Asgeir S. Jakola

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

OBJECTIVEnGross 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.nnnMETHODSnWe 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.nnnRESULTSnA 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.nnnCONCLUSIONnPatients 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.

Ultrasound imaging in neurosurgery: approaches to minimize surgically induced image artefacts for improved resection control

BackgroundIntraoperative ultrasound imaging is used in brain tumor surgery to identify tumor remnants. The ultrasound images may in some cases be more difficult to interpret in the later stages of the operation than in the beginning of the operation. The aim of this paper is to explain the causes of surgically induced ultrasound artefacts and how they can be recognized and reduced.MethodsThe theoretical reasons for artefacts are addressed and the impact of surgery is discussed. Different setups for ultrasound acquisition and different acoustic coupling fluids to fill up the resection cavity are evaluated with respect to improved image quality.ResultsThe enhancement artefact caused by differences in attenuation of the resection cavity fluid and the surrounding brain is the most dominating surgically induced ultrasound artefact. The influence of the artefact may be reduced by inserting ultrasound probes with small footprint into the resection cavity for a close-up view of the areas with suspected tumor remnants. A novel acoustic coupling fluid developed for use during ultrasound imaging in brain tumor surgery has the potential to reduce surgically induced ultrasound artefacts to a minimum.ConclusionsSurgeons should be aware of artefacts in ultrasound images that may occur during brain tumor surgery. Techniques to identify and reduce image artefacts are useful and should be known to users of ultrasound in brain tumor surgery.

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.

Postoperative deterioration in health related quality of life as predictor for survival in patients with glioblastoma: a prospective study.

Background Studies indicate that acquired deficits negatively affect patients self-reported health related quality of life (HRQOL) and survival, but the impact of HRQOL deterioration after surgery on survival has not been explored. Objective Assess if change in HRQOL after surgery is a predictor for survival in patients with glioblastoma. Methods Sixty-one patients with glioblastoma were included. The majority of patients (nu200a=u200a56, 91.8%) were operated using a neuronavigation system which utilizes 3D preoperative MRI and updated intraoperative 3D ultrasound volumes to guide resection. HRQOL was assessed using EuroQol 5D (EQ-5D), a generic instrument. HRQOL data were collected 1–3 days preoperatively and after 6 weeks. The mean change in EQ-5D index was −0.05 (95% CI −0.15–0.05) 6 weeks after surgery (pu200a=u200a0.285). There were 30 patients (49.2%) reporting deterioration 6 weeks after surgery. In a Cox multivariate survival analysis we evaluated deterioration in HRQOL after surgery together with established risk factors (age, preoperative condition, radiotherapy, temozolomide and extent of resection). Results There were significant independent associations between survival and use of temozolomide (HR 0.30, pu200a=u200a0.019), radiotherapy (HR 0.26, pu200a=u200a0.030), and deterioration in HRQOL after surgery (HR 2.02, pu200a=u200a0.045). Inclusion of surgically acquired deficits in the model did not alter the conclusion. Conclusion Early deterioration in HRQOL after surgery is independently and markedly associated with impaired survival in patients with glioblastoma. Deterioration in patient reported HRQOL after surgery is a meaningful outcome in surgical neuro-oncology, as the measure reflects both the burden of symptoms and treatment hazards and is linked to overall survival.

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

BACKGROUNDnAs 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.nnnMETHODSnFrom the Norwegian Cancer Registry, we included 2882 patients who were diagnosed with glioblastoma between 1988 and 2008.nnnRESULTSnThe 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.nnnCONCLUSIONSnAdvancing 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.

