The spectrum of acute and chronic consequences of neurotrauma in professional and amateur boxing - A call to action is advocated to better understand and prevent this phenomenon.

Introduction: Despite changes in regulations, boxing-related injuries and fatalities are still occurring. The numbers available in the literature regarding mortality and long-term consequences may not accurately represent the actual situation. Indeed, the real extent of this phenomenon remains poorly known. Research question: Delineating the spectrum of acute and chronic consequences of boxing-related traumatic brain injuries (TBI). Material and methods: Narrative review of the literature concerning acute and chronic boxing-related TBI. Keywords such as mortality, boxing, subdural hematoma were used to search in PubMed and Google scholar. An updated analysis of the Velazquez fatalities collection in boxing was undertaken. Results: The Velazquez collection includes 2076 fatalities from 1720 to the present with a death rate of 10 athletes per year. More than half of the deaths (N = 1354, 65.2%) occurred after a knock-out, and nearly 75% happened during professional bouts. In Australia, from 1832 to 2020, 163 fatalities were recorded (75% professional). In Japan, from 1952 to 2016, 38 deaths were recorded with a mean age of 23.9 years. Up to 40% of retired professional boxers in the United States were diagnosed with symptoms of chronic brain injury. Clinical dementia is far more prevalent among professional boxers than in amateurs with an incidence of 20%. Discussion and conclusions: A concerted effort to raise awareness and shed light on boxing-related neuro-trauma is required. Similar considerations can be made for other combat sports or contact sports. A call to action to address this knowledge gap, decrease and prevent this phenomenon is advocated.

Tetraparesis following thoracic spine surgery in a patient with Klippel-Feil syndrome and ABCB4 mutation: a case report.

BACKGROUND: Klippel-Feil syndrome is a rare condition described in 1912 by Maurice Klippel and André Feil. It is defined as a congenital cervical fusion of at least two vertebrae, associated with a classical triad of clinical signs: short neck, low posterior hairline, and limited range of movement. However, Klippel-Feil syndrome manifests with a vast spectrum of phenotypes, ranging from no symptoms to complete triad, with or without other associated malformations. Most commonly, CCF results from sporadic mutations, even though autosomal recessive, autosomal dominant, or even X-linked inheritance can be detected. The ATP-binding cassette subfamily B member 4 is only expressed in the liver and is involved in biliary phospholipid secretion. The clinical spectrum includes various hepatobiliary pathologies, including low phospholipid-associated cholelithiasis, and has never been associated with musculoskeletal anomalies. CASE PRESENTATION: A 55-year-old male Caucasian patient presenting with low phospholipid-associated cholelithiasis syndrome with ATP-binding cassette subfamily B member 4 mutation and liver cirrhosis was referred to our clinic for a liver transplant. A period of 6 months before, the patient underwent a T7-T9 posterior fixation for a T8 osteoporotic fracture. Postoperatively, he was tetraparetic, whereas he was neurologically intact before the operation. At admission to our hospital, he was still tetraparetic and presented with clinical signs of cervical myelopathy. Moreover, he suffered a limitation of cervical range of motion in all directions, short neck, and low posterior hairline. Imaging showed multiple cervical and thoracic vertebral bodies fusion, as well as cervical spine stenosis. Based on the available data, we diagnosed a type 3 Klippel-Feil syndrome according to Samartzis' classification. CONCLUSIONS: The heterogeneity of KFS and the various potential hereditary links that are known indicate that it is important to highlight all potential cases related to known genetic defects. At present, no association between ATP-binding cassette subfamily B member 4 mutation and congenital cervical fusions has been reported. The other important clinical focus of this case is the appearance of spontaneous tetraparesis after thoracic spine surgery. This mechanism remains unclear, but considering different spinal anatomy it might have been due to difficult intubation and patient's positioning during his previous operation.

Posterior spine fusion in a Jehovah's Witness patient with severe rigid idiopathic scoliosis - A case report.

