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Atypical meningiomas (AM) comprise a heterogeneous conglomeration of meningiomas with higher local recurrence rates than their benign counterparts. Although adjuvant therapy following subtotal resection is the standard, the use of adjuvant therapy following gross total resection (GTR) remains controversial. This study seeks to add to the literature by identifying radiopathologic predictors of recurrence in patients with a GTR AM and better identify those patients who may benefit from adjuvant therapy.A total of 103 consecutive patients who received gross total resection for AM at our center between Apr 2010 and Apr 2019 were evaluated retrospectively. Recurrence was defined as new enhancing masses on MRI without requiring biopsy confirmation. Cumulative incidence plots were used to estimate survival, and the log-rank test was used to assess differences between groups. Cox proportional hazards models were used to evaluate the effect of radiopathologic variables on the hazard of recurrence.Of the 103 patients included in this study, 68 (66.0%) were female, and the mean age was 51.1 ± 11.4. The median overall survival for patients following surgery was 71 months while the median progression-free survival was 64 months. Recurrence occurred in 36 (35.0%) patients. Factors correlated with AM recurrence following GTR included peritumoral edema (p = 0.005), necrosis (p 0.001), mitotic rate greater than 7/10 high-power field (HPF) (p 0.001), and Ki67 15% (p 0.001). However, following Cox proportional hazards regression analysis, only mitotic rate greater than 7/10HPF (p = 0.018) and Ki67 15% (p = 0.035) were significantly associated with AM recurrence.Our results showed high mitotic index (greater than 7/10 HPF) and Ki67 greater than 15% as independent predictors of recurrence in patients with a GTR AM. These findings could help stratify patients who may benefit from adjuvant therapy.

STUDY DESIGN Michigan Spine Surgery Improvement Collaborative (MSSIC) prospectively collects data on all patients undergoing operations for degenerative and/or deformity indications. OBJECTIVE We aimed to identify which factors are significantly associated with return-to-work after lumbar surgery at long-term follow-up. SUMMARY OF BACKGROUND DATA Prior publications have created a clinically relevant predictive model for return-to-work, wherein education, gender, race, comorbidities, and preoperative symptoms increased likelihood of return-to-work at 3 months after lumbar surgery. We sought to determine if these trends 1) persisted at 1 year and 2 years postoperatively; or 2) differed among preoperatively employed versus unemployed patients. METHODS MSSIC was queried for all patients undergoing lumbar operations (2014-2019). All patients intended to return-to-work postoperatively. Patients were followed for up to 2 years postoperatively. Measures of association were calculated with multivariable generalized estimating equations (GEE). RESULTS Return-to-work increased from 63% (3542/5591) at 90 days postoperatively to 75% (3143/4147) at 1 year and 74% (2133/2866) at 2 years postoperatively. Following GEE, neither clinical nor surgical variables predicted return-to-work at all three time intervals: 90 days, 1 year, and 2 years postoperatively. Only socioeconomic factors reached statistical significance at all follow-up points. Preoperative employment followed by insurance status had the greatest associations with return-to-work. In a sub-analysis of patients who were preoperatively employed, insurance was the only factor with significant associations with return-to-work at all three follow-up intervals. The return-to-work rates among unemployed patients at baseline increased from 29% (455/1100) at 90 days, 44% (495/608) at 1 year, and 46% (366/426) at 2 years postoperatively. The only two significant factors associated with return-to-work at all three follow-up intervals were Medicaid, as compared to private insurance, and male gender. CONCLUSION In patients inquiring about long-term return-to-work after lumbar surgery, insurance status represents the important determinant of employment status.Level of Evidence: 2.

The 2019 coronavirus pandemic (COVID-19) has affected all of society at different levels. Similarly, COVID-19 has significantly impacted every medical field, including neurosurgery. By exposing scarcities in the healthcare industry and requiring the reallocation of available resources towards the priority setting and away from elective surgeries and outpatient visits, the pandemic posed new, unprecedented challenges to the medical community. Despite the redistribution of resources towards COVID-19 patients and away from elective surgeries, urgent and emergent surgeries for life-threatening conditions needed to be continued. The neurosurgical community, like other specialties not directly involved in the care of COVID-19 patients, initially struggled to balance the needs of COVID-19 patients with those of neurosurgical patients, residents, and researchers. Several articles describing the effect of COVID-19 on neurosurgical practice and training have been published throughout the COVID-19 pandemic. This article aims to provide a focused review of the impact COVID-19 has had on neurosurgical practice and training as well as describe neurological manifestations of the disease.

