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Atman Desai, Perry A. Ball, Kimon Bekelis, Jon D. Lurie, Sohail K. Mirza, Tor D. Tosteson and James N. Weinstein

Object

Incidental durotomy is an infrequent but well-recognized complication during lumbar disc surgery. The effect of a durotomy on long-term outcomes is, however, controversial. The authors sought to examine whether the occurrence of durotomy during surgery impacts long-term clinical outcome.

Methods

Spine Patient Outcomes Research Trial (SPORT) participants who had a confirmed diagnosis of intervertebral disc herniation and were undergoing standard first-time open discectomy were followed up at 6 weeks and at 3, 6, and 12 months after surgery and annually thereafter at 13 spine clinics in 11 US states. Patient data from this prospectively gathered database were reviewed. As of May 2009, the mean (± SD) duration of follow-up among all of the intervertebral disc herniation patients whose data were analyzed was 41.5 ± 14.5 months (41.4 months in those with no durotomy vs 40.2 months in those with durotomy, p < 0.68). The median duration of follow-up among all of these patients was 47 months (range 1–95 months).

Results

A total of 799 patients underwent first-time lumbar discectomy. There was an incidental durotomy in 25 (3.1%) of these cases. There were no significant differences between the durotomy and no-durotomy groups with respect to age, sex, race, body mass index, herniation level or type, or the prevalence of smoking, diabetes, or hypertension. When outcome differences between the groups were analyzed, the durotomy group was found to have significantly increased operative duration, operative blood loss, and length of inpatient stay. However, there were no significant differences in incidence rates for nerve root injury, postoperative mortality, additional surgeries, or SF-36 scores for Bodily Pain or Physical Function, or Oswestry Disability Index scores at 1, 2, 3, or 4 years.

Conclusions

Incidental durotomy during first-time lumbar discectomy does not appear to impact long-term outcome in affected patients.

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Pablo A. Valdés, Frederic Leblond, Anthony Kim, Brent T. Harris, Brian C. Wilson, Xiaoyao Fan, Tor D. Tosteson, Alex Hartov, Songbai Ji, Kadir Erkmen, Nathan E. Simmons, Keith D. Paulsen and David W. Roberts

Object

Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies.

Methods

The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo.

Results

A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors.

Conclusions

These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

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Daniel Ikeda and E. Antonio Chiocca

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David W. Roberts, Pablo A. Valdés, Brent T. Harris, Kathryn M. Fontaine, Alexander Hartov, Xiaoyao Fan, Songbai Ji, S. Scott Lollis, Brian W. Pogue, Frederic Leblond, Tor D. Tosteson, Brian C. Wilson and Keith D. Paulsen

Object

The aim of this study was to investigate the relationships between intraoperative fluorescence, features on MR imaging, and neuropathological parameters in 11 cases of newly diagnosed glioblastoma multiforme (GBM) treated using protoporphyrin IX (PpIX) fluorescence-guided resection.

Methods

In 11 patients with a newly diagnosed GBM, δ-aminolevulinic acid (ALA) was administered to enhance endogenous synthesis of the fluorophore PpIX. The patients then underwent fluorescence-guided resection, coregistered with conventional neuronavigational image guidance. Biopsy specimens were collected at different times during surgery and assigned a fluorescence level of 0–3 (0, no fluorescence; 1, low fluorescence; 2, moderate fluorescence; or 3, high fluorescence). Contrast enhancement on MR imaging was quantified using two image metrics: 1) Gd-enhanced signal intensity (GdE) on T1-weighted subtraction MR image volumes, and 2) normalized contrast ratios (nCRs) in T1-weighted, postGd-injection MR image volumes for each biopsy specimen, using the biopsy-specific image-space coordinate transformation provided by the navigation system. Subsequently, each GdE and nCR value was grouped into one of two fluorescence categories, defined by its corresponding biopsy specimen fluorescence assessment as negative fluorescence (fluorescence level 0) or positive fluorescence (fluorescence level 1, 2, or 3). A single neuropathologist analyzed the H & E–stained tissue slides of each biopsy specimen and measured three neuropathological parameters: 1) histopathological score (0–IV); 2) tumor burden score (0–III); and 3) necrotic burden score (0–III).

Results

Mixed-model analyses with random effects for individuals show a highly statistically significant difference between fluorescing and nonfluorescing tissue in GdE (mean difference 8.33, p = 0.018) and nCRs (mean difference 5.15, p < 0.001). An analysis of association demonstrated a significant relationship between the levels of intraoperative fluorescence and histopathological score (χ2 = 58.8, p < 0.001), between fluorescence levels and tumor burden (χ2 = 42.7, p < 0.001), and between fluorescence levels and necrotic burden (χ2 = 30.9, p < 0.001). The corresponding Spearman rank correlation coefficients were 0.51 (p < 0.001) for fluorescence and histopathological score, and 0.49 (p < 0.001) for fluorescence and tumor burden, suggesting a strongly positive relationship for each of these variables.

Conclusions

These results demonstrate a significant relationship between contrast enhancement on preoperative MR imaging and observable intraoperative PpIX fluorescence. The finding that preoperative MR image signatures are predictive of intraoperative PpIX fluorescence is of practical importance for identifying candidates for the procedure. Furthermore, this study provides evidence that a strong relationship exists between tumor aggressiveness and the degree of tissue fluorescence that is observable intraoperatively, and that observable fluorescence has an excellent positive predictive value but a low negative predictive value.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010