Tag: Oncology

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Predictive value of intraoperative 5-aminolevulinic acid–induced fluorescence for detecting bone invasion in meningioma surgery

Predictive value of intraoperative 5-aminolevulinic

J Neurosurg 120:840–845, 2014

Bone invasion is a major concern in meningioma surgery, since it is predictive of the recurrence of cranial involvement, morbidity, and mortality. Bone invasion has been reported in 20%–68% of studies with histopathologically confirmed data. Unfortunately, radical resection of bone invasion remains challenging. The aim of this study was to assess the role of 5-aminolevulinic acid (5-ALA) fluorescence in guiding the resection of bone-invading meningiomas. To this purpose, the sensitivity, specificity, and positive and negative predictive values of 5-ALA in detecting meningioma bone invasion were evaluated.

Methods. Data from 12 patients affected by bone-invading meningiomas (7 with skull base and 5 with convexity meningiomas) who had undergone surgery with the assistance of 5-ALA fluorescence and neuronavigation between July 2012 and March 2013 at the Department of Neurosurgery of Padua were retrospectively analyzed. To evaluate the sensitivity and specificity of 5-ALA fluorescence in detecting meningioma tissue, a pathologist analyzed 98 surgical bone samples under blue light, according to different fluorescence patterns. Magnetic resonance images and CT scans were obtained pre- and postoperatively to determine the extent of bone invasion resection.

Results. The rate of 5-ALA–induced fluorescence of both tumor and bone invasion was 100%. Based on the pathological examination of bone specimens, 5-ALA presented a sensitivity of 89.06% (95% CI 81.41%–96.71%) and a specificity of 100% in detecting meningioma bone invasion, while the positive and negative predictive values were 100% and 82.93% (95% CI 71.41%–94.45%), respectively. At the postoperative stage, MRI did not detect cases of meningioma bone invasion, whereas CT scans revealed residual hyperostosis in 2 cases.

Conclusions. In summary, 5-ALA fluorescence represents a suitable and reliable technique for identifying and removing bone infiltration by meningiomas. However, further studies are needed to prove the clinical consequences of this promising technique in a larger population.

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Conus medullaris and cauda equina tumors

Conus and cauda equina tumors

J Neurosurg Spine 20:335–343, 2014

Intradural cauda equina and conus medullaris tumors (CECMTs) are rare. Only a few large clinical series exist to date. Therefore, clinical symptoms, surgical complications, and outcomes are poorly understood. The aim of the present study was to evaluate outcome after surgery of CECMTs and to identify the factors associated with a worse clinical prognosis based on the results of a series with sufficiently high number of cases.

Methods. All cases of intradural CECMTs treated surgically at the authors’ department between March 2006 and May 2012 were retrospectively evaluated. Arachnoid cysts and multifocal tumors were excluded. Sixty-eight adult patients met the inclusion criteria (35 female and 33 male patients; median age 56 years). Follow-up data were available for 72% (n = 49) in a median period of 9 months.

Results. Overall, 18 tumors were located intramedullary and 50 extramedullary. The majority were nerve sheath tumors (n = 27), ependymomas (n = 17), and meningiomas (n = 9). The most common preoperative symptom was pain. The rate of new transient postoperative impairment was 18% (n = 12), and new permanent deficits were observed in only 6% (n = 4). Overall neurological improvement was achieved in 62%. The reversibility of preoperative symptoms was related to the interval between the time of symptom onset and the time of surgery and to the presence of preoperative neurological deficits. Surgery of ependymoma and carcinoma metastases was associated with a higher rate of morbidity.

Conclusions. Intradural CECMTs present as a group of tumors with varying histological features and clinical symptoms. Symptomatic manifestation is usually unspecific, mimicking degenerative lumbar spine syndromes. Despite a significant risk of transient deterioration, early surgery is advisable because more than 94% of patients maintain at least their preoperative status and more than 60% improve during follow-up. The reversibility of preoperative symptoms is related to the duration between symptom onset and surgery and to the presence of preoperative neurological deficits. The prognosis for recovery from cauda equina or conus medullaris syndrome is less favorable than for other deficits. Surgery of ependymoma is associated with a higher morbidity rate than other benign entities.