OBJECTIVENormal percentile growth charts for head circumference, length, and weight are well-established tools for clinicians to detect abnormal growth patterns. Currently, no standard exists for evaluating normal size or growth of cerebral ventricular volume. The current standard practice relies on clinical experience for a subjective assessment of cerebral ventricular size to determine whether a patient is outside the normal volume range. An improved definition of normal ventricular volumes would facilitate a more data-driven diagnostic process. The authors sought to develop a growth curve of cerebral ventricular volumes using a large number of normal pediatric brain MR images.METHODSThe authors performed a retrospective analysis of patients aged 0 to 18 years, who were evaluated at their institution between 2009 and 2016 with brain MRI performed for headaches, convulsions, or head injury. Patients were excluded for diagnoses of hydrocephalus, congenital brain malformations, intracranial hemorrhage, meningitis, or intracranial mass lesions established at any time during a 3- to 10-year follow-up. The volume of the cerebral ventricles for each T2-weighted MRI sequence was calculated with a custom semiautomated segmentation program written in MATLAB. Normal percentile curves were calculated using the lambda-mu-sigma smoothing method.RESULTSVentricular volume was calculated for 687 normal brain MR images obtained in 617 different patients. A chart with standardized growth curves was developed from this set of normal ventricular volumes representing the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles. The charted data were binned by age at scan date by 3-month intervals for ages 0–1 year, 6-month intervals for ages 1–3 years, and 12-month intervals for ages 3–18 years. Additional percentile values were calculated for boys only and girls only.CONCLUSIONSThe authors developed centile estimation growth charts of normal 3D ventricular volumes measured on brain MRI for pediatric patients. These charts may serve as a quantitative clinical reference to help discern normal variance from pathologic ventriculomegaly.

Background A paucity of randomized trials have compared prophylactic dose of unfractionated heparin (UFH) versus low-molecular-weight heparin (LMWH) for the prevention of venous thromboembolic events in spinal surgery. Our objective was to determine the most prevalent chemoprophylactic techniques in spine surgery. Methods The Accreditation Council for Graduate Medical Education was queried for all neurosurgical residency programs, which were subsequently sent an electronic survey about prophylactic UFH versus LMWH in spine surgery for (1) degenerative/deformity, (2) traumatic, and (3) neoplastic pathologies. Results Of 69 unique responding residencies, the first dose of chemoprophylaxis for degenerative/deformity spinal disease started most commonly on postoperative day (POD) 1 in 75.3% of neurosurgery programs, followed by POD 2 in 10.1% of programs, POD 0 (same day of surgery) in 8.7% of programs, POD 3 in 1.4% of programs, and morning of surgery in 1.4% of programs. Choice of postoperative chemoprophylaxis did not differ statistically significantly between UFH versus LMWH: 56.5% versus 36.2% in degenerative/deformity pathologies (P = 0.080) and 50.7% versus 43.4% in traumatic pathologies (P = 0.535). Three programs (4.3%) in both the degenerative/deformity and trauma groups documented no chemoprophylaxis. Neoplastic pathologies saw a statistically significantly higher proportion of prophylactic UFH (60.8%) compared with prophylactic LMWH (36.2%) (P = 0.037). One program (1.4%) in the neoplastic group did not utilize chemoprophylaxis. Two institutions (2.8%) in the degenerative/deformity cohort and 1 institution (1.4%) in the trauma and cancer cohorts reported “other”. Conclusions Prophylactic UFH was statistically more common than LMWH in neoplastic spinal surgery, but not in the degenerative/deformity and trauma groups (cohorts). Further trials are warranted.

