Volumetric Resection Research Articles

Large Pituitary Adenoma: Strategies to Maximize Volumetric Resection Using Endoscopic Endonasal Approaches and an Analysis of Factors Limiting Resection

Large pituitary adenomas (LPAs), which constitute ∼5%-14% of all pituitary adenomas, are considered challenging tumors owing to their locally aggressive behavior, low gross total resection rate, and high prevalence of visual deficits and hypopituitarism. We evaluated the utility of various extended endoscopic endonasal approaches in maximizing the resection of LPAs and studied the factors affecting the extent of surgical resection. A retrospective study of all LPAs (defined as a minimum diameter >3 cm and tumor volume >10 cm3) treated via an endoscopic endonasal approach between January 2015 and December 2020 was performed. The volumetric extent of resection (3-dimensional volumetric analysis software) was correlated with various demographic, tumor-related, pathologic, and immunohistochemical factors and its effects on the clinical outcomes studied. The present study included 106 patients with LPAs. The mean extent of the resection volume was 79.18 ± 21.75 cm3. The factors that affected the extent of resection included the preoperative tumor volume (P= 0.03) and Knosp grade (P= 0.03). The percentage increase in the extent of resection with the use of 2 endonasal corridors was 10.6% and with 3 corridors was 14%. Visual improvement occurred in 82% of patients, and new-onset persistent hormonal insufficiency occurred in 2.9% of patients. Mortality directly related to surgery occurred in 1.8% of cases. Extended endoscopic endonasal approaches can safely and effectively be used for gross total resection of LPAs. However, we found that the preoperative tumor volume and Knosp grade were significant factors affecting the extent of tumor resection. The use of multiple endoscopic endonasal corridors can increase the volumetric extent of resection for LPAs.

Volumetric Resection and Complications in Nonfunctioning Pituitary Adenoma by Fully Endoscopic Transsphenoidal Approach along 15 Years of Single-Center Experience.

Objective The aim of this study was to evaluate the rate of complications and the extent of resection (EOR) of nonfunctioning pituitary adenomas by endoscopic endonasal approach (EEA) in a 15-year learning curve. Methods A total of 100 patients operated by the same surgical team were divided chronologically into two, three, and four groups, comparing differences in EOR measured by a semiautomatic software (Smartbrush, Brainlab), rate of immediate postoperative complications, and the visual and hormonal status at 6 months. Results There were no significant differences over the years in rates of postoperative complications and in visual status at 6 months. A significant linear correlation between the EOR and the number of surgeries (rho = 0.259, p = 0.007) was found. The analysis was performed in three groups because of the remarkable differences among them; the EOR were: 87.2% (early group), 93.03% (intermediate group), and 95.1% (late group) ( p = 0.019). Gross total resection was achieved in 30.3, 51.5, and 64%, respectively ( p = 0.017); also, the rate of reoperation and the worsening of at least one new hormonal axis were worse in the early group. Consequently, the early group had a higher risk of incomplete resection compared with the late group (odds ratio: 4.2; 95% confidence interval: 1.5-11.7). The three groups were not different in demographic and volume tumor variables preoperatively. Conclusions The first 33 interventions were associated with a lower EOR, a high volume of residual tumor, a high reoperation rate, and a higher rate of hormonal dysfunction. We did not find differences in terms of postoperative complications and the visual status at 6-month follow-up.

Pituitary Tumor Surgery: Comparison of Endoscopic and Microscopic Techniques at a Single Center

ObjectiveTo understand the transition from microscopic surgery (MS) to endoscopic surgery (ES) on the pituitary across the United States, we assessed a single institution practicing both procedures to discern advantages and disadvantages for each. Patients and MethodsRetrospective institutional chart review of 534 patients in a large practice over a 6-year period (January 1, 2014, to December 31, 2019) comparing a single MS neurosurgeon with a single ES neurosurgeon operating on the same days. ResultsIn this series, 14% (n=75) of patients had a prior operation, there were no carotid artery injuries, the overall risk for a postoperative infection was 0.4% (n=2), and risk for a postoperative cerebrospinal fluid leak requiring treatment was 2.0% (n=11). Mean ± SD hospital stay was 1.3±0.04 days; readmission for any reason within 30 days occurred in 3.4% (n=18) of patients. The mean volumetric resection for MS was 86.9%±1.7% and for ES was 91.7%±1.3% (P=.03). There was a higher rate of notable events (P=.015) with MS, but MS had 16% lower cost and operative times were 48 minutes shorter than for ES (83±7 vs 131±6 minutes). The ES required substantially fewer postoperative secondary treatments such as radiation therapy (P=.003). ConclusionPituitary surgery is a very safe and effective procedure regardless of technique. The MS has shorter operative times and overall lower cost. The ES results in increased volumetric resection and fewer secondary treatments. Both techniques can be valuable to a large practice, and understanding these niches is important when selecting optimal approaches to pituitary surgery for a given patient.

