Sasha Gulati

The Risk of Getting Worse: Surgically Acquired Deficits, Perioperative Complications, and Functional Outcomes After Primary Resection of Glioblastoma

OBJECTIVE Gross total resection (GTR) prolongs survival but is unfortunately not achievable in the majority of patients with glioblastoma multiforme (GBM). Cytoreductive debulkings may relieve symptoms of mass effect, but it is unknown how long such effects sustain and to what degree the potential benefits exceed risks. We explore the impact of surgical morbidity on functional outcome and survival in unselected GBM patients. METHODS We retrospectively included 144 consecutive adult patients operated on for primary GBM at a single institution between 2004 and 2009. Reporting of adverse events was done in compliance with Good Clinical Practice Guidelines. RESULTS A total of 141 (98%) operations were resections and 3 (2%) were biopsies. A decrease in Karnofsky performance status (KPS) scores was observed in 39% of patients after 6 weeks. There was a significant decrease between pre- and postoperative KPS scores (P < 0.001). Twenty-two (15.3%) patients had surgically acquired neurological deficits. Among patients who underwent surgical resection, those with surgically acquired neurological deficits were less likely to receive radiotherapy (P < 0.001), normofractioned radiotherapy (P = 0.010), and chemotherapy (P = 0.003). Twenty-eight (19.4%) patients had perioperative complications. Among patients who underwent surgical resection, those with perioperative complications were less likely to receive normofractioned radiotherapy (P = 0.010) and chemotherapy (P = 0.009). Age (P = 0.019), surgically acquired neurological deficits (P < 0.001), and surgical complications (P = 0.006) were significant predictors for worsened functional outcome after 6 weeks. GTR (P = 0.035), perioperative complications (P = 0.008), radiotherapy (P < 0.001), and chemotherapy (P = 0.045) were independent factors associated with 12-month postoperative survival. CONCLUSION Patients with perioperative complications and surgically acquired deficits were less likely to receive adjuvant therapy. While cytoreductive debulking may not improve survival in GBM, it may decrease the likelihood of patients receiving adjuvant therapy that does.

Minimally invasive decompression versus open laminectomy for central stenosis of the lumbar spine: pragmatic comparative effectiveness study

Objective To test the equivalence for clinical effectiveness between microdecompression and laminectomy in patients with central lumbar spinal stenosis. Design Multicentre observational study. Setting Prospective data from the Norwegian Registry for Spine Surgery. Participants 885 patients with central stenosis of the lumbar spine who underwent surgery at 34 Norwegian orthopaedic or neurosurgical departments. Patients were treated from October 2006 to December 2011. Interventions Laminectomy and microdecompression. Main outcome measures The primary outcome was change in Oswestry disability index score one year after surgery. Secondary endpoints were quality of life (EuroQol EQ-5D), perioperative complications, and duration of surgical procedures and hospital stays. A blinded biostatistician performed predefined statistical analyses in unmatched and propensity matched cohorts. Results The study was powered to detect a difference between the groups of eight points on the Oswestry disability index at one year. 721 patients (81%) completed the one year follow-up. Equivalence between microdecompression and laminectomy was shown for the Oswestry disability index (difference 1.3 points, 95% confidence interval −1.36 to 3.92, P<0.001 for equivalence). Equivalence was confirmed in the propensity matched cohort and full information regression analyses. No difference was found between groups in quality of life (EQ-5D) one year after surgery. The number of patients with complications was higher in the laminectomy group (15.0% v 9.8%, P=0.018), but after propensity matching for complications the groups did not differ (P=0.23). The duration of surgery for single level decompression was shorter in the microdecompression group (difference 11.2 minutes, 95% confidence interval 4.9 to 17.5, P<0.001), but after propensity matching the groups did not differ (P=0.15). Patients in the microdecompression group had shorter hospital stays, both for single level decompression (difference 1.5 days, 95% confidence interval 1.7 to 2.6, P<0.001) and two level decompression (0.8 days, 1.0 to 2.2, P=0.003). Conclusion At one year the effectiveness of microdecompression is equivalent to laminectomy in the surgical treatment of central stenosis of the lumbar spine. Favourable outcomes were observed at one year in both treatment groups. Trial registration ClinicalTrials.gov NCT02006901.

