Daniel Coluccia

First noninvasive thermal ablation of a brain tumor with MR-guided focusedultrasound

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precisethermal ablation of target tissues. While this emerging modality is increasinglyused for the treatment of various types of extracranial soft tissue tumors, ithas only recently been acknowledged as a modality for noninvasive neurosurgery.MRgFUS has been particularly successful for functional neurosurgery, whereas itsclinical application for tumor neurosurgery has been delayed for varioustechnical and procedural reasons. Here, we report the case of a 63-year-oldpatient presenting with a centrally located recurrent glioblastoma who wasincluded in our ongoing clinical phase I study aimed at evaluating thefeasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying25 high-power sonications under MR imaging guidance, partial tumor ablationcould be achieved without provoking neurological deficits or other adverseeffects in the patient. This proves, for the first time, the feasibility ofusing transcranial MR-guided focused ultrasound to safely ablate substantialvolumes of brain tumor tissue.

Use of Fluorescence to Guide Resection or Biopsy of Primary Brain Tumors and Brain Metastases

OBJECT The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)-induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. METHODS The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA-guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. RESULTS A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA-positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA-positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA-positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. CONCLUSIONS Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

Intraoperative Patient-Specific Reconstruction of Partial Bone Flap Defects After Convexity Meningioma Resection

OBJECTIVE To evaluate implant accuracy and cosmetic outcome of a new intraoperative patient-specific cranioplasty method after convexity meningioma resection. METHODS The patients own bone flap served as a template to mold a negative form with the use of polymethyl methacrylate (PMMA). The area of bone invasion was determined and broadly excised under white light illumination with a safety margin of at least 1 cm. The definitive replica was cast within the remaining bone flap frame and the imprint. Clinical and radiologic follow-up examinations were performed 3 months after surgery. RESULTS Four women and two men (mean age 51.4 years±12.8) underwent reconstruction of bone flap defects after meningioma resection. Mean duration of intraoperative reconstruction of the partial bone flap defects was 19 minutes±4 (range 14-24 minutes). Implant sizes ranged from 17-35 cm2 (mean size 22 cm2±8). Radiologic and clinical follow-up examinations revealed excellent implant alignment and favorable cosmesis (visual analogue scale for cosmesis [VASC]=97±5) in all patients. CONCLUSIONS Patient-specific reconstruction of partial bone flap defects after convexity meningioma resection using the presented intraoperative PMMA cast method resulted in excellent bony alignment and a favorable cosmetic outcome. Relatively low costs and minimized operation time for adjustment and insertion of the cranioplasty implant justify use of this method in small bony defects as well.

5-Aminolevulinic Acid Fluorescence-Guided Surgery for Spinal Meningioma

OBJECTIVE Fluorescence-guided surgery for cranial meningioma has been reported to be useful. There are no reports about spinal cases using this technique. We report on a meningioma of the cervical spine for which fluorescence-guided surgery was used. CASE DESCRIPTION A 78-year-old female patient with a meningioma located in the cervical spine underwent surgery using fluorescence guidance. After complete removal of the meningioma and removal and coagulation of the dural attachment (equal to Simpson grade II resection), a fluorescence-positive remnant could be identified and successfully removed. The remnant was found to harbor meningioma tissue on histological examination. CONCLUSIONS Fluorescence-guided microsurgery is helpful in achieving a total resection of spinal meningiomas, and might therefore reduce the risk of recurrence.