Objective The evidence regarding the consequences of subsidence with lateral lumbar interbody fusion (LLIF) has been sparse. The objective of this study is to calculate the incidence of subsidence and reoperation for subsidence after LLIF. A secondary outcome examined the quantitative degree of subsidence by calculating the percent change in the height of the intervertebral space secondary to interbody subsidence at various postoperative follow-up times. Methods Following the MOOSE (Meta-analysis [and Systematic Review] Of Observational Studies in Epidemiology) guidelines, a systematic review searched for all cohort studies that focused on subsidence rates after LLIF, including extreme lateral interbody fusions (XLIFs) and direct lateral interbody fusion. Neoplastic, infectious, and/or metabolic indications for LLIF were similarly excluded because these diseases may compromise bone quality and, thus, confound the rate of cage subsidence. Corpectomies were removed from the systematic review because 1) indications for removal of vertebral body typically reflect those excluded diseases and 2) subsidence refers to a different biomechanical process. Results This systematic review identified a subsidence incidence with LLIF of 10.3% (N = 141/1362 patients in 14 articles) and reoperation rate for subsidence of 2.7% (N = 41/1470 patients in 16 articles). In the secondary outcome measure, the disc height decreased from 5.6% after 3 months, 6.0% after 6 months, and 10.2% after 12 months, to 8.9% after 24 months (P Conclusions Subsidence after LLIF carries a nonnegligible risk that may be incorporated in surgical consent discussions in selected patients.

Introduction: The establishment of mechanical thrombectomy (MT) as a first line treatment for select patients with ischemic stroke (IS) and the resulting expansion of stroke systems of care have been major advancements in the care of IS patients. Our study aims to identify temporal trends in the usage of tPA and MT, as well as mortality for IS patients from 2012-2018. Hypothesis: We hypothesize that not only MT but also tPA utilization increased after 2015 compared to years previous, while mortality likely improved, given enhanced public education and optimization of stroke systems of care. Methods: Using a nation-wide, private health insurance database, we identified 141,959 patients who presented with a primary IS between 2012 and 2018. We evaluated trends in tPA and MT usage, and mortality stratified by treatment group using chi square and Cochran-Armitage testing. Results: Among patients presenting with IS in this population, the average age was 69.00 ± 12.23, and 47.43% were male. Between 2012-2018, the proportional use of tPA and MT increased significantly (tPA: 6.30%% to 11.79%, p Conclusion: From 2012-18, we found the use of tPA and MT increased significantly while 30-day mortality decreased in the entire IS population. The most dramatic decrease in mortality was seen in the MT population, followed by tPA and no treatment groups.

OBJECTIVE The establishment of mechanical thrombectomy (MT) as a first-line treatment for select patients with acute ischemic stroke (AIS) and the expansion of stroke systems of care have been major advancements in the care of patients with AIS. In this study, the authors aimed to identify temporal trends in the usage of tissue-type plasminogen activator (tPA) and MT within the AIS population from 2012 to 2018, and the relationship to mortality. METHODS Using a nationwide private health insurance database, 117,834 patients who presented with a primary AIS between 2012 and 2018 in the United States were identified. The authors evaluated temporal trends in tPA and MT usage and clinical outcomes stratified by treatment and age using descriptive statistics. RESULTS Among patients presenting with AIS in this population, the mean age was 69.1 years (SD ± 12.3 years), and 51.7% were female. Between 2012 and 2018, the use of tPA and MT increased significantly (tPA, 6.3% to 11.8%, p < 0.0001; MT, 1.6% to 5.7%, p < 0.0001). Mortality at 90 days decreased significantly in the overall AIS population (8.7% to 6.7%, p < 0.0001). The largest reduction in 90-day mortality was seen in patients treated with MT (21.4% to 14.1%, p = 0.0414) versus tPA (11.8% to 7.0%, p < 0.0001) versus no treatment (8.3% to 6.3%, p < 0.0001). Age-standardized mortality at 90 days decreased significantly only in patients aged 71–80 years (11.4% to 7.8%, p < 0.0001) and > 81 years (17.8% to 11.6%, p < 0.0001). Mortality at 90 days stagnated in patients aged 18 to 50 years (3.0% to 2.2%, p = 0.4919), 51 to 60 years (3.8% to 3.9%, p = 0.7632), and 61 to 70 years (5.5% to 5.2%, p = 0.2448). CONCLUSIONS From 2012 to 2018, use of tPA and MT increased significantly, irrespective of age, while mortality decreased in the entire AIS population. The most dramatic decrease in mortality was seen in the MT-treated population. Age-standardized mortality improved only in patients older than 70 years, with no change in younger patients.

