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Following the light in glioma surgery: a comparison of sodium fluorescein and 5-aminolevulinic acid as surgical adjuncts in glioma resection.
Navarro-Bonnet, J, Suarez-Meade, P, Brown, DA, Chaichana, KL, Quinones-Hinojosa, A
Journal of neurosurgical sciences. 2019;(6):633-647
Abstract
Gliomas are molecularly complex neoplasms and require a multidisciplinary approach to treatment. Maximal safe resection is often the initial goal of treatment and extent of resection (EOR) is an important prognostic factor correlating with both progression-free-survival (PFS) and overall survival (OS). Postoperative patient outcome is also a critical and independent prognosticator and high EOR must not be achieved at the expense of good functional outcome. Several intraoperative adjuvant techniques have been developed to help the surgeon push the boundaries of EOR while maintaining safety. Fluorescence-guided surgery for brain tumors is a contemporary adjuvant technique that allows for intraoperative delineation of diseased and normal brain thus improving maximal safe resection. The most extensively used fluorophores are 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SFL). These fluorophores have different spectrophotometric properties, mechanisms of action and considerations for use. Both have demonstrated utility in neurosurgical oncology. They are safe and both are FDA approved for use as surgical adjuncts during resection of primary CNS neoplasms although they have been used with varying success for other tumor types. When combined with other surgical adjuvant strategies such as neuronavigation, intraoperative ultrasound, intraoperative MRI, awake resection and/or electrophysiological mapping/monitoring, fluorescence-guided resection appears to further improve resection quality in regard to EOR and safety. In this article, we review the current knowledge related to both fluorophores for brain tumor resection, their benefits, and pitfalls, as well as the major advantages associated with their use. We also briefly review additional fluorophores in early clinical development. Fluorescence-guided surgery is a novel surgical adjuvant which allows for real-time delineation of neoplastic tissues. The most widely used fluorophores are 5-ALA and SFL. They are safe compounds and there is a large body of evidence suggesting improvement in EOR when these are employed. There are nuances to the use of each; the fluorescence intensity is dose-dependent in either case and the sensitivity and specificity for various tumors vary widely. Additional prospective studies will be necessary to parse the impact of this technique and these fluorophores on survival metrics.
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Comparison of normal saline and balanced crystalloid (plasmalyte) in patients undergoing elective craniotomy for supratentorial brain tumors: A randomized controlled trial.
Dey, A, Adinarayanan, S, Bidkar, PU, Bangera, RK, Balasubramaniyan, V
Neurology India. 2018;(5):1338-1344
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Abstract
BACKGROUND The choice of fluid is important in neurosurgical patients, who may be dehydrated due to the administration of diuretics in order to reduce cerebral edema. Normal saline, the infused fluid routinely used in neurosurgical patients, can cause hyperchloremic metabolic acidosis. A balanced crystalloid (BC) may help to maintain the metabolic status more favorably in these patients, without adversely affecting brain relaxation. METHODS We conducted a prospective, randomized controlled trial on patients undergoing elective craniotomy for supratentorial tumor resection under general anesthesia. 44 patients were randomly allocated into two groups of 22 each to receive either normal saline or BC (Plasmalyte) as the maintenance fluid, intra-operatively. The metabolic parameters and osmolality were measured at regular intervals. Brain relaxation score was assessed by the operating surgeon. The patients were monitored with serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea and serum creatinine for assessing the degree of acute kidney injury. RESULTS The metabolic profile was better maintained with the BC. The brain relaxation score was comparable between the two groups. The postoperative NGAL, urea and creatinine values were significantly higher in the normal saline group compared to the BC group. CONCLUSION The balanced crystalloid maintains metabolic status more favorably than normal saline in neurosurgical patients. Hyperchloremic metabolic acidosis, and the other problems which occur as a consequence of normal saline infusion may be circumvented by choosing a balanced crystalloid electrolyte solution. Neither of the crystalloids appeared to have any adverse effect on brain relaxation.
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A comparison of equivolume, equiosmolar solutions of hypertonic saline and mannitol for brain relaxation in patients undergoing elective intracranial tumor surgery: a randomized clinical trial.
