Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Low-dose GBCA administration for brain tumour dynamic contrast enhanced MRI: a feasibility study.

A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (ve, Ktrans, vp) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p < 0.0001, t-test). Kinetic parameters derived using the low-dose interleaved protocol correlated significantly with parameters derived from a full-dose acquisition (p < 0.001) and demonstrated a significant association with tissue markers of microvessel density (p < 0.05). Our results suggest accurate high-spatial resolution kinetic parameter mapping is feasible with significantly reduced GBCA dose.

Perioperative Means to Prevent Surgical Site Infections following Elective Craniotomies: A Single-Center Experience.

Background Postoperative surgical site infections are a recognized complication following craniotomies with an associated increase in morbidity and mortality. Several studies have attempted to identify bundles of care to reduce the incidence of infections. Our study aims to clarify which perioperative measures play a role in reducing surgical infection rates further. Methods This study is a retrospective audit of all elective craniotomies in years 2018 to 2019. The primary endpoint was the surgical site infection rate at 30 days and 4 months after the procedure. Univariate analysis was used to identify factors predictive of postoperative infection. Results 344 patients were included in this study. Postoperative infections were observed in 5.2% of our cohort. No postoperative infections occurred within 4 months in patients receiving perioperative hair wash and intrawound vancomycin powder. In univariate analysis, craniotomy size (Fisher's exact test, p = 0.05), lack of perioperative hair wash, and vancomycin powder use (Fisher's exact test, p = 0.01) were predictive of postoperative infection. No complications relative to the use of intrawound vancomycin were observed. Conclusion Our study demonstrates that simple measures such as perioperative hair wash combined with intrawound vancomycin powder in addition to standard practice can help reducing infection rates with negligible risks and acceptable costs. Our results should be validated further in future prospective studies.

Do the indices of deprivation or smoking affect post-operative 1-year mortality in patients undergoing a craniotomy for a brain tumour in a public healthcare system?

OBJECTIVE: We sought to determine the 1-year survival following craniotomy for tumour resection in a public healthcare system and analyse the effect of indices of multiple deprivation (IMD) as well as smoking, alcohol, BMI, ASA grade and medical co-morbidities on post-operative morbidity and mortality. METHODS: This is a retrospective, single-centre study in a high volume neurosurgical centre, over a 2-year period. All patients undergoing a craniotomy for a brain tumour were included. Data was collected from the neuro-oncology database and electronic patient records. Individual patient IMD data was obtained using their postcode from a national government database. Each English postcode being ranked from 1 to 32,844, with 1 being the most deprived and 32,844 the most affluent. Descriptive results are described along with further data analysis using multiple linear and logistic regression analyses. RESULTS: 630 patients underwent an elective or urgent craniotomy for tumour. 10% of all patients underwent urgent surgery. 68% (95% CI: 64 to 71%) survived at least 1-year post-surgery. Our study found that social deprivation (IMD postcode rank) was not associated with mortality at 1 year after adjusting for potential confounding factors. Those from decile 1 had the lowest risk of death at 12 months for all tumour types (p = 0.0070). Previous smokers carried an increased risk of death at 12 months when compared with people who had never smoked RR 1.40 CI 1.10-1.78 (p = 0.006) but this risk was not evident in current smokers RR 0.92 CI 0.65-1.31 (p = 0.64). Increasing age and male gender were also found to be associated with higher mortality at 1 year (p = < 0.001). CONCLUSIONS: In the UK despite the discrepancy in the health of the general population between the north and south, social deprivation does not appear to be detrimental to neurooncological outcomes although smoking status, advancing age and male sex are.

Increased Circulating Chemokines and Macrophage Recruitment in Growing Vestibular Schwannomas.