Prone transpsoas lateral lumbar interbody fusion is the newest frontier in surgical approach to the lumbar spine. Prone positioning facilitates segmental lordosis and facile posterior segmental fixation. However, even in experienced hands, transitioning from a lateral decubitus to prone position necessitates alterations to the traditional technique. In this video, the authors highlight the nuances of adopting the prone transpsoas lateral lumbar interbody fusion technique and strategies to overcome them. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2224

Introduction Conventional grading scales in aneurysmal subarachnoid hemorrhage (aSAH) do not take into account the total blood volume and have been criticized for being open to variability in interpretation. We aimed to evaluate an automatic tool for quantification of the hemorrhage volume in aSAH. Methods Blood volumes were retrospectively analyzed and added to a comprehensive prospectively maintained institutional SAH database. Patients with non-aSAH were excluded. We designed an automatic quantitative blood volume analysis tool that utilizes a segmentation system that differentiates seed points corresponding to the different intracranial compartments. Through logistic regression analysis, we evaluated the association of blood volume with clinical cerebral vasospasm, delayed cerebral infarction (DCI) and 3-months clinical outcome. The diagnostic accuracy (AUC) of the quantitative blood volume analysis was compared to the modified Fisher score, the Hunt and Hess sore, the Hijdra score, and the World Federation of Neurosurgical Societies (WFNS) score. Results 288 aSAH patients with a mean total blood volume of 74.9 ml (± 39.7 ml) made up the study population. 73 patients developed clinical vasospasm (25.3%) and 52 patients developed DCI (18.06%). In univariate and multivariate analysis, total blood volume was significantly predictive of clinical vasospasm, DCI and clinical outcome. Blood volume had the highest AUC for clinical vasospasm as well as DCI when compared to conventional SAH scales. The modified Fisher score was not significantly predictive of either outcome. Conclusion Quantitative analysis of blood volume in aSAH provides a tool for prediction of cerebral vasospasm, DCI and clinical outcome that may have a higher performance and improved accuracy when compared to grading systems used in current practice. Disclosures B. Daou: None. S. Khalsa: None. S. Anand: None. C. Williamson: None. K. Rajajee: None. K. Sheehan: None. A. Pandey: None.

OBJECTIVEHydrocephalus and seizures greatly impact outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH); however, reliable tools to predict these outcomes are lacking. The authors used a volumetric quantitative analysis tool to evaluate the association of total aSAH volume with the outcomes of shunt-dependent hydrocephalus and seizures.METHODSTotal hemorrhage volume following aneurysm rupture was retrospectively analyzed on presentation CT imaging using a custom semiautomated computer program developed in MATLAB that employs intensity-based k-means clustering to automatically separate blood voxels from other tissues. Volume data were added to a prospectively maintained aSAH database. The association of hemorrhage volume with shunted hydrocephalus and seizures was evaluated through logistic regression analysis and the diagnostic accuracy through analysis of the area under the receiver operating characteristic curve (AUC).RESULTSThe study population comprised 288 consecutive patients with aSAH. The mean total hemorrhage volume was 74.9 ml. Thirty-eight patients (13.2%) developed seizures. The mean hemorrhage volume in patients who developed seizures was significantly higher than that in patients with no seizures (mean difference 17.3 ml, p = 0.01). In multivariate analysis, larger hemorrhage volume on initial CT scan and hemorrhage volume > 50 ml (OR 2.81, p = 0.047, 95% CI 1.03–7.80) were predictive of seizures. Forty-eight patients (17%) developed shunt-dependent hydrocephalus. The mean hemorrhage volume in patients who developed shunt-dependent hydrocephalus was significantly higher than that in patients who did not (mean difference 17.2 ml, p = 0.006). Larger hemorrhage volume and hemorrhage volume > 50 ml (OR 2.45, p = 0.03, 95% CI 1.08–5.54) were predictive of shunt-dependent hydrocephalus. Hemorrhage volume had adequate discrimination for the development of seizures (AUC 0.635) and shunted hydrocephalus (AUC 0.629).CONCLUSIONSHemorrhage volume is an independent predictor of seizures and shunt-dependent hydrocephalus in patients with aSAH. Further evaluation of aSAH quantitative volumetric analysis may complement existing scales used in clinical practice and assist in patient prognostication and management.