Dostal, P, Dostalova, V, Schreiberova, J, Tyll, T, Habalova, J, Cerny, V, Rehak, S, Cesak, T
Journal of neurosurgical anesthesiology. 2015;(1):51-6
Abstract
BACKGROUND Hyperosmolar solutions have been used in neurosurgery to modify brain bulk and prevent neurological deterioration. The purpose of the study was to compare the effects of equivolume, equiosmolar solutions of mannitol and hypertonic saline (HTS) on brain relaxation and postoperative complications in patients undergoing elective intracranial tumor surgery. METHODS In this prospective, randomized study, patients with American Society of Anesthesiologists physical status I to III scheduled to undergo a craniotomy for intracranial tumors were enrolled. Patients received a 3.75 mL/kg intravenous infusion of either 3.2% HTS (group HTS, n=36) or 20% mannitol (group M, n=38). The surgeon assessed the condition of the brain using a 4-point scale after opening the dura. Recorded measures included duration of surgery, blood loss, urine output, volume and type of infused fluids, hemodynamic variables, electrolytes, glucose, creatinine, predefined postoperative complications, and length of intensive care unit and hospital stays. RESULTS Brain relaxation conditions in group HTS (score 1/2/3/4, n=10/17/2/7) were better than those in group M (score 1/2/3/4, n=3/18/3/14, P=0.0281). Patients in group M had higher urine output, received more crystalloids during surgery, and displayed lower central venous pressure and lower natremia at the end of surgery than did patients in group HTS. No significant differences in postoperative complications or lengths of intensive care unit and hospital stays were observed between the groups. CONCLUSIONS Our results suggest that HTS provides better brain relaxation than mannitol during elective intracranial tumor surgery.
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Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.
Brown, PD, Pugh, S, Laack, NN, Wefel, JS, Khuntia, D, Meyers, C, Choucair, A, Fox, S, Suh, JH, Roberge, D, et al
Neuro-oncology. 2013;(10):1429-37
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BACKGROUND To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). METHODS Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. RESULTS Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. CONCLUSIONS Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.
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A randomised controlled trial of Hartmann's solution versus half normal saline in postoperative paediatric spinal instrumentation and craniotomy patients.
Coulthard, MG, Long, DA, Ullman, AJ, Ware, RS
Archives of disease in childhood. 2012;(6):491-6
Abstract
OBJECTIVE To compare the difference in plasma sodium at 16-18 h following major surgery in children who were prescribed either Hartmann's and 5% dextrose or 0.45% saline and 5% dextrose. DESIGN A prospective, randomised, open label study. SETTING The paediatric intensive care unit (650 admissions per annum) in a tertiary children's hospital in Brisbane, Australia. PATIENTS The study group comprised 82 children undergoing spinal instrumentation, craniotomy for brain tumour resection, or cranial vault remodelling. INTERVENTIONS Patients received either Hartmann's and 5% dextrose at full maintenance rate or 0.45% saline and 5% dextrose at two-thirds maintenance rate. PRIMARY OUTCOME MEASURE plasma sodium at 16-18 h postoperatively; secondary outcome measure: number of fluid boluses administered. RESULTS Mean postoperative plasma sodium levels of children receiving 0.45% saline and 5% dextrose were 1.4 mmol/l (95% CI 0.4 to 2.5) lower than those receiving Hartmann's and 5% dextrose (p=0.008). In the 0.45% saline group, seven patients (18%) became hyponatraemic (Na <135 mmol/l) at 16-18 h postoperatively; in the Hartmann's group no patient became hyponatraemic (p=0.01). No child in either fluid group became hypernatraemic. CONCLUSIONS The postoperative fall in plasma sodium was smaller in children who received Hartmann's and 5% dextrose compared to those who received 0.45% saline and 5% dextrose. It is suggested that Hartmann's and 5% dextrose should be administered at full maintenance rate postoperatively to children who have undergone major surgery in preference to hypotonic fluids.
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Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigation.