BACKGROUND: There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target. OBJECTIVE: To characterize the relationship between growth, TAM infiltration, and circulating monocyte chemokines in a large cohort of patients with VS. METHODS: Immunostaining for Iba1 (macrophages), CD31 (endothelium), and fibrinogen (permeability) was performed on 101 growing and 19 static sporadic VS. The concentrations of monocyte-specific chemokines were measured in the plasma of 50 patients with growing VS and 25 patients with static VS. RESULTS: The Iba1 + cell count was significantly higher in growing as compared with static VS (592 vs 226/×20 HPF, P =<0.001). Similarly, the CD31 + % surface area was higher in growing VS (2.19% vs 1.32%, P = .01). There was a positive correlation between TAM infiltration and VS growth rate, which persisted after controlling for the effect of tumor volume (aR2 = 0.263, P =<0.001). The plasma concentrations of several monocytic chemokines were higher in patients with growing rather than static VS. CONCLUSION: There is a strong positive correlation between TAM infiltration and volumetric growth of VS, and this relationship is independent of tumor size. There is a colinear relationship between TAM infiltration and tumor vascularity, implying that inflammation and angiogenesis are interlinked in VS. Chemokines known to induce monocyte chemotaxis are found in higher concentrations in patients with growing VS, suggestive of a potential pathophysiological mechanism.

Study protocol: PreOperative Brain Irradiation in Glioblastoma (POBIG) - A phase I trial.

Background: Glioblastoma is a high-grade aggressive neoplasm whose outcomes have not changed in decades. In the current treatment pathway, tumour growth continues and remains untreated for several weeks post-diagnosis. Intensified upfront therapy could target otherwise untreated tumour cells and improve the treatment outcome. POBIG will evaluate the safety and feasibility of single-fraction preoperative radiotherapy for newly diagnosed glioblastoma, assessed by the maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV). Methods: POBIG is an open-label, dual-centre phase I dose and volume escalation trial that has received ethical approval. Patients with a new radiological diagnosis of glioblastoma will be screened for eligibility. This is deemed sufficient due to the high accuracy of imaging and to avoid treatment delay. Eligible patients will receive a single fraction of preoperative radiotherapy ranging from 6 to 14 Gy followed by their standard of care treatment comprising maximal safe resection and postoperative chemoradiotherapy (60 Gy/30 fr) with concurrent and adjuvant temozolomide). Preoperative radiotherapy will be directed to the part of the tumour that is highest risk for remaining as postoperative residual disease (hot spot). Part of the tumour will remain unirradiated (cold spot) and sampled separately for diagnostic purposes. Dose/volume escalation will be guided by a Continual Reassessment Method (CRM) model. Translational opportunities will be afforded through comparison of irradiated and unirradiated primary glioblastoma tissue. Discussion: POBIG will help establish the role of radiotherapy in preoperative modalities for glioblastoma. Trial registration: NCT03582514 (clinicaltrials.gov).

External validation of the GCS-Pupils Score as an outcome predictor after traumatic brain injury in adults: a single-center experience.

OBJECTIVE: The GCS-Pupils (GCS-P) score is a recently described scoring system to aid outcome prediction in patients with traumatic brain injury (TBI). The aim of this study was to provide the first external validation of the GCS-P score by identifying independent predictors of outcome in TBI patients. METHODS: Review of prospective adult (≥ 16 years) TBI database at a tertiary neurosurgical center with a catchment population of 1.5 million over a 12-month period commencing October 2016. Multivariate logistic regression was used to identify predictors of discharge destination and 30-day mortality. RESULTS: Three hundred and fifty-eight patients were included. The median age was 60 years with a male predominance of 64%. The median GCS-P was 14 (interquartile range 12-15) and the commonest GCS-P category was mild (13-15; 238/358, 66%). Discharge destination was home in 69% of patients and rehab services or equivalent in 31%. Multivariate analysis identified age (p = 0.01), CT findings of an acute subdural hematoma (p = 0.01) or diffuse axonal injury (p = 0.02), and a neurosurgical operation (p = 0.02) as independent predictors of discharge destination. The 30-day mortality rate was 11%. Within the category of severe TBI (GCS-P ≤ 8), GCS-P was able to identify patients with a very high likelihood of 30-day mortality (GCS-P ≤ 4; 16/31, 52%). Multivariate analysis revealed the Charlson comorbidity score (p = 0.01), GCS-P (p = 0.02), and traumatic subarachnoid hemorrhage (p = 0.05) as independent predictors of mortality. CONCLUSION: The GCS-P is a useful predictor of 30-day mortality, although its usefulness for other clinical outcomes remains to be proven.

Multimodal mapping and monitoring is beneficial during awake craniotomy for intra-cranial tumours: results of a dual centre retrospective study.