Low Grade Gliomas in Eloquent Locations – Implications for Surgical Strategy, Survival and Long Term Quality of Life

Background Surgical management of suspected LGG remains controversial. A key factor when deciding a surgical strategy is often the tumors’ perceived relationship to eloquent brain regions Objective To study the association between tumor location, survival and long-term health related quality of life (HRQL) in patients with supratentorial low-grade gliomas (LGG). Methods Adults (≥18 years) operated due to newly diagnosed LGG from 1998 through 2009 included from two Norwegian university hospitals. After review of initial histopathology, 153 adults with supratentorial WHO grade II LGG were included in the study. Tumors’ anatomical location and the relationship to eloquent regions were graded. Survival analysis was adjusted for known prognostic factors and the initial surgical procedure (biopsy or resection). In long-term survivors, HRQL was assessed with disease specific questionnaires (EORTC QLQ-C30 and BN20) as well as a generic questionnaire (EuroQol 5D). Results There was a significant association between eloquence and survival (log-rank, p<0.001). The estimated 5-year survival was 77% in non-eloquent tumors, 71% in intermediate located tumors and 54% in eloquent tumors. In the adjusted analysis the hazard ratio of increasing eloquence was 1.5 (95% CI 1.1–2.0, pu200a=u200a0.022). There were no differences in HRQL between patients with eloquent and non-eloquent tumors. The most frequent self-reported symptoms were related to fatigue, cognition, and future uncertainty. Conclusion Eloquently located LGGs are associated with impaired survival compared to non-eloquently located LGG, but in long-term survivors HRQL is similar. Although causal inference from observational data should be done with caution, the findings illuminate the delicate balance in surgical decision making in LGGs, and add support to the probable survival benefits of aggressive surgical strategies, perhaps also in eloquent locations.

The case for duraplasty in adults undergoing posterior fossa decompression for Chiari I malformation: A systematic review and meta-analysis of observational studies

BACKGROUNDnPosterior fossa decompression is carried out to improve passage of cerebrospinal fluid (CSF) in patients with symptomatic Chiari 1 malformations (CM1), but the extent and means of decompression remains controversial. Dural opening with subsequent duraplasty may contribute to clinical outcome, but may also increase complication risk. The aim of this systematic review and meta-analysis is to assess the effects of durotomy with subsequent duraplasty on clinical outcome in surgical treatment of adults with CM1.nnnDATA SOURCES AND STUDY ELIGIBILITY CRITERIAnWe systematically searched MEDLINE, Embase and CENTRAL, and screened references in relevant articles and in UpToDate. Publications with previously untreated adults (>15 years) with CM1 with or without associated syringomyelia, treated in the period 1990-2013 were eligible.nnnINTERVENTIONSnPosterior fossa decompression with duraplasty (PFDD group) was compared to posterior fossa decompression with bony decompression alone (PFD group).nnnRESULTSnThe search retrieved 233 articles. After the review we included 12 articles, but only 4 articles included posterior fossa decompression with both techniques. Only 2 out of 12 studies were prospective. The odds ratio (OR) for reoperation was 0.15 (95% CI 0.05-0.49) in the PFDD group compared to PFD (p=0.002). The OR of clinical failure at follow-up was 1.06 (95% CI 0.52-2.14) for PFDD compared to PFD (p=0.88). There was also no difference in syringomyelia improvement between techniques (p=0.60). The OR for CSF-related complications were 6.12 (95% CI 0.37-101.83) for PFDD compared to PFD (p=0.21).nnnCONCLUSIONnThis systematic review of observational studies reveals higher reoperation rates after bony decompression alone, but clinical improvement was not higher after primary decompression with duraplasty. There are so far no high-quality studies that offer guidance in the choice of decompressive technique in adult CM1 patients. We think that a randomized controlled trial on this topic is both needed and feasible.

Quality of life assessed with EQ-5D in patients undergoing glioma surgery: What is the responsiveness and minimal clinically important difference?

PurposeTo evaluate the responsiveness of EQ-5D 3L in patients undergoing intracranial glioma surgery and estimate the minimal clinically important difference (MCID).Materials and methodsEQ-5D 3L index values from 164 patients who underwent glioma surgery in the period 2007–2012 were analysed. Responsiveness and MCID were estimated using a combination of distribution-based and anchor-based methods. Karnofsky performance status served as an anchor.ResultsPatients who improved functionally did not report significantly higher EQ-5D 3L scores post operatively with a standardized response mean (SRM) of 0.04 (pxa0=xa00.13). Patients who deteriorated functionally reported significantly lower EQ-5D 3L scores post operatively with a SRM of 0.72 (pxa0<xa00.001). With different approaches, we determined a range of MCID values from 0.13 to 0.15.ConclusionsEQ-5D 3L is responsive to changes when glioma patients are deteriorating functionally after surgery but not responsive when the patients are improving. The MCID values for EQ-5D 3L in glioma surgery seem higher than reported MCID values for other types of cancers.

