Zoher Ghogawala

Spinal radiation before surgical decompression adversely affects outcomes of surgery for symptomatic metastatic spinal cord compression.

Study Design. A retrospective chart review was performed. Objective. To determine whether preoperative spinal radiation increases the number of major wound complications in patients with cancer who have symptomatic spinal cord compression. Summary of Background Data. Many factors have increased the number of patients hospitalized with symptomatic spinal cord compression after spinal irradiation. The surgical management of metastatic spinal cord compression may be complicated by preoperative radiation. Methods. A retrospective review of 123 patients admitted with symptomatic metastatic spinal cord compression from 1970 through 1996 was conducted. The final study population of 85 patients was separated into three treatment groups: 1) radiation only, 2) radiation followed by surgery, and 3) de novo surgery followed by radiation. Results. The major wound complication rate for patients who had radiation before surgical decompression and stabilization was 32%, or threefold, higher than the 12% observed in patients who had de novo surgery (P < 0.05). No other clinical factor or condition predicted the development of a major wound complication. Patients treated initially with surgery had superior functional outcomes in an analysis stratified by Frankel grade (P < 0.05). Of the ambulatory patients who underwent de novo surgery, 75% remained ambulatory and continent 30 days after treatment, whereas only 50% of those treated with radiation before surgery had similar outcomes. Conclusions. Spinal radiation before surgical decompression for metastatic spinal cord compression is associated with a significantly higher major wound complication rate. In addition, preoperative spinal irradiation might adversely affect the surgical outcome.

Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis.

BACKGROUND The comparative effectiveness of performing instrumented (rigid pedicle screws affixed to titanium alloy rods) lumbar spinal fusion in addition to decompressive laminectomy in patients with symptomatic lumbar grade I degenerative spondylolisthesis with spinal stenosis is unknown. METHODS In this randomized, controlled trial, we assigned patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone (decompression-alone group) or laminectomy with posterolateral instrumented fusion (fusion group). The primary outcome measure was the change in the physical-component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; range, 0 to 100, with higher scores indicating better quality of life) 2 years after surgery. The secondary outcome measure was the score on the Oswestry Disability Index (range, 0 to 100, with higher scores indicating more disability related to back pain). Patients were followed for 4 years. RESULTS A total of 66 patients (mean age, 67 years; 80% women) underwent randomization. The rate of follow-up was 89% at 1 year, 86% at 2 years, and 68% at 4 years. The fusion group had a greater increase in SF-36 physical-component summary scores at 2 years after surgery than did the decompression-alone group (15.2 vs. 9.5, for a difference of 5.7; 95% confidence interval, 0.1 to 11.3; P=0.046). The increases in the SF-36 physical-component summary scores in the fusion group remained greater than those in the decompression-alone group at 3 years and at 4 years (P=0.02 for both years). With respect to reductions in disability related to back pain, the changes in the Oswestry Disability Index scores at 2 years after surgery did not differ significantly between the study groups (-17.9 in the decompression-alone group and -26.3 in the fusion group, P=0.06). More blood loss and longer hospital stays occurred in the fusion group than in the decompression-alone group (P<0.001 for both comparisons). The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group (P=0.05). CONCLUSIONS Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).

Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors

The demonstration that angiogenesis is required for the growth of solid tumors has fueled an intense interest in the development of new therapeutic strategies that target the tumor vasculature. Here we report the development of an immune-based antiangiogenic strategy that is based on the generation of T lymphocytes that possess a killing specificity for cells expressing vascular endothelial growth factor receptors (VEGFRs). To target VEGFR-expressing cells, recombinant retroviral vectors were generated that encoded a chimeric T cell receptor comprised of VEGF sequences linked to intracellular signaling sequences derived from the ζ chain of the T cell receptor. After transduction of primary murine CD8 lymphocytes by such vectors, the transduced cells were shown to possess an efficient killing specificity for cells expressing the VEGF receptor, Flk-1, as measured by in vitro cytotoxicity assays. After adoptive transfer into tumor-bearing mice, the genetically modified cytotoxic T lymphocytes strongly inhibited the growth of a variety of syngeneic murine tumors and human tumor xenografts. An increased effect on in vivo tumor growth inhibition was seen when this therapy was combined with the systemic administration of TNP-470, a conventional angiogenesis inhibitor. The utilization of the immune system to target angiogenic markers expressed on tumor vasculature may prove to be a powerful means for controlling tumor growth.

Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 11: interbody techniques for lumbar fusion.

Interbody fusion techniques have been promoted as an adjunct to lumbar fusion procedures in an effort to enhance fusion rates and potentially improve clinical outcome. The medical evidence continues to suggest that interbody techniques are associated with higher fusion rates compared with posterolateral lumbar fusion (PLF) in patients with degenerative spondylolisthesis who demonstrate preoperative instability. There is no conclusive evidence demonstrating improved clinical or radiographic outcomes based on the different interbody fusion techniques. The addition of a PLF when posterior or anterior interbody lumbar fusion is performed remains an option, although due to increased cost and complications, it is not recommended. No substantial clinical benefit has been demonstrated when a PLF is included with an interbody fusion. For lumbar degenerative disc disease without instability, there is moderate evidence that the standalone anterior lumbar interbody fusion (ALIF) has better clinical outcomes than the ALIF plus instrumented, open PLF. With regard to type of interbody spacer used, frozen allograft is associated with lower pseudarthrosis rates compared with freeze-dried allograft; however, this was not associated with a difference in clinical outcome.

Cognitive outcomes after carotid revascularization: the role of cerebral emboli and hypoperfusion.

