjusting for demographic and medical covariates. Subsequent models assessed interactions with cognitive status and apolipoprotein E (APOE) ε4 status. RESULTS: Smaller baseline grey matter volumes, particularly in regions commonly affected by Alzheimer's disease (AD), and greater baseline WMHs were associated with faster functional decline over a mean 5-year follow-up. Effects were stronger in APOE-ε4 carriers on grey matter variables. Cognitive status interacted with most MRI variables. DISCUSSION: Greater atrophy in AD-related regions and higher WMH burden at study entry were associated with faster functional decline, particularly among participants at increased risk of AD.

Resolution of venous pressure gradient in a patient with idiopathic intracranial hypertension after ventriculoperitoneal shunt placement: A proof of secondary cerebral sinovenous stenosis.

BACKGROUND: The relationship between idiopathic intracranial hypertension (IIH) and cerebral sinovenous stenosis (CSS) remains unclear. The effects of cerebrospinal fluid (CSF) diversion on venous sinus physiology have not been rigorously investigated. We describe the effect of ventriculoperitoneal shunt (VPS) placement on sinovenous pressures in the setting of IIH and CSS. CASE DESCRIPTION: A patient in their 30 s presented with headache and transient visual obscurations for few months and was diagnosed with IIH. Catheter cerebral venography showed focal stenosis of the right transverse sinus (TS) with a trans-stenosis pressure gradient (TSG) of 20 mmHg. The patient was treated with VPS. During the procedure, we performed a real-time measurement of ventricular CSF and cerebral sinovenous pressures. VPS selectively reduced the TS pressure and abolished the preoperative TS-TSG within 20 min of CSF diversion without altering the sigmoid sinus (SS) pressure. Our findings suggest that CSS can be an epiphenomenon, rather than the primary etiology in some patients with IIH. CONCLUSION: IIH is a challenging condition, in certain patients the radiographic stenosis and trans-stenosis gradient were an epiphenomenon because of the increased intracranial pressure that resulted in reversible TS-SS stenosis.

"I Have Nowhere to Go": A Multiple-Case Study of Transgender and Gender Diverse Youth, Their Families, and Healthcare Experiences.

Transgender and gender diverse (TGD) youth experience health disparities due to stigma and victimization. Gender-affirming healthcare mitigates these challenges; yet, we have limited understanding of TGD youth's healthcare experiences in the U.S. Midwest and South. Using a multiple case study design, we aimed to develop an in-depth and cross-contextual understanding of TGD youth healthcare experiences in one Midwestern state. Families with a TGD child under 18 were recruited with the goal of cross-case diversity by child age, gender, race, and/or region of the state; we obtained diversity in child age and region only. Four white families with TGD boys or non-binary youth (4-16) in rural, suburban, and small towns participated in interviews and observations for one year; public data were collected from each family's community. Thematic analysis was used within and across cases to develop both family-level understanding and identify themes across families. Findings include a summary of each family as it relates to their child's TGD healthcare experiences as well as the themes identified across cases: accessibility and affirming care. Although limited by a small sample with lack of gender and race diversity, this study contributes to our understanding of TGD youth healthcare in understudied regions.

Cerebrospinal fluid area and syringogenesis in Chiari malformation type I.

OBJECTIVE: Syringogenesis in Chiari malformation type I (CM-I) is thought to occur secondary to impaction of the cerebellar tonsils within the foramen magnum (FM). However, the correlation between the CSF area and syringogenesis has yet to be elucidated. The authors sought to determine whether the diminution in subarachnoid space is associated with syringogenesis. Further, the authors sought to determine if syrinx resolution was associated with the degree of expansion of subarachnoid spaces after surgery. METHODS: The authors performed a retrospective review of all patients undergoing posterior fossa decompression for CM-I from 2004 to 2016 at the University of Virginia Health System. The subarachnoid spaces at the FM and at the level of the most severe stenosis were measured before and after surgery by manual delineation of the canal and neural tissue area on MRI and verified through automated CSF intensity measurements. Imaging and clinical outcomes were then compared. RESULTS: Of 68 patients, 26 had a syrinx at presentation. Syrinx patients had significantly less subarachnoid space at the FM (13% vs 19%, p = 0.0070) compared to those without syrinx. Following matching based on degree of tonsillar herniation and age, the subarachnoid space was significantly smaller in patients with a syrinx (12% vs 19%, p = 0.0015). Syrinx resolution was associated with an increase in patients' subarachnoid space after surgery compared with those patients without resolution (23% vs 10%, p = 0.0323). CONCLUSIONS: Syrinx development in CM-I patients is correlated with the degree to which the subarachnoid CSF spaces are diminished at the cranial outlet. Successful syrinx reduction is associated with the degree to which the subarachnoid spaces are increased following surgery.