Multiplatform Molecular Profiling of Vestibular Schwannoma Reveals Immune Enrichment after Radiosurgery and a Methylation-Based Predictor of Recurrence

Vestibular schwannomas (VS) can cause significant morbidity from cranial nerve deficits and mass effect. Broad molecular differences have been described for intracranial versus spinal axis schwannomas, but little is known about the molecular heterogeneity of VS or predictors of VS recurrence. The objective of this study was to understand VS biology and identify molecular predictors of VS recurrence. Sixty-six sporadic VS from 59 consecutive patients with available tissue who underwent initial resection (44), resection for recurrence after prior surgery (5), resection for recurrence after prior stereotactic radiosurgery (SRS) (11), or resection after both prior surgery and prior SRS (6) at a single institution from 2003-2017 were profiled using Illumina 850K DNA methylation arrays (median follow-up: 4.2 years, median volumetric resection: 91%). Twenty-four VS were further characterized using RNA sequencing (RNA-seq), and 7 were analyzed by single nuclei RNA-seq. Molecular subtyping was performed by hierarchical clustering of differentially-methylated DNA probes and validated using transcriptomic data. In vitro functional experiments were performed using human VS cells. Clustering of genome-wide DNA methylation probes revealed that VS are comprised of 2 subgroups that are delineated by enrichment of neural crest or immune genes. Fifteen of 35 immune-enriched VS (43%) had prior SRS, while only 2 of 31 neural crest-enriched VS (6%) had prior SRS (p<0.001). Analysis of 6 patients with matched primary and recurrent VS samples revealed that all recurrent VS after prior SRS exhibited similar methylation profiles and were enriched in immune genes. In contrast, the methylation profile of VS that recurred after prior surgery did not deviate from the primary tumor. Hypomethylation of G protein-coupled estrogen receptor 1 (GPER) promoter was prognostic for local failure in multivariate regression irrespective of primary treatment modality (p<0.0001). Radiation of VS cells in vitro recapitulated gene expression of immune-enriched VS. VS are comprised of 2 molecular subgroups characterized by differential enrichment of neural crest or immune genes. VS with prior SRS are associated with immune-enrichment. GPER promoter hypomethylation is prognostic for VS recurrence. These data illuminate the biology of VS and shed light on potential molecular therapies.

Multiplatform Molecular Profiling of Vestibular Schwannoma Reveals 2 Subgroups of Tumors With Distinct Radiographic Features and a Methylation-Based Predictor of Local Recurrence

Abstract INTRODUCTION Vestibular schwannomas (VS) can cause significant morbidity from cranial neuropathies and mass effect. Broad molecular differences have been described for intracranial versus spinal axis schwannomas, but little is known about the molecular heterogeneity of VS or predictors of recurrence. METHODS A total of 66 sporadic VS from 59 consecutive patients with available tissue who underwent initial resection (44), resection for recurrence after prior surgery (5), resection for recurrence after prior stereotactic radiosurgery (SRS) (11), or resection after both prior surgery and prior SRS (6) at a single institution from 2003 to 2017 were profiled using 850 K DNA methylation arrays (median follow-up: 4.2 yr, median volumetric resection: 91%). A total of 24 VS were further characterized using RNA sequencing. Molecular subtyping was performed using differential-DNA methylation analysis and validated using transcriptomic data. Preoperative magnetic resonance imaging (MRI) studies were centrally reviewed by a board-certified neuro-radiologist. RESULTS NA methylation profiling revealed 2 novel subgroups of VS, delineated by enrichment of neural crest genes (31 tumors) or immune genes (35 tumors). Neural crest-enriched VS were more likely to show reduced diffusion on MRI (P &lt; .01), while immune-enriched VS were more likely to show cystic changes (P &lt; .05), mass effect (P &lt; .01), and edema (P &lt; .05). Immune-enriched VS were significantly more likely to be adherent to the brainstem and left as residual at the time of resection. A total of 15 immune-enriched VS (43%) had prior SRS, while only 2 neural crest-enriched VS (6%) had prior SRS (P &lt; .001). Hypomethylation of G protein-coupled estrogen receptor 1 (GPER) promoter was prognostic for local failure in multivariate regression irrespective of primary treatment modality (P &lt; .0001). CONCLUSION VS are comprised of 2 molecular subgroups characterized by differential enrichment of neural crest or immune genes. VS treated with prior SRS are associated with immune-enrichment. GPER promoter hypomethylation is prognostic for VS recurrence. These data illuminate the biology of VS and shed light on potential molecular therapies.

Automating neurosurgical tumor resection surgery: Volumetric laser ablation of cadaveric porcine brain with integrated surface mapping.