Introduction: Early onset scoliosis (EOS) represent a challenge for spine surgeons. The selection of the best treatment is complex. Some patients, such as Jehovah's Witnesses who refuse blood transfusions, are at high risk of complication when surgical treatment is required because blood loss is a major cause of morbidity and postoperative transfusion rates. Research question: Describe blood-saving techniques that allowed an extensive and invasive surgical procedure in a Jehovah's Witness patient. Material and method: 17-year-old Jehovah's Witness girl with severe 120° Cobb Lenke 1A idiopathic scoliosis started as EOS was prepared with 4 cycles of recombinant human erythropoietin, iron and folic acid supplementation that brought her hemoglobin level from 13.6 g/dl to 16.2 g/dl. In the first surgical time, a temporary rod was implanted. Spine dissection using bipolar sealer and a special electrocautery that operates at lower temperatures than traditional ones was performed. Facetectomies and multilevel Ponte osteotomies was performed using an ultrasonic bone scalpel. The second surgical time, the definitive rods were placed, and the correction of the deformity was achieved using the rod link reducer technique. Results: A good correction of the main curve in the coronal plane is achieve. The Hb nadir was 7.2 g/dl four days after the second operation. The postoperative course was uneventful. Discussion and conclusion: The integration of modern and traditional preoperative, intraoperative, and postoperative blood sparing techniques allowed us to perform an extensive and invasive surgical procedure in a Jehovah's Witness girl with a severe idiopathic scoliosis.

The Impact of Controlled Ovarian Stimulation on Serum Oxidative Stress Markers in Infertile Women with Endometriosis Undergoing ICSI.

Endometriosis-related infertility is associated with oxidative stress (OS). The present study aims to compare serum OS markers of infertile women with endometriosis and controls during the follicular phase of the natural cycle (D1), after pituitary downregulation using a GnRH agonist (D2), after controlled ovarian stimulation (COS) on the day of human chorionic gonadotropin administration (D3), and on the day of oocyte retrieval (D4). One hundred and eight serum samples (58 controls and 35 early and 18 advanced endometriosis cases) were collected at these four timepoints. OS markers were compared among the groups and timepoints using a linear regression model with mixed effects and a post-test using orthogonal contrasts. The significance was set at 5%. We observed altered OS markers in the endometriosis patients during the D1, D2, D3, and D4 timepoints compared to the controls. The evidence of systemic OS in infertile patients with endometriosis during COS suggests the mobilization of potent antioxidants in an attempt to protect the oocyte from oxidative damage, especially on the day of oocyte retrieval.

Transcriptomic analysis of cumulus cells shows altered pathways in patients with minimal and mild endometriosis.

Endometriosis is a chronic inflammatory disorder that is highly associated with infertility. This association seems to be related to oocyte impairment, mainly in the initial stages of endometriosis (minimal and mild), where no distortions or adhesions are present. Nonetheless, invasive oocyte analyses are not routinely feasible; thus, indirect assessment of oocyte quality is highly desirable, and, in this context, cumulus cells (CCs) may be more suitable targets of analysis. CCs are crucial in oocyte development and could be used as an index of oocyte quality. Therefore, this prospective case-control study aimed to shed light on the infertility mechanisms of endometriosis I/II by analyzing the CCs' mRNA transcription profile (women with endometriosis I/II, n = 9) compared to controls (women with tubal abnormalities or male factor, n = 9). The transcriptomic analyses of CCs from patients with minimal and mild endometriosis revealed 26 differentially expressed genes compared to the controls. The enrichment analysis evidenced some altered molecular processes: Cytokine-cytokine receptor interactions, Chemokine signaling, TNF signaling, NOD-like receptor signaling, NF-kappa B signaling, and inflammatory response. With the exception of CXCL12, all enriched genes were downregulated in CCs from patients with endometriosis. These findings provide a significant achievement in the field of reproductive biology, directing future studies to discover biomarkers of oocyte quality in endometriosis.

Screening of Variants in the Transcript Profile of Eutopic Endometrium from Infertile Women with Endometriosis during the Implantation Window.