Systemic interleukin-6 concentrations in patients with perimesencephalic non-aneurysmal subarachnoid hemorrhage

Patients with spontaneous non-aneurysmal subarachnoid hemorrhage (non-aSAH) are considered to have a benign illness in contrast to patients with aSAH. The occurrence of the systemic inflammatory response syndrome has been linked to worse outcomes in patients with aSAH. We analyzed systemic interleukin (IL)-6, a proinflammatory cytokine, to determine whether its concentration differs between patients with non-aSAH and those with aSAH, reflecting the more benign illness. Daily systemic IL-6 levels were measured in the acute phase in 11 patients with non-aneurysmal perimesencephalic SAH (pmSAH), with bleeding strictly located around the midbrain, and in nine patients with non-aneurysmal non-perimesencephalic (non-pmSAH), with hemorrhage extending into adjacent cisterns (group 1). IL-6 levels were compared with those from patients suffering from aSAH with cerebral vasospasm (CVS) (group 2) and without CVS (group 3). The mean IL-6 level (±standard error of the mean) was significantly lower in group 1 compared to group 2 (9.9±1.9 vs. 29.1±6.7 pg/mL, p=0.018). The difference in mean IL-6 level between group 1 and 3 fell short of significance (9.9±1.9 vs. 14.9±1.1 pg/mL, p=0.073). Patients in group 1 had a significantly better outcome (Glasgow Outcome Scale score 4-5) compared to group 2 (p<0.001) and a trend towards better outcome compared to group 3 (p=0.102). A subgroup analysis revealed a higher mean IL-6 concentration in patients with non-pmSAH compared to patients with pm-SAH (p=0.001). We concluded that systemic IL-6 concentration reflects the severity of the inflammatory stress response and course of the illness. The more benign illness and good prognosis of patients with pmSAH or non-pmSAH in contrast to patients with aSAH is reflected by the lower concentrations of IL-6.

Long-term patency of complex bilobular, bisaccular, and broad-neck aneurysms in the rabbit microsurgical venous pouch bifurcation model.

Abstract Objectives: In experimental aneurysm models, long-term patency without spontaneous thrombosis is the most important precondition for analyses of embolization devices. We recently reported the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, low mortality, and high short-term aneurysm patency. In order to further evaluate our model, we examined the long-term patency rate. Methods: Various sizes of complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both common carotid arteries in 17 rabbits. Early aggressive anticoagulation was continued for 1 month. The rabbits were followed up using contrast-enhanced three-dimensional 1·5-T magnetic resonance angiography (CE-3D-MRA) at 1 month and up to 1 year after creation of the bifurcation. Results: At 1-month follow-up, all but one of the created aneurysms and all parent vessels proved to be patent. Three animals (18%) were lost during follow-up for reasons unrelated to aneurysm surgery. At 1-year follow-up, one animal showed partial and one complete spontaneous aneurysm thrombosis (aneurysm patency rate: 86%). Six out of 42 parent vessels were occluded at that time (vessel patency rate: 86%). Conclusions: Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model demonstrates a high long-term patency rate but is complicated by high rates of unrelated procedural mortality and morbidity. There is no need for prolonged (>4 weeks) anticoagulation to achieve good long-term patency in complex venous pouch bifurcation aneurysms.

Intraoperative Fluoroscopy for Ventriculoperitoneal Shunt Placement.

OBJECTIVE Catheter malpositioning is one of the most frequent causes of ventriculoperitoneal shunt dysfunction and revision surgery. Most intraoperative tools used to improve the accuracy of catheter insertion are time consuming and expensive or do not display the final position. We evaluate the usefulness of intraoperative fluoroscopy to decrease catheter malpositioning, and define radiological landmarks to identify the correct localization. METHODS A total of 104 patients undergoing ventriculoperitoneal shunt placement were analyzed for shunt position, revision surgery and outcome. The results for patients operated on using intraoperative biplanar fluoroscopic assessment of catheter location (X-ray group, n = 57) were compared with a control group operated without intraoperative radiography (control, n = 47). In order to generate a surgical reference map for intraoperative validation of shunt location, different ventricular system landmarks were defined on three-dimensional computed tomography reconstructions of hydrocephalic patients (n = 60) and exported to a two-dimensional layer of the skull. RESULTS The use of intraoperative X-ray imaging correlated with a significant increase of optimal catheter positions (X-ray group, n = 45, 79%; control group, n = 23, 49%; P = 0.0018). The sensitivity and positive predictive value for estimating an optimal shunt catheter position on biplanar imaging was 96% (95% confidence interval, 87%-99%). The specificity and negative predictive value were both 92% (95% confidence interval, 78%-98%). CONCLUSIONS Intraoperative fluoroscopy is easy to perform and is a reliable method to assess correct catheter positioning. Based on its predictive value, corrections of malpositioned ventricular catheters can be performed during the same procedure. The use of intraoperative fluoroscopy decreases early surgical revisions in ventriculoperitoneal shunt treatment.