Primary aldosteronism affects ≈5% to 10% of hypertensive patients and has unilateral and bilateral forms. Most unilateral primary aldosteronism is caused by computed tomography-detectable aldosterone-producing adenomas, which express CYP11B2 (aldosterone synthase) and frequently harbor somatic mutations in aldosterone-regulating genes. The cause of the most common bilateral form of primary aldosteronism, idiopathic hyperaldosteronism (IHA), is believed to be diffuse hyperplasia of aldosterone-producing cells within the adrenal cortex. Herein, a multi-institution cohort of 15 IHA adrenals was examined with CYP11B2 immunohistochemistry and next-generation sequencing. CYP11B2 immunoreactivity in adrenal glomerulosa harboring non-nodular hyperplasia was only observed in 4/15 IHA adrenals suggesting that hyperplasia of CYP11B2-expressing cells may not be the major cause of IHA. However, the adrenal cortex of all IHA adrenals harbored at least 1 CYP11B2-positive aldosterone-producing cell cluster (APCC) or micro-aldosterone-producing adenomas. The number of APCCs per case (and individual APCC area) in IHA adrenals was significantly larger than in normotensive controls. Next-generation sequencing of DNA from 99 IHA APCCs demonstrated somatic mutations in genes encoding the L-type calcium voltage-gated channel subunit α 1-D ( CACNA1D , n=57; 58%) and potassium voltage-gated channel subfamily J-5 ( KCNJ5 , n=1; 1%). These data suggest that IHA may result from not only hyperplasia but also the accumulation or enlargement of computed tomography-undetectable APCC harboring somatic aldosterone-driver gene mutations. The high prevalence of mutations in the CACNA1D L-type calcium channel provides a potential actionable therapeutic target that could complement mineralocorticoid blockade and inhibit aldosterone overproduction in some IHA patients.

Background Novel methods in predicting survival in patients with spinal metastases may help guide clinical decision-making and stratify treatments regarding surgery vs palliative care. Objective To evaluate whether the frailty/sarcopenia paradigm is predictive of survival and morbidity in patients undergoing surgery for spinal metastasis. Methods A total of 271 patients from 4 tertiary care centers who had undergone surgery for spinal metastasis were identified. Frailty/sarcopenia was defined by psoas muscle size. Survival hazard ratios were calculated using multivariate analysis, with variables from demographic, functional, oncological, and surgical factors. Secondary outcomes included improvement of neurological function and postoperative morbidity. Results Patients in the smallest psoas tertile had shorter overall survival compared to the middle and largest tertile. Psoas size (PS) predicted overall mortality more strongly than Tokuhashi score, Tomita score, and Karnofsky Performance Status (KPS). PS predicted 90-d mortality more strongly than Tokuhashi score, Tomita score, and KPS. Patients with a larger PS were more likely to have an improvement in deficit compared to the middle tertile. PS was not predictive of 30-d morbidity. Conclusion In patients undergoing surgery for spine metastases, PS as a surrogate for frailty/sarcopenia predicts 90-d and overall mortality, independent of demographic, functional, oncological, and surgical characteristics. The frailty/sarcopenia paradigm is a stronger predictor of survival at these time points than other standards. PS can be used in clinical decision-making to select which patients with metastatic spine tumors are appropriate surgical candidates.

Background Stroke is a feared complication of cardiac surgery. Modern clot-retrieval techniques provide effective treatment for large vessel occlusion (LVO) strokes. The purpose of this study was to 1) report the incidence of LVO stroke after cardiac surgery at a large academic center, and 2) describe outcomes of postoperative LVO strokes. Methods All patients experiencing stroke within 30 days after undergoing cardiac surgery at a single center in 2014-2018 were reviewed. LVOs were identified through review of imaging and medical records, and their characteristics and clinical courses were examined. Results Over the study period, 7,112 cardiac surgeries, including endovascular procedures, were performed. Acute ischemic stroke within 30 days after surgery was noted in 163 patients (2.3%). Among those with a stroke, 51/163 (31.3%) had a CTA or MRA, and 15/163 (9.2%) presented with LVO stroke. For all stroke patients, the median time from surgery to stroke was 2 days (interquartile range, IQR, 0–6 days), and for patients with LVO, the median time from surgery to stroke was 4 days (IQR 0–6 days). The overall rate of postoperative LVO was 0.2% (95% CI 0.1–0.4%), though only 6/15 received thrombectomy. LVO patients receiving thrombectomy were significantly more likely to return to independent living compared to those managed medically (n = 4/6, 66.6% for mechanical thrombectomy vs. n = 0/9, 0% for medical management, P = .01). Of the 9 patients who did not get thrombectomy, 6 may currently be candidates for thrombectomy given new expanded treatment windows. Conclusions The rate of LVO after cardiac surgery is low, though substantially elevated above the general population, and the majority do not receive thrombectomy currently. Patients receiving thrombectomy had improved neurologic outcomes compared to patients managed medically. Optimized postoperative care may increase the rate of LVO recognition, and cardiac surgery patients and their caregivers should be aware of this effective therapy.

