Category: Oncology

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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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A prospective randomized trial of the optimal dose of mannitol for intraoperative brain relaxation in patients undergoing craniotomy for supratentorial brain tumor resection

J Neurosurg 126:1839–1846, 2017

Mannitol is used intraoperatively to induce brain relaxation in patients undergoing supratentorial brain tumor resection. The authors sought to determine the dose of mannitol that provides adequate brain relaxation with the fewest adverse effects.

METHODS A total of 124 patients were randomized to receive mannitol at 0.25 g/kg (Group A), 0.5 g/kg (Group B), 1.0 g/kg (Group C), and 1.5 g/kg (Group D). The degree of brain relaxation was classified according to a 4-point scale (1, bulging; 2, firm; 3, adequate; and 4, perfectly relaxed) by neurosurgeons; Classes 3 and 4 were considered to indicate satisfactory brain relaxation. The osmolality gap (OG) and serum electrolytes were measured before and after mannitol administration.

RESULTS The brain relaxation score showed an increasing trend in patients receiving higher doses of mannitol (p = 0.005). The incidence of satisfactory brain relaxation was higher in Groups C and D than in Group A (67.7% and 64.5% vs 32.2%, p = 0.011 and 0.022, respectively). The incidence of OG greater than 10 mOsm/kg was also higher in Groups C and D than in Group A (100.0% in both groups vs 77.4%, p = 0.011 for both). The incidence of moderate hyponatremia (125 mmol/L ≤ Na+ < 130 mmol/L) was significantly higher in Group D than in other groups (38.7% vs 0.0%, 9.7%, and 12.9% in Groups A, B, and C; p < 0.001, p = 0.008, and p = 0.020, respectively). Hyperkalemia (K+ > 5.0 mmol/L) was observed in 12.9% of patients in Group D only.

CONCLUSIONS The higher doses of mannitol provided better brain relaxation but were associated with more adverse effects. Considering the balance between the benefits and risks of mannitol, the authors suggest the use of 1.0 g/kg of intraoperative mannitol for satisfactory brain relaxation with the fewest adverse effects.

Clinical trial registration no.: NCT02168075 (clinicaltrials.gov)

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Cyst Fluid From Cystic, Malignant Brain Tumors: A Reservoir of Nutrients, Including Growth Factor-Like Nutrients, for Tumor Cells

Neurosurgery 80:917–924, 2017

Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth.

OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors.

METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors.

RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = –0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 μmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5 -phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 μmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs.

CONCLUSION: Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid.

 

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A method for safely resecting anterior butterfly gliomas

J Neurosurg 126:1795–1811, 2017

Gliomas invading the anterior corpus callosum are commonly deemed unresectable due to an unacceptable risk/benefit ratio, including the risk of abulia. In this study, the authors investigated the anatomy of the cingulum and its connectivity within the default mode network (DMN). A technique is described involving awake subcortical mapping with higher attention tasks to preserve the cingulum and reduce the incidence of postoperative abulia for patients with so-called butterfly gliomas.

METHODS The authors reviewed clinical data on all patients undergoing glioma surgery performed by the senior author during a 4-year period at the University of Oklahoma Health Sciences Center. Forty patients were identified who underwent surgery for butterfly gliomas. Each patient was designated as having undergone surgery either with or without the use of awake subcortical mapping and preservation of the cingulum. Data recorded on these patients included the incidence of abulia/akinetic mutism. In the context of the study findings, the authors conducted a detailed anatomical study of the cingulum and its role within the DMN using postmortem fiber tract dissections of 10 cerebral hemispheres and in vivo diffusion tractography of 10 healthy subjects.

RESULTS Forty patients with butterfly gliomas were treated, 25 (62%) with standard surgical methods and 15 (38%) with awake subcortical mapping and preservation of the cingulum. One patient (1/15, 7%) experienced postoperative abulia following surgery with the cingulum-sparing technique. Greater than 90% resection was achieved in 13/15 (87%) of these patients.