Whole Sella vs Targeted Stereotactic Radiosurgery for Acromegaly: A Multicenter Matched Cohort Study.

BACKGROUND: Targeted stereotactic radiosurgery (SRS) with sparing of the residual pituitary is the traditional radiosurgical method for pituitary adenomas. Whole-sella SRS is an alternative choice for radiologically indeterminate or large adenomas, the safety and efficacy of which has yet to be determined. OBJECTIVE: To determine if whole-sella SRS in acromegaly would have comparable radiographic and biochemical control to targeted SRS. We performed a multicenter, retrospective matched cohort study to compare outcomes between groups. METHODS: We conducted a retrospective review of acromegalic patients who underwent SRS from 1990 to 2016 at 10 centers participating in the International Radiosurgery Research Foundation. Whole-sella and targeted SRS patients were then matched in a 1:1 ratio. RESULTS: A total of 128 patients were eligible for inclusion. Whole-sella patients had a higher pre-SRS random serum growth hormone, larger treatment volume, and higher maximum point dose to the optic apparatus. The rates of initial/durable endocrine remission, new loss of pituitary function, and new cranial neuropathy were similar between groups. Mortality and new visual deficit were higher in the whole-sella cohort, though not statistically significant. CONCLUSION: There was no difference in biochemical remission or recurrence between treatment groups. Although not statistically significant, the higher rates of tumor regression and lower rates of mortality and new visual deficit may suggest consideration of targeted SRS over whole-sella SRS in acromegaly treatment. Further research is needed to determine the association between visual deficits and mortality with whole-sella SRS.

Postoperative Low-Dose Tranexamic Acid After Major Spine Surgery: A Matched Cohort Analysis.

OBJECTIVE: This was a retrospective, cohort study investigating the efficacy and safety of continuous low-dose postoperative tranexamic acid (PTXA) on drain output and transfusion requirements following adult spinal deformity surgery. METHODS: One hundred forty-seven patients undergoing posterior instrumented thoracolumbar fusion of ≥ 3 vertebral levels at a single institution who received low-dose PTXA infusion (0.5-1 mg/kg/hr) for 24 hours were compared to 292 control patients who did not receive PTXA. The cohorts were propensity matched based on age, sex, American Society of Anesthesiologist physical status classification, body mass index, number of surgical levels, revision surgery, operative duration, and total intraoperative TXA dose (n = 106 in each group). Primary outcome was 72-hour postoperative drain output. Secondary outcomes were number of allogeneic blood transfusions. RESULTS: There was no significant difference in postoperative drain output in the PTXA group compared to control (660 ± 420 mL vs. 710 ± 490 mL, p = 0.46). The PTXA group received significantly more crystalloid (6,100 ± 3,100 mL vs. 4,600 ± 2,400 mL, p < 0.001) and red blood cell transfusions postoperatively (median [interquartile range]: 1 [0-2] units vs. 0 [0-1] units; incidence rate ratio [95% confidence interval], 1.6 [1.2-2.2]; p = 0.001). Rates of adverse events were comparable between groups. CONCLUSION: Continuous low-dose PTXA infusion was not associated with reduced drain output after spinal deformity surgery. No difference in thromboembolic incidence was observed. A prospective dose escalation study is warranted to investigate the efficacy of higher dose PTXA.

Surgery for Pediatric Pituitary Adenomas.

Pituitary adenomas are a rare but important central nervous system tumor in children. Because of differences in growth and development, the manifestations of pituitary adenomas in children may differ from those seen in adults. Unlike adult patients, the pediatric population more often presents with clinically secretory adenomas. Although medical management is first-line treatment of prolactinomas, transsphenoidal surgery is appropriate for most children with Cushing disease and gigantism. Although some pediatric patients present surgical challenges because of small anatomic dimensions or an incompletely developed sphenoid sinus, transsphenoidal surgery can be safely and effectively undertaken in most children, with low complication rates.