OBJECTIVE Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are currently being compared in ongoing randomized, controlled trials using postprocedural 30-day stroke rate, myocardial infarction, and mortality as primary endpoints. Recent data suggest that cognitive function may decline after CEA. Understanding the mechanisms that affect cognitive outcomes after carotid revascularization will be important in the design of future comparative studies of CAS and CEA incorporating cognitive outcome as an endpoint. SUMMARY OF REVIEW The effects of carotid revascularization procedures on cognitive outcome are unclear. Several factors contribute to the difficulty in interpreting cognitive data, including patient heterogeneity, variability of surgical techniques, and the differences in neuropsychological testing methodology. Mechanisms underlying cognitive effects during CEA have emerged, including the potential detrimental effect of procedural emboli and the beneficial effect of improved cerebral hemodynamics. The emergence of CAS as an alternative to CEA for treating carotid stenosis again raises questions about cognitive outcomes. Despite the use of distal protection devices, CAS is associated with a higher burden of microemboli. CAS does not, however, require the extent of temporary vessel occlusion associated with CEA. Quantifying microemboli and changes in cerebral hemodynamics along with standardization of neuropsychological testing may lead to meaningful comparisons of cognitive data for patients undergoing carotid revascularization procedures. CONCLUSION As use of CAS increases, it is important for randomized, controlled trials comparing CAS with CEA to include cognitive outcomes assessments. Furthermore, understanding the key mechanisms resulting in cognitive impairment during carotid revascularization procedures might limit injury.

Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 4: radiographic assessment of fusion status.

The ability to identify a successful arthrodesis is an essential element in the management of patients undergoing lumbar fusion procedures. The hypothetical gold standard of intraoperative exploration to identify, under direct observation, a solid arthrodesis is an impractical alternative. Therefore, radiographic assessment remains the most viable instrument to evaluate for a successful arthrodesis. Static radiographs, particularly in the presence of instrumentation, are not recommended. In the absence of spinal instrumentation, lack of motion on flexion-extension radiographs is highly suggestive of a successful fusion; however, motion observed at the treated levels does not necessarily predict pseudarthrosis. The degree of motion on dynamic views that would distinguish between a successful arthrodesis and pseudarthrosis has not been clearly defined. Computed tomography with fine-cut axial images and multiplanar views is recommended and appears to be the most sensitive for assessing fusion following instrumented posterolateral and anterior lumbar interbody fusions. For suspected symptomatic pseudarthrosis, a combination of techniques including static and dynamic radiographs as well as CT images is recommended as an option. Lack of facet fusion is considered to be more suggestive of a pseudarthrosis compared with absence of bridging posterolateral bone. Studies exploring additional noninvasive modalities of fusion assessment have demonstrated either poor potential, such as with (99m)Tc bone scans, or provide insufficient information to formulate a definitive recommendation.

Comparative Effectiveness of Ventral vs Dorsal Surgery for Cervical Spondylotic Myelopathy

BACKGROUND:Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction. OBJECTIVE:To determine the feasibility of a randomized clinical trial comparing the clinical effectiveness and costs of ventral vs dorsal decompression with fusion surgery for treating CSM. METHODS:A nonrandomized, prospective, clinical pilot trial was conducted. Patients ages 40 to 85 years with degenerative CSM were enrolled at 7 sites over 2 years (2007-2009). Outcome assessments were obtained preoperatively and at 3 months, 6 months, and 1 year postoperatively. A hospital-based economic analysis used costs derived from hospital charges and Medicare cost-to-charge ratios. RESULTS:The pilot study enrolled 50 patients. Twenty-eight were treated with ventral fusion surgery and 22 with dorsal fusion surgery. The average age was 61.6 years. Baseline demographics and health-related quality of life (HR-QOL) scores were comparable between groups; however, dorsal surgery patients had significantly more severe myelopathy (P < .01). Comprehensive 1-year follow-up was obtained in 46 of 50 patients (92%). Greater HR-QOL improvement (Short-Form 36 Physical Component Summary) was observed after ventral surgery (P = .05). The complication rate (16.6% overall) was comparable between groups. Significant improvement in the modified Japanese Orthopedic Association scale score was observed in both groups (P < .01). Dorsal fusion surgery had significantly greater mean hospital costs (

Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 8: lumbar fusion for disc herniation and radiculopathy.

29 465 vs

Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 9: Lumbar fusion for stenosis with spondylolisthesis

19 245; P < .01) and longer average length of hospital stay (4.0 vs 2.6 days; P < .01) compared with ventral fusion surgery. CONCLUSION:Surgery for treating CSM was followed by significant improvement in disease-specific symptoms and in HR-QOL. Greater improvement in HR-QOL was observed after ventral surgery. Dorsal fusion surgery was associated with longer length of hospital stay and higher hospital costs. The pilot study demonstrated feasibility for a larger randomized clinical trial.

The National Neurosurgery Quality and Outcomes Database and NeuroPoint Alliance: rationale, development, and implementation.

Patients suffering from a lumbar herniated disc will typically present with signs and symptoms consistent with radiculopathy. They may also have low-back pain, however, and the source of this pain is less certain, as it may be from the degenerative process that led to the herniation. The surgical alternative of choice remains a lumbar discectomy, but fusions have been performed for both primary and recurrent disc herniations. In the original guidelines, the inclusion of a fusion for routine discectomies was not recommended. This recommendation continues to be supported by more recent evidence. Based on low-level evidence, the incorporation of a lumbar fusion may be considered an option when a herniation is associated with evidence of spinal instability, chronic low-back pain, and/or severe degenerative changes, or if the patient participates in heavy manual labor. For recurrent disc herniations, there is low-level evidence to support the inclusion of lumbar fusion for patients with evidence of instability or chronic low-back pain.