An Interlaminotomy New Zealand White Rabbit Model to Evaluate Novel Epidural Strategies.

OBJECTIVE The New Zealand White (NZW) rabbit model is an established animal model for examining surgical methods to prevent epidural scar formation after spine surgery. As most approaches include complete laminectomy of the rabbit vertebra, this procedure is associated with high morbidity and mortality rates. We examined a less invasive technique, the microsurgical interlaminotomy, for testing epidural substance application in the rabbit spine. METHODS Surgery was performed in the cadaver rabbit spine to evaluate the approach before performing it in NZW rabbits. All surgical procedures were performed under an operation microscope. Female rabbits with a mean weight of 4770 g  ±  240 g were used. Neurologic symptoms were analyzed based on predefined scores. After resection of the spinal process, the caudal part of the upper lamina was resected using a drill and a 1-mm Kerrison punch. The yellow ligament was resected resulting in a dural exposure of ∼ 5 × 10 mm. RESULTS Eight pilot interlaminotomies were performed on three cadaveric spines to establish the surgical approach. Twenty-one NZW rabbits were then operated on using the interlaminotomy model. Three rabbits (14.3%) died during surgery due to anesthesia-related complications. Two rabbits (9.5%) showed partial paresis of the lower extremities and one (4.8%) a complete paraplegia. The remaining 15 rabbits (71.4%) had an uneventful recovery without neurologic symptoms. The mean surgical duration was 88 +/- 28 minutes. CONCLUSION The rabbit interlaminotomy model is associated with few neurologic deficits and a relatively short operating time.

Comparison between routine cylindrical cerebral aneurysm volume approximation and three-dimensional volume measurements in experimental aneurysms

Abstract Objectives: Aneurysm volume is routinely approximated calculating cylindrical volumes. Exact aneurysm volume assessment is crucial for liquid polymer embolization. The aim of this study was to compare simple cylindrical volume approximations with direct multiplanar reconstruction (MPR) segmentational volumetry in a saccular/complex experimental rabbit bifurcation aneurysm model. Methods: In 12 female New Zealand white rabbits, saccular, broad-based, bilobular, and bisaccular aneurysms (three of each) were created using the rabbit venous pouch bifurcation model. Contrast-enhanced magnetic resonance angiography (CE-MRA) was performed, and maximal intensity projection (MIP) reconstructions as well as an MPR dataset were acquired. Aneurysm width and length were measured in MIP images, and the volume was approximated calculating cylindrical volumes. Three-dimensional (3D) segmentational volumetry using the MPR dataset was performed in a semi-automated manner. Results: Maximal intensity projection cylindrical volumes ranged from 53·6 to 503·5 mm3 (mean 186·5±118 mm3). Multiplanar reconstruction segmentation-based volumes ranged from 74·7 to 581·0 mm3 (mean 202·2±133 mm3). The mean relative difference between MIP cylindrical and MPR segmentation volume calculation was 24·7% (range −77·5 to +50·8%). Only 4 of 12 MPR segmentational volumes were within a 10% range of results calculated for MIP cylindrical volume, and 3 of those were in broad-based aneurysms. Conclusion: This descriptive study demonstrates that estimated MIP cylindrical volumes differ from those measured by MPR segmentation volumetry. With the increasing acquisition of 3D data as 3D-MRA and the increasing need for exact volume determination, studies on the accuracy of computational segmentational volumetry of CE-MRA are necessary.

Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model. Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing >500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique. Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 ± 22 min, 26 ± 6 min and 11 ± 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis). The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing.