Asgeir Store Jakola

Ultrasound-guided operations in unselected high-grade gliomas--overall results, impact of image quality and patient selection.

BackgroundA number of tools, including intraoperative ultrasound, are reported to facilitate surgical resection of high-grade gliomas. However, results from selected surgical series do not necessarily reflect the effectiveness in common neurosurgical practice. Delineation of seemingly similar brain tumours vary in different ultrasound-guided operations, perhaps limiting usefulness in certain patients.MethodsWe explore and describe the results associated with use of the SonoWand system with intraoperative ultrasound in a population-based, unselected, high-grade glioma series. Surgeons filled out questionnaires about presumed extent of resection, use of ultrasound and ultrasound image quality just after surgery. We evaluate the impact of ultrasound image quality. We also explore the importance of patient selection for surgical results.ResultsOf 156 consecutive malignant glioma operations, 142 (91%) were resections whilst 14 (9%) were only biopsies. We achieved gross total resection (GTR) in 37% of all high-grade glioma resections, whilst worsening of functional status was seen in 13%. The risk of getting worse was significantly higher in reoperations, resections in eloquent locations, resections in cases with poor ultrasound image quality, resection when surgeons’ resection grade estimates were inaccurate and in cases with surgery-related complications. Aiming for GTR, unifocality of lesion, non-eloquent location and medium or good ultrasound image quality were identified as independent factors associated with achieving GTR.ConclusionWe report good overall results, both in terms of resection grades and functional outcome in consecutive malignant glioma resections, in which intraoperative ultrasound was used in 95%. We observed a seeming dose–response relationship between ultrasound image quality and clinical and radiological results. This may suggest that better ultrasound facilitates better surgery. The study also clearly demonstrates that, in terms of surgical results, the selection of patients seems to be much more important than the selection of surgical tools.

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.

Surgical resection versus watchful waiting in low-grade gliomas

Abstract Background Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers. Materials and methods Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival. Results A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8 years (95% CI 4.5–7.2) in region A compared with 14.4 years (95% CI 10.4–18.5) in region B (P < 0.01). The effect of surgical strategy remained after adjustment for molecular markers (P = 0.001). Conclusion In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.

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.

Surgical strategies in low-grade gliomas and implications for long-term quality of life.

Reports on long-term health related quality of life (HRQL) after surgery for World Health Organization grade II diffuse low-grade gliomas (LGG) are rare. We aimed to compare long-term HRQL in two hospital cohorts with different surgical strategies. Biopsy and watchful waiting was favored in one hospital, while early resections guided with three-dimensional (3D) ultrasound was favored in the other. With a population-based approach 153 patients with histologically verified LGG treated from 1998-2009 were included. Patients still alive were contacted for HRQL assessment (n=91) using generic (EQ-5D; EuroQol Group, Rotterdam, The Netherlands) and disease specific (EORTC QLQ-C30 and BN20; EORTC Quality of Life Department, Brussels, Belgium) questionnaires. Results on HRQL were available in 79 patients (87%), 25 from the hospital that favored biopsy and 54 from the hospital that favored early resection. Among living patients there was no difference in EQ-5D index scores (p=0.426). When imputing scores defined as death (zero) in patients dead at follow-up, a clinically relevant difference in EQ-5D score was observed in favor of early resections (p=0.022, mean difference 0.16, 95% confidence interval 0.02-0.29). In EORTC questionnaires pain, depression and concern about disruption in family life were more common with a strategy of initial biopsy only (p=0.043, p=0.032 and p=0.045 respectively). In long-term survivors an aggressive surgical approach using intraoperative 3D ultrasound image guidance in LGG does not lower HRQL compared to a more conservative surgical approach. This finding further weakens a possible role for watchful waiting in LGG.

Differentiating diffuse World Health Organization grade II and IV astrocytomas with ex vivo magnetic resonance spectroscopy.