BACKGROUND: The combination of awake craniotomy with multimodal neurophysiological mapping and monitoring in intra-axial tumour resection is not well described, but may have theoretical benefits which we sought to investigate. METHODS: All patients undergoing awake craniotomy for tumour resection with cortical and/or subcortical stimulation together with one or more of electrocorticography (ECoG/EEG), motor or somatosensory evoked potentials were identified from the operative records of two surgeons at two centres over a 5 year period. Patient, operative and outcome data were collated. Statistical analysis was performed to evaluate factors predictive of intra-operative seizures and surgical outcomes. RESULTS: 83 patients with a median age 50 years (18-80 years) were included. 80% had gliomas (37% low grade) and 13% metastases. Cortical mapping was negative in 35% (language areas) and 24% (motor areas). Complete or near total resection was achieved in 80% with 5% severe long-term neurological deficits. Negative cortical mapping was combined with positive subcortical mapping in 42% with no significant difference in extent of resection rates to patients undergoing positive cortical mapping (p = 0.95). Awake mapping could not be completed in 14%, but with no compromise to extent of resection (p = 0.55) or complication rates (p = 0.09). Intraoperative seizures occurred in 11% and were significantly associated with intra-operative EEG spikes (p = 0.003). CONCLUSIONS: Awake multi-modal monitoring is a safe and well tolerated technique. It provides preservation of extent of resection and clinical outcomes in cases of aborted awake craniotomy. Negative cortical mapping in combination with positive subcortical mapping was also shown to be safe, although not hitherto well described. Electrocorticography further enables the differentiation of seizure activity from true positive mapping, and the successful treatment of spikes prior to full clinical seizures occurring.

Visualising spatial heterogeneity in glioblastoma using imaging habitats.

Glioblastoma is a high-grade aggressive neoplasm characterised by significant intra-tumoral spatial heterogeneity. Personalising therapy for this tumour requires non-invasive tools to visualise its heterogeneity to monitor treatment response on a regional level. To date, efforts to characterise glioblastoma's imaging features and heterogeneity have focussed on individual imaging biomarkers, or high-throughput radiomic approaches that consider a vast number of imaging variables across the tumour as a whole. Habitat imaging is a novel approach to cancer imaging that identifies tumour regions or 'habitats' based on shared imaging characteristics, usually defined using multiple imaging biomarkers. Habitat imaging reflects the evolution of imaging biomarkers and offers spatially preserved assessment of tumour physiological processes such perfusion and cellularity. This allows for regional assessment of treatment response to facilitate personalised therapy. In this review, we explore different methodologies to derive imaging habitats in glioblastoma, strategies to overcome its technical challenges, contrast experiences to other cancers, and describe potential clinical applications.

Rapid early progression (REP) of glioblastoma is an independent negative prognostic factor: Results from a systematic review and meta-analysis.

Background: In patients with newly diagnosed glioblastoma, rapid early progression (REP) refers to tumor regrowth between surgery and postoperative chemoradiotherapy. This systematic review and meta-analysis appraised previously published data on REP to better characterize and understand it. Methods: Systematic searches of MEDLINE, EMBASE and the Cochrane database from inception to October 21, 2021. Studies describing the incidence of REP-tumor growth between the postoperative MRI scan and pre-radiotherapy MRI scan in newly diagnosed glioblastoma were included. The primary outcome was REP incidence. Results: From 1590 search results, 9 studies were included with 716 patients. The median age was 56.9 years (IQR 54.0-58.8 y). There was a male predominance with a median male-to-female ratio of 1.4 (IQR 1.1-1.5). The median number of days between MRI scans was 34 days (IQR 18-45 days). The mean incidence rate of REP was 45.9% (range 19.3%-72.0%) and significantly lower in studies employing functional imaging to define REP (P < .001). REP/non-REP groups were comparable with respect to age (P = .99), gender (P = .33) and time between scans (P = .81). REP was associated with shortened overall survival (HR 1.78, 95% CI 1.30-2.43, P < .001), shortened progression-free survival (HR 1.78, 95% CI 1.30-2.43, P < .001), subtotal resection (OR 6.96, 95% CI 4.51-10.73, P < .001) and IDH wild-type versus mutant tumors (OR 0.20, 95% CI 0.02-0.38, P = .03). MGMT promoter methylation was not associated with REP (OR 1.29, 95% CI 0.72-2.28, P = .39). Conclusions: REP occurs in almost half of patients with newly diagnosed glioblastoma and has a strongly negative prognostic effect. Future studies should investigate its biology and effective treatment strategies.