Current surgical instruments for soft tissue resection including neurosurgical procedures rely on the accuracy and precision of the human operator and are fundamentally constrained by the human hand. Automated surgical action with the integration of intraoperative data sources can enable highly accurate and fast tissue manipulation using laser ablation. This study presents the first experiments with a prototype designed for automated tumor resection via laser ablation. We demonstrate targeted soft tissue resection in porcine brain with an integrated device that combines 3D scanning capabilities with a steerable surgical laser and discuss implications for future automated robotic neurosurgical procedures. A device consisting of a two-axis galvanometer for steering a cutting laser and a 3D surface profiler is used to perform volumetric removal of tissue of ex vivo porcine brain. Three-dimensional surface profiles are gathered between cuts and used to estimate ablation rate. Volumetric ablation of porcine brain tissue is performed and subsequently surface profiled. The average ablation rates across the area cutting areas were 2.6 mm3 /s and 3.7 mm3 /s for the initial and subsequent cuts, respectively. A Kruskal-Wallis and post-hoc Tukey test show statistical significance between the initial and subsequent cuts. Accuracy between cuts when benchmarked against a human surgeon varied from 47 to 88%. A feed-forward volumetric resection is demonstrated with sensing and cutting housed within a single device, thereby opening the potential for automated soft tissue resection as necessary during the surgical removal of pathologic tissues. High variance around target cut depths motivates future work in developing a closed-loop ablation tool as well as characterization of laser-tissue interactions for predictive modelling. Objective Lasers Surg. 50:1017-1024, 2018. © 2018 Wiley Periodicals, Inc.

Beyond Gross Total and Subtotal: Does Volumetric Resection Matter in Nonfunctioning Pituitary Macroadenomas?

No study has volumetrically examined resection degree and recurrence in pituitary macroadenoma (PMA). We analyzed the impact of volumetric tumor resection on prediction of tumor recurrence and retreatment in a cohort of patients with nonfunctioning PMA ≥2 cm. Records were reviewed from 1998-2008 for patients with null cell or nonsecreting PMA ≥2 cm. Inclusioncriteria were surgically resected PMA and ≥4 years' follow-up or recurrence before 4 years. Seventy-eight patients were found. PMA tissue volume preoperatively and postoperatively was quantified by a board-certified neuroradiologist. Extent of resection (EOR) was calculated. The primary end point was tumor recurrence with a secondary end point of treated tumor recurrence. Median age was 58 (20-85). Forty-one (53%) had no tumor recurrence at a median of 113 (48-203) months. Thirty-seven (47%) patients had tumor recurrence with a median time of 55 (9-176) months. On univariate analysis, increasing age, decreasing preoperative and postoperative volumes, and increasing EOR were statistically significant for decreasing the risk of recurrence or treated recurrence. On multivariate analysis, only age and EOR remained significant. Receiver operating characteristic showed EOR <86% was associated with PMA regrowth. Kaplan-Meier analysis demonstrated a statistically significant difference for recurrence comparing groups by EOR ≥86% or <85%. We found younger age and increasing EOR are significant predictors of tumor regrowth and retreatment. These results indicate EOR assessment may have a role in large PMA. Further study with volumetric analysis is needed in a larger cohort of patients.

Volumetry in the Assessment of Pituitary Adenoma Resection: Endoscopy versus Microscopy

Background Assessment of the extent of resection after surgical resection of pituitary adenomas is most commonly reported in terms of the presence or absence of residual tumor. A quantitative comparison of volumetric resection between endonasal endoscopy (EE) and microsurgery (MS) has rarely been done. Methods A retrospective analysis was performed on a consecutive series of 154 patients with pituitary adenomas treated by the same surgeon at a single institution. We employed volumetric analysis pre- and postoperatively on two cohorts of pituitary adenoma patients treated through MS ( n = 37) versus EE approach ( n = 117). Results Volumetric analysis revealed a higher incidence of complete resection (64.4 vs. 56.8%) and mean volume reduction in the EE cohort (92.7 vs. 88.4%), although not significant. Recurrence rates were significantly lower in the EE group (7.7% vs 24.3%, p = 0.015). Subgroup analysis identified that patients with preoperative tumor volumes >1 mL were less likely to recur through EE (7.8 vs. MS: 29.6%; p = 0.0063). A higher incidence of complete resection was also noted in patients with favorable Knosp grades (0-1) (EE: 87.8 vs. MS: 63.2%; p = 0.036). Postoperative complication rates were not significantly different between both techniques. Conclusion Both microscopy and endoscopy are well-tolerated, effective approaches in the treatment of pituitary adenomas. Our series demonstrated that EE may be superior to MS in preventing tumor recurrence and achieving a complete resection in certain subsets of patients. EE provides a slight advantage in tumor control outcomes that may justify the paradigm shift to pure endoscopy at our center.

799 Comparison of a Novel Technique and Conventional Approach for Flexible Endoscopic Zenker's Diverticulum Repair

Incision of the crico-pharyngeal (CP) muscle with flexible endoscopy has emerged as an alternative approach to treat Zenker’s Diverticulum (ZD). Symptomatic resolution is achieved in 90% of cases, but recurrence had been reported to be 20-24%. We report our experience of a new endoscopic wedge-shaped excision (volumetric resection cohort) of the CP muscle (Figure 1) and compare the outcome with the conventional myotomy of ZD (conventional cohort).

