Establishing a Standardized Clinical Consensus for Reporting Complications Following Lateral Lumbar Interbody Fusion.

Background and Objectives: Mitigating post-operative complications is a key metric of success following interbody fusion. LLIF is associated with a unique complication profile when compared to other approaches, and while numerous studies have attempted to report the incidence of post-operative complications, there is currently no consensus regarding their definitions or reporting structure. The aim of this study was to standardize the classification of complications specific to lateral lumbar interbody fusion (LLIF). Materials and Methods: A search algorithm was employed to identify all the articles that described complications following LLIF. A modified Delphi technique was then used to perform three rounds of consensus among twenty-six anonymized experts across seven countries. Published complications were classified as major, minor, or non-complications using a 60% agreement threshold for consensus. Results: A total of 23 articles were extracted, describing 52 individual complications associated with LLIF. In Round 1, forty-one of the fifty-two events were identified as a complication, while seven were considered to be approach-related occurrences. In Round 2, 36 of the 41 events with complication consensus were classified as major or minor. In Round 3, forty-nine of the fifty-two events were ultimately classified into major or minor complications with consensus, while three events remained without agreement. Vascular injuries, long-term neurologic deficits, and return to the operating room for various etiologies were identified as important consensus complications following LLIF. Non-union did not reach significance and was not classified as a complication. Conclusions: These data provide the first, systematic classification scheme of complications following LLIF. These findings may improve the consistency in the future reporting and analysis of surgical outcomes following LLIF.

The use of a new high-speed shielded curved drill is associated with improved intraoperative and clinical outcomes after cervical corpectomy and fusion procedures: a retrospective case series.

BACKGROUND: Anterior cervical corpectomy and fusion (ACCF) is an effective technique to address multi-level degenerative cervical myelopathy. However, as the number of surgical levels increases, the outcomes worsen with respect to complication rates, range of motion and length of surgery. This study aimed to determine the clinical outcome of ACCF procedures performed using a new distally curved and shielded drilling device. METHODS: A retrospective study was conducted on 43 ACCF procedures in which the device was used for osteophyte removal. Patient files were reviewed to assess the early clinical results and complications following ACCF. Clinical outcomes were evaluated using patient neck and arm pain scores and SF-36 questionnaires. Hospitalization characteristics were compared with historical controls. RESULTS: All procedures were uneventful and without major complications or neurological deterioration. Single-level ACCF procedures required an average of 71 min and followed by an average hospitalization of 3.3 days. Osteophyte removal, verified by intraoperative imaging, was satisfactory. Average neck pain score was improved by 0.9 points (p = 0.24). Average arm pain score was improved by 1.8 points (p = 0.06). SF-36 scores were improved in all domains. CONCLUSIONS: The new curved device enabled safe and efficient removal of osteophytes sparing adjacent vertebral removal in ACCF procedures, thus improving the clinical outcome.

Can a bioactive interbody device reduce the cost burden of achieving lateral lumbar fusion?