CONCLUSIONS This study presents evidence that anterior butterfly gliomas can be safely removed using a novel, attention-task based, awake brain surgery technique that focuses on preserving the anatomical connectivity of the cingulum and relevant aspects of the cingulate gyrus.

 

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Degree of Vascular Encasement in Sphenoid Wing Meningiomas Predicts Postoperative Ischemic Complications

Neurosurgery 80:957–966, 2017

Sphenoid wing meningiomas (SWMs) can encase arteries of the circle of Willis, increasing their susceptibility to intraoperative vascular injury and severe ischemic complications.

OBJECTIVE: To demonstrate the effect of circumferential vascular encasement in SWM on postoperative ischemia.

METHODS: A retrospective review of 75 patients surgically treated for SWM from 2009 to 2015 was undertaken to determine the degree of circumferential vascular encasement (0◦-360◦) as assessed by preoperativemagnetic resonance imaging (MRI). A novel grading system describing “maximum”and “total” arterial encasement scores was created. Postoperative MRIs were reviewed for total ischemia volume measured on sequential diffusionweighted images.

RESULTS: Of the 75 patients, 89.3% had some degree of vascular involvement with a median maximum encasement score of 3.0 (2.0-3.0) in the internal carotid artery (ICA), M1, M2, and A1 segments; 76% of patients had some degree of ischemia with median infarct volume of 3.75 cm3 (0.81-9.3 cm3). Univariate analysis determined risk factors associated with larger infarction volume, which were encasement of the supraclinoid ICA (P < .001), M1 segment (P < .001), A1 segment (P = .015), and diabetes (P = .019). As the maximum encasement score increased from 1 to 5 in each of the significant arterial segments, so did mean and median infarction volume (P < .001). Risk for devastating ischemic injury >62 cm3 was found when the ICA, M1, and A1 vessels all had ≥360◦ involvement (P = .001). Residual tumorwas associated with smaller infarct volumes (P=.022). As infarction volume increased, so did modified Rankin Score at discharge (P = .025).

CONCLUSION: Subtotal resection should be considered in SWM with significant vascular encasement of proximal arteries to limit postoperative ischemic complications.

 

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Putamen involvement and survival outcomes in patients with insular low-grade gliomas

J Neurosurg 126:1788–1794, 2017

Insular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system’s association with survival outcome.

METHODS A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil’s classification, was examined using multivariate analyses.

RESULTS Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil’s classification.

CONCLUSIONS The current study’s findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.

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Cystic Craniopharyngiomas: Microsurgical or Stereotactic Treatment?

Neurosurgery (2017) 80 (5): 733-743

Prognosis and treatment of cystic craniopharyngiomas are poorly defined.

OBJECTIVE: To analyze progression-free survival (PFS) and safety profile of cystic craniopharyngiomas undergoing resection or minimally invasive drainage procedures. We compared further outcome measurements for cystic and solid tumors undergoing resection to elucidate the impact of the initial tumor composition on both PFS and the toxicity profile.

METHODS: All patients with craniopharyngiomas consecutively treated between 1999 and 2014 were included. A treatment decision in favor of microsurgery or stereotactic treatment was made interdisciplinarily. For stereotactic drainage, a catheter was implanted, allowing both permanent upstream (into ventricular spaces) and downstream (into prepontine cistern) drainage. Study endpoints were tumor progression, functional outcome, and treatment toxicity. Functional endocrinological and visual outcome analyses referred to data obtained preoperatively and 6 weeks after treatment. The Kaplan-Meier method was used for survival analysis. Prognostic factors were obtained from proportional hazard models.

RESULTS: Seventy-nine patients were included. The distribution of clinical and tumor-related data was well balanced among patients with solid (n = 35) and cystic (n = 44) tumors and those undergoing microsurgical or stereotactic treatment. Cystic tumors had shorter PFS (5-year PFS: 53.6% vs 66.8%, P= .10) and needed significantly more therapeutic interventions, which was independent of the initial treatment mode. The endocrinological deterioration rate was high for both solid and cystic tumors after microsurgery (59.4% and 85.7%, respectively), whereas it was significantly lower for cystic tumors undergoing stereotactic treatment (23.1%, P < .001).

CONCLUSION: Stereotactic bidirectional drainage of cystic craniopharyngiomas is effective and provides a better endocrinological outcome than conventional microsurgery.

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Craniotomy for perisellar meningiomas: comparison of simple (appropriate for endoscopic approach) versus complex anatomy and surgical outcomes

J Neurosurg 126:1191–1200, 2017

Microsurgical resection of perisellar meningiomas has remained the gold standard for treatment, with extended endoscopic endonasal surgery emerging as a viable alternative. Historical microsurgical series do not distinguish based on tumor anatomy, but are being used as a comparison against endonasal surgery. In this study, the authors retrospectively reviewed and compared the anatomy of perisellar meningiomas seen at their institution. The tumors were separated into 2 groups based on whether they would be appropriate for endoscopic resection, and the authors compared the surgical outcomes.

METHODS Between 2001 and 2013, 53 patients (73.6% women) with perisellar meningiomas underwent open microsurgical resection at Vancouver General Hospital performed by the senior author (R.A.). These tumors were separated into 2 groups based on their anatomy, and the authors analyzed the resection rates, surgical results, patient quality of life, and complications.

RESULTS Among the 53 patients who presented with perisellar meningiomas, the authors were able to identify 18 lesions with “simple” anatomy suitable for endoscopic resection and 35 lesions with “complex” anatomy suitable for craniotomy resection. The mean age of patients in the study cohort was 57.4 years (range 33–91 years), and most patients presented with visual loss (68.0%) and visual field restriction (64.2%). There were no major differences in patient demographic data between the 2 groups. Patients with simple anatomy had smaller lesions (2.1 vs 3.5 cm; p = 0.004), no optic canal invasion (89% vs 26%; p < 0.0001), minimal vascular encasement (cortical cuff 83% vs 9%; p < 0.0001), and a rounded tumor shape (100% vs 31.8%; p = 0.0001) when compared with those with complex anatomy. The majority of lesions originated from the tuberculum sellae and planum sphenoidale. A greater degree of resection was achieved in the favorable anatomy group (99% vs 87.1%; p < 0.0001). Vision was improved or normalized in 96.6% of patients. Patients in the cohort with complex anatomy had more transient complications; there were no incidents of surgical-site infection, meningitis, or death in this series. One patient who underwent removal of a recurrent lesion experienced a CSF leak that required endoscopic repair. The overall persisting complications rate was higher in the group with complex anatomy (11.1% vs 37.1%; p = 0.0498); overall, 28.3% of patients experienced disabling complications. Patient-perceived quality of life improved in the simple anatomy group following surgery (DSF-36 +16.6 vs -8.4; p = 0.0045).

CONCLUSIONS Extended endoscopic surgery is emerging as a viable alternative to microsurgical resection of perisellar meningiomas. The authors identified 2 patient groups based on tumor anatomy, with distinctly separate surgical outcomes. In the future, patients considered for endoscopic resection should be compared against the surgical group with simple anatomy that includes smaller tumors, no vascular encasement, and limited optic canal invasion.

 

 

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Surgery for meningioma in the elderly and long-term survival

J Neurosurg 126:1201–1211, 2017

The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population.

METHODS Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into “elderly” (age ≥ 65 years, n = 162) and “younger” (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population.

RESULTS The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. Highgrade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75–8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70–1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23–144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23–50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross-total resection than after subtotal resection (HR 2.7, 95% CI 1.09–6.69; p = 0.032).

CONCLUSIONS Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society.

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Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy

Neurosurgery 80:635–645, 2017

Diffuse low-grade gliomas (DLGGs) represent several pathological entities that infiltrate and invade cortical and subcortical structures in the brain.

OBJECTIVE: To describe methods for rapid prototyping of DLGGs and surgically relevant anatomy.

METHODS: Using high-definition imaging data and rapid prototyping technologies, we were able to generate 3 patient DLGGs to scale and represent the associated whitematter tracts in 3 dimensions using advanced diffusion tensor imaging techniques.

RESULTS: This report represents a novel application of 3-dimensional (3-D) printing in neurosurgery and a means to model individualized tumors in 3-D space with respect to subcorticalwhite matter tract anatomy. Faculty and resident evaluations of this technology were favorable at our institution.

CONCLUSION: Developing an understanding of the anatomic relationships existing within individuals is fundamental to successful neurosurgical therapy. Imaging-based rapid prototyping may improve on our ability to plan for and treat complex neuro-oncologic pathology.

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Three-Dimensional Printed Modeling of Diffuse Low-Grade Gliomas and Associated White Matter Tract Anatomy

Neurosurgery 80:635–645, 2017

Diffuse low-grade gliomas (DLGGs) represent several pathological entities that infiltrate and invade cortical and subcortical structures in the brain.

OBJECTIVE: To describe methods for rapid prototyping of DLGGs and surgically relevant anatomy.

METHODS: Using high-definition imaging data and rapid prototyping technologies, we were able to generate 3 patient DLGGs to scale and represent the associated whitematter tracts in 3 dimensions using advanced diffusion tensor imaging techniques.

RESULTS: This report represents a novel application of 3-dimensional (3-D) printing in neurosurgery and a means to model individualized tumors in 3-D space with respect to subcorticalwhite matter tract anatomy. Faculty and resident evaluations of this technology were favorable at our institution.

CONCLUSION: Developing an understanding of the anatomic relationships existing within individuals is fundamental to successful neurosurgical therapy. Imaging-based rapid prototyping may improve on our ability to plan for and treat complex neuro-oncologic pathology.

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Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome

Acta Neurochir (2017) 159:435–445

Tumour growth has been used to successfully predict progression-free survival in low-grade glioma. This systematic review sought to establish the evidence base regarding the correlation of volumetric growth rates with histological diagnosis and potential to predict clinical outcome in patients with meningioma.

Methods This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Databases were searched for full text English articles analysing volumetric growth rates in patients with a meningioma.

Results Four retrospective cohort studies were accepted, demonstrating limited evidence of significantly different tumour doubling rates and shapes of growth curves between benign and atypical meningiomas. Heterogeneity of patient characteristics and timing of volumetric assessment, both pre- and post-operatively, limited pooled analysis of the data. No studies performed statistical analysis to demonstrate the clinical utility of growth rates in predicting clinical outcome.

Conclusion This systematic review provides limited evidence in support of the use of volumetric growth rates in meningioma to predict histological diagnosis and clinical outcome to guide future monitoring and treatment.

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Surgical treatment of brain metastases in the central region

J Neurosurg 126:698–707, 2017

Brain metastases are the most frequent intracranial malignant tumor in adults. Surgical intervention for metastases in eloquent areas remains controversial and challenging. Even when metastases are not in ltrating intra- parenchymal tumors, eloquent areas can be affected. Therefore, this study aimed to describe the role of a functional guided approach for the resection of brain metastases in the central region.

METHODS Thirty-three patients (19 men and 14 women) with perirolandic metastases who were treated at the authors’ institution were reviewed. All participants underwent resection using a functional guided approach, which consisted of using intraoperative brain mapping and/or neurophysiological monitoring to aid in the resection, depending on the functionality of the brain parenchyma surrounding each metastasis. Motor and sensory functions were monitored in all patients, and supplementary motor and language area functions were assessed in 5 and 4 patients, respectively. Clinical data were analyzed at presentation, discharge, and the 6-month follow-up.

RESULTS The most frequent presenting symptom was seizure, followed by paresis. Gross-total removal of the metastasis was achieved in 31 patients (93.9%). There were 6 deaths during the follow-up period. After the removal of the metastasis, 6 patients (18.2%) presented with transient neurological worsening, of whom 4 had worsening of motor function impairment and 2 had acquired new sensory disturbances. Total recovery was achieved before the 3rd month of follow-up in all cases. Excluding those patients who died due to the progression of systemic illness, 88.9% of patients had a Karnofsky Performance Scale score greater than 80% at the 6-month follow-up. The mean survival time was 24.4 months after surgery.

CONCLUSIONS The implementation of intraoperative electrical brain stimulation techniques in the resection of central region metastases may improve surgical planning and resection and may spare eloquent areas. This approach also facilitates maximal resection in these and other critical functional areas, thereby helping to avoid new postoperative neurological deficits. Avoiding permanent neurological de cits is critical for a good quality of life, especially in patients with a life expectancy of over a year.

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Foramen magnum meningiomas: surgical results and risks predicting poor outcomes based on a modified classification

J Neurosurg 126:661–676, 2017

This study aimed to evaluate neurological function and progression/recurrence (P/R) outcome of foramen magnum meningioma (FMM) based on a modified classification.

METHODS This study included 185 consecutive patients harboring FMMs (mean age 49.4 years; 124 females). The authors classified the FMMs into 4 types according to the previous classification of Bruneau and George as follows: Type A (n = 49, 26.5%), the dural attachment of the lesion grows below the vertebral artery (VA); Type B (n = 39, 21.1%), the dural attachment of the lesion grows above the VA; Type C1 (n = 84, 45.4%), the VA courses across the lesion with or without VA encasement or large lesions grow both above and below the bilateral VA; and Type C2 (n = 13, 7.0%), Type C1 plus partial/total encasement of the VA and extradural growth.

RESULTS The median preoperative Karnofsky Performance Scale (KPS) score was 80. Gross-total resection (GTR) was achieved in 154 patients (83.2%). Lower cranial nerve morbidity was lowest in Type A lesions (16.3%). Type C2 lesions were inherently larger (p = 0.001), had a greater percentage of ventrolateral location (p = 0.009) and VA encase-ment (p < 0.001), lower GTR rate (p < 0.001), longer surgical duration (p = 0.015), higher morbidity (38.5%), higher P/R rate (30.8%, p = 0.009), and poorer recent KPS score compared with other types. After a mean follow-up duration of 110.3 months, the most recent follow-up data were obtained in 163 patients (88.1%). P/R was observed in 13 patients (7.2%). The median follow-up KPS score was 90. Compared with preoperative status, recent neurological status was improved in 91 (49.2%), stabilized in 76 (41.1%), and worsened in 18 (9.7%) patients. The multivariate Cox proportional hazard regression model demonstrated Type C2 (HR 3.94, 95% CI 1.04–15.0, p = 0.044), nontotal resection (HR 6.30, 95% CI 1.91–20.8, p = 0.003), and pathological mitosis (HR 7.11, 95% CI 1.96–25.8, p = 0.003) as independent adverse predictors for tumor P/R. Multivariate logistic regression analysis identified nontotal resection (OR 4.06, 95% CI 1.16–14.2, p = 0.029) and pathological mitosis (OR 6.29, 95% CI 1.47–27.0, p = 0.013) as independent risks for poor outcome (KPS score < 80).

CONCLUSIONS The modified classification helped to predict surgical outcome and P/R in addition to the position of the lower cranial nerves. Preoperative imaging studies and neurological function should be reviewed carefully to establish an individualized management strategy to improve long-term outcome.