Anterior inferior petrosectomy: defining the role of endonasal endoscopic techniques for petrous apex approaches

Historically, surgery to the petrous apex has been addressed via craniotomy and open microscopic anterior petrosectomy (OAP). However, with the popularization of endoscopic approaches, the petrous apex can further be approached endonasally by way of an endoscopic endonasal anterior petrosectomy (EAP). Endonasal anterior petrosectomy is a relatively new procedure and has not been compared anatomically with OAP. The authors hypothesized that the EAP and OAP techniques approach different portions of the petrous apex and therefore may have different applications. Four cadaveric heads were used. An OAP was performed on one side and an EAP was performed on the contralateral side; the limits of bony resection were defined. The extent of bony resection was then evaluated using predissection and postdissection thin-slice CT scans. The comparative resection was then reconstructed using 3D modeling on Brainlab workstations. The average resection volumes for EAP and OAP were 0.297 cm(3) and 0.649 cm(3), respectively, representing a comparative percentage of 46% (EAP/OAP). An EAP and OAP achieved resection of 29% and 64% of the total petrous apex volume, respectively. Indeed, EAP addressed the inferior portion of the petrous apex located adjacent to the petroclival suture more completely than OAP, where 45% of the bone overlying the petroclival suture (petroclival angle to the jugular foramen) was resected with the EAP, while 0% was resected with the OAP. In anatomically normal cadavers, OAP achieved nearly a 50% larger volumetric resection than EAP. Furthermore, while OAP appears to completely address the superior portion of the petrous apex, EAP appears to have a niche in approaches to lesions in the inferior petrous apex. Given these results, the authors propose that OAP be redefined as the "superior anterior petrosectomy," while EAP be referred to as the "inferior anterior petrosectomy," which more clearly defines the role of each approach in anterior petrosectomy.

Awake language mapping and 3-Tesla intraoperative MRI-guided volumetric resection for gliomas in language areas

The use of both awake surgery and intraoperative MRI (iMRI) has been reported to optimize the maximal safe resection of gliomas. However, there has been little research into combining these two demanding procedures. We report our unique experience with, and methodology of, awake surgery in a movable iMRI system, and we quantitatively evaluate the contribution of the combination on the extent of resection (EOR) and functional outcome of patients with gliomas involving language areas. From March 2011 to November 2011, 30 consecutive patients who underwent awake surgery with iMRI guidance were prospectively investigated. The EOR was assessed by volumetric analysis. Language assessment was conducted before surgery and 1week, 1month, 3months and 6months after surgery using the Aphasia Battery of Chinese. Awake language mapping integrated with 3.0Tesla iMRI was safely performed for all patients. An additional resection was conducted in 11 of 30 patients (36.7%) after iMRI. The median EOR significantly increased from 92.5% (range, 75.1–97.0%) to 100% (range, 92.6–100%) as a result of iMRI (p<0.01). Gross total resection was achieved in 18 patients (60.0%), and in seven of those patients (23.3%), the gross total resection could be attributed to iMRI. A total of 12 patients (40.0%) suffered from transient language deficits; however, only one (3.3%) patient developed a permanent deficit. This study demonstrates the potential utility of combining awake craniotomy with iMRI; it is safe and reliable to perform awake surgery using a movable iMRI.

Intraoperative use of diffusion tensor imaging-based tractography for resection of gliomas located near the pyramidal tract: comparison with subcortical stimulation mapping and contribution to surgical outcomes

Introduction. For gliomas, the goal of surgery is maximal tumour removal with the preservation of neurological function. We evaluated the contribution of the combination of diffusion tensor imaging-based fibre tracking (DTI-FT) of the pyramidal tract (PT) integrated to the navigation and subcortical direct electrical stimulations (DESs) to surgical outcomes. Method. Ten patients underwent surgery for gliomas located in close relationship with the subcortical course of the PT. Preoperative DTI was performed with a three-Tesla magnetic resonance scanner applying an echo-planar sequence with 20 diffusion directions. DTI-FT data were systematically loaded into the navigation for intraoperative guidance. When the resection closely approached the PT as illustrated on navigation images, subcortical DESs were used to confirm the proximity of the PT by observing motor responses. The location of all subcortically stimulated points with positive motor response was correlated with the illustrated PT. Motor deficits were evaluated pre- and postoperatively, and compared with the extent of tumour removal. Results. DTI-FT of the PT was successfully performed in all patients. A total of fifteen positive subcortical DESs were obtained in 8 of 10 patients; in these cases, the mean distance from the stimulated point to the PT was 6.2 ± 3.6 mm. The mean tumoural volumetric resection was 90.8 ± 10.4%, with a gross total resection in four patients. At one month after surgery, only one patient had a slight impairment of motor function (decreased fine motor hand skills). Conclusions. DTI-FT is an accurate technique to map the PT in the vicinity of brain tumours. By combining anatomical (DTI-FT) and functional (subcortical DES) studies for intraoperative localization of the PT, the authors achieved a good volumetric resection of tumours located in eloquent motor areas, with low morbidity. Careful use of this protocol requires the knowledge of some pitfalls, mainly the occurrence of brain shift during removal of large tumours.

Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery

For gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES). The authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR. Tractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0 ± 10.4 % of the preoperative tumour volume, with a gross total resection in 60 % of patients. The intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

Surgical Neurology International Stereotactic: Inaugural Editorial

Surgical Neurology International Stereotactic (SNI Stereotactic) is the first open access journal dedicated to stereotactic surgery. It is a “spin off” of SNI. The success of SNI hinges on rapid and free spread of the neurosurgery progress. Stereotactic surgery is the most suited of neurosurgery's subspecialties for informatics. The need for mathematical precision to reach specific areas of the brain with minimal disruption of its structure led to the inception of stereotactic surgery. The penetration of stereotaxis in medicine followed the evolution of computation and imaging. It was born with ventriculography for functional neurosurgery. Angiography initiated the morphologic stereotactic surgery, and finally computers made image-guided volumetric resections possible. Stereotactic surgery is fast progressing, paced by informatics and the rapidly growing understanding of brain function. This has been led by functional imaging, either blood flow dependent through functional MRI or through isotope/molecular imaging, PET, and SPECT. Computing of all this information for surgery planning and execution brings the ultimate security for surgeons at work and their patients. Stereotacticians provided this integration for general neurosurgery and surgery at large. Although these general technical developments in stereotaxis rapidly became common place in neurosurgery, the challenge for stereotactic surgeons continues, not only as a support for the treatment of morphological abnormalities but also in creating therapies for a multitude of malfunctioning and degenerative diseases of the brain, hereto not in the realm of neurosurgery. Stereotactic surgeons used to work initially on mapping and modifying the brain function through mere disruption of the brain pathways and nuclei with metal loops, caustic injections, and extreme cold or heat. Now elegant methods are available, allowing minimal and reversible invasion of the brain. Electrical stimulation can modify perception of pain and correct movement disorders and behavior abnormalities. It has paved the way either for non-reversible therapies such as radiosurgery and high-frequency ultrasound (HIFU) or for reversible ones such as low-frequency ultrasound (LOFU) and transcranial magnetic stimulation (TMS). The brain structure has been also respected using peripheral nerve stimulation as port to the brain for treatment of epilepsy, pain, depression, and other disorders. These exciting techniques are building the future of functional neurosurgery and stereotactic treatments for structural diseases of the central nervous system, such as vascular abnormalities and tumors. Brain repair with delivery of stem cells, growth factors, viral vectors, and the ever-growing biologics and nano-devices promises a curious and bright future for stereotactic surgery. SNI Stereotactic was started to update professionals of this burgeoning specialty, with an initial year of relevant review articles depicting the multidisciplinary nature of stereotactic surgery. We expect four supplements to SNI during this inauguration year. They will be followed by open submissions of scientific articles in the years to come. SNIS will promote editorials, peer review opinions, and stereotactic controversies, and encourage clinical and translational research articles, bringing bench findings to clinical practice. A strong Editorial Board is being established with worldwide representation of young leaders in neurosurgery, neurology, psychiatry, radiation oncology, radiology, medical physics, bioengineering, and basic scientists. It is expected that this open access journal will bring the world of stereotaxis together based on free easy access to knowledge and the communication power of the Ethernet, making SNIS available in all corners of the world. This inaugural issue reviews the techniques and pitfalls of stereotactic surgery, radiosurgery and its effects in the central nervous and peripheral nervous system, neuromodulation central and through peripheral ports, ethics and novelties of behavioral surgery, and futuristic views of the field. The following issues will feature image guidance, peripheral stimulation, imaging, recording, and close feedback loops for neurointerfaces. The financial burden of such an endeavor has to be borne either by the authors or by the readers. Obviously this would limit the readership and authorship to the wealthier. Organization of a journal indiscriminately available to all is a work that has to be properly supported to preserve its quality and readability. Industry sponsorship becomes necessary and is welcome. This inaugural issue was generously supported by an Elekta donation. We expect that the industry at large follows Elekta's example of taking pivotal creative and educational role in neurosurgery. Physicians and scientists dedicated to stereotaxis expect that those profiting from our work pitch in for the dissemination of good science, and their own products. Larger the pool of industry participants, less commercial bias will exist. We are actively seeking further support of the industry to make SNIS successful and decrease the burden on those writing and working to develop novel stereotactic therapies. Publication of this manuscript has been made possible by an educational grant from ELEKTA

Stereotactic volumetric resection, intracavitary carmustine wafers, and radiation therapy for brain metastases: The Moffitt Cancer Center experience.