OBJECTIVE: Intervertebral devices are increasingly utilized for fusion in the lumbar spine, along with a variety of bone graft materials. These various grafting materials often have substantial cost burdens for the surgical procedure, although they are necessary to overcome the limitations in healing capacity for many traditional interbody devices. The use of bioactive interbody fusion devices, which have demonstrable stimulatory capacity for the surrounding osteoblasts and osteoprogenitor cells and allow for osseointegration, may reduce this heavy reliance on osteobiologics for achieving interbody fusion. The objective of this study was to evaluate the rate of successful interbody fusion with a bioactive lateral lumbar interbody titanium implant with limited volume and low-cost graft material. METHODS: The authors conducted a retrospective study (May 2017 to October 2018) of consecutively performed lateral lumbar interbody fusions with a bioactive 3D-printed porous titanium interbody device. Each interbody device was filled with 2-3 cm3/cage of a commercially available ceramic bone extender (ß-tricalcium phosphate-hydroxyapatite) and combined with posterior pedicle screw fixation. No other biological agents or grafts were utilized. Demographic, clinical, and radiographic variables were captured. Fusion success was the primary endpoint of the study, with graft subsidence, fixation failure, and patient-reported outcomes (Oswestry Disability Index [ODI] and visual analog scale [VAS]-back and -leg pain scores) collected as secondary endpoints. The authors utilized a CT-based fusion classification system that accounted for both intervertebral through-growth (bone bridging) and ingrowth (integration of bone at the endplate-implant interface). RESULTS: In total, 136 lumbar levels were treated in 90 patients. The mean age was 69 years, and 63% of the included patients were female. Half (50.0%) had undergone previous spinal surgery, and a third (33.7%) had undergone prior lumbar fusion. A third (33.7%) were treated at multiple levels (mean levels per patient 1.51). One year after surgery, the mean improvements in patient-reported outcomes (vs preoperative scores) were -17.8 for ODI (p < 0.0001), -3.1 for VAS-back pain (p < 0.0001), and -2.9 for VAS-leg pain (p < 0.0001). Bone bridging and/or appositional integrity was achieved in 99.3% of patients, including 97.8% who had complete bone bridging. No fixation loosening or implant failure was observed at any segment. Low-grade graft subsidence (Marchi grade ≤ I) occurred in 3 levels (2.2%), and intraoperative endplate violation occurred twice (1.5%). High-grade subsidence was not found. No implant failure or revision surgery for pseudarthrosis/subsidence was necessary. CONCLUSIONS: The use of bioactive titanium interbody devices with a large surface footprint appears to result in a very high rate of effective fusion, despite the use of a small volume of low-cost biological material. This potential change in the osteobiologics required to achieve high fusion rates may have a substantially beneficial impact on the economic burden inherent to spinal fusion.

Multilevel Minimally Invasive Lumbar Decompression: Clinical Efficacy and Durability to 2 Years.

BACKGROUND: The clinical efficacy of single-level minimally invasive lumbar decompression and/or microdiscectomy is well established, with improved postoperative functional outcome and pain scores. However, there is a paucity of clinical data supporting the use of minimally invasive (MIS) techniques in a single operation to address pathology at multiple lumbar levels, and this study attempts to address this issue. METHODS: A retrospective review of prospectively collected data from patients with symptomatic lumbar stenosis and/or disc herniations who underwent multilevel minimally invasive decompression or microdiscectomy from November 2014 to February 2018 was conducted at a single academic medical center. Patient-reported outcome measures (PROMs), including the Oswestry Disability Index (ODI), visual analog scale (VAS) for back and leg pain, 12-Item Short Form Health Survey (SF-12) Physical Component Summary Score (PCS) and Mental Component Summary Score (MCS), and Scoliosis Research Society survey (SRS-30), were prospectively collected before surgery and at 3 months, 6 months, 1 year, and 2 years postoperatively. RESULTS: During the study period, 92 patients received multilevel (≥2 level) MIS lumbar decompression and/or discectomy (69 two level, 21 three level, 2 four level). The mean age at surgery was 69.7 years, and 23 (25%) patients were women. Patient-reported outcomes were significantly improved both in the short and long term except for the SF-12 MCS. Average improvement from baseline was (at 3 months and 2 years, respectively): VAS back, -3.9 and -2.8; VAS leg, -3.6 and -2.6; ODI, -13 and -14.6; SF-12 MCS, 2.8 and -0.3; SF-12 PCS, 6.9 and 10.1; and SRS-30, 0.57 and 0.55. Minimal clinically important difference for the study population was reached for every PROM except SF-12 MCS. Surgical complications occurred in 16 patients (17.4%), and 8 patients (8.6%) required postoperative fusions within 2 years. CONCLUSION: The use of MIS techniques to perform lumbar decompression and/or discectomy at multiple levels was found to be both clinically effective and durable. Fusion rates remained low 2 years after the index surgery and were consistent with literature data for open procedures. LEVEL OF EVIDENCE: 2.

Transforaminal lumbar interbody fusion using a novel minimally invasive expandable interbody cage: patient-reported outcomes and radiographic parameters.