Is There an Association Between Radiological Severity of Lumbar Spinal Stenosis and Disability, Pain, or Surgical Outcome?: A Multicenter Observational Study.

Study Design. Observational multicenter study. Objective. To evaluate if the severity of lumbar spinal stenosis (LSS) on magnetic resonance imaging (MRI) correlates with preoperative disability, pain, or surgical outcomes. Summary of Background Data. Surgeons use the morphological appearance of LSS on MRI for clinical decision making. However, the associations between radiological severity of LSS and disability, pain, or surgical outcomes remain unclear. Methods. Evaluation of severity of LSS on preoperative MRI according to the Schizas morphological classification. Patient and treatment data were retrieved from the Norwegian Registry for Spine Surgery. Preopertaive outcome measures were Oswestry disability index (ODI) and numeric rating scale (NRS) scores for back and leg pain. Postopertive outcome measures were ODI and NRS scores for back and leg pain at 1 year, changes in ODI and NRS scores after treatment, duration of surgery, length of hospital stay, and perioperative complications. Results. Of 202 patients included, 7 were found to have mild stenosis, 38 had moderate stenosis, 108 had severe stenosis, and 49 had extreme stenosis. The radiological severity of LSS was not linked to preoperative ODI (Pu200a=u200a0.089), NRS back pain (Pu200a=u200a0.273), or NRS leg pain (Pu200a=u200a0.282) scores. There were no differences in ODI (Pu200a=u200a0.933), NRS back pain (Pu200a=u200a0.652), or NRS leg pain (Pu200a=u200a0.912) scores after 1 year. The radiological severity of stenosis was not associated with change in ODI (Pu200a=u200a0.494), NRS back pain (Pu200a=u200a0.235), NRS leg pain (Pu200a=u200a0.790), duration of surgery (Pu200a=u200a0.661), length of hospital stay (Pu200a=u200a0.739), or perioperative complication rates (Pu200a=u200a0.467). Conclusion. Among patients who underwent decompressive surgery for LSS, radiological severity of stenosis was not associated with preoperative disability and pain, or clinical outcomes 1 year after surgery. In this patient group, the radiological severity of LSS has no clear clinical correlation and should therefore not be overemphasized in clinical decision making. Level of Evidence: 2

The influence of surgery on quality of life in patients with intracranial meningiomas: a prospective study

Meningiomas may influence both survival and neurological functions. Studies assessing the impact of surgery on health-related quality of life (HRQL) remain absent. In this prospective study we aimed to describe HRQL dynamics before and after surgery in patients with meningiomas. HRQL assessments were performed using EuroQol-5D (EQ-5D), a generic HRQL instrument. All adult patients with suspected intracranial meningioma from 2007 through 2011 were eligible for inclusion, and 54 patients were included after informed consent. All patients received a histopathological diagnosis of meningioma. The average preoperative EQ-5D index value (±SD) was 0.69xa0±xa00.26. The mean improvement 6xa0weeks after surgery was 0.06 (95xa0% CI, −0.03 to 0.16; pxa0=xa00.161) and the mean long term improvement was 0.09 (95xa0% CI, 0.00–0.17; pxa0=xa00.040). Surgery reduced pain/discomfort and anxiety/depression and improved the capability of performing usual activities. Clinically significant improvement at long-term assessment was noted in 25 patients (49xa0%) while a significant deterioration was reported in 10 patients (20xa0%). Patients who reported postoperative worsening of HRQL were also reporting better preoperative scores, suggesting a possible ceiling effect of EQ-5D in some of these patients. In our patients a modest average improvement in HRQL was seen after surgery for meningioma. About half of the patients reported a clinical important improvement at the late follow-up assessment. This improvement was mainly observed in the domains usual activities, pain/discomfort and anxiety/depression. However, one in five patients fared worse on late follow-up assessment, a figure of particular importance when treating asymptomatic meningiomas.