Tag: Glioma

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Prognostic Importance of Age, Tumor Location, and Tumor Grade in Grade II Astrocytomas

World Neurosurg. (2019) 121:e411-e418

Previous work in anaplastic astrocytoma (AA) demonstrated that the survival benefit from gross total resection (GTR) is modified by age and tumor location. Here, we determined the influence of age and tumor location on survival benefit from GTR in diffuse astrocytoma (DA).

METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database (1999-2010). We used Kaplan- Meier curves and Cox survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. We determined the prevalence of the mutated isocitrate dehydrogenase (mIDH) using The Cancer Genome Atlas (TCGA).

RESULTS: We identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P [ 0.002; age >50 years HR, 0.41; P < 0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P [ 0.002; age >50 years HR, 0.78; P [ 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P [ 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P [ 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P [ 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P [ 0.49).

CONCLUSIONS: Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey nonredundant prognostic information in select clinical contexts

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Conscious sedation with dexmedetomidine compared with asleep-awake-asleep craniotomies in glioma surgery

J Neurosurg 129:1223–1230, 2018

Awake craniotomies have become a feasible tool over time to treat brain tumors located in eloquent regions. Different techniques have been applied in neurooncology centers. Both “asleep-awake-asleep” (asleep) and “conscious sedation” were used subsequently at the authors’ neurosurgical department. Since 2013, the authors have only performed conscious sedation surgeries, predominantly using the alfa2-receptor agonist dexmedetomidine as the anesthetic drug. The aim of this study was to compare both mentioned techniques and evaluate the clinical use of dexmedetomidine in the setting of awake craniotomies for glioma surgery.

METHODS The authors retrospectively analyzed patients who underwent operations either under the asleep condition using propofol-remifentanil or under conscious sedation conditions using dexmedetomidine infusions. In the asleep group patients were intubated with a laryngeal mask and extubated for the assessment period. Adverse events, as well as applied drugs with doses and frequency of usage, were recorded.

RESULTS From 224 awake surgeries between 2009 and 2015, 180 were performed for the resection of gliomas and included in the study. In the conscious sedation group (n = 75) significantly fewer opiates (p < 0.001) and vasoactive (p < 0.001) and antihypertensive (p < 0.001) drugs were used in comparison with the asleep group (n = 105). Furthermore, the postoperative length of stay (p < 0.001) and the surgical duration (p < 0.001) were significantly lower in the conscious sedation group.

CONCLUSIONS Use of dexmedetomidine creates excellent conditions for awake surgeries. It sedates moderately and acts as an anxiolytic. Thus, after ceasing infusion it enables quick and reliable clinical neurological assessment of patients. This might lead to reducing the amount of administered antihypertensive and vasoactive drugs as well as the length of hospitalization, while likely ensuring more rapid surgery.

 

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Resection of gliomas deemed inoperable by neurosurgeons based on preoperative imaging studies

J Neurosurg 129:567–575, 2018

Maximal safe resection is a primary objective in the management of gliomas. Despite this objective, surgeons and referring physicians may, on the basis of radiological studies alone, assume a glioma to be unresectable. Because imaging studies, including functional MRI, may not localize brain functions (such as language) with high fidelity, this simplistic approach may exclude some patients from what could be a safe resection. Intraoperative direct electrical stimulation (DES) allows for the accurate localization of functional areas, thereby enabling maximal resection of tumors, including those that may appear inoperable based solely on radiological studies. In this paper the authors describe the extent of resection (EOR) and functional outcomes following resections of tumors deemed inoperable by referring physicians and neurosurgeons.

METHODS The authors retrospectively examined the cases of 58 adult patients who underwent glioma resection within 6 months of undergoing a brain biopsy of the same lesion at an outside hospital. All patients exhibited unifocal supratentorial disease and preoperative Karnofsky Performance Scale scores ≥ 70. The EOR and 6-month functional outcomes for this population were characterized.

RESULTS Intraoperative DES mapping was performed on 96.6% (56 of 58) of patients. Nearly half of the patients (46.6%, 27 of 58) underwent an awake surgical procedure with DES. Overall, the mean EOR was 87.6% ± 13.6% (range 39.0%–100%). Gross-total resection (resection of more than 99% of the preoperative tumor volume) was achieved in 29.3% (17 of 58) of patients. Subtotal resection (95%–99% resection) and partial resection (PR; < 95% resection) were achieved in 12.1% (7 of 58) and 58.6% (34 of 58) of patients, respectively. Of the cases that involved PR, the mean EOR was 79.4% ± 12.2%. Six months after surgery, no patient was found to have a new postoperative neurological deficit. The majority of patients (89.7%, 52 of 58) were free of neurological deficits both pre- and postoperatively. The remainder of patients exhibited either residual but stable deficits (5.2%, 3 of 58) or complete correction of preoperative deficits (5.2%, 3 of 58).

