Closure intracranial pressure as a determinant of surgical decompression adequacy in spontaneous supratentorial intracerebral haematoma: a multicentre observational study.

PURPOSE: Despite significant advances, the literature on the optimal surgical treatment for spontaneous supratentorial intracerebral haematoma (ICH) remains lacking. Intraoperative ICP measured on closure (closure ICP) was reported to be a potential marker of adequate decompression in various neurosurgical conditions. We hypothesize that closure ICP also correlates with outcomes in ICH. METHODS: A multicentre retrospective study of 203 decompressive surgeries performed for ICHs was conducted (clot evacuation with either craniectomy or craniotomy). Receiver operating characteristic analysis on closure ICP was performed and an optimal threshold of 5 separated the patients into inadequate (iICP; ICP > 5 mmHg) and good decompression (gICP; ICP ≤ 5 mmHg). Postoperative ICP control, modified Rankin scale (mRS) and mortality were reported. RESULTS: There were 85 patients in the iICP and 118 patients in the gICP group respectively. The mean age, median preoperative Glasgow coma scale, ICH laterality, location, and volume were similar. After multivariable analysis, the need for (OR 2.55 [1.31-4.97]) and the duration of postoperative hyperosmolar therapy (iICP: 3 days, gICP: 1 day; p = 0.045), and repeat surgery for refractory ICP (OR 5.80 [1.53-22]) were more likely in the iICP group. The likelihood of mRS improvement at 1-year follow up was significantly worse in the iICP group (OR 0.38 [0.17-0.83], p = 0.015). CONCLUSION: Closure ICP is an objective and reproducible surgical target. When planning for surgical decompression, obtaining closure ICP of ≤ 5 mmHg is potentially able to improve postoperative ICP management and optimise functional recovery in a well selected patient population.

Clinical Outcomes of 3D-Printed Bioresorbable Scaffolds for Bone Tissue Engineering-A Pilot Study on 126 Patients for Burrhole Covers in Subdural Hematoma.

Burrhole craniostomy is commonly performed for subdural hematoma (SDH) evacuation, but residual scalp depressions are often cosmetically suboptimal for patients. OsteoplugTM, a bioresorbable polycaprolactone burrhole cover, was introduced by the National University Hospital, Singapore, in 2006 to cover these defects, allowing osseous integration and vascular ingrowth. However, the cosmetic and safety outcomes of OsteoplugTM-C-the latest (2017) iteration, with a chamfered hole for subdural drains-remain unexplored. Data were collected from a single institution from April 2017 to March 2021. Patient-reported aesthetic outcomes (Aesthetic Numeric Analog (ANA)) and quality of life (EQ-5D-3L including Visual Analog Scale (VAS)) were assessed via telephone interviews. Clinical outcomes included SDH recurrence, postoperative infections, and drain complications. OsteoplugTM-C patients had significantly higher satisfaction and quality of life compared to those without a burrhole cover (ANA: 9 [7, 9] vs. 7 [5, 8], p = 0.019; VAS: 85 [75, 90] vs. 70 [50, 80], p = 0.021), and the absence of a burrhole cover was associated with poorer aesthetic outcomes after multivariable adjustment (adjusted OR: 4.55, 95% CI: 1.09-22.68, p = 0.047). No significant differences in other clinical outcomes were observed between OsteoplugTM-C, OsteoplugTM, or no burrhole cover. Our pilot study supports OsteoplugTM-C and its material polycaprolactone as suitable adjuncts to burrhole craniostomy, improving cosmetic outcomes while achieving comparable safety outcomes.

Is there any survival benefit from post-operative radiation in brain metastases? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The benefits of adding upfront post-operative radiation, either whole-brain (WBRT) or cavity, after resection of brain metastases have been debated, particularly due to the long-term sequalae post radiation. We sought to compare the efficacy and safety between post-operative radiation versus resection alone. METHODS: We searched various biomedical databases from 1983 to 2018, for eligible randomized controlled trials (RCT). Outcomes studied were local recurrence (LR), overall survival (OS) and serious (Grade 3 + ) adverse events. We used the random effects model to pool outcomes. Methodological quality of each study was assessed using the Cochrane Risk of Bias tool. We employed the GRADE approach to assess the certainty of evidence. RESULTS: We included 5 RCTs comprising of 673 patients. The pooled odds ratio (OR) for LR is 0.26 (95% confidence interval (CI) 0.19-0.37, P < 0.001, GRADE certainty high), strongly supporting the use of post-operative radiation. Meta-regression analysis done comparing cavity and WBRT, did not show any difference in LR. The pooled hazard ratio (HR) for overall survival (OS) is 1.1 (95% CI 0.90-1.34, P = 0.37, GRADE certainty high). The treatment-related toxicities could not be pooled; the 2 studies which reported this did not find differences between the approaches. The risk of bias across the included studies was low. CONCLUSION: Our analysis confirms that upfront post-operative radiation significantly reduces the risk of LR. However, the lack of improvement in OS suggests that local control alone may not impact survival. Balancing local control, and neuro-cognitive effects of WBRT, cavity radiation seems to be a safe and effective option.

Impact of time to resumption of antithrombotic therapy on outcomes after surgical evacuation of chronic subdural hematoma: A multicenter cohort study.

