Multiple surgical resections for progressive IDH wildtype glioblastoma-is it beneficial?

PURPOSE: The role of repeat resection for recurrent glioblastoma (rGB) remains equivocal. This study aims to assess the overall survival and complications rates of single or repeat resection for rGB. METHODS: A single-centre retrospective review of all patients with IDH-wildtype glioblastoma managed surgically, between January 2014 and January 2022, was carried out. Patient survival and factors influencing prognosis were analysed, using Kaplan-Meier and Cox regression methods. RESULTS: Four hundred thirty-two patients were included, of whom 329 underwent single resection, 83 had two resections and 20 patients underwent three resections. Median OS (mOS) in the cohort who underwent a single operation was 13.7 months (95% CI: 12.7-14.7 months). The mOS was observed to be extended in patients who underwent second or third-time resection, at 22.9 months and 44.7 months respectively (p < 0.001). On second operation achieving > 95% resection or residual tumour volume of < 2.25 cc was significantly associated with prolonged survival. There was no significant difference in overall complication rates between primary versus second (p = 0.973) or third-time resections (p = 0.312). The use of diffusion tensor imaging (DTI) guided resection was associated with reduced post-operative neurological deficit (RR 0.37, p = 0.002), as was use of intraoperative ultrasound (iUSS) (RR 0.45, p = 0.04). CONCLUSIONS: This study demonstrates potential prolongation of survival for rGB patients undergoing repeat resection, without significant increase in complication rates with repeat resections. Achieving a more complete repeat resection improved survival. Moreover, the use of intraoperative imaging adjuncts can maximise tumour resection, whilst minimising the risk of neurological deficit.

The role of [18F]fluorodopa positron emission tomography in grading of gliomas.

PURPOSE: Gliomas are the most commonly occurring brain tumour in adults and there remains no cure for these tumours with treatment strategies being based on tumour grade. All treatment options aim to prolong survival, maintain quality of life and slow the inevitable progression from low-grade to high-grade. Despite imaging advancements, the only reliable method to grade a glioma is to perform a biopsy, and even this is fraught with errors associated with under grading. Positron emission tomography (PET) imaging with amino acid tracers such as [18F]fluorodopa (18F-FDOPA), [11C]methionine (11C-MET), [18F]fluoroethyltyrosine (18F-FET), and 18F-FDOPA are being increasingly used in the diagnosis and management of gliomas. METHODS: In this review we discuss the literature available on the ability of 18F-FDOPA-PET to distinguish low- from high-grade in newly diagnosed gliomas. RESULTS: In 2016 the Response Assessment in Neuro-Oncology (RANO) and European Association for Neuro-Oncology (EANO) published recommendations on the clinical use of PET imaging in gliomas. However, since these recommendations there have been a number of studies performed looking at whether 18F-FDOPA-PET can identify areas of high-grade transformation before the typical radiological features of transformation such as contrast enhancement are visible on standard magnetic resonance imaging (MRI). CONCLUSION: Larger studies are needed to validate 18F-FDOPA-PET as a non-invasive marker of glioma grade and prediction of tumour molecular characteristics which could guide decisions surrounding surgical resection.

Prospective, multicentre study of external ventricular drainage-related infections in the UK and Ireland.

OBJECTIVES: External ventricular drain (EVD) insertion is a common neurosurgical procedure. EVD-related infection (ERI) is a major complication that can lead to morbidity and mortality. In this study, we aimed to establish a national ERI rate in the UK and Ireland and determine key factors influencing the infection risk. METHODS: A prospective multicentre cohort study of EVD insertions in 21 neurosurgical units was performed over 6 months. The primary outcome measure was 30-day ERI. A Cox regression model was used for multivariate analysis to calculate HR. RESULTS: A total of 495 EVD catheters were inserted into 452 patients with EVDs remaining in situ for 4700 days (median 8 days; IQR 4-13). Of the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an infection risk of 9.3%. Cox regression analysis demonstrated that factors independently associated with increased infection risk included duration of EVD placement for ≥8 days (HR=2.47 (1.12-5.45); p=0.03), regular sampling (daily sampling (HR=4.73 (1.28-17.42), p=0.02) and alternate day sampling (HR=5.28 (2.25-12.38); p<0.01). There was no association between catheter type or tunnelling distance and ERI. CONCLUSIONS: In the UK and Ireland, the ERI rate was 9.3% during the study period. The study demonstrated that EVDs left in situ for ≥8 days and those sampled more frequently were associated with a higher risk of infection. Importantly, the study showed no significant difference in ERI risk between different catheter types.