Does the Use of Surgical Adjuncts Affect Postoperative Infection Rates in Neuro-oncology Surgery?

BACKGROUND: Surgical site infection (SSI) is a significant cause of postoperative morbidity and mortality. As oncologic care advances, the use of surgical adjuncts such as intraoperative ultrasound (US), 5-aminolevulinic acid (5-ALA), and neurophysiologic monitoring has increased. This study set out to identify whether the use of surgical adjuncts in supratentorial tumor surgery lead to increased operative time or increased rates of SSI. METHODS: This is a retrospective study at a large tertiary clinical neurosciences center in the UK. We included all patients who underwent an elective supratentorial craniotomy for a tumor over a 12 month period. We retrospectively assessed whether patients had had a postoperative infection at 30 days or 4 months using our electronic patient record system. RESULTS: A total of 267 patients were included. The median age was 58 years (range: 17-87 years) with roughly equal numbers of men and women (men: 138 of 267, 52%). Most operations were carried out for gliomas (149 of 267, 56%) or metastases (61 of 267, 23%). The median length of surgery was 3 hours 6 minutes, with 24% lasting >4 hours. The overall infection rate was 4.5%. Intraoperative monitoring and 5-ALA was associated with longer operative times although not necessarily larger craniotomy sizes, whereas intraoperative US was associated with a shorter operative time and smaller craniotomy size. These adjuncts were not associated with an increased risk of infection. CONCLUSIONS: This study adds reassurance that although some surgical adjuncts lead to increased operative times, in our study there was no apparent increased risk of infection as a result of this.

Early Therapeutic Interventions for Newly Diagnosed Glioblastoma: Rationale and Review of the Literature.

PURPOSE OF REVIEW: Glioblastoma is the commonest primary brain cancer in adults whose outcomes are amongst the worst of any cancer. The current treatment pathway comprises surgery and postoperative chemoradiotherapy though unresectable diffusely infiltrative tumour cells remain untreated for several weeks post-diagnosis. Intratumoural heterogeneity combined with increased hypoxia in the postoperative tumour microenvironment potentially decreases the efficacy of adjuvant interventions and fails to prevent early postoperative regrowth, called rapid early progression (REP). In this review, we discuss the clinical implications and biological foundations of post-surgery REP. Subsequently, clinical interventions potentially targeting this phenomenon are reviewed systematically. RECENT FINDINGS: Early interventions include early systemic chemotherapy, neoadjuvant immunotherapy, local therapies delivered during surgery (including Gliadel wafers, nanoparticles and stem cell therapy) and several radiotherapy techniques. We critically appraise and compare these strategies in terms of their efficacy, toxicity, challenges and potential to prolong survival. Finally, we discuss the most promising strategies that could benefit future glioblastoma patients. There is biological rationale to suggest that early interventions could improve the outcome of glioblastoma patients and they should be investigated in future trials.

Long-term oncological outcomes after haemorrhagic apoplexy in pituitary adenoma managed operatively and non-operatively.

INTRODUCTION: Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively. METHODS: Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up. RESULTS: One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups. CONCLUSION: Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.

Value of Early Post-Operative Growth Hormone Testing in Predicting Long-Term Remission and Residual Disease after Transsphenoidal Surgery for Acromegaly.