Functional magnetic resonance imaging and diffusion tensor tractography incorporated into an intraoperative 3-dimensional ultrasound-based neuronavigation system: impact on therapeutic strategies, extent of resection, and clinical outcome.

BACKGROUNDFunctional neuronavigation with intraoperative 3-dimensional (3D) ultrasound may facilitate safer brain lesion resections than conventional neuronavigation. OBJECTIVEIn this study, functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) were used to map eloquent areas. We assessed the use of fMRI and DTT for preoperative assessments and determined whether using these data together with 3D ultrasound during surgery enabled safer lesion resection. METHODSWe reviewed 51 consecutive patients with intracranial lesions in whom fMRI with or without DTT was used to map eloquent areas. To assess a possible impact of fMRI/DTT, we reviewed and analyzed the quality of the fMRI/DTT data, any change in therapeutic strategies, lesion to eloquent area distance (LEAD), extent of resection, and clinical outcome. RESULTSAs a result of the fMRI/DTT mapping, the therapeutic strategies were changed in 4 patients. The median tumor residue for glioma patients was 11% (n = 33) and 0% for nonglioma lesions (n = 12). For gliomas, there was a significant correlation between decreasing LEAD and increasing tumor residue. Of the glioma patients, 42% underwent gross total resection (≥ 95%) and 12% suffered neurological worsening after surgery as a result of complications. Of glioma patients with an LEAD of ≤ 5 mm, 24% underwent gross total resection and 10% experienced neurological deterioration. CONCLUSIONThis study demonstrates that preoperative fMRI and DTT had direct consequences for therapeutic strategies and indicates their impact on intraoperative strategies to spare eloquent cortex and tracts. Functional neuronavigation combined with intraoperative 3D ultrasound can, in most patients, enable resection of brain lesions with general anesthesia without jeopardizing neurological function.

Clinical outcomes and safety assessment in elderly patients undergoing decompressive laminectomy for lumbar spinal stenosis: a prospective study

BackgroundTo assess safety, risk factors and clinical outcomes in elderly patients with spinal stenosis after decompressive laminectomy.MethodsA prospective cohort of patients 70 years and older with spinal stenosis undergoing conventional laminectomy without fusion (n = 101) were consecutively enrolled from regular clinical practice and reassessed at 3 and 12 months. Primary outcome was change in health related quality of life measured (HRQL) with EuroQol-5 D (EQ-5D). Secondary outcomes were safety assessment, changes in Oswestry disability index (ODI), Visual Analogue Scale (EQ-VAS) score for self reported health, VAS score for leg and back pain and patient satisfaction. We used regression analyses to evaluate risk factors for less improvement.ResultsThe mean EQ-5 D total score were 0.32, 0.63 and 0.60 at baseline, 3 months and 12 months respectively, and represents a statistically significant (P < 0.001) improvement. Effect size was > 0.8. Mean ODI score at baseline was 44.2, at 3 months 25.6 and at 27.9. This represents an improvement for all post-operative scores. A total of 18 (18.0%) complications were registered with 6 (6.0%) classified as major, including one perioperative death. Patients stating that the surgery had been beneficial at 3 months was 82 (89.1%) and at 12 months 73 (86.9%). The only predictor found was patients with longer duration of leg pain had less improvement in ODI (P < 0.001). Increased age or having complications did not predict a worse outcome in any of the outcome variables.ConclusionsProperly selected patients of 70 years and older can expect a clinical meaningful improvement of HRQL, functional status and pain after open laminectomy without fusion. The treatment seems to be safe. However, patients with longstanding leg-pain prior to operation are less likely to improve one year after surgery.

Evaluation of the proliferation markers Ki-67/MIB-1, mitosin, survivin, pHH3, and DNA topoisomerase IIα in human anaplastic astrocytomas - an immunohistochemical study

BackgroundHistological malignancy grading of astrocytomas can be challenging despite criteria given by the World Health Organisation (WHO). Grading is fundamental for optimal prognostication and treatment, and additional biomarkers are needed to support the histopathological diagnosis. Estimation of proliferative activity has gained much enthusiasm, and the present study was designed to evaluate and compare novel immunohistochemical proliferative markers in human anaplastic astrocytomas.MethodsProliferative activity was determined in twenty-seven cases with antibodies reactive against the Ki-67 antigen, mitosin, survivin, pHH3, and DNA topoisomerase IIα, and they were mutually compared as well as related to mitotic activity.ResultsThe markers correlated well with each other, but poorly with mitoses, probably because of small and squeezed tumour samples, in which identification of mitoses can be difficult. Positive association to overall survival was observed as well.ConclusionsOur data show that these markers may assist significantly in the evaluation of proliferative activity in anaplastic astrocytomas and even have prognostic value.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2653263345404531.

Survival and Treatment Patterns of Glioblastoma in the Elderly : A Population-based Study.

BACKGROUND As the older segment of the population grows faster than any other age group, the number of elderly diagnosed with glioblastoma is expected to increase. The aim of this study was to explore survival and the treatment provided to elderly patients diagnosed with glioblastoma in a population-based setting. We further studied whether increased treatment aggressiveness may have contributed to a clinically important survival benefit in the elderly population. METHODS From the Norwegian Cancer Registry, we included 2882 patients who were diagnosed with glioblastoma between 1988 and 2008. RESULTS The proportion of patients ≥66 years was 42.5% (n = 1224), and 15.9% of patients (n = 459) were ≥75 years at diagnosis. Treatment patterns varied significantly between age groups (P < 0.001). Elderly patients (66 years) were less likely to receive multimodal treatment with resection combined with radiotherapy and/or chemotherapy. Elderly patients were more likely to receive a diagnosis of glioblastoma without histopathologic verification (P < 0.001). Among patients receiving multimodal treatment with surgical resection, radiotherapy, and chemotherapy, shorter survival was seen in the elderly (P < 0.001). Belonging to the age group ≥75 years was the strongest predictor of decreased survival (P < 0.001), thus seemingly of higher prognostic impact than the patterns of care. Increasing age, no tumor resection, no radiotherapy, and no chemotherapy were identified as independent predictors of reduced survival. There was a statistically significant, albeit debatable, clinically relevant survival advantage for the oldest patients (≥75 years) diagnosed in the last 5 years of the study. CONCLUSIONS Advancing age remains a very strong and independent negative prognostic factor in glioblastoma. Although there has been an increase in the aggressiveness of treatment provided to elderly with glioblastoma, the gain for the oldest age group seems at best very modest. The prognosis of the oldest age group remains very poor, despite multimodal treatment.

On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study

Objective To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. Methods Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. Results There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. Conclusions Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP.

Incidence and causes of perioperative mortality after primary surgery for intracranial tumors: a national, population-based study

OBJECT Surgical mortality is a frequent outcome measure in studies of volume-outcome relationships, and the Agency for Healthcare Research and Quality has endorsed surgical mortality after craniotomies as an Inpatient Quality Indicator. Still, the frequency and causes of 30-day mortality after neurosurgical procedures have not been much explored. The authors sought to study the frequency and possible causes of death following primary intracranial tumor operations. They also sought to explore a possible predictive value of perioperative mortality rates from neurosurgical centers in relation to long-term survival. METHODS Using population-based data from the Norwegian cancer registry, the authors identified 15,918 primary operations for primary CNS tumors treated in Norway in the period from August 1955 through December 2008. Patients were followed up until death, emigration, or September 2009. Causes of mortality as indicated on death certificates were studied. Factors associated with an increased risk of perioperative death were identified. RESULTS The overall risk of perioperative death after first-time surgery for primary intracranial tumors is currently 2.2% and has decreased over the last decades. An age ≥ 70 years and histopathological entities with poor long-term prognoses are risk factors. Overlapping lesions are also associated with excess risk, indicating that lesion size or multifocality may matter. The overall risk of perioperative death is also higher in biopsy cases than in resection cases. Perioperative mortality rates of the 4 Norwegian neurosurgical centers were not predictive of their respective long-term survival rates. CONCLUSIONS Although considered surgically related if they occur within the first 30 days of surgery, most early postoperative deaths can happen independent of the handiwork of the operating surgeon or anesthesiologist. Overall prognosis of the disease seems to be a strong predictor of perioperative death-perhaps not surprisingly since the 30-day mortality rate is merely the intonation of the Kaplan-Meier curve. Both referral and treatment policies at a neurosurgical center will therefore markedly affect such early outcomes, but early deaths may not necessarily reflect overall quality of care or long-term results. The low incidence of perioperative death in intracranial tumor surgery also greatly limits the statistical power in comparative analyses, such as between published patient series or between centers and certainly between surgeons. Therefore the authors question the value of perioperative mortality rates as a quality indicator in modern neurosurgery for tumors.