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Microsurgical resection of extensive craniopharyngiomas using a frontolateral approach

Microsurgical resection of extensive craniopharyngiomas using a frontolateral approach

J Neurosurg 120:559–570, 2014

An extensive craniopharyngioma is a tumor that extends into multiple compartments (subarachnoid spaces) and attains a size larger than 4 cm. A wide spectrum of approaches and strategies has been used for resection of such craniopharyngiomas. In this report the authors focused on the feasibility and efficacy of microsurgical resection of extensive craniopharyngiomas using a frontolateral approach.

Methods. A retrospective analysis was performed on 16 patients with extensive craniopharyngiomas who underwent operations using a frontolateral approach at one institution. The preoperative and postoperative clinical and radiological data, as well as the operative videos, were reviewed. The main focus of the review was the extent of radical tumor removal, early postoperative outcome, and approach-related complications.

Results. Gross-total resection of craniopharyngioma was achieved in 14 (87.5%) of 16 cases. Early after surgery (within 3 months), 1 patient showed improvement in hormonal status, while in the remaining 15 patients it worsened. No major neurological morbidity was observed. Two patients experienced temporary psychotic disorders. Visual function improved in 6 patients and remained unchanged in 9. One patient experienced a new bitemporal hemianopsia. Three patients with features of short-term memory disturbances at presentation did show improvement after surgery. There were no deaths or significant approach-related morbidity in this patient series. Only 1 patient required revision surgery for a CSF leak.

Conclusions. The safe and simple frontolateral approach provides adequate access even to extensive craniopharyngiomas and enables their complete removal with a reasonable morbidity and approach-related complication rate.

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True petroclival meningiomas

True petroclival meningiomas- results of surgical management

J Neurosurg 120:40–51, 2014

The relentless natural progression of petroclival meningiomas mandates their treatment. The management of these tumors, however, is challenging. Among the issues debated are goals of treatment, outcomes, and quality of life, appropriate extent of surgical removal, the role of skull base approaches, and the efficacy of combined decompressive surgery and radiosurgery. The authors report on the outcome in a series of patients treated with the goal of total removal.

Methods. The authors conducted a retrospective analysis of 64 cases of petroclival meningiomas operated on by the senior author (O.A.) from 1988 to 2012, strictly defined as those originating medial to the fifth cranial nerve on the upper two-thirds of the clivus. The patients’ average age was 49 years; the average tumor size (maximum diameter) was 35.48 ± 10.09 mm (with 59 tumors > 20 mm), and cavernous sinus extension was present in 39 patients. The mean duration of follow-up was 71.57 months (range 4–276 months).

Results. In 42 patients, the operative reports allowed the grading of resection. Grade I resection (tumor, dura, and bone) was achieved in 17 patients (40.4%); there was no recurrence in this group (p = 0.0045). Grade II (tumor, dura) was achieved in 15 patients (36%). There was a statistically significant difference in the rate of recurrence with respect to resection grade (Grades I and II vs other grades, p = 0.0052). In all patients, tumor removal was classified based on postoperative contrast-enhanced MRI, and gross-total resection (GTR) was considered to be achieved if there was no enhancement present; on this basis, GTR was achieved in 41 (64%) of 64 patients, with a significantly lower recurrence rate in these patients than in the group with residual enhancement (p = 0.00348). One patient died from pulmonary embolism after discharge. The mean Karnofsky Performance Status (KPS) score was 85.31 preoperatively (median 90) and improved on follow-up to 88, with 30 patients (47%) having an improved KPS score on follow-up. Three patients suffered a permanent deficit that significantly affected their KPS. Cerebrospinal fluid leak occurred in 8 patients (12.5%), with 2 of them requiring exploration. Eighty-nine percent of the patients had cranial nerve deficits on presentation; of the 54 patients with more than 2 months of follow-up, 21 (32.8%) had persisting cranial nerve deficits. The overall odds of permanent cranial nerve deficit of treated petroclival meningioma was 6.2%. There was no difference with respect to immediate postoperative cranial nerve deficit in patients who had GTR compared with those who had subtotal resection.