CONCLUSIONS The use of DES enabled maximal safe resections of gliomas deemed inoperable by referring neurosurgeons. With rare exceptions, tumor resectability cannot be determined solely by radiological studies.

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Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes

Neurosurgery 83:76–85, 2018

Thalamic glioblastomas (GBMs) represent a significant neurosurgical challenge. In view of the low incidence of these tumors, outcome data and management strategies are not well defined.

OBJECTIVE: To identify the natural history and factors associated with survival in patients with thalamic glioblastoma.

METHODS: A retrospective review of all patients with thalamic glioblastoma over a 10-yr period was performed. Presenting clinical, radiological, and outcome data were collected. Chi-squared and Fisher’s exact tests were used to compare clinical characteristics across tumor groups. Cox proportional hazard models were utilized to investigate variables of interest with regard to overall survival.

RESULTS: Fifty-seven patients met inclusion criteria, with a median age of 53 and median Karnofsky Performance Scale (KPS) score of 80. The most common presenting symptoms were weakness, confusion, and headache. Hydrocephalus was present in 47% of patients preoperatively. Stereotactic biopsy was performed in 47 cases, and 10 patients underwent craniotomy. The median overall survival was 12.2 mo. Higher KPS, younger age, and cerebrospinal fluid (CSF) diversionwere correlatedwith better overall survival univariately, respectively, while the presence of language deficits at initial presentation was associated with poorer survival. In multivariate analysis, the only significant predictor of survival was presenting KPS.

CONCLUSION: The overall survival of patients with thalamic glioblastoma is comparable to unresectable lobar supratentorial GBMs. Younger patients and those with good presenting functional status had improved survival. Midbrain involvement by the tumor is not a negative prognostic factor. Improved therapies are needed, and patients should be considered for early trial involvement and aggressive upfront therapy.

 

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Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection

J Neurosurg 128:1690–1697, 2018

The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination.

METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620–640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis.

RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery.

CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional bluelight excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov)

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Intraoperative perception and estimates on extent of resection during awake glioma surgery: overcoming the learning curve

J Neurosurg 128:1410–1418, 2018

There is ample evidence that extent of resection (EOR) is associated with improved outcomes for glioma surgery. However, it is often difficult to accurately estimate EOR intraoperatively, and surgeon accuracy has yet to be reviewed. In this study, the authors quantitatively assessed the accuracy of intraoperative perception of EOR during awake craniotomy for tumor resection.

METHODS A single-surgeon experience of performing awake craniotomies for tumor resection over a 17-year period was examined. Retrospective review of operative reports for quantitative estimation of EOR was recorded. Definitive EOR was based on postoperative MRI. Analysis of accuracy of EOR estimation was examined both as a general outcome (gross-total resection [GTR] or subtotal resection [STR]), and quantitatively (5% within EOR on postoperative MRI). Patient demographics, tumor characteristics, and surgeon experience were examined. The effects of accuracy on motor and language outcomes were assessed.

RESULTS A total of 451 patients were included in the study. Overall accuracy of intraoperative perception of whether GTR or STR was achieved was 79.6%, and overall accuracy of quantitative perception of resection (within 5% of postoperative MRI) was 81.4%. There was a significant difference (p = 0.049) in accuracy for gross perception over the 17- year period, with improvement over the later years: 1997–2000 (72.6%), 2001–2004 (78.5%), 2005–2008 (80.7%), and 2009–2013 (84.4%). Similarly, there was a significant improvement (p = 0.015) in accuracy of quantitative perception of EOR over the 17-year period: 1997–2000 (72.2%), 2001–2004 (69.8%), 2005–2008 (84.8%), and 2009–2013 (93.4%). This improvement in accuracy is demonstrated by the significantly higher odds of correctly estimating quantitative EOR in the later years of the series on multivariate logistic regression. Insular tumors were associated with the highest accuracy of gross perception (89.3%; p = 0.034), but lowest accuracy of quantitative perception (61.1% correct; p < 0.001) compared with tumors in other locations. Even after adjusting for surgeon experience, this particular trend for insular tumors remained true. The absence of 1p19q co-deletion was associated with higher quantitative perception accuracy (96.9% vs 81.5%; p = 0.051). Tumor grade, recurrence, diagnosis, and isocitrate dehydrogenase-1 (IDH-1) status were not associated with accurate perception of EOR. Overall, new neurological deficits occurred in 8.4% of cases, and 42.1% of those new neurological deficits persisted after the 3-month follow-up. Correct quantitative perception was associated with lower postoperative motor deficits (2.4%) compared with incorrect perceptions (8.0%; p = 0.029). There were no detectable differences in language outcomes based on perception of EOR.