Radiation dose to neuroanatomical structures of pituitary adenomas and the effect of Gamma Knife radiosurgery on pituitary function.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) provides a safe and effective management option for patients with all types of pituitary adenomas. The long-term adverse effects of targeted radiation to the hypothalamic-pituitary axis in relationship to radiation dose remain unclear. In this retrospective review, the authors investigated the role of differential radiation doses in predicting long-term clinical outcomes and pituitary function after GKRS for pituitary adenomas. METHODS: A cohort of 236 patients with pituitary tumors (41.5% nonfunctioning, 58.5% functioning adenomas) was treated with GKRS between 1998 and 2015. Point dosimetric measurements, with no minimum volume, to 14 consistent points along the hypothalamus bilaterally, pituitary stalk, and normal pituitary were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiological, and endocrine outcomes. RESULTS: With a median follow-up duration of 42.9 months, 18.6% of patients developed new loss of pituitary function. The median time to endocrinopathy was 21 months (range 2-157 months). The median dose was 2.1 Gy to the hypothalamus, 9.1 Gy to the pituitary stalk, and 15.3 Gy to the normal pituitary. Increasing age (p = 0.015, HR 0.98) and ratio of maximum dose to the pituitary stalk over the normal pituitary gland (p = 0.013, HR 0.22) were independent predictors of new or worsening hypopituitarism in the multivariate analysis. Sex, margin dose, treatment volume, nonfunctioning adenoma status, or ratio between doses to the pituitary stalk and hypothalamus were not significant predictors. CONCLUSIONS: GKRS offers a low rate of delayed pituitary insufficiency for pituitary adenomas. Doses to the hypothalamus are low and generally do not portend endocrine deficits. Patients who are treated with a high dose to the pituitary stalk relative to the normal gland are at higher risk of post-GKRS endocrinopathy. Point dosimetry to specific neuroanatomical structures revealed that a ratio of stalk-to-gland radiation dose of 0.8 or more significantly increased the risk of endocrinopathy following GKRS. Improvement in the gradient index toward the stalk and normal gland may help preserve endocrine function.

Preoperative embolization of skull base meningiomas: A systematic review.

Neoadjuvant endovascular embolization of skull base meningiomas may facilitate surgical resection, thereby potentially decreasing operative morbidity. However, due to variation in the reported efficacy and complication rates, the utility of embolization remains incompletely defined. The aim of this systematic review is to assess the outcomes of preoperative embolization for skull base meningiomas. A literature review was performed to identify studies reporting outcomes of patients with skull base meningiomas who underwent preoperative embolization. Baseline, treatment, and outcomes data were analyzed. Major complications included death, new cranial neuropathy, retinal artery ischemia, permanent neurologic deficit, or intracerebral hemorrhage. The pooled analysis consisted of 15 studies, comprising a total of 403 patients with skull base meningiomas treated with preoperative embolization. The most common locations were the sphenoid wing (34%, 87/256 cases), petroclival region (31%, 80/256 cases), and cavernous sinus (12%, 31/256 cases). The median tumor size ranged from 5.0 to 8.0 cm. Based on pooled data, angiographic absence of tumor blush was achieved in 17% (13/79 cases). The median estimated blood loss (EBL) ranged from 225 to 580 mL. Simpson grade I-III resection was achieved in 74% (40/54) of patients. The overall complication, major complication, and mortality rates were 12% (47/403 patients), 6% (21/328 patients), and 0.2% (1/403 patients), respectively. Preoperative embolization is a reasonable adjunct to resection for appropriately selected skull base meningiomas. Future comparative analyses are necessary to ascertain the benefits of preoperative embolization of skull base meningiomas with respect to extent of resection, operative duration, operative blood loss, and surgical morbidity.

Low rates of complications after spinopelvic fixation with iliac screws in 260 adult patients with a minimum 2-year follow-up.