INTRODUCTION: Surgical remission for acromegaly is dependent on a number of factors including tumour size, invasiveness, and surgical expertise. We studied the value of early post-operative growth hormone (GH) level as a predictor of outcome and to guide early surgical re-exploration for residual disease in patients with acromegaly. METHODS: Patients with acromegaly undergoing first-time endoscopic transsphenoidal surgery between 2005 and 2015, in 2 regional neurosurgical centres, were studied. Insulin-like growth factor-1 (IGF-1), basal GH (i.e., sample before oral glucose), and GH nadir on oral glucose tolerance test (OGTT) were tested at various time points, including 2-5 days post-operatively. Definition of disease remission was according to the 2010 consensus statement (i.e., GH nadir <0.4 µg/L during an OGTT and normalized population-matched IGF-1). Forward stepwise logistic regression was used to determine factors associated with remission. RESULTS: We investigated 81 consecutive patients with acromegaly, 67 (83%) of which had macroadenomas and 22 (27%) were noted to be invasive at surgery. Mean follow-up was 44 ± 25 months. Overall, surgical remission was achieved in 55 (68%) patients at final follow-up. On univariate analysis, the remission rates at the end of the study period for patients with early post-operative GH nadir on OGTT of <0.4 (N = 43), between 0.4 and 1 (N = 28), and >1 µg/L (N = 8) were 88, 54, and 20%, respectively. Similar results were seen with basal GH on early post-operative OGTT. On multivariate regression analysis, pre-operative IGF-1 (odds ratio of 13.1) and early post-operative basal GH (odds ratio of 5.0) and GH nadir on OGTT (odds ratio of 6.8) were significant predictors of residual disease. Based on a raised early GH nadir and post-operative MR findings, 10 patients underwent early surgical re-exploration. There was reduction in post-operative GH levels in 9 cases, of which 5 (50%) achieved long-term remission. There was an increased risk of new pituitary hormone deficiencies in patients having surgical re-exploration compared to those having a single operation (60 vs. 14%). CONCLUSIONS: An early post-operative basal GH and GH nadir on OGTT are reliable predictors of long-term disease remission. It can be used to guide patients for early surgical re-exploration for residual disease, although there is increased risk of hypopituitarism.

Venous thromboembolism chemical prophylaxis after endoscopic trans-sphenoidal pituitary surgery.

PURPOSE: There is no compelling outcome data or clear guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using low molecular weight heparin (chemoprophylaxis) in patients undergoing pituitary surgery. Here we describe our experience of early chemoprophylaxis (post-operative day 1) following trans-sphenoidal pituitary surgery. METHODS: Single-centre review of a prospective surgical database and VTE records. Adults undergoing first time trans-sphenoidal pituitary surgery were included (2009-2018). VTE was defined as either deep vein thrombosis and/or pulmonary embolism within 3 months of surgery. Postoperative haematomas were those associated with a clinical deterioration together with radiological evidence. RESULTS: 651 Patients included with a median age of 55 years (range 16-86 years). Most (99%) patients underwent trans-sphenoidal surgery using a standard endoscopic single nostril or bi-nostril trans-sphenoidal technique. More than three quarters had pituitary adenomas (n = 520, 80%). Postoperative chemoprophylaxis to prevent VTE was administered in 478 patients (73%). Chemoprophylaxis was initiated at a median of 1 day post-procedure (range 1-5 days postoperatively; 92% on postoperative day 1). Tinzaparin was used in 465/478 patients (97%) and enoxaparin was used in 14/478 (3%). There were no cases of VTE, even in 78 ACTH-dependent Cushing's disease patients. Six patients (1%) developed postoperative haematomas. Chemoprophylaxis was not associated with a significantly higher rate of postoperative haematoma formation (Fisher's Exact, p = 0.99) or epistaxis (Fisher's Exact, p > 0.99). CONCLUSIONS: Chemoprophylaxis after trans-sphenoidal pituitary surgery on post-operative day 1 is a safe strategy to reduce the risk of VTE without significantly increasing the risk of postoperative bleeding events.

Foramen magnum decompression in adults with Chiari type 1 malformation: use of intraoperative ultrasound to guide extent of surgery.

BACKGROUND: Foramen magnum decompression (FMD) is an established technique for patients with Chiari-1 malformation. However, the extent of decompressive surgery is controversial, in particular whether dural opening is undertaken. OBJECTIVE: In this study, we report outcomes with our technique utilising intraoperative ultrasound (iOU) findings. Decision to proceed for further decompression was based on CSF flow around foramen magnum and visualisation of tip of tonsils. METHODS: Review of adults with CM-1 undergoing FMD 2013-2018. Patients underwent a suboccipital craniectomy ± partial C1 superior laminectomy ± duraplasty in a stepwise manner. Favourable iOU findings of CSF flow around the foramen magnum and pulsation of the tonsillar tips were sought at each step. Post-operative outcomes were assessed using the Chicago Chiari Outcome Score (CCOS). RESULTS: Fifty-seven patients were included. The mean age was 47 years (range 18-77 years). There was a strong female preponderance (48 females to nine males). The mean follow-up was 3.2 years (range 1-5 years). Surgery included: suboccipital craniectomy (52/57, 91%), plus partial C1 superior laminectomy (2/57, 4%), and plus duraplasty (3/57, 6%). Redo surgery was undertaken in 7/57 patients (12%). At final follow-up, 56/57 (98%) patients achieved a good (CCOS 13-16) or satisfactory (CCOS 9-12) outcome based on COSS. CONCLUSIONS: A patient centred approach to surgery utilising findings from iOU can achieve favourable outcomes. Dural opening is not routinely required.