Does Obesity Affect Outcomes After Decompressive Surgery for Lumbar Spinal Stenosis? A Multicenter, Observational, Registry-Based Study.

OBJECTIVE To evaluate the association between obesity and outcomes 1 year after laminectomy or microdecompression for lumbar spinal stenosis (LSS). METHODS The primary outcome measure was the Oswestry Disability Index (ODI). Obesity was defined as body mass index (BMI) ≥ 30. Prospective data were retrieved from the Norwegian Registry for Spine Surgery. RESULTS For all patients (n = 1473) the mean improvement in ODI at 1 year was 16.7 points (95% CI 15.7-17.7, P < 0.001). The improvement in ODI was 17.5 points in nonobese and 14.3 points in obese patients (P = 0 .007). Obese patients were less likely to achieve a minimal clinically important difference in ODI (defined as ≥ 8 points improvement) than nonobese patients (62.2 vs. 70.3%, P = 0.013). Obesity was identified as a negative predictor for ODI improvement in a multiple regression analysis (P < 0.001). Nonobese patients experienced more improvement in both back pain (0.7 points, P = 0.002) and leg pain (0.8 points, P = 0.001) measured by numeric rating scales. Duration of surgery was shorter for nonobese patients for both single- (79 vs. 89 minutes, P = 0.001) and 2-level (102 vs. 114 minutes, P = 0.004) surgery. There was no difference in complication rates (10.4% vs. 10.8%, P = 0.84). There was no difference in length of hospital stays for single- (2.7 vs. 3.0 days, P = 0.229) or 2-level (3.5 vs. 3.6 days, P = 0.704) surgery. CONCLUSIONS Both nonobese and obese patients report considerable clinical improvement 1 year after surgery for LSS, but improvement was less in obese patients. Obese patients were less likely to achieve a minimal clinically important difference.

Three-dimensional ultrasound-guided placement of ventricular catheters.

OBJECTIVE Many studies demonstrate that the accuracy of freehand catheter placement for cerebrospinal fluid drainage is suboptimal. The aim of placement should be a single pass with a free-floating catheter tip in the intended position. The objective of this study was to achieve an accurate and user-friendly system for three-dimensional (3D) ultrasound-navigated catheter placement through a regular burr hole. METHODS A new phased-array ultrasound burr hole probe (4-10 MHz, 8 mm×9 mm footprint) was especially developed and optimized for navigated 3D ultrasound with the SonoWand Invite system. A catheter holder for optical tracking was also developed. Head immobilization was achieved with a vacuum cushion. With the described setup, 4 patients underwent surgery. RESULTS Ultrasound image quality and visualization of the ventricles was good in all cases. Optimal placement of the catheter was achieved in a single pass in all patients. One of the trajectories was slightly more medial on postoperative computed tomography than anticipated from the neuronavigation system. None of the patients experienced any adverse event related to the procedure. CONCLUSIONS 3D ultrasound with the described setup is a promising technique for accurate, fast, and user-friendly navigated placement of catheters for cerebrospinal fluid diversion.