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The new WHO 2016 classification of brain tumors

Acta Neurochir (2017) 159:403–418

The understanding of molecular alterations of tumors has severely changed the concept of classification in all fields of pathology. The availability of high-throughput technologies such as next-generation sequencing allows for a much more precise definition of tumor entities. Also in the field of brain tumors a dramatic increase of knowledge has occurred over the last years partially calling into question the purely morphologically based concepts that were used as exclusive defining criteria in the WHO 2007 classification.

Methods Review of the WHO 2016 classification of brain tumors as well as a search and review of publications in the liter- ature relevant for brain tumor classification from 2007 up to now.

Results The idea of incorporating the molecular features in classifying tumors of the central nervous system led the authors of the new WHO 2016 classification to encounter inevitable conceptual problems, particularly with respect to linking morphology to molecular alterations. As a solution they introduced the concept of a “layered diagnosis” to the classification of brain tumors that still allows at a lower level a purely morphologically based diagnosis while partially forcing the incorporation of molecular characteristics for an “integrated diagnosis” at the highest diagnostic level. In this context the broad availability of molecular assays was debated. On the one hand molecular antibodies specifically targeting mutated proteins should be available in nearly all neuropathological laboratories. On the other hand, different high-throughput assays are
accessible only in few first-world neuropathological institutions. As examples oligodendrogliomas are now primarily defined by molecular characteristics since the required assays are generally established, whereas molecular grouping of ependymomas, found to clearly outperform morphologically based tumor interpretation, was rejected from inclusion in the WHO 2016 classification because the required assays are currently only established in a small number of institutions.

Conclusion In summary, while neuropathologists have now encountered various challenges in the transitional phase from the previous WHO 2007 version to the new WHO 2016 clas- sification of brain tumors, clinical neurooncologists now face many new diagnoses allowing a clearly improved understand- ing that could offer them more effective therapeutic opportu- nities in neurooncological treatment. The new WHO 2016 classification presumably presents the highest number of modifications since the initial WHO classification of 1979 and there- by forces all professionals in the field of neurooncology to intensively understand the new concepts. This review article aims to present the basic concepts of the new WHO 2016 brain tumor classification for neurosurgeons with a focus on neurooncology.

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The Impact of Intracranial Tumor Proximity to White Matter Tracts on Morbidity and Mortality

Neurosurgery 80:193–200, 2017

Using difusion tensor imaging (DTI) in neurosurgical planning allows identification of white matter tracts and has been associated with a reduction in postoperative functional deficits.
OBJECTIVE: This study explores the relationship between the lesion-to-tract distance (LTD) and postoperative morbidity and mortality in patients with brain tumors in order to evaluate the role of DTI in predicting postoperative outcomes.

METHODS: Adult patients with brain tumors (n = 60) underwent preoperative DTI. Three major white matter pathways (superior longitudinal fasciculi [SLF], cingulum, and corticospinal tract) were identified using DTI images, and the shortest LTD was measured for each tract. Postoperative morbidity and mortality information was collected from electronic medical records.

RESULTS: The ipsilesional corticospinal tract LTD and left SLF LTD were significantly associated with the occurrence rate of total postoperative motor (P = .018) and language (P < .001) deficits, respectively. The left SLF LTD was also significantly associated with the occurrence rate of new postoperative language deficits (P = .003), and the LTD threshold that best predicted this occurrence was 1 cm (P < .001). Kaplan–Meier log-rank survival analyses in patients having high-grade tumors demonstrated a significantly higher mortality for patients with a left SLF LTD <1 cm (P = .01).

CONCLUSION: Measuring tumor proximity to major white matter tracts using DTI can inform clinicians of the likelihood of postoperative functional deficits. A distance of 1 cm or less from eloquent white matter structures most significantly predicts the occurrence of new deficits with current surgical and imaging techniques.