Lehnhardt, FG, Bock, C, Röhn, G, Ernestus, RI, Hoehn, M
NMR in biomedicine. 2005;(6):371-82
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Abstract
High-resolution proton magnetic resonance spectroscopy was performed on tissue specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11 glioblastomas) and 13 patients with meningiomas. For all patients, samples of primary tumors and their first recurrences were examined. Increased anaplasia, with respect to malignant transformation, resulting in a higher malignancy grade, was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features of tumor types, as determined on samples of the primary occurrences, were in good agreement with previous studies. Compared with the respective primary astrocytomas, characteristic features of glioblastomas were significantly increased concentrations of alanine (Ala) (p = 0.005), increased metabolite ratios of glycine (Gly)/total creatine (tCr) (p = 0.0001) and glutamate (Glu)/glutamine (Gln) (p = 0.004). Meningiomas showed increased Ala (p = 0.02) and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p = 0.001) relative to astrocytomas, and N-acetylaspartate and myo-inositol were absent. Metabolic changes of an evolving tumor were observed in recurrent astrocytomas: owing to their consecutive assessments, more indicators of malignant degeneration were detected in astrocytoma recurrences (e.g. Gly, p = 0.029; tCho, p = 0.034; Glu, p = 0.015; tCho/tCr, p = 0.001) in contrast to the comparison of primary astrocytomas with primary glioblastomas. The present investigation demonstrated a correlation of the tCho-signal with tumor progression. Significantly elevated concentrations of Ala (p = 0.037) and Glu (p = 0.003) and metabolite ratio tCho/tCr (p = 0.005) were even found in recurrent low-grade astrocytomas with unchanged histopathological grading (n = 11). This may be related to an early stage of malignant transformation, not yet detectable morphologically, and emphasizes the high sensitivity of 1H NMR spectroscopy in elucidating characteristics of brain tumor metabolism.
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Proton MRS imaging in the follow-up of patients with suspected low-grade gliomas.
Reijneveld, JC, van der Grond, J, Ramos, LM, Bromberg, JE, Taphoorn, MJ
Neuroradiology. 2005;(12):887-91
Abstract
We compared the value of changes in proton magnetic resonance spectroscopic imaging ((1)H-MRSI) with changes in clinical status and/or contrast-enhanced magnetic resonance imaging (MRI) in the monitoring of patients with suspected low-grade glioma (LGG). From June 1, 1999 till May 31, 2002, we included consecutive, neurologically intact adult patients suspected of having an LGG, demonstrating non-enhancing supratentorial lesions without edema or mass effect on MRI, and in whom all treatment (including a diagnostic biopsy) was deferred. Till January 1, 2003, patients were surveyed clinically and radiologically (contrast-enhanced MRI and (1)H-MRSI). Patients who showed progression on clinical examination and/or MRI were denoted as progressive disease. Other patients were denoted as stable disease. A decrease in NAA/CHO ratio of > or =20% compared to the baseline value was considered as indicative for progression on (1)H-MRSI. We included 14 patients with suspected LGG. Seven patients demonstrated progressive disease during the follow-up period, preceded or accompanied by concomitant (1)H-MRSI changes in five patients. Four of these five patients were operated on within the follow-up interval. The histological diagnosis demonstrated high-grade glioma in three and LGG in one patient. In the other two patients with progressive disease, no progression was found on (1)H-MRSI. The other seven patients demonstrated stable disease, but four of them showed progression on (1)H-MRSI. Our data do not show convincing evidence that (1)H-MRSI contributes to adequate monitoring and follow-up of patients with suspected LGG. Future research should preferably include pathological data at the time of (1)H-MRSI changes.
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A comparative study between a calcium channel blocker (Nicardipine) and a combined alpha-beta-blocker (Labetalol) for the control of emergence hypertension during craniotomy for tumor surgery.
Kross, RA, Ferri, E, Leung, D, Pratila, M, Broad, C, Veronesi, M, Melendez, JA
Anesthesia and analgesia. 2000;(4):904-9
Abstract
We compared the efficacy of the combination of enalaprilat/labetalol with that of enalaprilat/nicardipine to prevent emergence postcraniotomy hypertension. A prospective, randomized open labeled clinical trial was designed to compare the incidence of breakthrough hypertension (systolic blood pressure [SBP] > 140 mm Hg) and adverse effects (hypotension, tachycardia, and bradycardia) between the two drug combinations. Secondarily, the effects of the drugs on SBP, mean blood pressure, and diastolic blood pressure were evaluated over the course of the study. Forty-two patients received enalaprilat 1.25 mg IV at dural closure followed by either multidose nicardipine 2 mg IV or labetalol 5 mg IV to maintain the SBP below 140 mm Hg. SBP was similarly controlled in both groups. There was a marginally smaller incidence of failures and adverse effects with labetalol. Blood pressure profiles were similar for both groups.