Conclusions. Total removal (Grade I or II resection) of petroclival meningiomas is achievable in 76.4% of cases and is facilitated by the use of skull base approaches, with good outcome and functional status. In cases in which circumstances prevent total removal, residual tumors can be followed until progression is evident, at which point further intervention can be planned.

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Transpetrosal approach for challenging craniopharyngiomas

Transpetrosal approach for challenging craniopharyngiomas

J Neurosurg 120:1–11, 2014

Retrochiasmatic craniopharyngiomas are surgically challenging tumors. Retrochiasmatic craniopharyngiomas with complicated conditions such as large diameter, major calcification, or significant extension to the third ventricle or posterior fossa present surgical challenges; moreover, recurrent retrochiasmatic craniopharyngiomas are particularly formidable challenges. Although the transpetrosal approach to retrochiasmatic craniopharyngiomas published by Hakuba in 1985 can provide unique advantageous exposure of the retrochiasmatic area to allow safe neurovascular dissection and facilitate radical tumor removal, the procedure is viewed as complicated and time consuming and has a high risk of damaging hearing functions. The authors have modified Hakuba’s technique to minimize petrosectomy and reduce surgical complications and have applied this modified approach to retrochiasmatic craniopharyngiomas with complicated conditions. In this study, the authors describe their technique and surgical outcomes to elucidate the role of this modified transpetrosal approach for retrochiasmatic craniopharyngiomas with complicated conditions. This is the first study to report surgical outcomes of the transpetrosal approach for retrochiasmatic craniopharyngiomas.

Methods. Between 1999 and 2011, the minimum anterior and posterior combined (MAPC) transpetrosal approach, which is a modification of Hakuba’s transpetrosal approach, was applied in 16 cases of retrochiasmatic craniopharyngiomas with complicated conditions. Eight cases were recurrent tumors, 4 had previously received radiotherapy, 11 had a large diameter, 10 had large calcification, 15 had superior extension of the tumor into the third ventricle, and 10 had a posterior extension of the tumor that compressed the midbrain and pons. In all 16 patients, more than 2 of these complicated conditions were present. The follow-up duration ranged from 0.8 to 12.5 years (mean 5.3 years). Surgical outcomes assessed were the extent of resection, surgical complications, visual function, endocrinological status, and neuropsychological function. Five-year and 10-year recurrence-free survival rates were also calculated.

Results. Gross-total or near-total resection was achieved in 15 cases (93.8%). Facial nerve function was completely maintained in all 16 patients. Serviceable hearing was preserved in 15 cases (93.8%). Visual function improved in 13 out of 14 cases (92.9%) that had visual disturbance before surgery. None of the patients experienced deterioration of their visual function. Twelve cases had endocrinological deficit and received hormonal replacement before surgery. New endocrinological deficit occurred in 2 cases (12.5%). Neuropsychological function was maintained in 14 cases (87.5%) and improved in 1 case (6.3%). One case that had received previous conventional radiotherapy treatment showed a gradual decline in neuropsychological function. The 5-year and 10-year recurrence-free survival rates were both 86.5%.

Conclusions. The authors obtained good results by using the MAPC transpetrosal approach for the removal of retrochiasmatic craniopharyngiomas with complicated conditions. The MAPC transpetrosal approach should be considered as a therapeutic option for selected cases of retrochiasmatic craniopharyngiomas with complicated conditions.

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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.

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Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson Grade IV resection

Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson Grade IV resection

J Neurosurg 119:1373–1379, 2013

Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrencefree survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection.

Methods. This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth.

Results. A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm3 or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [HR] 6.42, 95% CI 1.41–45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18–218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm3 or more was not a statistically significant risk factor.

Conclusions. Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.

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Intraoperative optical imaging for functional mapping

Intraoperative optical imaging for functional mapping

J Neurosurg 119:853–863, 2013

Intraoperative optical imaging (IOI) is an experimental technique used for visualizing functional brain areas after surgical exposure of the cerebral cortex. This technique identifies areas of local changes in blood volume and oxygenation caused by stimulation of specific brain functions. The authors describe a new IOI method, including innovative data analysis, that can facilitate intraoperative functional imaging on a routine basis. To evaluate the reliability and validity of this approach, they used the new IOI method to demonstrate visualization of the median nerve area of the somatosensory cortex.