Radiologically defined acute hydrocephalus in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Ventriculomegaly is common in aneurysmal subarachnoid haemorrhage (aSAH). An imaging measure to predict the need for cerebrospinal fluid (CSF) diversion may be useful. The bicaudate index (BCI) has been previously applied to aSAH. Our aim was to derive and test a threshold BCI above which CSF diversion may be required. METHODS: Review of prospective registry. The derivation group (2009-2015) included WFNS grade 1-2 aSAH patients who deteriorated clinically, had a repeat CT brain and underwent CSF diversion. BCI was measured on post-deterioration CTs and the lower limit of the 95% confidence interval (95%CI) was the hydrocephalus threshold. In a separate test group (2016), in WFNS ≥ 2 patients, we compared BCI on diagnostic CTs with CSF diversion within 24 hours. RESULTS: The derivation group (n = 62) received an external ventricular (n = 57, 92%) or lumbar drain (n = 5, 8%). Mean post-deterioration BCI was 0.19 (95%CI 0.17-0.22) for age ≤49 years, 0.22 (95%CI 0.20-0.23) for age 50-64 years and 0.24 (95%CI 0.22-0.27) for age ≥65 years. Hydrocephalus thresholds were therefore 0.17, 0.20 and 0.22, respectively. In the test group (n = 105), there was no significant difference in BCI on the diagnostic CT between good and poor grade patients aged ≤49 years (p = 0.31) and ≥65 years (p = 0.96). 30/66 WFNS ≥ 2 patients underwent CSF diversion, although only 15/30 (50%) exceeded BCI thresholds for hydrocephalus. CONCLUSION: A significant proportion of aSAH patients may undergo CSF diversion without objective evidence of hydrocephalus. Our threshold values require further testing but may provide an objective measure to aid clinical decision making in aSAH.

Cerebral and tumoral blood flow in adult gliomas: a systematic review of results from magnetic resonance imaging.

OBJECTIVE: Blood flow is the rate of blood movement and relevant to numerous processes, though understudied in gliomas. The aim of this review was to pool blood flow metrics obtained from MRI modalities in adult supratentorial gliomas. METHODS: MEDLINE, EMBASE and the Cochrane database were queried 01/01/2000-31/12/2019. Studies measuring blood flow in adult Grade II-IV supratentorial gliomas using dynamic susceptibility contrast (DSC) MRI, dynamic contrast enhanced MRI (DCE-MRI) or arterial spin labelling (ASL) were included. Absolute and relative cerebral blood flow (CBF), peritumoral blood flow and tumoral blood flow (TBF) were reported. RESULTS: 34 studies were included with 1415 patients and 1460 scans. The mean age was 52.4 ± 7.3 years. Most patients had glioblastoma (n = 880, 64.6%). The most common imaging modality was ASL (n = 765, 52.4%) followed by DSC (n = 538, 36.8%). Most studies were performed pre-operatively (n = 1268, 86.8%). With increasing glioma grade (II vs IV), TBF increased (70.8 vs 145.5 ml/100 g/min, p < 0.001) and CBF decreased (85.3 vs 49.6 ml/100 g/min, p < 0.001). In Grade IV gliomas, following treatment, CBF increased in ipsilateral (24.9 ± 1.2 vs 26.1 ± 0.0 ml/100 g/min, p < 0.001) and contralateral white matter (25.6 ± 0.2 vs 26.0± 0.0 ml/100 g/min, p < 0.001). CONCLUSION: Our findings demonstrate that increased mass effect from high-grade gliomas impairs blood flow within the surrounding brain that can improve with surgery. ADVANCES IN KNOWLEDGE: This systematic review demonstrates how mass effect from brain tumours impairs blood flow in the surrounding brain parenchyma that can improve with treatment.