OBJECTIVE: Abnormalities in the eutopic endometrium of women with endometriosis may be related to disease-associated infertility. Although previous RNA-sequencing analysis did not show differential expression in endometrial transcripts of endometriosis patients, other molecular alterations could impact protein synthesis and endometrial receptivity. Our aim was to screen for functional mutations in the transcripts of eutopic endometria of infertile women with endometriosis and controls during the implantation window. METHODS: Data from RNA-Sequencing of endometrial biopsies collected during the implantation window from 17 patients (6 infertile women with endometriosis, 6 infertile controls, 5 fertile controls) were analyzed for variant discovery and identification of functional mutations. A targeted study of the alterations found was performed to understand the data into disease's context. RESULTS: None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls. In the endometriosis group, nine predicted deleterious mutations were identified, but only one was previously associated to a clinical condition with no endometrial impact. When crossing the mutated genes with the descriptors endometriosis and/or endometrium, the gene CMKLR1 was associated either with inflammatory response in endometriosis or with endometrial processes for pregnancy establishment. CONCLUSION: Despite no pattern of mutation having been found, we ponder the small sample size and the analysis on RNA-sequencing data. Considering the purpose of the study of screening and the importance of the CMKLR1 gene on endometrial modulation, it could be a candidate gene for powered further studies evaluating mutations in eutopic endometria from endometriosis patients.

OBJETIVO: Anormalidades no endométrio eutópico de mulheres com endometriose podem estar relacionadas à infertilidade associada à doença. Embora a análise prévia de sequenciamento de RNA não tenha evidenciado expressão diferencial em transcritos endometriais de pacientes com endometriose, outras alterações moleculares poderiam afetar a síntese de proteínas e a receptividade endometrial. Nosso objetivo foi rastrear mutações funcionais em transcritos de endométrios eutópicos de mulheres inférteis com endometriose e de controles durante a janela de implantação. MéTODOS: Os dados do sequenciamento de RNA de biópsias endometriais coletados durante a janela de implantação de 17 pacientes (6 mulheres inférteis com endometriose, 6 controles inférteis, 5 controles férteis) foram analisados para a descoberta de variantes e a identificação de mutações funcionais. Um estudo direcionado das alterações encontradas foi realizado para compreender os dados no contexto da doença. RESULTADOS: Nenhuma das variantes identificadas foi comum a outras amostras dentro do mesmo grupo, assim como nenhuma mutação se repetiu entre pacientes com endometriose, controles inférteis e férteis. No grupo de endometriose, foram identificadas nove mutações deletérias preditas, mas apenas uma foi previamente associada a uma condição clínica sem impacto endometrial. Ao cruzar os genes mutados com os descritores endometriose e/ou endométrio, o gene CMKLR1 foi associado a resposta inflamatória na endometriose e a processos endometriais para estabelecimento da gravidez. CONCLUSãO: Apesar de nenhum padrão de mutação ter sido encontrado, ponderamos o pequeno tamanho da amostra e a análise dos dados de sequenciamento de RNA. Considerando o objetivo do estudo de triagem e a importância do gene CMKLR1 na modulação endometrial, este poderia ser um gene candidato para estudos adicionais que avaliem mutações no endométrio eutópico de pacientes com endometriose.

Predictors of Survival in Subtotally Resected WHO Grade I Skull Base Meningiomas.

BACKGROUND: Although gross total resection (GTR) is the goal in meningioma surgery, this can sometimes be difficult to achieve in skull base meningiomas. We analyzed clinical outcomes and predictors of survival for subtotally resected benign meningiomas. METHODS: A total of 212 consecutive patients who underwent subtotal resection (STR) for benign skull base meningioma between 1990-2010 were investigated. RESULTS: Median age was 57.7 [IQR 18.8] years, median preoperative Karnofsky performance status (KPS) was 80.0 [IQR 20.0], 75 patients (35.4%) had posterior fossa meningioma. After a median follow-up of 6.2 [IQR 7.9] years, retreatment (either radiotherapy or repeated surgery) rate was 16% at 1-year, 27% at 3-years, 34% at 5-years, and 38% at 10-years. Ten patients (4.7%) died perioperatively, 9 (3.5%) had postoperative hematomas, and 2 (0.8%) had postoperative infections. Neurological outcome at final visit was improved/stable in 122 patients (70%). Multivariable analysis identified advanced age and preoperative KPS < 70 as negative predictors for overall survival (OS). Patients who underwent retreatment had no significant reduction of OS. CONCLUSIONS: Advanced age and preoperative KPS were independent predictors of OS. Retreatments did not prolong nor shorten the OS. Clinical outcomes in STR skull base meningiomas were generally worse compared to cohorts with high rates of GTR.

Predictors of Survival in Atypical Meningiomas.

INTRODUCTION: Predictors of survival and progression of disease in atypical meningiomas are less well documented in the literature compared to benign meningiomas. Higher grade meningiomas tend to recur often and one of the most critical aspects is how to best deal with relapses. METHODS: A total of 77 consecutive patients who underwent craniotomy for atypical meningioma between 1990-2010 at Oslo University Hospital (OUH) were reviewed. RESULTS: Median age at surgery was 62.21 [interquartile range (IQR): 22.87] years. Fifty-one patients (66.2%) had neurological deficits at presentation. Fifty-four patients (70.1%) underwent gross total resection (GTR). Thirty-nine patients (50.7%) had improved/stable neurological outcomes at 6-12 months. Twenty-two patients (28.6%) underwent retreatment, of whom 20 (26.0%) were subjected to resection followed by adjuvant radiotherapy. Overall survival (OS) was significantly longer in patients <65 years (p < 0.001), with preoperative Karnofsky performance scale (KPS) score of ≥ 70 (p = 0.006), and who required no retreatment (p = 0.033). GTR significantly prolonged the retreatment-free survival rate (p < 0.001). STR carried almost a six-fold greater risk of neurological outcome deterioration (p = 0.044). CONCLUSIONS: GTR significantly prolonged retreatment-free survival but had no significant impact on OS. STR was a significant risk factor for deteriorated neurological outcome. Age, preoperative KPS, and retreatment were all strong predictors of OS. Median time-to-retreatment (TTR) did not shorten significantly throughout repeated surgeries.

Altered transcriptome in cumulus cells of infertile women with advanced endometriosis with and without endometrioma.

RESEARCH QUESTION: Is the transcriptome of cumulus cells of infertile women with advanced endometriosis (EIII/IV), with and without endometrioma, altered? DESIGN: In this prospective case-control study, next-generation RNA sequencing was used to compare the transcript profile of cumulus cells among infertile patients undergoing ovarian stimulation for intracytoplasmic sperm injection with EIII/IV, with (n = 9) and without endometrioma (n = 9), and controls (n = 9). An in-silico enrichment analysis was conducted to establish the possibly altered pathways in cumulus cells of patients with endometriosis. RESULTS: Most of the differentially expressed genes (DEG) were found when cumulus cells from women with EIII/IV with endometrioma were compared with controls (DEG, n = 461). In women with EIII/IV without endometrioma, only 66 DEG were verified compared with controls. The enrichment analysis showed that some DEG in cumulus cells of endometriosis are involved in important pathways for the oocyte competence acquisition, such as oxidative phosphorylation, metabolism, mitochondrial function, acetylation and steroid biosynthesis. No DEG were found when cumulus cells from women with EIII/IV with and without endometrioma were compared. CONCLUSION: RNA sequencing results suggest that cumulus cells of infertile women with EIII/IV have an altered transcriptome, regardless of endometrioma. The present findings offer a better understanding of the genes and molecular mechanisms that may be involved in endometriosis-related infertility, mostly in the oocyte competence acquisition process.

miR-532-3p: a possible altered miRNA in cumulus cells of infertile women with advanced endometriosis.

RESEARCH QUESTION: Is the profile of microRNA (miRNA) altered in cumulus cells of infertile women with early (EI/II) and advanced (EIII/IV) endometriosis? DESIGN: In this prospective case-control study, a miRNA profile including 754 targets was evaluated in samples of cumulus cells from infertile women with endometriosis (5 EI/II, 5 EIII/IV) and infertile controls (5, male and/or tubal factor) undergoing ovarian stimulation for intracytoplasmic sperm injection, using TaqMan® Array Human MicroRNA Cards A and B. The groups were compared with Kruskal-Wallis test, followed by Benjamini-Hochberg correction and Dunn's post hoc test. An in silico enrichment analysis was performed to list the possibly altered pathways in which the altered miRNA target genes are involved. RESULTS: Only the miRNA miR-532-3p showed significant differences among the analysed groups, being down-regulated in the EIII/IV group compared with the infertile control group, as well as compared with the EI/II group. The enrichment analysis showed that some genes regulated by this miRNA are involved in important pathways for the acquisition of oocyte competence, such as the oxytocin, calcium, Wnt, FoxO, ErbB and Ras signalling pathways, as well as the oocyte meiosis pathway. CONCLUSION: The present findings bring new perspectives to understanding the follicular microenvironment of infertile women with different stages of endometriosis. It is suggested that the dysregulation of miR-532-3p may be a potential mechanism involved in the aetiopathogenesis of endometriosis-related infertility. Further studies are needed to evaluate these pathways in cumulus cells of infertile women with the disease, as well as their impact on the acquisition of oocyte competence.