Methods. In 41 patients with tumor lesions adjacent to the postcentral gyrus, lesions were surgically removed by using IOI during stimulation of the contralateral median nerve. Optical properties of the cortical tissue were measured with a sensitive camera system connected to a surgical microscope. Imaging was performed by using 9 cycles of alternating prolonged stimulation and rest periods of 30 seconds. Intraoperative optical imaging was based on blood volume changes detected by using a filter at an isosbestic wavelength (delta = 568 nm). A spectral analysis algorithm was used to improve computation of the activity maps. Movement artifacts were compensated for by an elastic registration algorithm. For validation, intraoperative conduction of the phase reversal over the central sulcus and postoperative evaluation of the craniotomy site were used.

Results. The new method and analysis enabled significant differentiation (p < 0.005) between functional and nonfunctional tissue. The identification and visualization of functionally intact somatosensory cortex was highly reliable; sensitivity was 94.4% and specificity was almost 100%. The surgeon was provided with a 2D high-resolution activity map within 12 minutes. No method-related side effects occurred in any of the 41 patients.

Conclusions. The authors’ new approach makes IOI a contact-free and label-free optical technique that can be used safely in a routine clinical setup. Intraoperative optical imaging can be used as an alternative to other methods for the identification of sensory cortex areas and offers the added benefit of a high-resolution map of functional activity. It has great potential for visualizing and monitoring additional specific functional brain areas such as the visual, motor, and speech cortex. A prospective national multicenter clinical trial is currently being planned.

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Displacement of mammillary bodies by craniopharyngiomas involving the third ventricle

Displacement of mammillary bodies by craniopharyngiomas involving the third ventricle- surgical-MRI correlation and use in topographical diagnosis

J Neurosurg 119:381–405, 2013

Accurate diagnosis of the topographical relationships of craniopharyngiomas (CPs) involving the third ventricle and/or hypothalamus remains a challenging issue that critically influences the prediction of risks associated with their radical surgical removal. This study evaluates the diagnostic accuracy of MRI to define the precise topographical relationships between intraventricular CPs, the third ventricle, and the hypothalamus.

Methods. An extensive retrospective review of well-described CPs reported in the MRI era between 1990 and 2009 yielded 875 lesions largely or wholly involving the third ventricle. Craniopharyngiomas with midsagittal and coronal preoperative and postoperative MRI studies, in addition to detailed descriptions of clinical and surgical findings, were selected from this database (n = 130). The position of the CP and the morphological distortions caused by the tumor on the sella turcica, suprasellar cistern, optic chiasm, pituitary stalk, and third ventricle floor, including the infundibulum, tuber cinereum, and mammillary bodies (MBs), were analyzed on both preoperative and postoperative MRI studies. These changes were correlated with the definitive CP topography and type of third ventricle involvement by the lesion, as confirmed surgically.

Results. The mammillary body angle (MBA) is the angle formed by the intersection of a plane tangential to the base of the MBs and a plane parallel to the floor of the fourth ventricle in midsagittal MRI studies. Measurement of the MBA represented a reliable neuroradiological sign that could be used to discriminate the type of intraventricular involvement by the CP in 83% of cases in this series (n = 109). An acute MBA (< 60°) was indicative of a primary tuberal-intraventricular topography, whereas an obtuse MBA (> 90°) denoted a primary suprasellar CP position, causing either an invagination of the third ventricle (pseudointraventricular lesion) or its invasion (secondarily intraventricular lesion; p < 0.01). A multivariate model including a combination of 5 variables (the MBA, position of the hypothalamus, presence of hydrocephalus, psychiatric symptoms, and patient age) allowed an accurate definition of the CP topography preoperatively in 74%–90% of lesions, depending on the specific type of relationship between the tumor and third ventricle.

