Molecular Characteristics of Neuroblastoma with Special Reference to Novel Prognostic Factors and Diagnostic Applications

Molecular Characteristics of Neuroblastoma with Special Reference to Novel Prognostic Factors and Diagnostic Applications Department of Medical Biochemistry and Genetics Annales Universitatis Turkuensis, Medica-Odontologica, 2009, Turku, Finland Painosalama Oy, Turku, Finland 2009 Background: Neuroblastoma, which is the most common and extensively studied childhood solid cancer, shows a great clinical and biological heterogeneity. Most of the neuroblastoma patients older than one year have poor prognosis despite intensive therapies. The hallmark of neuroblastoma, biological heterogeneity, has hindered the discovery of prognostic tumour markers. At present, few molecular markers, such as MYCN oncogene status, have been adopted into clinical practice. Aims: The aim of the study was to improve the current prognostic methodology of neuroblastoma, especially by taking cognizance of the biological heterogeneity of neuroblastoma. Furthermore, unravelling novel molecular characteristics which associate with neuroblastoma tumour progression and cell differentiation was an additional objective. Results: A new strictly defined selection of neuroblastoma tumour spots of highest proliferation activity, hotspots, appeared to be representative and reliable in an analysis of MYCN amplification status using a chromogenic in situ hybridization technique (CISH). Based on the hotspot tumour tissue microarray immunohistochemistry and high-resolution oligo-array-based comparative genomic hybridization, which was integrated with gene expression and in silico analysis of existing transcriptomics, a polysialylated neural cell adhesion molecule (NCAM) and poorly characterized amplicon at 12q24.31 were discovered to associate with outcome. In addition, we found that a previously considered new neuroblastoma treatment target, the mutated c-kit receptor, was not mutated in neuroblastoma samples. Conclusions: Our studies indicate polysialylated NCAM and 12q24.31 amplicon to be new molecular markers with important value in prognostic evaluation of neuroblastoma. Moreover, the presented hotspot tumour tissue microarray method together with the CISH technique of the MYCN oncogene copy number is directly applicable to clinical use. Key words: neuroblastoma, polysialic acid, neural cell adhesion molecule, MYCN, c-kit, chromogenic in situ hybridization, hotspotSiirretty Doriast

Transient Intracranial Circulatory Arrest Evidenced at the Time of Intracranial Aneurysm Rupture : Case Report

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In Reply : Simple Preoperative Patient-Reported Factors Predict Adverse Outcome After Elective Cranial Neurosurgery

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Simple Preoperative Patient-Reported Factors Predict Adverse Outcome After Elective Cranial Neurosurgery

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Case Fatality Rates of Subarachnoid Hemorrhage Are Decreasing with Substantial between-Country Variation : A Systematic Review of Population-Based Studies between 1980 and 2020

Background: The declining prevalence of smoking and hypertension has been associated with the decrease of subarachnoid hemorrhage (SAH) incidence in the 21st century. Since these same risk factors are linked to SAH mortality, the case fatality rate (CFR) of SAH has potentially also decreased during recent decades. Thus, we conducted a systematic review to address SAH CFR changes over the last 40 years. Methods: We performed a systematic literature search in OVID Medline, Scopus, and Cochrane Library databases. We focused on population-based studies published between 1980 and 2020 that had included both hospitalized and nonhospitalized SAH cases, and reported 1-month CFRs for at least two individual study periods for the same population. Finally, we used a linear regression analysis to estimate the annual CFR changes in each identified population and pooled the regional changes for larger geographical and sex-specific analyses. Results: Of the 4,562 initial publications, we included 22 studies (three of which reached a high-quality classification) consisting of 17,593 SAH patients from 16 different populations and 10 countries. Between 1980 and 2020, SAH CFR declined in all but two populations by an average of -1.5%/year. In the continent-based pooled geographical analyses, CFR decline was the most noticeable in North America (-2.4%/year) and Oceania (-2.2%/year). The decline was more moderate in Northern Europe (-0.8%/year) and Southern Europe (-0.7%/year). Overall, CFRs declined both in women (-1.9%/year) and in men (-1.2%/year). When comparing the first and second half of the study period, CFRs declined from 41% to 31%. Conclusion: Short-term SAH CFRs seem to have declined since 1980. Time trends of SAH CFRs can still be identified for only a few populations, and high-quality data are scarce. Whether the observed decline relates to changes in risk factors, treatment outcomes or diagnostics remains to be studied. (C) 2022 S. Karger AG, BaselPeer reviewe