2077 Background: NCCN guidelines for brain metastases (BM) endorse surgery and whole brain radiation therapy (WBRT). Early clinical data suggest that addition of intracavitary carmustine wafers yields superior local control. Methods: A retrospective analysis of 49 consecutive BM patients undergoing MR-guided, gross total resection with chemowafers was compared to a similar cohort of 174 BM patients treated without wafers during a 6-year period at Moffitt Cancer Center. Results: Of the 49 patients, 4 had two sites of resection/wafer placement; 45 had a single surgical bed. The median age was 59 years; 49% had lung cancer, 24% melanoma, 26% were other histologies. Thirty-five patients had newly diagnosed BM; 14 were recurrent tumors. Fifteen patients were RPA class I, 27 class II, and 7 class III. The maximal resection bed diameter ranged from 1.0 to 7.2 cm (mean, 3.1). The median post-operative stay was one day. There were no infections. The KPS was stable or improved in 90% of the patients at 3 months, and 73% at 6 months (Table). The median survival for newly diagnosed patients was 9 months, and for those with recurrences, 6 months. For newly diagnosed metastases, treated with surgery + wafers + WBRT, only 1/35 (3%) patients had local recurrence. In 14 patients with recurrent metastases, there were no recurrences in those treated using surgery + wafer. By contrast, in tumor resected without wafers, local recurrence was 13% (17/130) and in those resected at recurrence, further recurrence occurred in 40% (6/15). The wafers were well-tolerated in tumors located within or near the primary motor cortex. Conclusions: Intracavitary carmustine wafers can be used in the treatment of upfront and recurrent brain metastases with excellent local control, minimal morbidity, and good neurological outcomes. Chemowafers can be useful near eloquent brain where the tumor-brain interface limits the surgical resection. KPS change from day of surgery Stable Improved (neurological) Declined (systemic) 3 months 59% 31% 10% 6 months 46% 27% 27%

Tratamiento de los tumores cerebrales intrínsecos de áreas motoras elocuentes: Resultados de un protocolo basado en la navegación, tractografía y monitorización neurofisiológica de estructuras corticales y subcorticales

The role of the microsurgical management of intrinsic brain tumors is to maximize the volumetric resection of the tumoral tissue minimizing the postoperative morbidity. The purpose of our paper has been to study the benefits of an original protocol developed for the microsurgical treatment of tumors located in eloquent motor areas where the navigation and electrical stimulation of motor subcortical pathways have been implemented. A total of 17 patients operated on for resection of cortical or subcortical tumors in motor areas were included in the series. Preoperative planning for multimodal navigation was done integrating anatomic studies, motor functional MRI (f-MRI) and subcortical pathways volumes generated by diffusion tensor imaging (DTI). Intraoperative neuromonitorization included motor mapping by direct cortical and subcortical electrical stimulation (CS and sCS) and localization of the central sulcus using cortical multipolar electrodes and the N20 wave inversion technique. The location of all cortical and subcortical stimulated points with positive motor response was stored in the navigator and correlated with the cortical or subcortical motor functional structures defined preoperatively. The mean tumoral volumetric resection was 89.1±14.2% of the preoperative volume, with a total resection (≥100%) in twelve patients. Preoperatively a total of 58.8% of the patients had some motor deficit, increasing 24 hours after surgery to 76.5% and decreasing to 41.1% a month later. There was a great correlation between anatomic and functional data, both cortically and subcortically. However, in six cases it was not possible to identify the central sulcus and in many cases fMRI gave contradictory information. A total of 52 cortical points submitted to CS had positive motor response, with a positive correlation of 83.7%. Also, a total of 55 subcortical points had positive motor response, being in these cases 7.3±3.1 mm the mean distance from the stimulated point to the subcortical tract. The integration of preoperative and intraoperative anatomic and functional studies allows a safe functional resection of the brain tumors located in eloquent areas, compared to the tumoral resection based on anatomic imaging studies. Multimodal navigation allows the integration and correlation among preoperative and intraoperative anatomic and functional data. Cortical motor functional areas are anatomically and functionally located preoperatively thanks to MRI and fMRI and subcortical motor pathways with TDI and tractography. Intraoperative confirmation is done with CS and N20 inversion wave for cortical structures and with sCS for subcortical pathways. With this protocol we achieved a mean of 90% of volumetric resection in cortical and subcortical tumors located in eloquent motor areas with an increase of neurological deficits in the immediate postoperative period that significantly decreased one month later. Ongoing studies will define the safe limits for functional resection taking into account the intraoperative brain shift. Finally, it must be demonstrated if this protocol has any benefit for patients concerning disease free or overall survival.

Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection—part 2: volumetric resection extent and subgroup analyses

This paper is addressing outcome differences in interesting subgroups from a previous randomized controlled trial of the extent of mesial temporal lobe resection (TLR) for drug-resistant epilepsy, by looking at effects of randomization, intended resection group, center, and true resection extent on seizure outcome. One hundred and seventy-nine cases with volumetrically assessed resection extent were used. Analyses of the extent of resection and subgroups and within subgroups for the two treatment arms will be performed, looking for confounding factors and using statistical methods (chi-square test, logistic regression analysis, and two-factorial ANOVA). True resection extent varied considerably. Outcome comparison for right versus left resections, subgroups with mesial temporal sclerosis (MTS), or largest and smallest resections revealed no remarkable difference, compared to overall class I outcome. The intent-to-treat analyses within these subgroups revealed differences for class I outcome, albeit lacking in significance, except for better TLR outcome. Small true resection volume differences or randomization into the two resection groups could not explain the outcome differences between the selective amygdalohippocampectomy (SAH) and TLR subgroups. Logistic regression analysis showed an interaction between intended resection length and surgery type, confirming the impression of different impacts of the intended resection length under the two surgery types. The outcome difference between SAH and TLR was more likely explained by a center effect. In a two-factorial ANOVA for resected hippocampal volume, Engel outcome class I, and resection type, the outcome was not found to be correlated with true resection volume. A multifactorial logistic regression showed a mild interaction between the resection type with center on the Engel outcome class, extent of resection, and surgery type interacted, as did the extent of resection and center. Patients with quite similar extent of resection can be seizure free or non-seizure free. In this cohort, seizure freedom rates fell again when the extent of mesial resection was maximized. Differences in class I outcome for SAH and TLR were not due to erroneous randomization, true resection extent, or presence of MTS, but were influenced by a center effect. Subgroup analyses did not help to provide arguments to favor one surgery type over the other.

Multimodal navigation in the functional microsurgical resection of intrinsic brain tumors located in eloquent motor areas: role of tractography

Nowadays the role of microsurgical management of intrinsic brain tumors is to maximize the volumetric resection of the tumoral tissue, minimizing the postoperative morbidity. The purpose of this paper was to study the benefits of an original protocol developed for the microsurgical treatment of tumors located in eloquent motor areas where the navigation and electrical stimulation of motor subcortical pathways have been implemented. A total of 17 patients who underwent resection of cortical or subcortical tumors in motor areas have been included in the series. The preoperative planning for multimodal navigation was done by integrating anatomical studies, motor functional MR (fMR) imaging, and subcortical pathway volumes generated by diffusion tensor (DT) imaging. Intraoperative neuromonitoring included motor mapping by direct cortical stimulation (CS) and subcortical stimulation (sCS), and localization of the central sulcus by using cortical multipolar electrodes and the N20 wave inversion technique. The location of all cortically and subcortically stimulated points with positive motor response was stored in the navigator and correlated with the cortical and subcortical motor functional structures defined preoperatively. The mean tumoral volumetric resection was 89.1 +/- 14.2% of the preoperative volume, with a total resection (> or = 100%) in 8 patients. Preoperatively a total of 58.8% of the patients had some kind of motor neurological deficit, increasing 24 hours after surgery to 70.6% and decreasing to 47.1% at 1 month later. There was a great correlation between anatomical and functional data, both cortically and subcortically. A total of 52 cortical points submitted to CS had positive motor response, with a positive correlation of 83.7%. Also, a total of 55 subcortical points had positive motor response; in these cases the mean distance from the stimulated point to the subcortical tract was 7.3 +/- 3.1 mm. The integration of anatomical and functional studies allows a safe functional resection of the brain tumors located in eloquent areas. Multimodal navigation allows integration and correlation among preoperative and intraoperative anatomical and functional data. Cortical motor functional areas are anatomically and functionally located preoperatively thanks to MR and fMR imaging and subcortical motor pathways with DT imaging and tractography. Intraoperative confirmation is done with CS and N20 inversion wave for cortical structures and with sCS for subcortical pathways. With this protocol the authors achieved a good volumetric resection in cortical and subcortical tumors located in eloquent motor areas, with an increase in the incidence of neurological deficits in the immediate postoperative period that significantly decreased 1 month later. Ongoing studies must define the safe limits for functional resection, taking into account the intraoperative brain shift. Finally, it must be demonstrated whether this protocol has any long-term benefit for patients by prolonging the disease-free interval, the time to recurrence, or the survival time.