WHO grade I meningiomas: classification-tree for prognostic factors of survival.

World Health Organization (WHO) grade I meningiomas are intracranial extracerebral tumors, in which microsurgery as a stand-alone therapy provides high rates of disease control and low recurrence rates. Our aim was to identify prognostic factors of overall survival and time-to-retreat (OS; TTR) in a cohort of patients with surgically managed WHO grade I meningioma. Patients with WHO grade I meningiomas from a retrospectively (1990 to 2002) and prospectively managed (2003 to 2010) databank of Oslo University Hospital, Norway, were included. The mean follow-up was 9.2 ± 5.7 years, with a total of 11,414 patient-years. One thousand three hundred fifty-five patients were included. The mean age was 58 ± 13.2, mean Karnofsky Performance Status (KPS) 92.6 ± 26.1 and female-to-male ratio 2.5:1. The 1-year, 5-year, 10-year, 15-year, and 20-year probabilities were 0.98, 0.91, 0.87, 0.84, and 0.8 for TTR. Patient age (OR 0.92 [0.91, 0.94]), male sex (OR 0.59 [0.45, 0.76]), preoperative KPS ≥ 70 (OR 2.22 [1.59, 3.13]), skull base location (OR 0.77 [0.60, 1]), and the occurrence of a postoperative hematoma (OR 0.44 [0.26, 0.76]) were identified as independent prognostic factors of OS. Patient age (OR 1.02 [1.01, 1.03]) and skull base location (OR 0.30 [0.21, 0.45]) were independent predictors of decreased PFS. Using a recursive partitioning analysis, we suggest a classification tree for the prediction of 5-year PFS based on patient and tumor characteristics. The findings from this cohort of meningioma WHO I patients helps to identify patients at risk of recurrence and tailor the therapeutic management.

Early Postoperative Complications in Meningioma: Predictive Factors and Impact on Outcome.

BACKGROUND: Craniotomies carry inherent risks of postoperative complications that may have a negative impact on patients' status. Recognizing and preventing surgical complications is of paramount importance, especially in meningioma surgery, where most of these tumors are benign and current management protocols are effective in terms of disease control and maintenance of higher quality of life. The objective of this study was to describe the early complications after surgery and their predictive factors in patients undergoing resection of intracranial meningiomas. METHODS: A partly retrospective, partly prospective review was conducted in a Norwegian population-based cohort of 1469 consecutive cases of meningioma surgery treated at the university hospitals of Oslo, totaling 11,414 patient-years of follow-up. RESULTS: 2.6% of patients had a postoperative hematoma, 2.7% a postoperative infection, 3.9% a postoperative worsening of neurologic status; 5.4% of patients died during a 30-day period after surgery. Predictive factors of increased risk of postoperative complications were patient's age for the hematoma, a non-skull base meningioma for infection, and postoperative hematoma for the risk of neurologic worsening or 30-day mortality. CONCLUSIONS: Early postoperative complications in meningioma surgery have a negative impact on patient survival and postoperative neurologic status, in a disease where survival is usually not limited by the meningioma itself. In this study, we identified risk factors for early postoperative complications, the identification of at-risk populations may help to prevent the occurrence of these risk factors.

Extent of Resection in Meningioma: Predictive Factors and Clinical Implications.