Context: Aldosterone synthase (CYP11B2) immunohistochemistry and next-generation sequencing (NGS) have revealed the frequent presence of aldosterone-producing cell clusters (APCCs) harboring somatic mutations in aldosterone-regulating genes in adrenals from Americans without defined hypertension status. Objective: Determine the frequency and somatic mutation status of APCCs in a Japanese nonhypertensive cohort. Design, Setting, Patients, and Interventions: Adrenals from 837 consecutive autopsies at a Japanese institution, Tohoku University Hospital, were screened to select 107 unilateral adrenal glands from nonhypertensive patients. APCC score (APCC number/adrenal cortex area per case) was assessed by CYP11B2 immunohistochemistry. DNA from all APCCs and adjacent adrenal cortex was subjected to NGS using two panels targeting aldosterone-regulating genes. Primary Outcome Measure: APCC frequency and somatic mutation spectrum. Results: In 107 adrenals, 61 APCCs were detected (average of 0.6 APCCs per gland). APCC score was positively correlated with age (r = 0.50, P < 0.0001). NGS demonstrated high confidence somatic mutations in 21 of 61 APCCs (34%). Notably, 16 of 21 APCCs (76%) harbored somatic mutations in CACNA1D, the most frequently mutated gene in our previous studies of APCCs in Americans and CYP11B2-positive micronodules in cross-sectional imaging (computed tomography) negative primary aldosteronism (PA), whereas no APCCs harbored mutations in KCNJ5, the most frequently mutated gene in aldosterone-producing adenoma. APCC score was significantly lower than our previous cohort of unilateral computed tomography–negative PA. Conclusions: APCCs are frequent in nonhypertensive Japanese adrenals, accumulate with age, and frequently harbor somatic mutations (most commonly in CACNA1D). The role of APCCs in PA pathobiology and non-PA hypertension warrants further investigation., We found APCCs accumulate with age in a large normotensive cohort. Thirty-four percent of APCCs harbored mutations in aldosterone-regulating genes, most frequently CACNA1D.

A study group on C5 palsy retrospectively reviewed 1001 cervical operations at their institutions in order to understand the incidence, prognosticators, pathogenesis, and outcome of C5 palsy after cervical operations. Three studies are summarized. C5 palsy was higher after posterior versus anterior operations. C4-C5 foraminotomy and age were the strongest predictors of C5 palsy after posterior surgeries and anterior cervical decompression-fusion, respectively. Among patients undergoing C4-C5 posterior laminoforaminotomy with instrumented fusion, cord shift on postoperative imaging was thought to be implicated in the pathogenesis of C5 palsy. Among affected patients, 81.4% recovered. Median time to resolution of C5 palsy was between 6 months to 1 year.

While the abscopal effect has been previously described, the phenomenon has been poorly defined in the case of spinal metastases. This article is unique in that we present the first systematic review of the abscopal effect after radiation therapy to metastatic spinal cancer, especially since the spinal column represents one of the most common metastatic locations. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) resources, a systematic review identified relevant studies via a computer-aided search of MEDLINE and Embase. Ten publications that met the inclusion and exclusion criteria from the PRISMA flow diagram described a total of 13 patients, 76.9% of whom demonstrated image findings of the abscopal effect. In summary, important trends in the nine patients who experienced the abscopal effect in this review include higher doses of radiation and treatment with immunomodulators, both of which may help guide treatment paradigms for spinal metastases superimposed on diffuse metastatic disease. These trends, however, still warrant further investigations with experimental and clinical studies for a mechanistic understanding of the abscopal effect.

Background: In recent years, improvements in oncological care have led to an increased incidence of intradural extramedullary spinal metastases (IESMs) attributed to uterine carcinosarcoma (UCS). When such lesions occur, they typically carry a poor prognosis. Here, we have evaluated newer treatments, management strategies, and outcomes for IESM due to UCS. Case Description: A 59-year-old female with a history of recurrent UCS presented with the new onset of the left lower extremity pain, numbness, and episodic urinary incontinence. When the MR revealed an enhancing intradural extramedullary mass posterior to the L1 vertebral body, she underwent a focal decompressive laminectomy. Although she improved neurologically postoperatively, she succumbed to the leptomeningeal spread of her disease within 2 postoperative months. Conclusion: Management of IESM due to UCS requires multifaceted, individualized treatment modalities, including neurosurgery, radiation therapy, and medical oncologic management to maximize outcomes.