BACKGROUND The prognosis and treatment of astrocytomas, which are primary brain tumors, vary depending on the grade of the tumor, necessitating a precise preoperative classification. Magnetic resonance spectroscopy (MRS) provides information about metabolites in tissues and is an emerging noninvasive tool to improve diagnostic accuracy in patients with intracranial neoplasia. OBJECTIVE To investigate whether ex vivo MRS could differentiate World Health Organization grade II (A-II) and IV astrocytomas (glioblastomas; GBM) and to correlate MR spectral profiles with clinical parameters. METHODS Patients with A-II and GBM (n = 58) scheduled for surgical resection were enrolled. Tumor specimens were collected during surgery and stored in liquid nitrogen before being analyzed with high-resolution magic angle spinning MRS. The tumors were histopathologically classified according to World Health Organization criteria as GBM (n = 48) and A-II (n = 10). RESULTS Multivariate analysis of ex vivo proton high-resolution magic angle spinning spectra MRS showed differences in the metabolic profiles of different grades of astrocytomas. A-II had higher levels of glycerophosphocholine and myo-inositol than GBM. The latter had more phosphocholine, glycine, and lipids. We observed a significant metabolic difference between recurrent and nonrecurrent GBM (P < .001). Primary GBM had more phosphocholine than recurrent GBM. A significant correlation (P < .001) between lipid and lactate signals and histologically estimated percentage of necrosis was observed in GBM. Spectral profiles were not correlated with age, survival, or magnetic resonance imaging-defined tumor volume. CONCLUSION Ex vivo MRS can differentiate astrocytomas based on their metabolic profiles.

Quality of survival the 1st year with glioblastoma: a longitudinal study of patient-reported quality of life

OBJECTIVE By exploring longitudinal patient-reported health-related quality of life (HRQoL), the authors sought to assess the quality of survival for patients in the 1st year after diagnosis of glioblastoma. METHODS Thirty unselected patients ≥ 18 years who underwent primary surgery for glioblastoma in the period 2011-2013 were included. Using the generic HRQoL questionnaire EQ-5D 3L, baseline HRQoL was assessed before surgery and at postoperative follow-up after 1, 2, 4, 6, 8, 10, and 12 months. RESULTS There was an apparent correlation between deterioration in HRQoL scores and tumor progression. Patients with permanent deterioration in HRQoL early after surgery represented a subgroup with rapid progression and short survival. Both positive and negative changes in HRQoL were more often seen after surgery than after radio- or chemotherapy. Patients with gross-total resection (GTR) reported better and more stable HRQoL. In a multivariable analysis preoperative cognitive symptoms (p = 0.02), preoperative functional status (p = 0.03), and GTR (p = 0.01) were independent predictors of quality of survival (area under the curve for EQ-5D 3L index values). CONCLUSIONS The results indicate that progression-free survival is not only a surrogate marker for survival, but also for quality of survival. Quality of survival seems to be associated with GTR, which adds further support for opting for extensive resections in glioblastoma patients with good preoperative functional levels.

Morbidity after intracranial tumor surgery: sensitivity and specificity of retrospective review of medical records compared with patient-reported outcomes at 30 days

OBJECT Published outcome reports in neurosurgical literature frequently rely on data from retrospective review of hospital records at discharge, but the sensitivity and specificity of retrospective assessments of surgical morbidity is not known. The aim of this study was to elucidate the sensitivity and specificity of retrospective assessment of morbidity after intracranial tumor surgery by comparing it to patient-reported outcomes at 30 days. METHODS In 191 patients who underwent surgery for the treatment of intracranial tumors, we evaluated newly acquired neurological deficits within the motor, language, and cognitive domains. Traditional retrospective discharge data were collected by review of hospital records. Patient-reported data were obtained by structured phone interviews at 30 days after surgery. Data on perioperative medical and surgical complications were obtained from both hospital records and patient interviews conducted 30 days postoperatively. RESULTS Sensitivity values for retrospective review of hospital records as compared with patient-reported outcomes were 0.52 for motor deficits, 0.4 for language deficits, and 0.07 for cognitive deficits. According to medical records, 158 patients were discharged with no new or worsened deficits, but only 117 (74%) of these patients confirmed this at 30 days after surgery. Specificity values were high (0.97-0.99), indicating that new deficits were unlikely to be found by retrospective review of hospital records at discharge when the patients did not report any at 30 days. Major perioperative complications were all identified through retrospective review of hospital records. CONCLUSIONS Retrospective assessment of medical records at discharge from hospital may greatly underestimate the incidence of new neurological deficits after brain tumor surgery when compared with patient-reported outcomes after 30 days.