Conclusions. The type of mammillary body displacement caused by CPs represents a valuable clue for ascertaining the topographical relationships between these lesions and the third ventricle on preoperative MRI studies. The MBA provides a useful sign to preoperatively differentiate a primary intraventricular CP originating at the infundibulotuberal area from a primary suprasellar CP, which either invaginated or secondarily invaded the third ventricle.

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Surgery for low-grade glioma infiltrating the central cerebral region

Surgery for low-grade glioma infiltrating the central cerebral region

J Neurosurg 119:318–323, 2013

A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient’s functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life.

Methods. Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution.

Results. For the central cohort, the median extent of resection was 92% (range 80%–97%), and for the frontal cohort, the median extent of resection was 93% (range 83%–98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001).

Conclusions. Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.

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Interactive presurgical simulation applying 3D techniques

Presurgical simulation 3Dimaging

J Neurosurg 119:94–105, 2013

In this paper, the authors’ goal was to report their novel presurgical simulation method applying interactive virtual simulation (IVS) using 3D computer graphics (CG) data and microscopic observation of color-printed plaster models based on these CG data in surgery for skull base and deep tumors.

Methods. For 25 operations in 23 patients with skull base or deep intracranial tumors (meningiomas, schwannomas, epidermoid tumors, chordomas, and others), the authors carried out presurgical simulation based on 3D CG data created by image analysis for radiological data. Interactive virtual simulation was performed by modifying the 3D CG data to imitate various surgical procedures, such as bone drilling, brain retraction, and tumor removal, with manipulation of a haptic device. The authors also produced color-printed plaster models of modified 3D CG data by a selective laser sintering method and observed them under the operative microscope.

Results. In all patients, IVS provided detailed and realistic surgical perspectives of sufficient quality, thereby allowing surgeons to determine an appropriate and feasible surgical approach. Surgeons agreed that in 44% of the 25 operations IVS showed high utility (as indicated by a rating of “prominent”) in comprehending 3D microsurgical anatomies for which reconstruction using only 2D images was complicated. Microscopic observation of color-printed plaster models in 12 patients provided further utility in confirming realistic surgical anatomies.

Conclusions. The authors’ presurgical simulation method applying advanced 3D imaging and modeling techniques provided a realistic environment for practicing microsurgical procedures virtually and enabled the authors to ascertain complex microsurgical anatomy, to determine the optimal surgical strategies, and also to efficiently educate neurosurgical trainees, especially during surgery for skull base and deep tumors.

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Modern surgical outcomes following surgery for sphenoid wing meningiomas

Sphenoid wing meningioma

J Neurosurg 119:86–93, 2013

Cushing and Eisenhardt were the first to describe sphenoid wing meningiomas in detail, categorizing globoid tumors into 3 groups: 1) medial; 2) middle; and 3) lateral. The authors review their experience with resection of sphenoid wing meningiomas at a single center, to examine whether this classification predicts clinical presentation and postsurgical outcome.

Methods. All patients undergoing resection of sphenoid wing meningioma at the authors’ institution over a 9-year period were identified. Clinical data were compared from patients with tumors arising at different points along the sphenoid wing to determine if these tumors behaved differently in terms of symptoms, radiographic characteristics, and postsurgical outcome.

Results. A total of 56 patients underwent microsurgical resection for sphenoid wing meningioma during this period. The rates of optic canal invasion (medial 50% vs middle 5% vs lateral 0%; p < 0.0001, chi-square test), supraclinoid internal carotid artery encasement (medial 32% vs middle 5% vs lateral 0%; p < 0.01, chi-square test), and middle cerebral artery encasement (medial 45% vs middle 24% vs lateral 0%; p < 0.01, chi-square test) were all highest with medial-third tumors. New or worsened neurological deficits occurred in 10 (19%) of 56 patients. Of all the imaging characteristics studied, only location of the tumor along the medial third of the sphenoid wing significantly predicted an increased rate of new or worsened neurological deficit (OR 2.7, p < 0.05).

Conclusions. The authors report outcomes in a large series of sphenoid wing meningiomas that were treated using modern surgical techniques.

