Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients

PURPOSE: Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity

Tailored Extended Bifrontal Craniotomy for Anterior Skull Base Tumors: Anatomic Description of a Modified Surgical Technique and Case Series.

BACKGROUND:Open transcranial approaches to the anterior skull base remain an integral component of current skull base practice. Evolution of these and other techniques has resulted in revisions of standard, tried-and-true methods in attempts to improve patient outcomes and cosmesis, while still providing the best combination of surgical exposure and ergonomics. OBJECTIVE:To describe a modified approach for midline tumors of the anterior skull base. METHODS:We describe the anatomy and techniques of a modified extended bifrontal craniotomy for anterior skull base tumors. Case examples and a postoperative 3-dimensional computed tomographic reconstruction of the craniotomy are provided. RESULTS:The technique has been employed with success in 3 tuberculum sellae meningiomas where the anterior limit of the tumor is several centimeters back from the inner table of the frontal bone. The mean distance from the tumor to inner table was 2.8 cm (range 1.3-3.8 cm). Mean tumor dimensions were 3.0 cm (transverse), 3.5 cm (anterior-posterior), and 2.2 cm (craniocaudal). Average operative time was 557 min. No cases had new T2/fluid-attenuated inversion recovery magnetic resonance imaging signal of the inferior frontal lobe to indicate retraction injury. CONCLUSION:The tailored extended bifrontal craniotomy for anterior skull base tumors provides adequate access to the anterior cranial fossa and has replaced our standard extended bifrontal approach. Keeping the osteotomy cut lines outside of the orbit reduces orbital swelling and mechanical disruption of conjugate eye movements in the early postoperative period, while allowing for minimal frontal lobe retraction and providing sufficient surgical exposure along the anterior skull base

Tailored Extended Bifrontal Craniotomy for Anterior Skull Base Tumors: Anatomic Description of a Modified Surgical Technique and Case Series.

BACKGROUND:Open transcranial approaches to the anterior skull base remain an integral component of current skull base practice. Evolution of these and other techniques has resulted in revisions of standard, tried-and-true methods in attempts to improve patient outcomes and cosmesis, while still providing the best combination of surgical exposure and ergonomics. OBJECTIVE:To describe a modified approach for midline tumors of the anterior skull base. METHODS:We describe the anatomy and techniques of a modified extended bifrontal craniotomy for anterior skull base tumors. Case examples and a postoperative 3-dimensional computed tomographic reconstruction of the craniotomy are provided. RESULTS:The technique has been employed with success in 3 tuberculum sellae meningiomas where the anterior limit of the tumor is several centimeters back from the inner table of the frontal bone. The mean distance from the tumor to inner table was 2.8 cm (range 1.3-3.8 cm). Mean tumor dimensions were 3.0 cm (transverse), 3.5 cm (anterior-posterior), and 2.2 cm (craniocaudal). Average operative time was 557 min. No cases had new T2/fluid-attenuated inversion recovery magnetic resonance imaging signal of the inferior frontal lobe to indicate retraction injury. CONCLUSION:The tailored extended bifrontal craniotomy for anterior skull base tumors provides adequate access to the anterior cranial fossa and has replaced our standard extended bifrontal approach. Keeping the osteotomy cut lines outside of the orbit reduces orbital swelling and mechanical disruption of conjugate eye movements in the early postoperative period, while allowing for minimal frontal lobe retraction and providing sufficient surgical exposure along the anterior skull base

Posterior osteotomy techniques for rigid cervical deformity correction

Posterior cervical osteotomies are powerful techniques for the correction of rigid cervical deformity. These include a variety of subtypes including partial facet joint resection, complete facet joint resection, opening wedge osteotomy (OWO), and closing wedge osteotomy (CWO). The partial facet joint resection provides limited lordosis but can be applied across multiple levels and provides bony surface for fusion. Complete facet joint resection can also be performed across multiple segments for a cumulative effect and like the partial facet joint resection requires mobility of the anterior column. The OWO is traditionally performed at C7 and involves complete a complete laminectomy, facetectomy, and pediculectomy with special care to fully decompress the C8 nerve roots prior to osteotomy closure. The osteotomy utilizes a fulcrum of rotation in the middle column with shortening of the posterior column and lengthening of the anterior column with an osteoclastic fracture that must be performed with significant care. The CWO is similar to an OWO with the addition of an osteotomy into the vertebral body that is closed like a pedicle subtraction osteotomy (PSO). The goal of this review article is to summarize posterior osteotomy techniques for cervical deformity correction

Sacral epidural arteriovenous fistulas: imitators of spinal dural arteriovenous fistulas with different pathologic anatomy: report of three cases and review of the literature

Background: Sacral epidural arteriovenous fistulas (eAVFs) are rare and often misdiagnosed because of the incongruence between the thoracic level of clinical deficits and the sacral location of the offending pathology. Failure to diagnose this lesion delays treatment, resulting in prolonged venous hypertension in the cord, progressive neurological deterioration, and decreased chances of recovery. Methods: A single-institution case series and the published literature were reviewed. Results: Three patients had sacral eAVFs are located in the ventral epidural space with outflow connections to radicular veins that arterialized spinal cord veins, all presenting with thoracic myelopathy, venous engorgement, and delayed diagnosis. All eAVFs were occluded completely with radiographic and clinical improvement. Conclusions: Sacral eAVF pathophysiology, namely venous hypertension and compromised spinal cord circulation, is exactly the same as dural AVFs, as is their treatment: the interruption of outflow by occlusion of the draining vein, which effectively eliminates venous hypertension, without occlusion of the actual fistula itself. Epidural exposure of sacral eAVFs is not necessary, whereas complete intradural occlusion of their radicular drainage is. Draining radicular veins intermingle with the nerve roots and their occasional multiplicity makes them more difficult to identify intraoperatively