Quality of British and American Nationwide Quality of Care and Patient Safety Benchmarking Programs : Case Neurosurgery

BACKGROUND: Multiple nationwide outcome registries are utilized for quality benchmarking between institutions and individual surgeons. OBJECTIVE: To evaluate whether nationwide quality of care programs in the United Kingdom and United States can measure differences in neurosurgical quality. METHODS: This prospective observational study comprised 418 consecutive adult patients undergoing elective craniotomy at Helsinki University Hospital between December 7, 2011 and December 31, 2012.We recorded outcome event rates and categorized them according to British Neurosurgical National Audit Programme (NNAP), American National Surgical Quality Improvement Program (NSQIP), and American National Neurosurgery Quality and Outcomes Database (N(2)QOD) to assess the applicability of these programs for quality benchmarking and estimated sample sizes required for reliable quality comparisons. RESULTS: The rate of in-hospital major and minor morbidity was 18.7% and 38.0%, respectively, and 30-d mortality rate was 2.4%. The NSQIP criteria identified 96.2% of major but only 38.4% of minor complications. N(2)QOD performed better, but almost one-fourth (23.2%) of all patients with adverse outcomes, mostly minor, went unnoticed. For NNAP, a sample size of over 4200 patients per surgeon is required to detect a 50.0% increase in mortality rates between surgeons. The sample size required for reliable comparisons between the rates of complications exceeds 600 patients per center per year. CONCLUSION: The implemented benchmarking programs in the United Kingdom and United States fail to identify a considerable number of complications in a high-volume center. Health care policy makers should be cautious as outcome comparisons between most centers and individual surgeons are questionable if based on the programs.Peer reviewe

In-hospital postoperative opioid use and its trends in neurosurgery between 2007 and 2018

Background Postoperative opioid use plays an important role in the global opioid crisis, but little is known about in-hospital opioid use trends of large surgical units. We investigated whether postoperative in-hospital opioid consumption changed in a large academic neurosurgical unit between 2007 and 2018. Methods We extracted the data of consumed opioids in the neurosurgical intensive care unit and two bed wards between 2007 and 2018. Besides overall consumption, we analyzed the trends for weak (tramadol and codeine), strong, and the most commonly used opioids. The use of various opioids was standardized using the defined daily doses (DDDs) of each opioid agent. A linear regression analysis was performed to estimate annual treatment day-adjusted changes with 95% confidence intervals. Results Overall, 121 361 opioid DDDs were consumed during the 196 199 treatment days. Oxycodone was the most commonly used postoperative opioid (49% of all used opioids) in neurosurgery. In the bed wards, the use of oral oxycodone increased 375% (on average 13% (9-17%) per year), and the use of transdermal buprenorphine 930% (on average 26% (9-45%) per year) over the 12-year period. Despite the increased use of strong opioids in the bed wards (on average 3% (1-4%) per year), overall opioid use decreased 39% (on average 6% (4-7%) per year) between 2007 and 2018. Conclusions Due to the increase of strong opioid use in the surgical bed wards, we encourage other large teaching hospitals and surgical units to investigate whether their opioid use trends are similarly worrisome and whether the opioid consumption changes in the hospital setting are transferred to opioid use patterns or opioid-related harms after discharge.Peer reviewe