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Interactive presurgical simulation applying 3D techniques

3D CG data and the color-printed plaster model for a left tentorial meningioma

J Neurosurg 119:94–105, 2013

In this paper, the authors’ goal was to report their novel presurgical simulation method applying interactive virtual simulation (IVS) using 3D computer graphics (CG) data and microscopic observation of color-printed plaster models based on these CG data in surgery for skull base and deep tumors.

Methods. For 25 operations in 23 patients with skull base or deep intracranial tumors (meningiomas, schwannomas, epidermoid tumors, chordomas, and others), the authors carried out presurgical simulation based on 3D CG data created by image analysis for radiological data. Interactive virtual simulation was performed by modifying the 3D CG data to imitate various surgical procedures, such as bone drilling, brain retraction, and tumor removal, with manipulation of a haptic device. The authors also produced color-printed plaster models of modified 3D CG data by a selective laser sintering method and observed them under the operative microscope.

Results. In all patients, IVS provided detailed and realistic surgical perspectives of sufficient quality, thereby allowing surgeons to determine an appropriate and feasible surgical approach. Surgeons agreed that in 44% of the 25 operations IVS showed high utility (as indicated by a rating of “prominent”) in comprehending 3D microsurgical anatomies for which reconstruction using only 2D images was complicated. Microscopic observation of color-printed plaster models in 12 patients provided further utility in confirming realistic surgical anatomies.

Conclusions. The authors’ presurgical simulation method applying advanced 3D imaging and modeling techniques provided a realistic environment for practicing microsurgical procedures virtually and enabled the authors to ascertain complex microsurgical anatomy, to determine the optimal surgical strategies, and also to efficiently educate neurosurgical trainees, especially during surgery for skull base and deep tumors.

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Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas

GIIG

J Neurosurg 118:1157–1168, 2013

The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed.

Methods. Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis.

Results. At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection.

Conclusions. This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

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Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma

 

NeuroBlate

J Neurosurg 118:1202–1219, 2013

Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose–escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).

Methods. Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, sidefiring laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation.

Results. Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals–Case Medical Center). Their average age was 55 years (range 34–69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70–90). The mean tumor volume was 6.8 ± 5 cm3 (range 2.6–19 cm3), the percentage of tumor treated was 78% ± 12% (range 57%–90%), and the conformality index was 1.21 ± 0.33 (range 1.00–2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62–767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose.

Conclusions. NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. Clinical trial registration no.: NCT00747253 (ClinicalTrials. gov).

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Prognostic factors of Grade II gliomas

neuronBig

J Neurosurg 118:1157–1168, 2013

The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed.

Methods. Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis.

Results. At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection.

Conclusions. This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.

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Postoperative ischemic changes following resection of newly diagnosed and recurrent gliomas and their clinical relevance

Postoperative ischemic changes following resection of newly diagnosed and recurrent gliomas and their clinical relevance

J Neurosurg 118:801–808, 2013

The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function.

Methods. Patients who underwent glioma resection for newly diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded.

Results. New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p < 0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than in patients with newly diagnosed tumors. Patients with neurological deficits had a significantly higher rate of ischemic lesions.

Conclusions. Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.

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Multiple resections for patients with glioblastoma: prolonging survival

Prolonged survival GBM

J Neurosurg 118:812–820, 2013

Glioblastoma is the most common and aggressive type of primary brain tumor in adults. These tumors recur regardless of intervention. This propensity to recur despite aggressive therapies has made many perceive that repeated resections have little utility. The goal of this study was to evaluate if patients who underwent repeat resections experienced improved survival as compared with patients with fewer numbers of resections, and whether the number of resections was an independent predictor of prolonged survival.

Methods. The records of adult patients who underwent surgery for an intracranial primary glioblastoma at an academic tertiary-care institution between 1997 and 2007 were retrospectively reviewed. Multivariate proportionalhazards regression analysis was used to identify an association between glioblastoma resection number and survival after controlling for factors known to be associated with survival, such as age, functional status, periventricular location, extent of resection, and adjuvant therapy. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analysis.