Meningiomas present as intracranial extra-axial lesions with dural attachment, which are primarily managed surgically. The extent of resection (EOR) may vary depending on patient- and tumor-related factors. The aim of this study is to identify preoperative predictive factors of EOR and to propose an estimation of the predicted gross total resection (GTR) based of patient- and tumor-characteristics. 1469 patients from a retrospectively (1990 to 2002) and prospectively managed (2003 to 2010) databank of Oslo University Hospital, Norway, totalling 11,414 patient-years of follow-up were included. Patients had a mean age at surgery of 64 ± 20.1 years with a female-to-male ratio was 2.4:1 and a mean KPS of 81.2 ± 12.1. Skull-base meningiomas represented 47% of all cases. WHO grades were I in 92.3%, II in 5.2%, and III in 2.2%. Bone infiltration was described in 18.7% of cases. 39.3% of patients had Simpson I resection, 34.3% had Simpson II, 5.4% had Simpson III, 20.6% had Simpson IV, and 0.5% had Simpson V. The risk factors for incomplete resection were: symptomatic presentation (OR 0.56 [0.43-0.72]), skull-base location (OR 0.79 [0.70-0.88]), and bone invasion (OR 0.85 [0.73-0.99]). Using a recursive partitioning analysis, we propose a classification-tree for the prediction of GTR rate based on preoperatively determinable patient- and tumor characteristics. The identification of preoperative predictors of poor GTR rate may aid clinicians managing meningioma patients. In selected cases were the predicted GTR rate is low, staged treatment with surgical debulking followed by adjuvant therapy may be favored in order to minimize postoperative morbidity and mortality.

Posterior fossa meningiomas: perioperative predictors of extent of resection, overall survival and progression-free survival.

BACKGROUND: Posterior fossa meningiomas (PFMs) often represent surgical challenges due to their proximity to neurovascular structures. Factors predicting the extent of resection (EOR), overall survival (OS), and progression-free survival (PFS) were identified and integrated in a prediction tool to offer evidence-based personalized therapeutic strategies. METHODS: All meningiomas managed surgically from 1990 to 2010 from a single-center were reviewed. A classification tree was created using the classification and regression tree recursive partitioning analysis that incorporated patient and tumor data available before surgery in order to predict the rates of gross total resection (GTR). RESULTS: A total of 198 patients were identified (female-to-male ratio, 2.7; mean age, 59.1 years) and compared with 1271 supratentorial meningiomas (STMs) operated in the same institution during the same time period. GTR was achieved less often (59.6% versus 81.9%; p < 0.01) in PFMs than STMs. Preoperative neurological symptoms were predictive of higher Simpson grades (OR, 2.19 [1.05; 4.58]; p = 0.04). Age was associated with reduced OS (OR, 1.08 [1.04;1.12]; p < 0.001). A KPS ≥ 70 was associated with higher survival rates (OR, 2.70 [2.19;2.92]; p = 0.02). Higher WHO grades were associated with reduced OS (OR, 3.56 [1.02;12.47]; p = 0.05). The GTR rate varies from 80% in patients without a preoperative deficit to 40% patients with a preoperative deficit, younger than 60 years old, and with adjacent bone invasion. CONCLUSIONS: This study provides a classification tree of the predictors of EOR in PFMs, based upon preoperative demographic, clinical, and radiological variables. An evidence-based management protocol with estimated EORs may guide the decision-making process in PFMs.

Progesterone Receptor B (PGR-B) Is Partially Methylated in Eutopic Endometrium From Infertile Women With Endometriosis.

Endometriosis is frequently related to infertility and little is known about the mechanisms underlying this association. Some studies point to an endometrial factor involved in this condition, which could compromise embryo implantation. Progesterone plays crucial role in endometrial receptivity by acting through progesterone receptor (PGR) isoforms PR-A and PR-B whose expression is epigenetically regulated by DNA methylation, in a specific promoter region for each isoform. Epigenetic changes in PGR-A and PGR-B may be related to progesterone resistance of endometriosis-related infertility. In order to better understand the mechanisms involved in endometrial receptivity, this case-control study aimed to compare the methylation pattern of PGR-A and PGR-B in eutopic endometrium from infertile women with and without endometriosis during the secretory phase. Endometrial biopsies from 19 patients (10 infertile women with endometriosis and 9 infertile controls) with regular cycles were performed during the secretory phase and were dated according to Noyes' criteria. The percentage of DNA methylation at PGR-A and PGR-B was carried out by high-resolution melting assay. The PGR-A gene showed 0% of DNA methylation (unmethylated) in both control and endometriosis groups. However, PGR-B gene showed a partially methylated pattern in majority of the patients (n = 7), with methylation percentage corresponding to 50%, while in the control group the percentage of methylation was 20% (hypomethylated; P = .04). The increased percentage of methylation at PGR-B may be related to reduced gene expression, which could compromise the endometrial receptivity in patients with endometriosis.