OBJECTIVE: The goal of this study was to evaluate the clinical and radiographic outcomes of a novel multidirectional in situ expandable minimally invasive surgery (MIS) transforaminal lumbar interbody fusion (TLIF) cage. METHODS: A retrospective analysis of 69 consecutive patients undergoing a 1- or 2-level MIS TLIF using an expandable cage was performed over a 2-year period. Standard MIS techniques with pedicle screw fixation were used in all cases. Upright lateral dynamic flexion/extension radiographs were reviewed prior to and at 1 year after surgery. Clinical metrics included numeric rating scale for back and leg pain, Oswestry Disability Index, and the SF-12 and VR-12 physical and mental health surveys. Radiographic parameters included anterior and posterior disc height, neuroforaminal height, spondylolisthesis, segmental lordosis, lumbar lordosis, and fusion rate. RESULTS: A total of 69 patients representing 75 operative levels met study inclusion criteria. The mean patient age at surgery was 63.4 ± 1.2 years, with a female predominance of 51%. The average radiographic and clinical follow-ups were 372 and 368 days, respectively. A total of 63 patients (91%) underwent 1-level surgery and 6 patients (9%) underwent 2-level surgery. Significant reductions of numeric rating scale scores for back and leg pain were observed-from 6.1 ± 0.7 to 2.5 ± 0.3 (p < 0.0001) and 4.9 ± 0.6 to 1.9 ± 0.2 (p < 0.0001), respectively. A similar reduction in Oswestry Disability Index from 38.0 ± 4.6 to 20.0 ± 2.3 (p < 0.0001) was noted. Likewise, SF-12 and VR-12 scores all showed statistically significant improvement from baseline (p < 0.001). The mean anterior and posterior disc heights improved from 8.7 ± 1.0 mm to 13.4 ± 1.5 mm (p = 0.0001) and 6.5 ± 0.8 mm to 9.6 ± 1.1 mm (p = 0.0001), respectively. Neuroforaminal height improved from 17.6 ± 2.0 mm to 21.9 ± 2.5 mm (p = 0.0001). When present, spondylolisthesis was, on average, reduced from 4.3 ± 0.5 mm to 1.9 ± 0.2 mm (p = 0.0001). Lumbar lordosis improved from 47.8° ± 5.5° to 58.5° ± 6.8° (p = 0.2687), and no significant change in segmental lordosis was observed. The overall rate of radiographic fusion was 93.3% at 1 year. No perioperative complications requiring operative revision were encountered. CONCLUSIONS: In this series of MIS TLIFs, use of this novel interbody cage was shown to be safe and effective. Significant improvements in pain and disability were observed. Effective and durable restoration of disc height and neuroforaminal height and reduction of spondylolisthesis were obtained, with concurrent gains in lumbar lordosis. Taken together, this device offers excellent clinical and radiographic outcomes via an MIS approach.

Uncertainty in the Relationship Between Sagittal Alignment and Patient-Reported Outcomes.

BACKGROUND: Previous studies have reported correlations and precise quantitative relationships between sagittal alignment and health-related quality-of-life (HRQOL) scores. These studies have not reported the extent of uncertainty in these relationships. OBJECTIVE: To explore the uncertainty in the overall relationships between sagittal alignment and HRQOL and in the predictions of individual patient pain and disability. METHODS: A retrospective analysis of all new adult patients with long-cassette radiographs and complete outcomes questionnaires presenting to the senior author from 2012 to 2014 was performed. Univariable maximum a posteriori linear regression analyses using Bayesian methods were performed. High-density probability intervals for mean regression relationships and for individual values were calculated using minimally informative prior distributions. RESULTS: A total of 134 patients satisfied inclusion criteria and were included. For Oswestry Disability Index (ODI) vs pelvic incidence-lumbar lordosis (LL), the 90% high-density probability interval ranged from -0.04 to 0.23, indicating that both the magnitude and direction of the relationship were uncertain. For both ODI vs sagittal vertical axis and ODI vs LL, there was uncertainty in the magnitude of the slope. Wide regions of uncertainty were also seen for predicting individual patient scores. CONCLUSION: We report the previously unpublished degree of uncertainty in the mean quantitative relationships between radiographic sagittal alignment and patient-reported outcomes and in individual patient outcomes scores. Based on these results, establishing treatment thresholds or predicting an individual's outcome is unreliable. Further research efforts should be focused on developing multilevel hierarchical models incorporating parameter uncertainty and heterogeneous effects.

Failure to Rescue and Mortality Following Resection of Intracranial Neoplasms.