Results. Five hundred seventy-eight patients with primary glioblastoma met the inclusion/exclusion criteria. At last follow-up, 354, 168, 41, and 15 patients underwent 1, 2, 3, or 4 resections, respectively. The median survival for patients who underwent 1, 2, 3, and 4 resections was 6.8, 15.5, 22.4, and 26.6 months (p < 0.05), respectively. In multivariate analysis, patients who underwent only 1 resection experienced shortened survival (relative risk [RR] 3.400, 95% CI 2.423–4.774; p < 0.0001) as compared with patients who underwent 2 (RR 0.688, 95% CI 0.525–0.898; p = 0.0006), 3 (RR 0.614, 95% CI 0.388–0.929; p = 0.02), or 4 (RR 0.600, 95% CI 0.238–0.853; p = 0.01) resections. These results were verified in a case-control evaluation, controlling for age, neurological function, periventricular tumor location, extent of resection, and adjuvant therapy. Patients who underwent 1, 2, or 3 resections had a median survival of 4.5, 16.2, and 24.4 months, respectively (p < 0.05). Additionally, the risk of infections or iatrogenic deficits did not increase with repeated resections in this patient population (p > 0.05).

Conclusions. Patients with glioblastoma will inevitably experience tumor recurrence. The present study shows that patients with recurrent glioblastoma can have improved survival with repeated resections. The findings of this study, however, may be limited by an intrinsic bias associated with patient selection. The authors attempted to minimize these biases by using strict inclusion criteria, multivariate analyses, and case-control evaluation.

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Brainstem gangliogliomas: a retrospective series

Brainstem gangliogliomas- a retrospective series

J Neurosurg 118:884–888, 2013

The authors retrospectively analyzed data on brainstem gangliogliomas treated in their department and reviewed the pertinent literature to foster understanding of the preoperative characteristics, management, and clinical outcomes of this disease.

Methods. In 2006, the authors established a database of treated lesions of the posterior fossa. The epidemiology findings, clinical presentations, radiological investigations, pathological diagnoses, management, and prognosis for brainstem gangliogliomas were retrospectively analyzed.

Results. Between 2006 and 2012, 7 patients suffering from brainstem ganglioglioma were treated at the West China Hospital of Sichuan University. The mean age of the patients, mean duration of symptoms prior to diagnosis, and mean duration of follow-up were 28.6 years, 19.4 months, and 38.1 months, respectively. The main presentations were progressive cranial nerve deficits and cerebellar signs. Subtotal resection was achieved in 2 patients, and partial resection in 5. All tumors were pathologically diagnosed as WHO Grade I or II ganglioglioma. Radiotherapy and adjuvant chemotherapy were not administered. After 21–69 months of follow-up, patient symptoms were resolved or stable without aggravation, and MRI showed that the size of residual lesions was unchanged without progression or recurrence.

Conclusions. The diagnosis of brainstem ganglioglioma is of great importance given its favorable prognosis. The authors recommend the maximal safe resection followed by close observation without adjuvant therapy as the optimal treatment for this disease.

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Separation surgery and postoperative SRS for spinal metastases

Local disease control for spinal metastases following “separation surgery” and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery

J Neurosurg Spine 18:207–214, 2013

Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurological function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression (ESCC). The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control.

Methods. A retrospective chart review identified 186 patients with ESCC from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (21.5%), high-dose hypofractionated SRS (24–30 Gy in 3 fractions) in 37 patients (19.9%), or low-dose hypofractionated SRS (18–36 Gy in 5 or 6 fractions) in 109 patients (58.6%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology–specific radiosensitivity, grade of ESCC, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis.

Results. The total cumulative incidence of local progression was 16.4% 1 year after SRS. Multivariate Gray competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year, HR 0.12, p = 0.04) as compared with low-dose hypofractionated SRS (22.6% local progression at 1 year, HR 1). Although univariate analysis demonstrated a trend toward greater risk of local progression for patients in whom preoperative conventional external beam radiation therapy failed (22.2% local progression at 1 year, HR 1.96, p = 0.07) compared with patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of ESCC, extent of surgical decompression, or patient sex.

Conclusions. Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology–specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated 1-year local progression rates of less than 5% (95% CI 0%–12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after singlefraction SRS was less than 10% (95% CI 0%–19.0%).

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