Obesity paradox in subarachnoid hemorrhage : a systematic review

As the number of obese people is globally increasing, reports about the putative protective effect of obesity in life-threatening diseases, such as subarachnoid hemorrhage (SAH), are gaining more interest. This theory-the obesity paradox-is challenging to study, and the impact of obesity has remained unclear in survival of several critical illnesses, including SAH. Thus, we performed a systematic review to clarify the relation of obesity and SAH mortality. Our study protocol included systematic literature search in PubMed, Scopus, and Cochrane library databases, whereas risk-of-bias estimation and quality of each selected study were evaluated by the Critical Appraisal Skills Program and Cochrane Collaboration guidelines. A directional power analysis was performed to estimate sufficient sample size for significant results. From 176 reviewed studies, six fulfilled our eligibility criteria for qualitative analysis. One study found paradoxical effect (odds ratio, OR = 0.83 (0.74-0.92)) between morbid obesity (body mass index (BMI) > 40) and in-hospital SAH mortality, and another study found the effect between continuously increasing BMI and both short-term (OR = 0.90 (0.82-0.99)) and long-term SAH mortalities (OR = 0.92 (0.85-0.98)). However, according to our quality assessment, methodological shortcomings expose all reviewed studies to a high-risk-of-bias. Even though two studies suggest that obesity may protect SAH patients from death in the acute phase, all reviewed studies suffered from methodological shortcomings that have been typical in the research field of obesity paradox. Therefore, no definite conclusions could be drawn.Peer reviewe

Modified Rankin Scale and Short-Term Outcome in Cranial Neurosurgery : A Prospective and Unselected Cohort Study

BACKGROUND: The modified Rankin Scale (mRS) was developed to monitor functional recovery after stroke, but nowadays it is a treatment outcome measure in elective neurosurgery. Our objective was to study how mRS changes associate with short-term postoperative outcome. METHODS: Preoperative, in-hospital, and 30-day mRS scores came from a prospective, consecutive and unselected cohort of 418 adult elective craniotomy patients enrolled between December 2011 and December 2012 in Helsinki, Finland. Recorded data included subjective and objective postoperative in-hospital complications as well as changes in mRS score after surgery. RESULTS: Minor or major complications were detectable in 46% of the patients. In-hospital and 30-day postoperative increases in mRS score were inconsistent; among patients with no complications, 17% had a greater mRS score at discharge and 24% at 30 days, whereas 28% of the patients with major complications showed no increase in mRS score at discharge. Of individual complications, only new or worsened hemiparesis, silent stroke, and pneumonia were associated with postoperative increase (>2) in mRS score after multivariable analysis. For mRS-score difference >1 at discharge in detecting major complications (including mortality), sensitivity was 45% and specificity 94%. CONCLUSIONS: The mRS changes after elective cranial neurosurgery are inconsistent. The mRS seems to represent functional changes, which do not necessarily associate with detected in-hospital complications.Peer reviewe

Symptomatic peritumoral edema is associated with surgical outcome : a consecutive series of 72 supratentorial meningioma patients >= 80 years of age

Purpose To assess the association of peritumoral brain edema (PTBE) with postoperative outcome in old (>= 80 years) meningioma patients. Methods All supratentorial meningioma patients (>= 80 years old) who underwent surgery between 2010 and 2018 were retrospectively identified. Patients were classified into poor (= 80) preoperative Karnofsky Performance Status (KPS) subgroups. Outcome was evaluated at 3 months and at last follow-up within the first year after surgery, and categorized as improved, stable, or deteriorated. Three-dimensional volumetric assessment of tumor and PTBE volume was conducted. Volumes were categorized as small ( 50 cm(3)). Results Seventy-two patients (mean age 83 +/- 3 years, median 83; median follow-up 3 years) were included. The mean tumor volume was 39 +/- 31 cm(3) (median 27), and mean PTBE volume was 57 +/- 79 cm(3) (median 27). The mean preoperative KPS and at last follow-up was 58 +/- 16 (median 60) and 59 +/- 30 (median 70). Thirty-three patients were classified as improved, 16 as stable, and 23 deteriorated; eleven patients died within the first year. Large PTBE volume was more common for patients with poor preoperative status (p = 0.001). However, patients with large PTBE and poor preoperative status improved most frequently following surgery (p = 0.037 at 3 months, p = 0.074 at last follow-up). Large PTBE volume was not associated with treatment-associated complications (p = 0.538) or mortality (p = 0.721). A decision support tool to predict outcome was developed (p = 0.038). Conclusion Elderly patients with large PTBE volumes usually had a poor preoperative performance status, but appeared to benefit most often from surgery.Peer reviewe