Intraoperative imaging technology to maximise extent of resection for glioma: a network meta-analysis.

BACKGROUND: Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach. OBJECTIVES: To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary. SEARCH METHODS: We searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. MAIN RESULTS: We identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound. Network meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies. One trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence). AUTHORS' CONCLUSIONS: Intraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, is needed.

ANTECEDENTES: En múltiples estudios se ha identificado la importancia pronóstica del alcance de la resección en el tratamiento del glioma. En los últimos años han surgido diferentes tecnologías intraoperatorias con una eficacia comparativa desconocida para optimizar el alcance de la resección. Una revisión Cochrane anterior proporcionó evidencia de certeza baja a muy baja en los análisis de un solo ensayo y no fue posible la síntesis de los resultados. La función de la tecnología intraoperatoria para maximizar el alcance de la resección aún no está clara. Debido a las múltiples tecnologías complementarias disponibles, esta pregunta de investigación se presta a un enfoque metodológico de metanálisis en red. OBJETIVOS: Establecer el perfil comparativo de efectividad y riesgo de determinadas tecnologías de imagenología intraoperatorias mediante un metanálisis en red e identificar análisis de costos y evaluaciones económicas como parte de un breve comentario económico. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en CENTRAL (2020, número 5), MEDLINE vía Ovid hasta la semana 2 de mayo de 2020, y Embase vía Ovid hasta la semana 20 de 2020. Se realizó una búsqueda retrospectiva de todos los estudios identificados. Se hicieron búsquedas manuales en dos revistas, Neuro­oncology y Journal of Neuro­oncology, desde 1990 hasta 2019, y se incluyeron todos los resúmenes de congresos. Finalmente, se estableció contacto con expertos reconocidos en neurooncología para identificar cualquier estudio elegible adicional y obtener información sobre los ensayos controlados aleatorizados (ECA) en curso. CRITERIOS DE SELECCIÓN: ECA que evaluaron a personas de todas las edades con presuntos tumores gliales nuevos o recidivantes (de cualquier ubicación o histología) a partir del examen clínico y la imagenología (tomografía computarizada [TC] o imagenología de resonancia magnética [IRM], o ambas). Las modalidades adicionales de imagenología (p.ej., tomografía de emisión de positrones, espectroscopia de resonancia magnética) no fueron obligatorias. Las intervenciones incluyeron cirugía guiada por fluorescencia, ecografía intraoperatoria, neuronavegación (con o sin procesamiento adicional de las imágenes, p.ej., tractografía) e IRM intraoperatoria. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los resultados de la búsqueda en cuanto a su relevancia, realizaron la evaluación crítica según las guías conocidas y extrajeron los datos mediante un formulario predeterminado. RESULTADOS PRINCIPALES: Se identificaron cuatro ECA, que utilizaron diferentes tecnologías de imagenología intraoperatorias: la resonancia magnética (IRM) intraoperatoria (dos ensayos, con 58 y 14 participantes); la cirugía guiada por fluorescencia con ácido 5­aminolevulínico (5­ALA) (un ensayo, 322 participantes); y la neuronavegación (un ensayo, 45 participantes). Se identificó un ensayo en curso que evaluó la IRM con un tamaño de la muestra planificado de 304 participantes, del que se espera la publicación de los resultados alrededor del invierno de 2020. No se han identificado ensayos publicados sobre la ecografía intraoperatoria. Los metanálisis en red o los metanálisis tradicionales no fueron apropiados debido a la falta de ensayos homogéneos en tecnologías de imagenología. De los ensayos incluidos, hubo una notable heterogeneidad en la localización de los tumores y en las tecnologías de imagenología utilizadas en los brazos control. Hubo inquietudes significativas con respecto al riesgo de sesgo en todos los estudios incluidos. Un ensayo de IRM encontró un aumento en la extensión de la resección (razón de riesgos [RR] para la resección incompleta 0,13; intervalo de confianza [IC] del 95%: 0,02 a 0,96; 49 participantes; evidencia de certeza muy baja) y un ensayo de 5­ALA (RR para la resección incompleta 0,55; IC del 95%: 0,42 a 0,71; 270 participantes; evidencia de certeza baja). El otro ensayo que evaluó la IRM se interrumpió de forma temprana después de un análisis intermedio no planificado que incluyó 14 participantes; por lo tanto, el ensayo proporciona evidencia de calidad muy baja. El ensayo de neuronavegación no proporcionó datos suficientes para evaluar los efectos sobre el grado de resección. El informe de los eventos adversos fue incompleto e indicó la presencia de sesgo de informe significativo (evidencia de certeza muy baja). En general, la proporción de eventos informados fue baja en la mayoría de los ensayos y, por lo tanto, pueden haber estado presentes o no problemas relacionados con el poder estadístico suficiente para detectar diferencias en los desenlaces. No se informó adecuadamente sobre los desenlaces de supervivencia, aunque un ensayo no informó evidencia de mejora en la supervivencia general con 5­ALA (cociente de riesgos instantáneos [CRI] 0,82; IC del 95%: 0,62 a 1,07; 270 participantes; evidencia de certeza baja). Solo hubo datos disponibles sobre la calidad de vida de un estudio, con un sesgo de desgaste significativo (evidencia de certeza muy baja). CONCLUSIONES DE LOS AUTORES: Las tecnologías de imagenología intraoperatoria, específicamente la IRM y el 5­ALA, pueden ser beneficiosas para maximizar el grado de resección en los participantes con glioma de grado alto. Sin embargo, lo anterior se basa en evidencia de certeza baja a muy baja. Por lo tanto, los efectos neurológicos a corto y a largo plazo no están claros. No están claros los efectos de la cirugía guiada por imágenes sobre la supervivencia general, la supervivencia sin progresión ni la calidad de vida. No fue posible realizar metanálisis en red ni tradicionales debido al alto riesgo de sesgo identificado, a la heterogeneidad y a los ensayos pequeños incluidos en esta revisión. Un comentario económico breve encontró evidencia económica limitada sobre el uso equívoco de la IRM en comparación con la cirugía convencional. En cuanto a los costos, una revisión no sistemática de estudios económicos indicó que, en comparación con la cirugía estándar, el uso de la cirugía guiada por imágenes no tiene un efecto claro sobre los costos y que el ácido 5­aminolevulínico fue más costoso. Se necesitan estudios de investigación adicionales, incluida la finalización de los ensayos en curso sobre la cirugía guiada por ecografía.

