Impact of Extent of Resection on Incidence of Postoperative Complications in PatientsWith Glioblastoma

Neurosurgery 86:625–630, 2020

Extent of resection (EOR) is well established as correlating with overall survival in patients with glioblastoma (GBM). The impact of EOR on reported quality metrics such as patient safety indicators (PSIs) and hospital-acquired conditions (HACs) is unknown.

OBJECTIVE: To perform a retrospective study to evaluate possible associations between EOR and the incidence of PSIs and HACs.

METHODS: We queried all patients diagnosed with GBM who underwent surgical resection at our institution between January 2011 and May 2017. Pre- and postoperative magnetic resonance imageswere analyzed for EOR. Each chart was reviewed to determine the incidence of PSIs and HACs.

RESULTS: A total of 284 patients met the inclusion criteria. EOR ranged from 39.00 to 100%, with a median of 99.84% and a mean of 95.7%. There were 16 PSI, and 13 HAC, events. There were no significant differences in the rates of PSIs or HACs when compared between patients stratified by gross total resection (EOR ≥ 95%) and subtotal resection (EOR < 95%). The odds of encountering a PSI or HAC were 2.5 times more likely in the subtotal resection group compared to the gross total resection group (P = .58). After adjusting for confounders, the odds of encountering a PSI or HAC in the subtotal resection group were 3.9 times greater than for the gross total resection group (P < .05).

CONCLUSION: Gross total resection of GBM is associated with a decreased incidence of PSIs and HACs, as compared to subtotal resection.

Intraoperative 3D ultrasound–guided resection of diffuse low-grade gliomas

J Neurosurg 132:518–529, 2020

Extent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)–guided resection under general anesthesia.

METHODS Consecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated.

RESULTS Forty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)– mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusionweighted postoperative MRI.

CONCLUSIONS Three-dimensional US–guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

Early postoperative delineation of residual tumor after low-grade glioma resection by probabilistic quantification of diffusion-weighted imaging

J Neurosurg 130:2016–2024, 2019

In WHO grade II low-grade gliomas (LGGs), early postoperative MRI (epMRI) may overestimate residual tumor on FLAIR sequences. Consequently, MRI at 3–6 months follow-up (fuMRI) is used for delineation of residual tumor. This study sought to evaluate if integration of apparent diffusion coefficient (ADC) maps permits an accurate estimation of residual tumor early on epMRI.

METHODS From a consecutive cohort, 43 cases with an initial surgery for an LGG, and complete epMRI (< 72 hours after resection) and fuMRI including ADC maps, were retrospectively identified. Residual FLAIR hyperintense tumor was manually segmented on epMRI and corresponding ADC maps were coregistered. Using an expectation maximization algorithm, residual tumor segments were probabilistically clustered into areas of residual tumor, ischemia, or normal white matter (NWM) by fitting a mixture model of superimposed Gaussian curves to the ADC histogram. Tumor volumes from epMRI, clustering, and fuMRI were statistically compared and agreement analysis was performed.

RESULTS Mean FLAIR hyperintensity suggesting residual tumor was significantly larger on epMRI compared to fuMRI (19.4 ± 16.5 ml vs 8.4 ± 10.2 ml, p < 0.0001). Probabilistic clustering of corresponding ADC histograms on epMRI identified subsegments that were interpreted as mean residual tumor (7.6 ± 10.2 ml), ischemia (8.1 ± 5.9 ml), and NWM (3.7 ± 4.9 ml). Therefore, mean tumor quantification error between epMRI and fuMRI was significantly reduced (11.0 ± 10.6 ml vs -0.8 ± 3.7 ml, p < 0.0001). Mean clustered tumor volumes on epMRI were no longer significantly different from the fuMRI reference (7.6 ± 10.2 ml vs 8.4 ± 10.2 ml, p = 0.16). Correlation (Pearson r = 0.96, p < 0.0001), concordance correlation coefficient (0.89, 95% confidence interval 0.83), and Bland-Altman analysis suggested strong agreement between both measures after clustering.

CONCLUSIONS Probabilistic segmentation of ADC maps facilitates accurate assessment of residual tumor within 72 hours after LGG resection. Multiparametric image analysis detected FLAIR signal alterations attributable to surgical trauma, which led to overestimation of residual LGG on epMRI compared to fuMRI. The prognostic value and clinical impact of this method has to be evaluated in larger case series in the future.

 

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.