Penile lymphangiomas are rare manifestations of lymphangiomas or lymphatic malformations which are more commonly found in the head or neck region of the body. Lymphangiomas are further categorized as lymphangioma circumscriptum, cavernous lymphangioma, cystic hygroma, or acquired lymphangiomas (also known as lymphangiectasia), based on their depth and etiology.A literature review revealed only 30 cases of penile lymphangioma between 1947 and March 30, 2018. Several causes were attributed to the acquired penile lymphangiomas, including trauma, phimosis, and infection. While penile lymphangiomas can be initially mistaken for an infection, a thorough history and physical examination is sufficient to clinically diagnose a lymphangioma of the penis. Historically, surgical excision has been the gold standard of treatment for this condition. When asymptomatic, patients may opt for conservative management with avoidance of mechanical trauma alone. Other physicians have revealed novel treatment plans to rid patients of their penile lymphangioma such as a staged laser procedure.In this article, we elucidate the causes, symptoms, treatments, and outcomes associated with penile lymphangiomas found in the literature while also presenting the case of a 30-year-old African-American man diagnosed with acquired penile lymphangioma.Les lymphangiomes du pénis sont des manifestations rares des lymphangiomes ou des malformations lymphatiques qui sont plus fréquemment observés dans les régions de la tête ou du cou au niveau du corps. Les lymphangiomes sont aussi classés en lymphangiome circumscriptum, lymphangiome caverneux, hygroma kystique, ou en lymphangiomes acquis (aussi connus sous l’appellation lymphangiectasie), selon leur profondeur et leur étiologie.Une revue de la littérature ne révèle que 30 cas de lymphangiomes du pénis rapportés entre 1947 et Mars 2018. Plusieurs causes ont été attribuées aux lymphangiomes acquis du pénis, parmi lesquelles les traumatismes, le phimosis et les infections. Bien que les lymphangiomes péniens puissent être initialement pris pour une infection, une recherche des antécédents et un examen clinique minutieux sont suffisants pour diagnostiquer cliniquement un lymphangiome du pénis. L’excision chirurgicale a toujours constitué le gold standard du traitement de cette maladie. Lorsqu’elle est asymptomatique, les patients peuvent choisir un traitement conservateur en évitant les seuls traumatismes mécaniques. D’autres médecins ont proposé de nouveaux traitements ayant pour objectif de débarrasser les patients de leurs lymphangiomes péniens, comme la procédure au laser par étapes.A partir des données de la littérature, nous avons clarifié dans cet article les causes, symptômes, traitements et résultats associés aux lymphangiomes du pénis ; nous avons aussi présenté le cas d’un homme afro-américain âgé de 30 ans diagnostiqué comme porteur d’un lymphangiome pénien acquis.Caverneux, Circumscriptum, Kystique, Hygroma, Lymphangiome, Lymphangiectasie, Pénien, Pénis.

Whether primary aldosteronism (PA) is the consequence of a monoclonal or multiclonal process is unclear.A 48-year-old man with severe bilateral PA refractory to medical therapy underwent unilateral adrenalectomy of the dominant adrenal. Although computed tomography showed three left-sided cortical nodules, postsurgical histopathology and genetic analysis revealed five different adrenocortical adenomas. Two zona fasciculata (ZF)-like aldosterone-producing adenomas (APAs) each harbored distinct known somatic KCNJ5 mutations (L168R and T158A). A zona glomerulosa-like APA harbored a known CACNA1D G403R somatic mutation, whereas a zona reticularis-like adenoma, which was grossly black in pigmentation with histologic characteristics more associated with cortisol-producing adenomas, expressed CYP11B2, CYP17, and DHEA-ST by immunohistochemistry (IHC) and harbored no known somatic mutations. The fifth adenoma was ZF-type, negative for CYP11B2 and CYP17 IHC, and harbored no known somatic mutations.This case highlights complex intertumor heterogeneity in histology, steroidogenesis, and somatic mutations in multiple adrenocortical adenomas arising in a single patient with PA. These findings suggest that the syndrome of PA can involve heterogeneous and multiclonal functional adrenal adenomas.