CONCLUSIONS The findings from this study suggest that there is a learning curve associated with the ability to accurately assess intraoperative EOR during glioma surgery, and it may take more than a decade to be truly proficient. Understanding the factors associated with this ability to accurately assess EOR will provide safer surgeries while maximizing tumor resection.

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Method for temporal keyhole lobectomies in resection of low- and high-grade gliomas

J Neurosurg 128:1388–1395, 2018

The purpose of this study was to describe a method of resecting temporal gliomas through a keyhole lobectomy and to share the results of using this technique.

METHODS The authors performed a retrospective review of data obtained in all patients in whom the senior author performed resection of temporal gliomas between 2012 and 2015. The authors describe their technique for resecting dominant and nondominant gliomas, using both awake and asleep keyhole craniotomy techniques.

RESULTS Fifty-two patients were included in the study. Twenty-six patients (50%) had not received prior surgery. Seventeen patients (33%) were diagnosed with WHO Grade II/III tumors, and 35 patients (67%) were diagnosed with a glioblastoma. Thirty tumors were left sided (58%). Thirty procedures (58%) were performed while the patient was awake. The median extent of resection was 95%, and at least 90% of the tumor was resected in 35 cases (67%). Five of 49 patients (10%) with clinical follow-up experienced permanent deficits, including 3 patients (6%) with hydrocephalus requiring placement of a ventriculoperitoneal shunt and 2 patients (4%) with weakness. Three patients experienced early postoperative anomia, but no patients had a new speech deficit at clinical follow-up.

CONCLUSIONS The authors provide their experience using a keyhole lobectomy for resecting temporal gliomas. Their data demonstrate the feasibility of using less invasive techniques to safely and aggressively treat these tumors.

 

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Sodium Fluorescein Facilitates Guided Sampling of Diagnostic Tumor Tissue in Nonenhancing Gliomas

Neurosurgery 82:719–727, 2018

Accurate tissue sampling in nonenhancing (NE) gliomas is a unique surgical challenge due to their intratumoral histological heterogeneity and absence of contrast enhancement as a guide for intraoperative stereotactic guidance. Instead, T2/fluid-attenuated inversion-recovery (FLAIR) hyperintensity on MRI is commonly used as an imaging surrogate for pathological tissue, but sampling from this region can yield nondiagnostic or underdiagnostic brain tissue. Sodium fluorescein is an intraoperative fluorescent dye that has a high predictive value for tumor identification in areas of contrast enhancement and NE in glioblastomas. However, the underlying histopathological alterations in fluorescent regions of NE gliomas remain undefined.

OBJECTIVE: To evaluate whether fluorescein can identify diagnostic tissue and differentiate regions with higher malignant potential during surgery for NE gliomas, thus improving sampling accuracy.

METHODS: Thirteen patients who presented with NE, T2/FLAIR hyperintense lesions suspicious for glioma received fluorescein (10%, 3 mg/kg intravenously) during surgical resection.

RESULTS: Patchy fluorescence was identified within the T2/FLAIR hyperintense area in 10 of 13 (77%) patients. Samples taken from fluorescent regions were more likely to demonstrate diagnostic glioma tissue and cytologic atypia (P < .05). Fluorescein demonstrated a 95% positive predictive value for the presence of diagnostic tissue. Samples from areas of fluorescence also demonstrated greater total cell density and higher Ki-67 labeling than nonfluorescent biopsies (P < .05).

CONCLUSION: Fluorescence in NE gliomas is highly predictive of diagnostic tumor tissue and regions of higher cell density and proliferative activity.

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Frontal Keyhole Craniotomy for Resection of Low- and High-Grade Gliomas

Neurosurgery 82:388–396, 2018

Minimally invasive techniques are increasingly being used to access intraaxial brain lesions.

OBJECTIVE: To describe a method of resecting frontal gliomas through a keyhole craniotomy and share the results with these techniques.