Gliomas: Survival, origin and early detection

I did some of my training with Paul Bucy. He had a special interest in the surgical treatment of glioblastoma. Bucy believed, as did many “cancer surgeons” of his day, that tumors resulted from good cells becoming bad cells that formed a mass of tumor and that cells from the tumor’s periphery invaded the surrounding normal tissue. He correctly observed that malignant gliomas usually grew locally and rarely metastasized outside of the central nervous system. If there was any surgically curable “cancer”, he believed, it was a glioblastoma; all that was necessary for a cure was an aggressive enough resection with an adequate margin.[1] Of course, his patients died right on schedule, just like anybody else’s patients. Bucy believed that this was because we just could not identify the true margin of the neoplasm at surgery and that the resection was rarely sufficiently adequate to provide a cure. The advent of computed tomography (CT scanning), magnetic resonance imaging (MRI) and image-guided neuronavigation would change all of this by potentially allowing us to accurately resect as much of a glioma as we chose to resect. Well, I have spent a career trying to cure gliomas with high technology-based surgery – in particular, imaging-based stereotactically guided volumetric resections – but the long-term survival in the vast majority of these patients is not much better than it was 60 years ago! We just do not hurt these patients as badly as we did 60 years ago. And what do we do? We keep throwing more and more expensive surgical high technology at the problem with marginal improvements in survival, if any. To be sure, there are some gliomas that we can cure with modern surgical techniques, such as pilocytic astrocytomas, the occasional oligodendroglioma, neurocytomas, gangliogliomas, subependymomas and a few xanthoastrocytomas and protoplasmic astrocytomas. But this is not a credit to neurosurgeons and our modern surgical methods. It is a function of the growth pattern of these particular tumors that lend themselves to complete and curative surgical excision. These tumors have a distinct boundary where tumor stops and normal brain begins. All that a surgeon has to do in these cases is identify the plane between tumor and surrounding brain tissue, develop that plane and remove the tumor. Image guidance helps a bit. But I will point out that Donald Matson claimed a 50% surgical cure rate in pilocytic astrocytomas over 50 years ago – without any “high technology”. Nonetheless, the “curable” tumors listed above are relatively rare compared to the overwhelmingly more common “fibrillary astrocytomas”, oligodendrogliomas and mixed gliomas. How are we doing with these tumors? Not so great! To be sure, there are many reports in the literature which show that patients having “total resection” and adjuvant therapy do better and live longer than those undergoing biopsy and adjuvant therapy. Comparisons to historical controls attempt to demonstrate the benefit of modern surgical techniques over methods used by past generations. An example of just such an exercise is shown in Figure 1. Figure 1 Post surgical survival following resection in patients with grade IV astrocytomas (glioblastoma) in a recent unpublished series (Kelly 2000) compared to survival curves adapted from earlier studies in the literature (Kelly 1992,[3] Burger 1986,[2] Bucy ... These life table survival curves compare my own experience with cases compiled in the years 1992 (published)[3] and 2000 (not published) to the 1986 series published by Burger et al,[2] Jelsma and Bucy’s series from 1967[4] and Ringertz’s experience from 1950.[2] At first glance at Figure 1, it appears that over the years, we have made some progress with better median and 2-year survivals. Regrettably, these experiences are not really comparable for two important reasons. First, survival times are measured from when surgery is performed and histology is available. Modern imaging methods allow patients to be diagnosed much earlier – usually at the onset of the first symptoms – in contrast to patients from the 1950s and 1960s, who could go for weeks or months before a diagnosis was made and surgery performed. Modern series have the benefit of therapy being delivered earlier in the natural history of the disease and a survival starting point that could be weeks or months earlier than in the past decades. Secondly, modern patients have had the benefit of more effective radiation therapy with linear accelerators instead of cobalt units and more specific chemotherapy. Indeed the improved 2-year survival noted in my 1992 and 2000 series more likely represents the efficacy of carboplatin in the 1980s and temazolamide in the 1990s and not necessarily “better surgery”.

A new approach to percutaneous transhepatic portal embolization using ethanolamine oleate iopamidol

We aimed to examine the therapeutic efficacy of ethanolamine oleate iopamidol (EOI) as an embolic material for percutaneous transhepatic portal embolization (PTPE). Eighty-two patients with liver tumors were treated with PTPE. Fifty-eight patients had hepatocellular carcinomas, 11 had liver metastases, and 13 had other liver tumors. A total of 55 patients (group E) were treated with 5% ethanolamine oleate after gelatin sponge administration. As a control, we evaluated 27 patients (group F) who were treated with fibrin glue and iodized oil. PTPE was mainly indicated before hepatic resection, for patients with high nontumorous volumetric resection ratios (the nontumorous volumetric resection ratio was estimated to be greater than 65% in patients with an indocyanine green retention ratio of 15 min (ICG R15) of 10% or less, and the nontumorous volumetric resection ratio was estimated to be greater than 40% in the patients with an ICG R15 of 10-20%). All patients were successfully treated percutaneously under local anesthesia. Balloon-occluded and ipsilateral approaches were used in 81 patients (99%) and 62 (75%) patients, respectively. The rate of insufficient embolization or recanalization was significantly lower in group E (7.3%) in comparison to group F (25.9%; p < 0.05). The volumetric resection ratios, before and after PTPE, decreased from 60 to 45% in group E and from 63 to 55% in group F. The post-PTPE resection ratio was significantly decreased in group E. Before and after PTPE, average ICG R15 values changed from 17 to 27% in group E and from 18 to 26% in group F. The complication rates in groups E and F were similar (7.3 vs. 7.4%). EOI is a safe embolic material that can be used to induce greater liver hypertrophy, in comparison to fibrin glue, in PTPE for liver tumors.