BACKGROUND: There is growing recognition that perioperative complication rates are similar between hospitals, but mortality rates are lower at high-volume centers. This may be due to differences in the ability to rescue patients from major complications. OBJECTIVE: To examine the relationship between hospital caseload and failure to rescue from complications following resection of intracranial neoplasms. METHODS: We identified adults in the Nationwide Inpatient Sample diagnosed with glioma, meningioma, brain metastasis, or acoustic neuroma, who underwent surgical resection between 1998 and 2010. We stratified hospitals by low, intermediate, and high surgical volume tertiles and calculated failure to rescue rates (mortality in patients after a major complication). RESULTS: A total of 550 054 patients were analyzed. Overall risk-adjusted complication rates were comparable between low- and medium-volume centers, and slightly lower at high-volume centers (15.3% [15.2, 15.5] vs 15.7% [15.5, 15.9] vs 14.3% [14.1, 14.6]). Risk-adjusted mortality decreased with increasing hospital surgical volume (10.3% [10.2, 10.5] vs 9.0% [8.9, 9.1] vs 7.1% [7.0, 7.2]). The overall risk-adjusted failure to rescue rate also decreased with increasing surgical volume (26.9% [26.3, 27.4] vs 24.8% [24.3, 25.3] vs 20.9% [20.5, 21.5]). CONCLUSION: While complication rates were similar between high-volume and low-volume hospitals following craniotomy for tumor, mortality rates were substantially lower at high-volume centers. This appears to be due to the ability of high-volume hospitals to rescue patients from major perioperative complications.

Rare Complications of Cervical Spine Surgery: Horner's Syndrome.

STUDY DESIGN: A multicenter retrospective case series. OBJECTIVE: Horner's syndrome is a known complication of anterior cervical spinal surgery, but it is rarely encountered in clinical practice. To better understand the incidence, risks, and neurologic outcomes associated with Horner's syndrome, a multicenter study was performed to review a large collective experience with this rare complication. METHODS: We conducted a retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records for 17 625 patients who received subaxial cervical spine surgery from 2005 to 2011 were reviewed to identify occurrence of 21 predefined treatment complications. Descriptive statistics were provided for baseline patient characteristics. Paired t test was used to analyze changes in clinical outcomes at follow-up compared to preoperative status. RESULTS: In total, 8887 patients who underwent anterior cervical spine surgery at the participating institutions were screened. Postoperative Horner's syndrome was identified in 5 (0.06%) patients. All patients experienced the complication following anterior cervical discectomy and fusion. The sympathetic trunk appeared to be more vulnerable when operating on midcervical levels (C5, C6), and most patients experienced at least a partial recovery without further treatment. CONCLUSIONS: This collective experience suggests that Horner's syndrome is an exceedingly rare complication following anterior cervical spine surgery. Injury to the sympathetic trunk may be limited by maintaining a midline surgical trajectory when possible, and performing careful dissection and retraction of the longus colli muscle when lateral exposure is necessary, especially at caudal cervical levels.

Efficacy and outcomes of facial nerve-sparing treatment approach to cerebellopontine angle meningiomas.

OBJECTIVE Advanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patient's life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC). METHODS Medical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve-sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated. RESULTS According to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes. CONCLUSIONS CPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance.

OBJECTIVE Extent of resection is an important prognostic factor in patients undergoing surgery for glioblastoma (GBM). Recent evidence suggests that intravenously administered fluorescein sodium associates with tumor tissue, facilitating safe maximal resection of GBM. In this study, the authors evaluate the safety and utility of intraoperative fluorescein guidance for the prediction of histopathological alteration both in the contrast-enhancing (CE) regions, where this relationship has been established, and into the non-CE (NCE), diffusely infiltrated margins. METHODS Thirty-two patients received fluorescein sodium (3 mg/kg) intravenously prior to resection. Fluorescence was intraoperatively visualized using a Zeiss Pentero surgical microscope equipped with a YELLOW 560 filter. Stereotactically localized biopsy specimens were acquired from CE and NCE regions based on preoperative MRI in conjunction with neuronavigation. The fluorescence intensity of these specimens was subjectively classified in real time with subsequent quantitative image analysis, histopathological evaluation of localized biopsy specimens, and radiological volumetric assessment of the extent of resection. RESULTS Bright fluorescence was observed in all GBMs and localized to the CE regions and portions of the NCE margins of the tumors, thus serving as a visual guide during resection. Gross-total resection (GTR) was achieved in 84% of the patients with an average resected volume of 95%, and this rate was higher among patients for whom GTR was the surgical goal (GTR achieved in 93.1% of patients, average resected volume of 99.7%). Intraoperative fluorescein staining correlated with histopathological alteration in both CE and NCE regions, with positive predictive values by subjective fluorescence evaluation greater than 96% in NCE regions. CONCLUSIONS Intraoperative administration of fluorescein provides an easily visualized marker for glioma pathology in both CE and NCE regions of GBM. These findings support the use of fluorescein as a microsurgical adjunct for guiding GBM resection to facilitate safe maximal removal.