METHODS: We performed a retrospective review of data obtained on all patients undergoing resection of frontal gliomas by the senior author between 2012 and 2015.We describe our technique for resecting dominant and nondominant gliomas utilizing both awake and asleep keyhole craniotomy techniques.

RESULTS: After excluding 1 patient who received a biopsy only, 48 patients were included in the study. Twenty-nine patients (60%) had not received prior surgery. Twenty-six patients (54%) were diagnosed with WHO grade II/III tumors, and 22 patients (46%) were diagnosedwith glioblastoma. Twenty-five cases (52%)were performed awake.At least 90% of the tumor was resected in 35 cases (73%). Three of 43 patients with clinical follow-up experienced permanent deficits.

CONCLUSION: We provide our experience in using keyhole craniotomies for resecting frontal gliomas. Our data demonstrate the feasibility of using minimally invasive techniques to safely and aggressively treat these tumors.

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Navigated 3D–ultrasound versus conventional neuronavigation during awake resections of eloquent low-grade gliomas

Acta Neurochir (2018) 160:331–342

The data showing usefulness of navigated 3D– ultrasound (3DUS) during awake resections of eloquent gliomas are sparse. Results of surgeries performed using 3DUS were never compared to procedures guided by standard neuronavigation. The aim of this work is to assess the effectiveness of 3DUS during awake resections of eloquent low-grade gliomas (LGGs) by comparing surgical results of two series of patients operated on using conventional neuronavigation and using 3DUS. To our knowledge, a similar study is lacking in the literature.

Methods During a 4-year period (September 2006 to August 2010) 21 awake resections of LGGs guided by neuronavigation (series 1, S1) were consecutively performed in Department of Neurosurgery in Bratislava. During another 4-year period (August 2010 to July 2014) 28 awake resections of LGGs guided by 3DUS (series 2, S2) were consecutively conducted. In both patients series, the eloquent cortical and subcortical structures were intraoperatively detected by direct electrical stimulation. Extent of tumor resection (EOR) and functional outcome in both series were compared.

Results EOR was significantly greater (p = 0.022) in S2 (median = 93.25%; mean = 86.79%), as compared to S1 (median 87.1%; mean = 75.85%). One permanent minor deficit in S1 and 2 minor deficits in S2 occurred, the difference was not significant (p = 0.999).

Conclusions Our work represents the first study comparing results of surgeries guided by 3DUS versus conventional navigation. The extent of awake resections of eloquent LGG guided by 3DUS was greater comparing to awake resections guided by standard neuronavigation; use of 3DUS had no impact on the number of new permanent deficits.

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Navigated transcranial magnetic stimulation for glioma removal- prognostic value in motor function recovery from postsurgical neurological deficits

J Neurosurg 127:877–891, 2017

The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits.

METHODS Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (DHS-L) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between DHS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change.

RESULTS From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (DHS-L < 10 mm, n = 6), the nonadjacent group (DHS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were correlations between DHS-L and recovery of grip strength at 1 week, 3 weeks, and 3 months after surgery (r = 0.74, 0.68, and 0.65, respectively). Postsurgical nTMS was accomplished in 13 patients. In 9 of 13 cases, nTMS-MEP from APB muscle was positive at 1 week after surgery. Excluding the case in which nTMS-MEP was negative from the presurgical nTMS study, recoveries in grip strength were compared between 2 groups, in which nTMS-MEP at 1 week after surgery was positive (n = 9) or negative (n = 3). Significant differences were observed between the 2 groups at 1 week, 3 weeks, and 3 months after surgery (p < 0.01). Positive nTMS-MEP at 1 week after surgery correlated well with the motor recovery at 1 week, 3 weeks, and 3 months after surgery (r = 0.87, 0.88, and 0.77, respectively).

CONCLUSIONS Navigated TMS is a useful tool for identifying motor eloquent areas. The results of the present study have demonstrated the predictive value of nTMS in upper-extremity motor function recovery from postsurgical neurological deficits. The longer DHS-L and positive nTMS-MEP at 1 week after surgery have prognostic values of better recovery from postsurgical neurological deficits.

 

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Awake Craniotomy vs Craniotomy Under General Anesthesia for Perirolandic Gliomas

Neurosurgery 81:481–489, 2017

A craniotomy with direct cortical/subcortical stimulation either awake or under general anesthesia (GA) present 2 approaches for removing eloquent region tumors. With a reported higher prevalence of intraoperative seizures occurring during awake resections of perirolandic lesions, oftentimes, surgery under GA is chosen for these lesions.