Clinical features and surgical outcomes of patients with skull base chordoma

J Neurosurg 127:1257–1267, 2017

Skull base chordoma is relatively rare, and a limited number of reports have been published regarding its clinical features. Moreover, the factors associated with extent of resection, as well as the value of marginal resection for long-term survival, are still in question for this disease. The objective of this study was to investigate these factors by evaluating their clinical features and surgical outcomes.

METHODS A retrospective analysis of 238 patients with skull base chordomas, who met the inclusion criteria, was performed. This study summarized the clinical features, selection of approaches, degree of resection, and postoperative complications by statistical description analyses; proposed modified classifications of tumor location and bone invasion; studied the contributions of the clinical and radiological factors to the extent of resection by Pearson c2, ANOVA, rank test, and binary logistic regression analysis; and estimated the differences in overall survival and progression-free survival rates with respect to therapeutic history, classification of tumor location, extent of bone invasion, and extent of tumor resection by the Kaplan-Meier method. A p value < 0.05 was considered statistically significant.

RESULTS The study included 140 male and 98 female patients with a mean age of 38.1 years. Headache and neck pain (33.2%) and diplopia (29%) were the most common initial symptoms. Sphenoclival type accounted for the largest proportion of tumor location (59.2%); endophytic chordoma was the more common type of bone invasion (81.5%). Lateral open approaches were performed in two-thirds of the study population (78.6%). The rate of marginal resection was 66%, composed of gross-total resection (11.8%) and near-total resection (54.2%). Meningitis (8%) and CSF leakage (3.8%) were the most frequent complications. The mean follow-up period was 43.7 months. The overall survival and progression-free survival rates at 5 years were 76% and 45%, respectively. Recurrent tumor and larger tumor volume (≥ 40 cm3) were identified as risk factors of marginal resection. Patients who presented with recurrent tumor and underwent intralesional resection had a worse long-term outcome.

CONCLUSIONS The classifications of both tumor location and bone invasion demonstrated clinical value. Marginal resection was more likely to be achieved for primary lesions with smaller volumes (< 40 cm3). The rate of CSF leakage declined due to improved dura mater repair with free fat grafts. Marginal resection, or gross-total resection when possible, should be performed in patients with primary chordomas to achieve better long-term survival.

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.

Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging

Hypnosis for Awake Surgery of Low-grade Gliomas

Neurosurgery 78:775–786, 2016

The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published.

OBJECTIVE: To investigate determinants for patient outcome and progression-freesurvival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging.

METHODS: A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and fieldstrength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment.

RESULTS: A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas “failed” GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits.

CONCLUSION: GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS.

Combination of Intraoperative Magnetic Resonance Imaging and Intraoperative Fluorescence to Enhance the Resection of Contrast Enhancing Gliomas

Combination of Intraoperative Magnetic Resonance Imaging and Intraoperative Fluorescence to Enhance the Resection of Contrast Enhancing Gliomaspdf

Neurosurgery 77:16–22, 2015

Evidence suggests that extent of resection (EOR) is a prognostic factor for patients harboring gliomas. Recent studies have displayed the importance of intraoperative magnetic resonance imaging (iMRI) with 5-aminolevulinic acid (5-ALA) fluorescence-guidance in order to maximize EOR.

OBJECTIVE: To compare iMRI and 5-ALA fluorescence-guidance and the impact on patient survival.

METHODS: Thirty-two patients with contrast-enhancing gliomas undergoing intended gross total resection (GTR) were included in a prospective study. Surgeries were started under white-light conditions. When GTR was thought to be achieved, an iMRI scan was performed and a blue light turned on to search for unintentionally remaining tumor tissue. iMRI findings were compared with intraoperative fluorescence findings. Histological examination of tumor bulk and any additionally resected tissue was performed. All patients underwent early postoperative high-field MRI to determine EOR.

RESULTS: In 13 patients (40.6%), iMRI and fluorescence unequivocally did not show residual tumor intraoperatively. In 19 patients (59.4%), resection was continued due to iMRI or fluorescence findings. In 9 of these (47.4%), iMRI and fluorescence findings were inconsistent regarding residual tumor. GTR according to postoperative MRI was achieved in all but 1 patient. Histological examination ruled out false positive findings in all additionally resected specimens. Sensitivity and specificity to detect residual tumor tissue were 75% and 100%, respectively, for iMRI and 70% and 100% for 5-ALA fluorescence.

CONCLUSION: Use of iMRI as well as fluorescence-guidance are appropriate methods to improve the extent of resection in surgery of contrast-enhancing gliomas. Best results can be achieved by complementary use of both modalities.