BACKGROUND: The decision to resume antithrombotic therapy after surgical evacuation of chronic subdural hematoma (CSDH) requires judicious weighing of the risk of bleeding against that of thromboembolism. This study aimed to investigate the impact of time to resumption of antithrombotic therapy on outcomes of patients after CSDH drainage. METHODS: Data were obtained retrospectively from three tertiary hospitals in Singapore from 2010 to 2017. Outcome measures analyzed were CSDH recurrence and any thromboembolic events. Logistic and Cox regression tests were used to identify associations between time to resumption and outcomes. RESULTS: A total of 621 patients underwent 761 CSDH surgeries. Preoperative antithrombotic therapy was used in 139 patients. 110 (79.1%) were on antiplatelets and 35 (25.2%) were on anticoagulants, with six patients (4.3%) being on both antiplatelet and anticoagulant therapy. Antithrombotic therapy was resumed in 84 patients (60.4%) after the surgery. Median time to resumption was 71 days (IQR 29 - 201). Recurrence requiring reoperation occurred in 15 patients (10.8%), of which 12 had recurrence before and three after resumption. Median time to recurrence was 35 days (IQR 27 - 47, range 4 - 82 days). Recurrence rates were similar between patients that were restarted on antithrombotic therapy before and after 14, 21, 28, 42, 56, 70 and 84 days, respectively. Thromboembolic events occurred in 12 patients (8.6%), of which five had the event prior to restarting antithrombosis. CONCLUSIONS: Time to antithrombotic resumption did not significantly affect CSDH recurrence. Early resumption of antithrombotic therapy can be safe for patients with a high thromboembolic risk.

Combined treatment of Nimotuzumab and rapamycin is effective against temozolomide-resistant human gliomas regardless of the EGFR mutation status.

BACKGROUND: The treatment of glioblastoma multiforme (GBM) is an unmet clinical need. The 5-year survival rate of patients with GBM is less than 3%. Temozolomide (TMZ) remains the standard first-line treatment regimen for gliomas despite the fact that more than 90% of recurrent gliomas do not respond to TMZ after repeated exposure. We have also independently shown that many of the Asian-derived glioma cell lines and primary cells derived from Singaporean high-grade glioma patients are indeed resistant to TMZ. This issue highlights the need to develop new effective anti-cancer treatment strategies. In a recent study, wild-type epidermal growth factor receptor (wtEGFR) has been shown to phosphorylate a truncated EGFR (known as EGFRvIII), leading to the phosphorylation of STAT proteins and progression in gliomagenesis. Despite the fact that combination of EGFR targeting drugs and rapamycin has been used before, the effect of mono-treatment of Nimotuzumab, rapamycin and combination therapy in human glioma expressing different types of EGFR is not well-studied. Herein, we evaluated the efficacy of dual blockage using monoclonal antibody against EGFR (Nimotuzumab) and an mTOR inhibitor (rapamycin) in Caucasian patient-derived human glioma cell lines, Asian patient-derived human glioma cell lines, primary glioma cells derived from the Mayo GBM xenografts, and primary short-term glioma culture derived from high-grade glioma patients. METHODS: The combination effect of Nimotuzumab and rapamycin was examined in a series of primary human glioma cell lines and glioma cell lines. The cell viability was compared to TMZ treatment alone. Endogenous expressions of EGFR in various GBM cells were determined by western blotting. RESULTS: The results showed that combination of Nimotuzumab with rapamycin significantly enhanced the therapeutic efficacy of human glioma cells compared to single treatment. More importantly, many of the Asian patient-derived glioma cell lines and primary cells derived from Singaporean high-grade gliomas, which showed resistance to TMZ, were susceptible to the combined treatments. CONCLUSIONS: In conclusion, our results strongly suggest that combination usage of Nimotuzumab and rapamycin exert higher cytotoxic activities than TMZ. Our data suggest that this combination may provide an alternative treatment for TMZ-resistant gliomas regardless of the EGFR status.

Gamma Knife surgery for central neurocytomas.

OBJECT: The optimal management of central neurocytoma (CN) remnants and recurrences is still not clear. To date no large series of patients treated with Gamma Knife surgery (GKS) for CNs has been published. For that reason the authors decided to combine data from 5 different centers so that they could analyze the largest population of patients treated with GKS for CN currently available. METHODS: Data obtained in 42 patients who were treated for CN with GKS before July 1, 2010, were retrospectively collected and analyzed. The median prescribed dose was 13 Gy (range 11-25 Gy). The follow-up time in these patients ranged from 0.5 to 14.7 years (mean 6.1 years, median 4.9 years). Eleven patients were followed up for 5-10 years and 9 patients for more than 10 years. All patients were alive and well at the closing of the study except 1 patient, who died of injuries sustained in a traffic accident. RESULTS: Two cases of local tumor progression and 2 cases of distant tumor recurrence occurred among the patient population, yielding 5- and 10-year tumor control rates of 91% and 81%, respectively. No permanent complications occurred. The findings were in line with results reported in earlier publications. Despite the high tumor control rate, enlargement of part of or the whole ventricular system was seen in 45% of patients. CONCLUSIONS: The high tumor control rate and the low complication rate following GKS indicate that GKS is the preferred treatment for CN tumor remnants or recurrences following microsurgery. However, data from longer follow-up times in more patients are needed before this conclusion can be validated. The patients need to be closely monitored and potential hydrocephalus managed despite tumor control.