OBJECTIVE: To evaluate a single-surgeon’s experience with awake craniotomies (AC) vs surgery under GA for resecting perirolandic, eloquent, motor-region gliomas.

METHODS: Between 2005 and 2015, a retrospective analysis of 27 patients with perirolandic, eloquent, motor-area gliomas that underwent an AC were case-control matched with 31 patients who underwent surgery under GA for gliomas in the same location. All patients underwent direct brain stimulation with neuromonitoring and perioperative risk factors, extent of resection, complications, and discharge status were assessed.

RESULTS: The postoperative Karnofsky Performance Score (KPS) was significantly lower for theGApatients at 81.1 compared to theACpatients at 93.3 (P=.040). The extent of resection for GA patients was 79.6% while the AC patients had an 86.3% resection (P = .136). There were significantly more 100% total resections in the AC patients 25.9% compared to the GA group (6.5%; P=.041). Patients in theGAgroup had a longer mean length of hospitalization of 7.9 days compared to the AC group at 4.2 days (P = .049).

CONCLUSION: We show that AC can be performed with more frequent total resections, better postoperative KPS, shorter hospitalizations, as well as similar perioperative complication rates compared to surgery under GA for perirolandic, eloquent motor-region glioma.

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FLAIR signal increase of the fluid within the resection cavity after glioma surgery: generally valid as early recurrence marker?

J Neurosurg 127:417–425, 2017

Recent studies have indicated that a signal intensity increase of the fluid within the resection cavity on FLAIR images may predict tumor recurrence after glioma surgery. The aim of this study was to assess the increase in FLAIR signal intensity in a large patient cohort and in subgroups to assess its prognostic value for early tumor recurrence in glioma patients.

METHODS A total of 212 patients (213 cases) who had undergone surgery for an intracranial glioma (WHO Grade IV [n = 103], WHO Grade III [n = 57], and WHO Grade II [n = 53]) were included in this retrospective study. FLAIR signal within the resection cavity at the time of tumor recurrence/last contact and on the previous MRI study was assessed qualitatively and quantitatively. Appearance of FLAIR signal increase was studied over time using Kaplan-Meier estimates in subgroups.

RESULTS Patients with WHO Grade II glioma and connection of the resection cavity to CSF who did not undergo radiotherapy did not regularly develop this sign and were excluded from further analysis. For the remaining 87 cases, FLAIR signal intensity increase was observed in 27 cases. Recurrent disease was found in 26 of these 27 cases, resulting in a specificity of 80.0%, a sensitivity of 31.7%, and positive and negative predictive values of 96.3% and 6.7%, respectively. In 4 cases this sign had been observed prior (range 2.8–8.5 months) to tumor recurrence defined by standard criteria. Quantitative analysis underlined the results of qualitative analysis, but it did not add a diagnostic value.

CONCLUSIONS Signal intensity increase of the fluid within the resection cavity on FLAIR images is a rare but highly specific and early sign for tumor recurrence/tumor progression in completely and incompletely resected high-grade glioma without connection of the resection cavity to CSF and with radiotherapy.

 

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The Cost of Brain Surgery: Awake vs Asleep Craniotomy for Perirolandic Region Tumors

Neurosurgery 81:307–314, 2017

Cost effectiveness has become an important factor in the health care system, requiring surgeons to improve efficacy of procedures while reducing costs. An awake craniotomy (AC) with direct cortical stimulation (DCS) presents one method to resect eloquent region tumors; however, some authors assert that this procedure is an expensive alternative to surgery under general anesthesia (GA) with neuromonitoring.

OBJECTIVE: To evaluate the cost effectiveness and clinical outcomes between AC and GA patients.

METHODS: Retrospective analysis of a cohort of 17 patients with perirolandic gliomas who underwent an AC with DCS were case-control matched with 23 patients with perirolandic gliomas who underwent surgery under GA with neuromonitoring (ie, motor-evoked potentials, somatosensory-evoked potentials, phase reversal). Inpatient costs, qualityadjusted life years (QALY), extent of resection, and neurological outcome were compared between the groups.

RESULTS: Total inpatient expense per patient was $34 804 in the AC group and $46 798 in the GA group (P = .046). QALY score for the AC group was 0.97 and 0.47 for the GA group (P = .041). The incremental cost per QALY for the AC group was $82 720 less than the GA group. Postoperative Karnofsky performance status was 91.8 in the AC group and 81.3 in the GA group (P=.047). Length of hospitalization was 4.12 days in the AC group and 7.61 days in the GA group (P = .049).