Meningioma Surgery-Are We Making Progress?

BACKGROUND: To study improvements in outcomes after surgery for intracranial meningiomas. METHODS: We performed a longitudinal observational study comparing 1469 patients operated on for intracranial meningioma in 4 consecutive time frames (1990-1994, 1995-1999, 2000-2004, and 2005-2010). RESULTS: Median age at surgery was 58.3 years. Median follow-up was 7 years. Patients in later periods were older than in the earlier ones (odds ratio [OR], 1.19 [1.09-1.32]; P < 0.0005), indicating a trend toward operating on more elderly patients. Before 2000, 42%, 32%, 6%, 19%, and 0.3% achieved Simpson grade (SG) I, II, III, IV, and V, respectively, whereas the SG rates were 35%, 37%, 4%, 23%, and 0.9% after 2000 (OR, 1.18 [1.06-1.30]; P < 0.005). The perioperative mortality (OR, 0.65 [0.46-0.91]; P < 0.05) and worsened neurologic outcome rate (OR, 0.70 [0.60-0.83]; P < 0.0001) were significantly lower in later decades, but the 4 surgical periods were similar regarding postoperative infections and hematomas. Retreatment-free survival (RFS) and overall survival (OS) increased significantly over the 4 time frames (P < 0.05 and P < 0.0001, respectively). Multivariate analysis confirmed the improvement of surgical radicality, neurologic outcome, perioperative mortality, OS, and RFS. CONCLUSIONS: Meningioma surgery as well as patient population changed over the 2 decades considered in this study. We observed higher rates of gross total resection in the later period and the perioperative outcomes improved or were unchanged, which signifies better long-term outcomes, RFS, and OS.

Meningiomas: skull base versus non-skull base.

To identify differences between skull base meningiomas (SBM) and non-skull base meningiomas (NSBM). All adult patients (18.0-69.9 years) operated for intracranial meningiomas between 1990 and 2010 at our institution were investigated. Al-Mefty's definition was used to dichotomize tumors into SBM and NSBM. Overall, 1148 consecutive patients were identified. Median age at surgery was 54.2 years [18.1-69.9]. Median follow-up was 7.4 years [0.0-20.9]. There were 562 patients (49%) with SBM and 586 (51%) with NSBM. The two groups were similar with respect to patient age, follow-up time, and number of patients. Overall female-to-male ratio was 2.6:1, but 3.2:1 in SBM and 2.2:1 in NSBM (p < 0.005). With respect to presenting symptoms, SBMs had more often neurological deficits (risk ratio (RR) 1.4; p < 0.0001) and less often seizures (RR 0.4; p < 0.0001). Gross total resections were less frequent in SBM than NSBM (62 vs 84%) (RR 1.3; p < 0.0001). SBMs had a lower risk of WHO grades II and III histology (4.5 vs 9.5%) (RR 0.5; p < 0.001). Worsening of neurological function was more frequent in SBM (21 vs 121%) (RR 1.8; p < 0.001). Retreatment-free survival at 5, 10, and 15 years, respectively, was 80, 70, and 62% for SBM versus 90, 82, and 74% for NSBM (p < 0.0001). Overall survival at 5, 10, and 15 years, respectively, was 93, 85, and 78% for SBM and 96, 91, and 79% for NSBM (p = 0.14). Patients with SBMs had more new-onset neurological deficits and significantly shorter retreatment-free survivals, but this did not adversely affect the overall survival.

Skull base versus non-skull base meningioma surgery in the elderly.