Background: Several studies have confirmed the role of prophylactic low-molecular-weight heparin (LMWH) for venous thromboembolism (VTE) in neurosurgery; however, a paucity of literature has assessed its safety and efficacy versus prophylactic unfractionated heparin (UFH). The objective is to present a meta-analysis directly comparing prophylactic LMWH to UFH for the prevention of VTE in neurosurgery. Materials and Methods: Relevant studies that directly compared LMWH to UFH for prophylaxis of VTE in neurosurgery and/or spine surgery were identified by MEDLINE and EMBASE searches plus a scrutiny of references from the original articles and reviews. Three randomized trials were included in the meta-analysis. Efficacy and safety were ascertained per three primary outcome measures: VTE, minor complications (decline in hemoglobin/hematocrit), and major complications. Forest plot analysis provided odds ratio (OR), 95% confidence intervals (CIs), and P-values. Results: Of the 429 patients in the pooled analysis, the postoperative VTE rate of 5.6% (12/213) after LMWH chemoprophylaxis was equivalent to 3.7% (8/216) after UFH chemoprophylaxis (OR = 1.42, 95% CI 0.62–3.75, P = 0.308). Minor complications of 4.7% versus 4.6%, respectively, were nearly equal (OR = 1.01, 95% CI 0.41– 2.50, P = 0.929). All four major complications included intracranial hemorrhages: three after LMWH (1.4%) and one after UFH (0.5%) (OR = 2.32, 95% CI 0.34–16.01, P = 0.831). Tests for heterogeneity were nonsignificant in all three outcome measures. Conclusion: Rates of VTE, minor complications, and major complications were equivalent between prophylactic LMWH and UFH in neurosurgery. Further, randomized clinical trials comparing the two heparin products are required to elucidate superior safety and efficacy in neurosurgical patients.

Somatic strongly activating KRAS mutations play an oncogenic role across numerous human cancers, while less activating germline KRAS mutations are associated with developmental disorders. KRAS encodes two splice variant products—KRAS-4A and KRAS-4B—differing in their C-terminus through alternative fourth coding exons. Though KRAS-4A is homologous to the original transforming transcript identified in Kirsten rat sarcoma virus, its role in human cancer is less characterized compared to KRAS-4B. Here, through genetic analyses of three cohorts of patients with hereditary and/or aggressive cancers, we identified a rare KRAS-4A specific C-terminal truncating germline mutation (KRAS-4A C180X; rs373169526) in affected men of three families with hereditary prostate cancer and a patient with hereditary melanoma (minor allele frequency [MAF] of 0.0014 in these combined cancer cohorts assessed vs. 0.000056 in the ExAC population database, odds ratio 24.6 [95% confidence interval 5.1-103.5], two sided Fisher’s exact test p = 9.0E-5). The KRAS-4A C180X mutation truncates the C-terminus, removing the polybasic region and -CAAX motifs previously demonstrated to be necessary for Ras family member membrane association, MAP kinase signaling activation and transformation, suggesting a loss of function phenotype. However, in silico assessment of reported human variation demonstrates truncating germline variants only in KRAS-4A and not KRAS-4B, consistent with tolerance. Expression of KRAS-4A protein in NIH3T3 and MDCK leads to loss of exclusive membrane association and inhibits GTP loading, as expected, but paradoxically resulted in modest but significantly increased proliferation and soft agar colony growth compared to control or wildtype KRAS expressing cells. Pro-oncogenic phenotypes were not dependent on MAPK signaling, but showed sensitivity to AKT inhibition. In summary, we identified a germline truncating KRAS-4A mutation over-represented in hereditary cancers that defines a novel mechanism of KRAS activation not dependent on the C-terminal polybasic and -CAAX motifs. Citation Format: Moloy T. Goswami, Daniel H. Hovelson, Anna Johnson, Scott A. Tomlins, Lucy Wang, Kimberly Zhulke, Bhavneet Singh, Sharath Kumar Anand, Andi Cani, Albert Liu, Steven Kamberov, Yi-Mi Wu, Dan Robinson, Arul Chinnaiyan, Kathleen A. Cooney. Identification of an oncogenic germline KRAS truncating mutation in hereditary cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1447. doi:10.1158/1538-7445.AM2017-1447