Trends in Fluorescence Image-Guided Surgery for Gliomas

Trends in Fluorescence Image-Guided Surgery for Gliomas

Neurosurgery 75:61–71, 2014

Mounting evidence suggests that a more extensive surgical resection is associated with an improved life expectancy for both low-grade and high-grade glioma patients. However, radiographically complete resections are not often achieved in many cases because of the lack of sensitivity and specificity of current neurosurgical guidance techniques at the margins of diffuse infiltrative gliomas.

Intraoperative fluorescence imaging offers the potential to improve the extent of resection and to investigate the possible benefits of resecting beyond the radiographic margins.

Here, we provide a review of wide-field and high-resolution fluorescence-imaging strategies that are being developed for neurosurgical guidance, with a focus on emerging imaging technologies and clinically viable contrast agents. The strengths and weaknesses of these approaches will be discussed, as well as issues that are being addressed to translate these technologies into the standard of care.

Use of High-Field Intraoperative Magnetic Resonance Imaging to Enhance the Extent of Resection of Enhancing and Nonenhancing Gliomas

Use of High-Field Intraoperative Magnetic Resonance Imaging to Enhance the Extent of Resection of Enhancing and Nonenhancing Gliomas

Neurosurgery 74:339–350, 2014

Intraoperative magnetic resonance imaging (IoMRI) is used to improve the extent of resection of brain tumors. Most previous studies evaluating the utility of IoMRI have focused on enhancing tumors.

OBJECTIVE: To report our experience with the use of high-field IoMRI (1.5 T) for both enhancing and nonenhancing gliomas.

METHODS: An institutional review board–approved retrospective review was performed of 102 consecutive glioma patients (104 surgeries, 2010-2012). Pre-, intra-, and postoperative tumor volumes were assessed. Analysis was performed with the use of volumetric T2 images in 43 nonenhancing and 13 minimally enhancing tumors and with postcontrast volumetric magnetization-prepared rapid gradient-echo images in 48 enhancing tumors.

RESULTS: In 58 cases, preoperative imaging showed tumors likely to be amenable to complete resection. Intraoperative electrocorticography was performed in 32 surgeries, and 14 cases resulted in intended subtotal resection of tumors due to involvement of deep functional structures. No further resection (complete resection before IoMRI) was required in 25 surgeries, and IoMRI showed residual tumor in 79 patients. Of these, 25 surgeries did not proceed to further resection (9 due to electrocorticography findings, 14 due to tumor in deep functional areas, and 2 due to surgeon choice). Additional resection that was performed in 54 patients resulted in a final median residual tumor volume of 0.21 mL (0.6%). In 79 patients amenable to complete resection, the intraoperative median residual tumor volume for the T2 group was higher than for the magnetization-prepared rapid gradient-echo group (1.088 mL vs 0.437 mL; P = .049), whereas the postoperative median residual tumor volume was not statistically significantly different between groups.

CONCLUSION: IoMRI enhances the extent of resection, particularly for nonenhancing gliomas.

Use of High-Field Intraoperative Magnetic Resonance Imaging to Enhance the Extent of Resection of Enhancing and Nonenhancing Gliomas

Use_of_High_Field_Intraoperative_Magnetic

Neurosurgery 74:339–350, 2014

Intraoperative magnetic resonance imaging (IoMRI) is used to improve the extent of resection of brain tumors. Most previous studies evaluating the utility of IoMRI have focused on enhancing tumors.

OBJECTIVE: To report our experience with the use of high-field IoMRI (1.5 T) for both enhancing and nonenhancing gliomas.

METHODS: An institutional review board–approved retrospective review was performed of 102 consecutive glioma patients (104 surgeries, 2010-2012). Pre-, intra-, and postoperative tumor volumes were assessed. Analysis was performed with the use of volumetric T2 images in 43 nonenhancing and 13 minimally enhancing tumors and with postcontrast volumetric magnetization-prepared rapid gradient-echo images in 48 enhancing tumors.

RESULTS: In 58 cases, preoperative imaging showed tumors likely to be amenable to complete resection. Intraoperative electrocorticography was performed in 32 surgeries, and 14 cases resulted in intended subtotal resection of tumors due to involvement of deep functional structures. No further resection (complete resection before IoMRI) was required in 25 surgeries, and IoMRI showed residual tumor in 79 patients. Of these, 25 surgeries did not proceed to further resection (9 due to electrocorticography findings, 14 due to tumor in deep functional areas, and 2 due to surgeon choice). Additional resection that was performed in 54 patients resulted in a final median residual tumor volume of 0.21 mL (0.6%). In 79 patients amenable to complete resection, the intraoperative median residual tumor volume for the T2 group was higher than for the magnetization-prepared rapid gradient-echo group (1.088 mL vs 0.437 mL; P = .049), whereas the postoperative median residual tumor volume was not statistically significantly different between groups.