To compare outcomes after surgery for skull base meningiomas (SBMs) with non-skull base meningiomas (NSBMs) in the elderly. Overall, 128 consecutive patients ≥ 70 years of age with intracranial SBMs operated between 1990 and 2010 were compared to 193 consecutive patients ≥ 70 years of age with NSBMs operated within the same time period. Median age at surgery was 75.0 years (mean 75.7, range 70.0-92.4). Follow-up was complete with median 4.7 years (mean 5.5, range 0-19). The female-to-male ratio was 2.8 for SBMs and 1.3 for NSBMs (p < 0.005). The groups had similar preoperative KPS (median 80, range 20-100), but SBMs presented significantly more frequently with raised ICP (RR = 2.2, p < 0.005) and less frequently with seizures (RR = 0.6, p < 0.05). WHO I was significantly more frequent in SBMs (p < 0.005). Gross-total resection (GTR) was less frequent in SBMs (63 vs 82%) (RR = 2.1, p < 0.0001). SBMs were similar to NSBMs with respect to neurological outcome at 6-12 months, reoperations for hematomas, postoperative infections, and 30-day mortality. Retreatment rates and time to retreatments were also similar. There were no differences between the two groups with respect to risk of retreatment and overall survival (OS) at 5, 10, 15, and 20 years. In elderly patients with SBMs selected to surgical treatment, the risks of surgery, risk of retreatment, and OS were similar to NBSMs. Therefore, surgery for SBMs may be considered as safe as NSBMs in the elderly population.

Efficacy of the Nordic and the MSKCC chemotherapy protocols on the overall and progression-free survival in intracranial PCNSL.

BACKGROUND: To compare the Nordic and the Memorial Sloan-Kettering Cancer Center (MSKCC) chemotherapy protocols for Overall Survival (OS) and Progression-Free Survival (PFS) for intracranial primary CNS lymphoma (PCNSL). METHODS: A prospective database at Oslo University Hospital of PCNSL was reviewed over a 12-year period (2003-2014). RESULTS: Overall, 79 patients with PCNSL were identified, of whom 57 received chemotherapy. MSKCC with Rituximab (RTX) was used in 18 patients (32%) who had median OS of 46.3 months [9.8-131.9] and median PFS of 34.6 months [6.4-131.9]. The Nordic protocol was used in 14 patients (25%) who had median OS of 30.9 months [2.7-106.3] and PFS of 14.3 months [0.0-106.3]. The MSKCC was used without RTX in 25 patients (44%) who had OS of 15.2 months [0.7-136.5] and PFS of 12.0 months [0.0-117.0]. MSKCC with RTX had a significantly longer median OS (p < 0.05) compared to the other regimens in univariate analysis. In multivariate analysis, the only prognostic factor for OS and PFS of significance was deep brain involvement (p < 0.005). CONCLUSIONS: In univariate analysis, the MSKCC with RTX achieved significantly longer median OS compared to the Nordic protocol. However, in multivariate analysis, the only prognostic factor for survival of statistical significance was deep brain involvement.

Is deep brain involvement in intracranial primary central nervous system lymphoma of importance for penetration of chemotherapeutic agents?

PURPOSE: The purposes of this study are to study the impact of deep brain involvement on overall survival (OS) and progression-free survival (PFS) in intracranial primary CNS lymphoma (PCNSL), and to explore possible mechanisms for this impact using advanced MRI techniques. METHODS: Seventy-nine patients with histologically verified PCNSL were identified from a prospective clinical database of patients treated at Oslo University Hospital between 2003 and 2014. Patients were treated per standard chemotherapeutic regimens (N = 57) or no chemotherapy (N = 22). Anatomical MRIs were available in all patients to assess tumor load and location based on contrast agent enhancement visible on T1-weighted images. Diffusion MRIs were available in 33 (42%) patients and perfusion MRI in 13 (16%) patients that received active treatment. RESULTS: Across all patients, OS and PFS were 16.4 and 9.8 months, respectively. In multivariate analysis, MRI-based deep brain involvement (80%) was the only negative significant factor of OS (OR = 14.2; P < 0.005). While a reduced Karnofsky performance status was associated with deep brain involvement (P < 0.05), neither chemotherapy regimen, neurologic status, nor patient age were independent significant factors for OS or PFS in this setting. Compared to other tumors and healthy tissue levels, MRI perfusion showed more pathologic hemodynamic flow signatures in tumors with deep brain involvement. CONCLUSION: In intracranial PCNSL, the only significant prognostic factor for OS and PFS in multivariate analysis was age and deep brain involvement. While contingent on a small study sample, we hypothesize this may in part be explained by regional differences in vascular supply and delivery from a dysfunctional perfusion signature.