 

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The Fluoropen: a simple low-cost device to detect intraoperative fluorescein fluorescence in stereotactic needle biopsy of brain tumors

Acta Neurochir (2017) 159:371–375

The use of fluorescein fluorescence-guided stereotactic needle biopsy has been shown to improve diagnostic accuracy and to expedite operative procedure in the stereotactic needle biopsy of high-grade gliomas. We developed a device (Fluoropen) for detecting fluorescence in brain tumor tissues obtained by fluorescein fluorescence-guided stereotactic needle biopsy.

Methods: The Fluoropen is a device consisting of a light source fitted with color filters to create the required emission and visualization wavelengths. The proof-of-concept study consisted of four consecutive patients who underwent fluorescein fluorescence-guided frameless stereotactic biopsy of brain tumor. Each sample was examined for the presence of fluorescence using the Fluoropen and compared with a microscope with fluorescence visualization capability.

Results: A total of six samples were obtained from four stereotactic needle biopsy procedures. Four out of five samples (80%) taken from the contrast-enhancing part of the tumors were shown to be fluorescent under the microscope fitted with fluorescence module and the Fluoropen. One non-contrast enhancing lesion was non-fluorescent using both the microscope fitted with fluorescence module and the Fluoropen. The Fluoropen was shown to have 100% concordance with the microscope fitted with fluorescence module.

Conclusions: The Fluoropen is a low-cost and simple standalone device for the detection of fluorescein fluorescence that can expedite stereotactic needle biopsy by providing instant confirmation of the diagnostic sample and therefore avoid the need for an intraoperative frozen section. In patients with non-contrast enhancing tumors and those who were pre-treated with dexamethasone prior to surgery, fluorescein fluorescence-guided stereotactic needle biopsy will need to be used with caution.

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Fluorescein sodium-guided resection of cerebral metastases

Acta Neurochir (2017) 159:363–367

Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identifi- cation of tumor tissue. In 2012, we started evaluating fluores- cein (FL) with the dedicated microscope filter in cerebral me- tastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients.

Methods: Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25–85 years); 5 mg/kg bodyweight of FL was intrave- nously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events.

Results: Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL stain- ing. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course.

Conclusions: FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

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Cushing’s disease: pathobiology, diagnosis, and management

J Neurosurg 126:404–417, 2017

Cushing’s disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol.
The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function.
Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the current pathophysiological principles, diagnostic methods, and management of CD.
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Efficacy of the transtemporal approach with awake brain mapping to reach the dominant posteromedial temporal lesions

Acta Neurochir (2017) 159: 177

Surgeries for lesions in the dominant hippocampal and parahippocampal gyrus involving the posteromedial temporal regions are challenging to perform because they are located close to Wernicke’s area; white matter fibers related with language; the optic radiations; and critical neurovascular structures. We performed a transtemporal approach with awake functional mapping for lesions affecting the dominant posteromedial temporal regions. The aim of this study was to assess the feasibility, safety, and efficacy of awake craniotomy for these lesions.

Methods: We retrospectively reviewed four consecutive patients with tumors or cavernous angiomas located in the left hippocampal and parahippocampal gyrus, which further extended to the posteromedial temporal regions, who underwent awake surgery between December 2014 and January 2016.

Results: Four patients with lesions associated with the left hippocampal and parahippocampal gyrus, including the posteromedial temporal area, who underwent awake surgery were registered in the study. In all four patients, cortical and subcortical eloquent areas were identified via direct electrical stimulation. This allowed determination of the optimal surgical route to the angioma or tumor, even in the language-dominant hippocampal and parahippocampal gyrus. In particular, this approach enabled access to the upper part of posteromedial temporal lesions, while protecting the subcortical language-related fibers, such as the superior longitudinal fasciculus.

Conclusions: This study revealed that awake brain mapping can enable the safe resection of dominant posteromedial temporal lesions, while protecting cortical and subcortical eloquent areas. Furthermore, our experience with four patients demonstrates the feasibility, safety, and efficacy of awake surgery for these lesions.

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