Occular and dermal toxicity of Jatropha curcas phorbol esters.

Jatropha curcas seeds are a promising feedstock for biodiesel production. However, Jatropha seed oil and other plant parts are toxic due to the presence of phorbol esters (PEs). The ever-increasing cultivation of toxic genotype of J. curcas runs the risk of increased human exposure to Jatropha products. In the present study, effects of J. curcas oil (from both toxic and nontoxic genotypes), purified PEs-rich extract and purified PEs (factors C1, C2, C(3mixture), (C4+C5)) on reconstituted human epithelium (RHE) and human corneal epithelium (HCE) were evaluated in vitro. The PEs were purified from toxic Jatropha oil. In both RHE and HCE, the topical application of PEs containing samples produced severe cellular alterations such as marked oedema, presence of less viable cell layers, necrosis and/or partial tissue disintegration in epithelium and increased inflammatory response (interleukin-1α and prostaglandin E2). When compared to toxic oil, histological alterations and inflammatory response were less evident (P<0.05) in nontoxic oil indicating the severity of toxicity was due to PEs. Conclusively, topical applications of Jatropha PEs are toxic towards RHE and HCE models, which represents dermal and occular toxicity respectively. Data obtained from this study would aid in the development of safety procedures for Jatropha biodiesel industries. It is advised to use protective gloves and glasses when handling PEs containing Jatropha products.

Evaluation of the impact of the Canadian subarachnoid haemorrhage clinical decision rules on British practice.

INTRODUCTION: Acute headache is among the commonest presenting complaints to emergency departments. While it is estimated that only 1-3% result from subarachnoid haemorrhage (SAH), because the disease carries such significant morbidity and mortality if missed, most clinicians have a low threshold for investigation. A recent prospective cohort study in Canada determined a number of high-risk clinical characteristics for SAH in patients with acute headache. We investigated the potential impact of incorporating the Canadian clinical decision rules on British practice. METHODS: A retrospective case note review on all adult patients presenting to our emergency department with acute headache between August and October 2011 was conducted. The Canadian decision rules for SAH were applied retrospectively to the cases identified, and the sensitivity, specificity and negative predictive values calculated. The two-tailed McNemar test was used to evaluate differences between proportions of patients undergoing investigations using the clinical decision rules against current practice. RESULTS: In all, 112 patients met the inclusion criteria in a 3-month period, of which 41 patients (36.6%) underwent unenhanced computed tomography and 4 (3.6%) were found to have SAH. Nine patients subsequently had a lumbar puncture and none demonstrated xanthochromia. None of the patients who were not fully investigated were readmitted to the regional neurosurgical centre within 6 months of discharge with missed SAH. Application of the Canadian clinical decision rules would have led to an investigation rate between 59% and 74%, compared to an actual rate of 37% (p < 0.05). CONCLUSION: The present study shows that application of the Canadian clinical decision rules for SAH would lead to more patients with acute headache being investigated than current British practice. However, much larger prospective studies are required to determine whether such clinical decision rules may identify patients at risk who would otherwise have been missed.

Endoscope-Assisted Resection for Cystic Cerebellar Hemangioblastomas.

BACKGROUND: Hemangioblastomas are benign, often cystic tumors occurring most commonly in the cerebellum. We describe resection of cystic cerebellar hemangioblastomas using an endoscope-assisted technique. METHODS: We present a series of 9 cases and discuss the endoscopic technique for resection of cystic hemangioblastoma. Frameless neuronavigation was used in all cases. A small 1- to 1.5-cm corticotomy lined with Surgicel and patties allows access to the peritumoral cyst. Using bimanual microsurgical techniques and the 30-degree rigid endoscope to provide visualization, the mural nodule can be resected and the cyst cavity inspected. RESULTS: Complete resection of the mural nodule was achieved in all cases. One patient had a postsurgery pseudomeningocele requiring ventriculoperitoneal shunt. Hospital length of stay was short for all the patients. CONCLUSIONS: Endoscope-assisted resection is a safe and effective technique for surgical resection of cystic hemangioblastoma.