CONCLUSION: IoMRI enhances the extent of resection, particularly for nonenhancing gliomas.

5-ALA complete resections go beyond MR contrast enhancement

5-ALA complete resections go beyond MR contrast

Acta Neurochir (2014) 156:305–312

The technique of 5-aminolevulinic acid (5-ALA) tumor fluorescence is increasingly used to improve visualization of tumor tissue and thereby to increase the rate of patients with gross total resections. In this study, we measured the resection volumes in patients who underwent 5-ALA-guided surgery for non-eloquent glioblastoma and compared them with the preoperative tumor volume.

Methods We selected 13 patients who had received a complete resection according to intraoperative 5-ALA induced fluorescence and CRET according to post-operative T1 contrast-enhanced MRI. The volumes of pre-operative contrast enhancing tissue, post-operative resection cavity and resected tissue were determined through shift-corrected volumetric analysis.

Results The mean resection cavity (29 cm3) was marginally smaller than the pre-operative contrast-enhancing tumor (39 cm3, p =0.32). However, the mean overall resection volume (84 cm3) was significantly larger than the pre-operative contrast-enhancing tumor (39 cm3, p=0.0087). This yields a mean volume of resected 5-ALA positive, but radiological non-enhancing tissue of 45 cm3. The mean calculated rim of resected tissue surpassed pre-operative tumor diameter by 6 mm(range 0–10 mm).

Conclusions Results of the current study imply that (i) the resection cavity underestimates the volume of resected tissue and (ii) 5-ALA complete resections go significantly beyond the volume of pre-operative contrast-enhancing tumor bulk on MRI, indicating that 5-ALA also stains MRI non-enhancing tumor tissue. Use of 5-ALA may thus enable extension of coalescent tumor resection beyond radiologically evident tumor. The impact of this more extended resection method on time to progression and overall survival has not been determined, and potentially puts adjacent and functionally intact tissue at risk.

Insular low-grade glioma and postoperative seizure outcome

Surgery for insular low-grade glioma- predictors of postoperative seizure outcome

J Neurosurg 120:12–23, 2014

Although a number of recent studies on the surgical treatment of insular low-grade glioma (LGG) have demonstrated that aggressive resection leads to increased overall patient survival and decreased malignant progression, less attention has been given to the results with respect to tumor-related epilepsy. The aim of this investigation was to evaluate the impact of volumetric, histological, and intraoperative neurophysiological factors on seizure outcome in patients with insular LGG.

Methods. The authors evaluated predictors of seizure outcome with special emphasis on both the extent of tumor resection (EOR) and the tumor’s infiltrative pattern quantified by computing the difference between the preoperative T2- and T1-weighted MR images (DVT2T1) in 52 patients with preoperative drug-resistant epilepsy.

Results. The 12-month postoperative seizure outcome (Engel class) was as follows: seizure free (Class I), 67.31%; rare seizures (Class II), 7.69%; meaningful seizure improvement (Class III), 15.38%; and no improvement or worsening (Class IV), 9.62%. Poor seizure control was more common in patients with a longer preoperative seizure history (p < 0.002) and higher frequency of seizures (p = 0.008). Better seizure control was achieved in cases with EOR ≥ 90% (p < 0.001) and DVT2T1 < 30 cm3 (p < 0.001). In the final model, DVT2T1 proved to be the strongest independent predictor of seizure outcome in insular LGG patients (p < 0.0001).

Conclusions. No or little postoperative seizure improvement occurs mainly in cases with a prevalent infiltrative tumor growth pattern, expressed by high DVT2T1 values, which consequently reflects a smaller EOR.

The “onco-functional balance” in surgery for diffuse low-grade glioma

LGG

Acta Neurochir (2013) 155:951–957

Diffuse low-grade glioma (DLGG) is a growing pre-cancerous tumor, often diagnosed in patients with no or only mild deficit. Maximal and early surgical resection is currently the first therapeutic option, in order to delay the malignant transformation and thus increase the overall survival. Preserving the quality of life (QoL) is nonetheless another priority. Here, our purpose is to weight the value of the extent of resection versus the neurological worsening that could be voluntarily generated by a radical resection; that is, to study the “onco-functional balance” at the individual level.