CONCLUSION: The total inpatient costs for awake craniotomies were lower than surgery under GA. This study suggests better cost effectiveness and neurological outcome with awake craniotomies for perirolandic gliomas.

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Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Acta Neurochir (2017) 159:151–167

Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all pre-clinically tested agents with the potential for FGS for glioma.

Methods: We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.

Results: The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5- aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.

Conclusions: 5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.

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Maximizing safe resection of low- and high-grade glioma

dti-gliomas

J Neurooncol (2016) 130:269–282

Surgical resection plays a central role in the management of gliomas. In this study, we review the evidence in support of extent of resection to improve survival, symptom management, and time to malignant transformation in low- and high-grade gliomas, and summarize the findings from our literature search regarding the role of extent of resection and intraoperative practices to maximize safety.

There is a growing body of evidence supporting improved overall survival, improved progression-free survival, and superior quality of life with greater extent of resection.

Additionally, a better understanding of central nervous system plasticity allows for a staged approach to the surgical management of low- and intermediate-grade gliomas.

A number of intraoperative techniques have been utilized to offer safer glioma surgery with greater extent of resection. Approaches such as awake brain tumor surgery can be safely performed with low failure rates and excellent long-term functional outcomes.

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Laser interstitial thermal therapy followed by minimal-access transsulcal resection for the treatment of large and dif cult to access brain tumors

litt

Neurosurg Focus 41 (4):E14, 2016

Laser interstitial thermal therapy (LITT), sometimes referred to as “stereotactic laser ablation,” has demonstrated utility in a subset of high-risk surgical patients with dificult to access (DTA) intracranial neoplasms. However, the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes and morbidity. This may limit the utility of LITT in dealing with precisely those large or deep tumors that are most dif cult to treat with conventional approaches. Recently, several groups have reported on minimally invasive transsulcal approaches utilizing tubular retracting systems. However, these approaches have been primarily used for intraventricular or paraventricular lesions, and subtotal resections have been reported for intraparenchymal lesions. Here, the authors describe a combined approach of LITT followed by minimally invasive transsulcal resection for large and DTA tumors.

Methoss The authors retrospectively reviewed the results of LITT immediately followed by minimally invasive, trans-sulcal, transportal resection in 10 consecutive patients with unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females, had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. The median tumor volume treated was 38.0 cm3.

Results The median tumor volume treated to the yellow thermal dose threshold (TDT) line was 83% (range 76%– 92%), the median tumor volume treated to the blue TDT line was 73% (range 60%–87%), and the median extent of resection was 93% (range 84%–100%). Two patients suffered mild postoperative neurological de cits, one transiently. Four patients have died since this analysis and 6 remain alive. Median progression-free survival was 280 days, and median overall survival was 482 days.

Conclusions Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms. There were no unexpected neurological complications in this series, and operative characteristics improved as surgeon experience increased. Further studies are needed to elucidate any differences in survival or quality of life metrics.

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Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas

intraoperative_probe_based_confocal_laser

Neurosurgery 79:604–612, 2016

The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection.

OBJECTIVE: To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas.

METHODS: In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment.

RESULTS: The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy “normal” tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed.

CONCLUSION: We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins.

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Accurate Delineation of Glioma Infiltration by Advanced PET/MR Neuro-Imaging (FRONTIER Study)

f1-largeNeurosurgery 79:535–540, 2016

Glioma imaging, used for diagnostics, treatment planning, and followup, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal.

OBJECTIVE: To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain.

METHODS: A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites.

DISCUSSION: In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment.

EXPECTED OUTCOME: We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma.

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Selective 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in Gliomas

selective-5-aminolevulinic-acid-induced-protoporphyrin-ix-fluorescence-in-gliomas

Acta Neurochir (2016) 158:1935–1941

Malignant gliomas are locally invasive tumors that offer a poor prognosis. Evidence shows that complete resection of the tumor at the time of surgery confers a significant improvement in overall survival.

In recent years, 5- aminolevulinic acid (ALA)-induced fluorescence has been used by neurosurgeons to good effect in increasing the rate of complete resection. Despite the considerable interest in the use of 5-ALA in fluorescence-guided neurosurgery, the mechanisms behind the accumulation of Protoporphyrin IX (PpIX) in neoplastic tissue are unclear.

In this review, we summarize the evidence in the literature on the mechanisms underlying the selective production of PpIX with a specific focus on gliomas.

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