Intracranial Masson Lesion Following Stereotactic Radiosurgery for Treatment of Intracranial Arteriovenous Malformations.

OBJECTIVES: Masson tumor or intravascular papillary endothelial cell proliferation was first described in 1923. Only a few cases of intracranial Masson tumor have been reported following stereotactic radiosurgery (SRS). We report a series of 6 cases, age range 28-56 years, with intracranial Masson tumor following SRS for treatment of an intracranial arteriovenous malformation (AVM). METHODS: We performed a retrospective case note review, reviewed the imaging, SRS records, and neuropathology specimens following surgical excision. RESULTS: In our series all patients received Leksell SRS with the periphery of the AVM receiving doses ranging from 22-25 Gy. The time lapse from SRS to a clear enhancing mass appearing on imaging ranged from 5-10 years. Four patients underwent craniotomy and excision of the enhancing lesion for persistent edema and an enlarging cyst resulting in a resolution of symptoms. CONCLUSIONS: SRS is an effective treatment for obliteration of intracranial AVMs.

Management evaluation of metastasis in the brain (MEMBRAIN)-a United Kingdom and Ireland prospective, multicenter observational study.

BACKGROUND: In recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making. METHODS: A prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database. RESULTS: A total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases. CONCLUSIONS: This study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making.

Characterization of a Dispiroketal Spirolide Subclass from Alexandrium ostenfeldii.

A new subclass of spirolide marine toxins, represented by spirolides H (1) and I (2), were isolated from the marine dinoflagellate Alexandrium ostenfeldii. Spirolides H and I are structurally distinct from other spirolides in that they contain a 5:6 dispiroketal ring system rather than the trispiroketal ring system characteristic of previously isolated spirolides. The structures were assigned using a combination of spectrometric and spectroscopic techniques. Previously isolated spirolides containing a cyclic imine moiety showed toxicity in the mouse bioassay. Spirolide H contains this cyclic imine moiety but does not show toxicity in the mouse assay, suggesting that the presence of the cyclic imine moiety is not the only structural requirement for toxicity.

Safety, Accuracy, and Cost Effectiveness of Bedside Bolt External Ventricular Drains (EVDs) in Comparison with Tunneled EVDs Inserted in Theaters.

OBJECTIVES: External ventricular drain (EVD) placement is required frequently in neurosurgical patients to divert cerebrospinal fluid and monitor intracranial pressure. The usual practice is the tunneled EVD technique performed in operating theaters. EVD insertion through a bolt in intensive care also is described. We employ both practices in our institute. Herein, we compare the indications, accuracy, safety, and costs of the 2 techniques. METHODS: This was a retrospective cohort study of a prospectively maintained EVD database of all patients undergoing first frontal EVD placement between January 2010 and December 2015. Those patients with preceding cerebrospinal fluid infection were excluded. We compared bolt EVD with tunneled EVD techniques in terms of accuracy of EVD tip location by analyzing computed tomography scans to grade catheter tip location as optimal (ipsilateral frontal horn) or otherwise suboptimal, and complications that include infection and revision rates. RESULTS: In total, 579 eligible patients aged 3 months to 84 years were identified; 430 had tunneled EVDs and 149 bolt EVDs. The most frequent diagnosis was intracranial hemorrhage (73% bolt vs. 50.4% tunneled group; P < 0.001). Other diagnoses included tumor (4.7% bolt vs. 19.1% tunneled; P < 0.001) and traumatic brain injury (17.5% bolt vs. 17.4% tunneled). In the bolt EVD group 66.4% of EVD tips were optimal, compared with 61.0% in the tunneled group (P = 0.33). Infection was confirmed in 15 (10.0%) bolt EVDs compared with 61 (14.2%) tunneled EVDs (P = 0.2). Each bolt EVD kit costs £260, whereas placing a tunneled one in the theater costs £1316. CONCLUSIONS: Bedside bolt EVD placement is safe, accurate, and cost effective in selective patients with hemorrhage-related hydrocephalus.

Image guidance and improved accuracy of external ventricular drain tip position particularly in patients with small ventricles.