Pre- and postoperative need for pituitary hormone replacement in non-adenomatous sellar and parasellar lesions: importance of the sellar encroachment score.

BACKGROUND: Pre-/postoperative pituitary endocrine deficiencies in patients with sellar/parasellar non-adenomatous lesions are poorly described and studies have not considered the effect of sellar invasion on endocrine outcome. The aim of this study was to relate the need for pituitary hormone replacement pre-/postoperatively, with sellar invasion, in non-adenomatous sellar/parasellar lesions. METHODS: Single-centre review of adults with histologically confirmed non-adenomatous sellar/parasellar lesion and follow-up ≥ 3 months or until postop radiotherapy. Pituitary dysfunction was defined by hormone replacement. The sellar encroachment score (0-6) was calculated as the sum of the thirds of radiological encroachment into the sellar region in the coronal and sagittal planes. Multivariate analysis with binary logistic regression was used to determine factors associated with pituitary hormone replacement. RESULTS: One hundred and seventeen patients were included with a median age of 49 years (range 16-84 years) and median follow-up of 13 months. Surgery was trans-sphenoidal (53%), trans-cranial (36%) or a combination (11%). The commonest histology types were meningioma (n = 33, 28%) and craniopharyngioma (n = 20, 17%). The median sellar encroachment score was 6 (range 0-6). Most (n = 86, 74%) did not require pituitary hormone replacement preoperatively. The need for pituitary hormones increased after surgery in 41 (35%) patients. In multivariate analysis, the sellar encroachment score was the only factor predictive of pre- (OR = 2.6, 95% CI = 1.2-5.5; p = 0.01) and postoperative risk of new pituitary hormone replacement (OR = 4.1, 95% CI = 1.7-10.1, p = 0.002). CONCLUSION: A significant proportion of these patients present with need for pituitary hormone replacement that may worsen postoperatively. The degree of sellar encroachment is predictive of pituitary hormone replacement status pre-/postoperatively.