OBJECTIVERecent literature describing complications associated with spinopelvic fixation with iliac screws in adult patients has been limited but has suggested high complication rates. The authors' objective was to report their experience with iliac screw fixation in a large series of patients with a 2-year minimum follow-up.METHODSOf 327 adult patients undergoing spinopelvic fixation with iliac screws at the authors' institution between 2010 and 2015, 260 met the study inclusion criteria (age ≥ 18 years, first-time iliac screw placement, and 2-year minimum follow-up). Patients with active spinal infection were excluded. All iliac screws were placed via a posterior midline approach using fluoroscopic guidance. Iliac screw heads were deeply recessed into the posterior superior iliac spine. Clinical and radiographic data were obtained and analyzed.RESULTSTwenty patients (7.7%) had iliac screw-related complication, which included fracture (12, 4.6%) and/or screw loosening (9, 3.5%). No patients had iliac screw head prominence that required revision surgery or resulted in pain, wound dehiscence, or poor cosmesis. Eleven patients (4.2%) had rod or connector fracture below S1. Overall, 23 patients (8.8%) had L5-S1 pseudarthrosis. Four patients (1.5%) had fracture of the S1 screw. Seven patients (2.7%) had wound dehiscence (unrelated to the iliac screw head) or infection. The rate of reoperation (excluding proximal junctional kyphosis) was 17.7%. On univariate analysis, an iliac screw-related complication rate was significantly associated with revision fusion (70.0% vs 41.2%, p = 0.013), a greater number of instrumented vertebrae (mean 12.6 vs 10.3, p = 0.014), and greater postoperative pelvic tilt (mean 27.7° vs 23.2°, p = 0.04). Lumbosacral junction-related complications were associated with a greater mean number of instrumented vertebrae (12.6 vs 10.3, p = 0.014). Reoperation was associated with a younger mean age at surgery (61.8 vs 65.8 years, p = 0.014), a greater mean number of instrumented vertebrae (12.2 vs 10.2, p = 0.001), and longer clinical and radiological mean follow-up duration (55.8 vs 44.5 months, p < 0.001; 55.8 vs 44.6 months, p < 0.001, respectively). On multivariate analysis, reoperation was associated with longer clinical follow-up (p < 0.001).CONCLUSIONSPrevious studies on iliac screw fixation have reported very high rates of complications and reoperation (as high as 53.6%). In this large, single-center series of adult patients, iliac screws were an effective method of spinopelvic fixation that had high rates of lumbosacral fusion and far lower complication rates than previously reported. Collectively, these findings argue that iliac screw fixation should remain a favored technique for spinopelvic fixation.

BRAF V600 Mutation and BRAF Kinase Inhibitors in Conjunction With Stereotactic Radiosurgery for Intracranial Melanoma Metastases: A Multicenter Retrospective Study.

BACKGROUND: The BRAF mutation has been identified as a potent target for the treatment of metastatic melanoma and BRAF inhibitors (BRAFi) have demonstrated promising results against melanoma brain metastases (BM). OBJECTIVE: To further investigate the effectiveness of this combined treatment regimen. METHODS: In this multicenter retrospective cohort study, 198 patients with known BRAF mutation status and treated with stereotactic radiosurgery (SRS) between 2011 and 2015 were identified. Kaplan-Meier methodology and multivariate regression analysis was then used to compare survival based on each parameter. RESULTS: The median survival after the diagnosis of BM in patients with BRAF mutation who received BRAFi was increased compared to survival in patients with wild-type BRAF (BRAF wt). In multivariate analysis, the BRAF mutation was an independent, positive prognostic factor with a hazard ratio of 0.59. BRAF mutated Patients who received BRAFi following SRS had improved survival compared to patients who received it before (P < .001) or concurrently (P = .007). PD-1 inhibitors improved survival, with more pronounced effect in patients not carrying the BRAF mutation. Among the patients who were treated with BRAFi, 10.4% developed intracerebral hematoma (ICH), in comparison to 3% of patients who were not treated with BRAFi (P = .03). CONCLUSION: In the setting of widespread use of BRAFi, the presence of a BRAF mutation is an independent predictor of better prognosis in patients with melanoma BM that underwent SRS. The effect of BRAFi is optimal when treatment is initiated at least 1 wk following SRS. BRAFi may increase the frequency of asymptomatic ICH.