OBJECTIVE: External ventricular drain (EVD) insertion is one of the most common emergency neurosurgical procedures. EVDs are traditionally inserted freehand (FH) in an emergency setting, but often result in suboptimal positioning. Image-guided surgery (IGS) is selectively used to assist placement. However, the accuracy and practicality of IGS use is yet to be reported. In this study, the authors set out to assess if IGS is practical and improves the accuracy of EVD placement. METHODS: Case notes and images obtained in patients who underwent frontal EVD placement were retrospectively reviewed. Ventriculomegaly was determined by the measurement of the Evans index. EVD location was classified as optimal (ipsilateral frontal horn) or suboptimal (any other location). Propensity score matching of the two groups (IGS vs FH) for the Evans index was performed. Data were analyzed for patient age, diagnosis, number of EVDs, and complications. Those without postoperative CT scans were excluded. RESULTS: A total of 607 patients with 760 EVDs placed were identified; 331 met inclusion criteria. Of these, 287 were inserted FH, and 44 were placed with IGS; 60.6% of all unmatched FH EVDs were optimal compared with 75% of the IGS group (p = 0.067). The IGS group had a significantly smaller Evans index (p < 0.0001). Propensity score matching demonstrated improved optimal position in the IGS group when compared with the matched FH group (75% vs 43.2%, OR 4.6 [1.5-14.6]; p = 0.002). Patients with an Evans index of ≥ 0.36 derived less benefit (75% in IGS vs 66% in FH, p = 0.5), and those with an Evans index < 0.36 derived more benefit (75% in IGS vs 53% in FH, p = 0.024). The overall EVD complication rate was 36% in the FH group versus 18% in the IGS group (p = 0.056). Revision rates were higher in the FH group (p = 0.035), and the operative times were similar (p = 0.69). Long intracranial EVD catheters were associated with tip malposition irrespective of the group. CONCLUSIONS: Image guidance is practical and improves the accuracy of EVD placement in patients with small ventricles; thus, it should be considered for these patients.

Review of ß-carboline alkaloids from the genus Aspidosperma.

Plants belonging to the genus Aspidosperma, a member of the family Apocynaceae, provide a rich source of ß-carboline alkaloids, which makes them potentially poisonous. However, some of these alkaloids possess antitumor and antimicrobial activity. The present review is a survey of the ß-carboline alkaloids and shows that they comprise of a diverse array of structural modifications.

Calcific myonecrosis: a case report and review of the literature.

Calcific myonecrosis is a rare post-traumatic sequel of the lower limb, presenting in a delayed manner several years after the initial injury. We report a case of a 43-year-old gentleman who presented emergently with an enlarging painful mass in the lateral side of his left leg, that although present for several years had recently worsened with respect to the pain and erythema. Following laboratory and radiological investigations this was diagnosed to be calcific myonecrosis, which was then treated conservatively, and patient discharged when symptomatically improved.

Isolation, stability and bioactivity of Jatropha curcas phorbol esters.

Jatropha curcas seed oil, which can be utilized for biodiesel production upon transesterification, is also rich in phorbol esters (PEs). In this study, PEs from J. curcas oil (Jatropha factors C1 and C2 (purified to homogeneity), Jatropha factors C3 and (C4+C5) (obtained as mixtures) and PE-rich extract (containing all the above stated Jatropha factors) were investigated. The concentrations of Jatropha PEs were expressed equivalent to Jatropha factor C1. In the snail (Physa fontinalis) bioassay, the order of potency (EC50, µg/L) was: PE-rich extract

Cassane diterpenoids of Caesalpinia pulcherrima.

Five new cassane diterpenoids (1-5) were isolated from the roots of Caesalpinia pulcherrima, along with the known isovouacapenol C (6), pulcherrimin A (11), and 6beta-cinnamoyl-7beta-hydroxyvouacapen-5alpha-ol (12). Compounds 3-5 possess the alpha,beta-butenolide moiety, whereas compounds 1 and 2 contain a more usual 2,3-disubstituted furan unit. Compounds 7 and 8 were derived from hydrolysis of 6, while 9 and 10 were derived from acetylation and oxidation of 6, respectively. The (1)H and (13)C NMR spectra of all compounds were completely assigned using a combination of 2D NMR experiments, including (1)H-(1)H COSY, HSQC, HMBC, and T-ROESY sequences.