To this end, we will examine DLGG involving the supplementary motor area and DLGG involving visual pathways. We will consider the benefit-risk ratio of different strategies of resection, according to the brain structures actually invaded and their plastic potential. The aim is to increase both the quantity of life and the time with a normal QoL, on the basis of strong interactions between the tumor course, brain reorganization and multistage surgical approach adapted to each patient over time.

To this end, beyond the conceptual and technical issues, the most important point remains the honest and unique relationship between the surgical oncologist and the patient, based on clear and complete information about the behavior of DLGG versus the expected medical and social consequences of a resection over years. In other words, in the era of “evidence-based medicine”, it is crucial to not forget “individual-based medicine” by offering tailored resections adapted to each patient.

Surgery of Insular Nonenhancing Gliomas: Volumetric Analysis of Tumoral Resection, Clinical Outcome, and Survival in a Consecutive Series of 66 Cases

Neurosurgery 70:1081–1094, 2012.  DOI: 10.1227/NEU.0b013e31823f5be5

Despite intraoperative technical improvements, the insula remains a challenging area for surgery because of its critical relationships with vascular and neurophysiological functional structures.
OBJECTIVE: To retrospectively investigate the morbidity profile in insular nonenhancing gliomas, with special emphasis on volumetric analysis of tumoral resection.

METHODS: From 2000 to 2010, 66 patients underwent surgery. All surgical procedures were conducted under cortical-subcortical stimulation and neurophysiological monitor- ing. Volumetric scan analysis was applied on T2-weighted magnetic resonance images (MRIs) to establish preoperative and postoperative tumoral volume.

RESULTS: The median preoperative tumor volume was 108 cm3. The median extent of resection was 80%. The median follow-up was 4.3 years. An immediate postoperative worsening was detected in 33.4% of cases; a definitive worsening resulted in 6% of cases. Patients with extent of resection of . 90% had an estimated 5-year overall survival rate of 92%, whereas those with extent of resection between 70% and 90% had a 5-year overall survival rate of 82% (P , .001). The difference between preoperative tumoral volumes on T2-weighted MRI and on postcontrast T1-weighted MRI ([T2 2 T1] MRI volume) was computed to evaluate the role of the diffusive tumoral growing pattern on overall survival. Patients with preoperative volumetric difference , 30 cm3 demonstrated a 5-year overall survival rate of 92%, whereas those with a difference of . 30 cm3 had a 5-year overall survival rate of 57% (P = .02).

CONCLUSION: With intraoperative cortico-subcortical mapping and neurophysiologi- cal monitoring, a major resection is possible with an acceptable risk and a significant result in the follow-up.

Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas

J Neurosurg 115:740–748, 2011. DOI: 10.3171/2011.6.JNS11252

Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5- ALA)–induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection.

Methods. Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence.

Results. Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses.

Conclusions. Intraoperative confocal microscopy can visualize cellular 5-ALA–induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors’ institution.

An extent of resection threshold for newly diagnosed glioblastomas

J Neurosurg 115:3–8, 2011. DOI: 10.3171/2011.2.JNS10998

The value of extent of resection (EOR) in improving survival in patients with glioblastoma multiforme (GBM) remains controversial. Specifically, it is unclear what proportion of contrast-enhancing tumor must be resected for a survival advantage and how much survival improves beyond this threshold. The authors attempt to define these values for the patient with newly diagnosed GBM in the modern neurosurgical era.

Methods. The authors identified 500 consecutive newly diagnosed patients with supratentorial GBM treated at the University of California, San Francisco between 1997 and 2009. Clinical, radiographic, and outcome parameters were measured for each case, including MR imaging–based volumetric tumor analysis.

Results. The patients had a median age of 60 years and presented with a median Karnofsky Performance Scale (KPS) score of 80. The mean clinical follow-up period was 15.3 months, and no patient was unaccounted for. All patients underwent resection followed by chemotherapy and radiation therapy. The median postoperative tumor volume was 2.3 cm3, equating to a 96% EOR. The median overall survival was 12.2 months. Using Cox proportional hazards analysis, age, KPS score, and EOR were predictive of survival (p < 0.0001). A significant survival advantage was seen with as little as 78% EOR, and stepwise improvement in survival was evident even in the 95%–100% EOR range. A recursive partitioning analysis validated these findings and provided additional risk stratification parameters related to age, EOR, and tumor burden.

Conclusions. For patients with newly diagnosed GBMs, aggressive EOR equates to improvement in overall survival, even at the highest levels of resection. Interestingly, subtotal resections as low as 78% also correspond to a survival benefit.