Assessment of the "July Effect": outcomes after early resident transition in adult neurosurgery.

OBJECT Each July, 4th-year medical students become 1st-year resident physicians and have much greater responsibility in making management decisions. In addition, incumbent residents and fellows advance to their next postgraduate year and face greater challenges. It has been suggested that among patients who have resident physicians as members of their neurosurgical team, this transition may be associated with increased rates of morbidity and mortality, a phenomenon known as the "July Effect." In this study, the authors compared morbidity and mortality rates between the initial and later months of the academic year to determine whether there is truly a July Effect that has an impact on this patient population. METHODS The authors compared 30-day postoperative outcomes of neurosurgery performed by surgical teams that included resident physicians in training during the first academic quarter (Q1, July through September) with outcomes of neurosurgery performed with resident participation during the final academic quarter (Q4, April through June), using 2006-2012 data from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Regression analyses were performed on outcome data that included mortality, surgical complications, and medical complications, which were graded as mild or severe. To determine whether a July Effect was present in subgroups, secondary analyses were performed to analyze the association of outcomes with each major neurosurgical subspecialty, the postgraduate year of the operating resident, and the academic quarter during which the surgery was performed. To control for possible seasonal trends in certain diseases, the authors compared patient outcomes at academic medical centers to those at community-based hospitals, where procedures were not performed by residents. In addition, the efficiency of academic centers was compared to that of community centers in terms of operative duration and total length of hospital stay. RESULTS Overall, there were no statistically significant differences in mortality, morbidity, or efficiency between the earlier and later quarters of the academic year, a finding that also held true among neurosurgical subspecialties and among postgraduate levels of training. There was, however, a slight increase in intraoperative transfusions associated with the transitional period in July (6.41% of procedures in Q4 compared to 7.99% in Q1 of the prior calendar year; p = 0.0005), which primarily occurred in cases involving junior (2nd- to 4th-year) residents. In addition, there was an increased rate of reoperation (1.73% in Q4 to 2.19% in Q1; p < 0.0001) observed mainly among senior (5th- to 7th-year) residents in the early academic months and not paralleled in our community cohort. CONCLUSIONS There is minimal evidence for a significant July Effect in adult neurosurgery. Our results suggest that, overall, the current resident training system provides enough guidance and support during this challenging transition period.

Convection-enhanced delivery for glioblastoma: targeted delivery of antitumor therapeutics.

Glioblastoma is the most common primary brain tumor in adults and carries a dismal prognosis despite advancements in treatment. Diffuse tumor infiltration precludes curative surgical resection and necessitates advancements in drug delivery mechanisms. Convection-enhanced delivery (CED) enables continuous local drug delivery for a diverse population of antitumor agents. Importantly, CED circumvents therapeutic challenges posed by the blood-brain barrier by facilitating concentrated local therapeutic drug delivery with limited systemic effects. Here, we present a concise review of properties essential for safe and efficient convection-enhanced drug delivery, as well as a focused review of clinical studies evaluating CED in the treatment of glioblastoma.

Complications Following Stereotactic Needle Biopsy of Intracranial Tumors.

BACKGROUND: Data from single-institution studies suggest that perioperative complication rates after stereotactic needle brain biopsies range from 6% to 12%, with permanent morbidity and mortality ranging from 3.1% to 6.4% and 0% to 1.7%, respectively. However, no population-level data are available. We conducted a population-based analysis to study complications after needle brain biopsy. METHODS: We analyzed patients recorded in the Nationwide Inpatient Sample who underwent stereotactic needle brain biopsy for neoplastic lesions between 2006 and 2012. A multivariate logistic model was used to identify factors associated with complications. RESULTS: We identified 7514 patients who underwent biopsy for various intracranial pathologies, including primary malignant neoplasm (52.3%), unspecified neoplasm (17.9%), metastasis (9.7%), meningioma (1.5%), radiation necrosis (0.8%), lymphoma (0.5%), and pineal region neoplasm (0.3%). Intracranial hemorrhage was the most frequent complication (5.8%). Other complications, including operative infection (0.1%) and wound breakdown (0.2%), were rare. Multivariate logistic regression analysis revealed that hemorrhage is associated with older age (reference <40 years; 40-59 years, odds ratio [OR] 2.26, 95% confidence interval [CI] 1.51-3.38; ≥60 years, OR 1.90, 95% CI 1.22-2.97), hydrocephalus (OR 3.02, 95% CI 2.20-4.14), and cerebral edema (OR 2.16, 95% CI 1.72-2.72). Hemorrhage is less likely when taking a biopsy from a primary malignant neoplasm (OR 0.73, 95% CI 0.59-0.90). Overall inpatient mortality after biopsy was 2.8%. Patients with intracranial hemorrhage were significantly more likely than patients without hemorrhage to die in the hospital (12.8% vs. 2.2%, P < 0.001) or be discharged to a rehabilitation/nursing facility (45.2% vs. 23.1%, P < 0.001). CONCLUSIONS: Intracranial hemorrhage is the most frequent complication associated with needle brain biopsy and is associated with inpatient mortality and hospital disposition. Other complications are rare.

Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.

OBJECT: Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas. METHODS: In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness. RESULTS: We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532) from gross total resection over subtotal/biopsy, while those with nodular (less diffuse) tumors showed a significant benefit (P = 0.00142) with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors). CONCLUSIONS: These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.

MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.

Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and nonneoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-sequencing (RNA-seq) and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the The Cancer Genome Atlas dataset showed that the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples from the NE regions predominantly resembled the neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from nonneoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type-specific alterations varied between the different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes. These subtype-specific patterns provide new insights into molecular and cellular composition of the infiltrative margins of GBM.

Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status.

BACKGROUND: Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than gliomas with wild-type IDH1. METHODS: Here we compare the IDH1 mutational status in 172 contrast-enhancing glioma patients with the invasion profile generated by a patient-specific mathematical model we developed based on MR imaging. RESULTS: We show that IDH1-mutated contrast-enhancing gliomas were relatively more invasive than wild-type IDH1 for all 172 contrast-enhancing gliomas as well as the subset of 158 histologically confirmed glioblastomas. The appearance of this relatively increased, model-predicted invasive profile appears to be determined more by a lower model-predicted net proliferation rate rather than an increased model-predicted dispersal rate of the glioma cells. Receiver operator curve analysis of the model-predicted MRI-based invasion profile revealed an area under the curve of 0.91, indicative of a predictive relationship. The robustness of this relationship was tested by cross-validation analysis of the invasion profile as a predictive metric for IDH1 status. CONCLUSIONS: The strong correlation between IDH1 mutation status and the MRI-based invasion profile suggests that use of our tumor growth model may lead to noninvasive clinical detection of IDH1 mutation status and thus lead to better treatment planning, particularly prior to surgical resection, for contrast-enhancing gliomas.

Angiographic warning of hemorrhagic transformation after stent retriever thrombectomy procedure.

This study reports cerebral angiographic findings observed after stent retriever thrombectomy that is suggestive of a higher risk of hemorrhagic transformation (HT). A woman aged 65-75 presented with a right middle cerebral artery syndrome confirmed by non-contrast CT brain scan. Endovascular revascularization using the Solitaire device was placed across the thromboembolic occlusion and thromboembolectomy was performed. Angiography showed complete recanalization of the left internal carotid artery, anterior and middle cerebral artery branches. Twelve hours following the procedure the patient had a hemorrhagic conversion of the ischemic infarct with significant mass effect causing herniation. Despite surgical intervention (hemicraniectomy) the patient died. The angiographic features following revascularization of the vessels distal to the occlusion showed subtle dilations which were visualized at the branch points of the vessels. This may be a warning sign of increased risk of HT.