Weak MGMT gene promoter methylation confers a clinically significant survival benefit in patients with newly diagnosed glioblastoma: a retrospective cohort study.

INTRODUCTION: Quantitative methylation specific PCR (qMSP) is a frequently used technique to assess MGMT gene promoter methylation in glioblastoma patients. The optimal technical cut-off value to distinguish methylated from unmethylated samples is nevertheless still undetermined. In literature, a "grey zone" of diagnostic uncertainty has been described. METHODS: We performed a retrospective analysis of newly diagnosed glioblastoma patients treated according to the Stupp protocol. Epidemiological data were gathered from the individual patient files. MGMT gene promoter methylation status was determined on stored tumour samples using qMSP. A strong, weak or absent promoter methylation was determined based on Cq values (quantification value) of the MGMT and ACTB primers as well as a positive control sample. RESULTS: In total, 181 patient files were reviewed and included for statistical analysis. MGMT promoter hypermethylation was detected in 38.7% of glioblastoma patients. The median overall survival of unmethylated and strongly methylated patients was 10.1 months and 19.7 months respectively. Furthermore, 11% of the total patient cohort had a weak MGMT gene promoter methylation. The median OS in this subgroup was 15.4 months, significantly better compared to the unmethylated cohort (P < 0.001). Multivariate Cox regression analysis showed weak MGMT promoter methylation as an independent prognostic parameter for overall survival. CONCLUSION: Glioblastoma patients with weak promoter methylation show a statistically significant longer overall survival when compared to clearly unmethylated patients. Patients with grey zone qMSP test results should receive additional molecular analysis in future to further direct individual therapy strategies.

Subventricular zone contacting glioblastoma: tumor size, molecular biological factors and patient survival.

BACKGROUND: Several studies show that subventricular zone (SVZ) contact of glioblastoma at diagnosis is a negative prognosticator of survival. In this report, we study glioblastoma patient survival, molecular biological and MRI-based volumetric findings according to SVZ contact. PATIENTS AND METHODS: We conducted a retrospective study of adult patients diagnosed with supratentorial glioblastoma and uniformly treated with temozolomide-based chemoradiotherapy after surgery. The patient cohort was dichotomized according to tumor contact with the SVZ at diagnosis as determined on preoperative MR imaging. Tumor volume was measured using semi-automated segmentation technique. MGMT-gene promoter methylation and IDH mutation status were determined on stored tumor tissue. Kaplan-Meier survival curves were constructed. Cox regression analysis was used to adjust for known confounding factors of glioblastoma patient survival. RESULTS: A total of 214 patients were included in the study of whom 68% belonged to the SVZpos group. Median tumor volume was significantly larger in the SVZpos group (33,8 mL vs 15,6 mL; p < .001). MGMT-unmethylated glioblastoma was more frequent in the SVZpos group (61.4% vs 44.9%; p = .028). The overall survival and progression-free survival were 12.2 months and 5.9 months for the SVZpos patient group but 16.9 months and 10.3 months for the SVZneg group (log-rank p = .016 and .007 respectively). In multivariate Cox survival analysis, SVZ contact proved a negative prognostic parameter, independent from age, KPS, extent of resection, MGMT-methylation and IDH mutation status. CONCLUSIONS: This study confirms SVZ contact at diagnosis as an independent negative prognostic factor for glioblastoma patient survival. SVZpos glioblastoma had larger tumor size and a larger proportion of unmethylated tumors than SVZneg glioblastoma. Further research is needed to establish whether the observed differences are solely explained by a different molecular profile of SVZpos glioblastoma or by interaction of glioblastoma with the unique SVZ microenvironment.

Cross-cultural adaptation and validation of the Dutch version of the core outcome measures index for low back pain.

PURPOSE: The core outcome measures index (COMI) is a validated multidimensional instrument for assessing patient-reported outcome in patients with back problems. The aim of the present study is to translate the COMI into Dutch and validate it for use in native Dutch speakers with low back pain. METHODS: The COMI was translated into Dutch following established guidelines and avoiding region-specific terminology. A total of 89 Dutch-speaking patients with low back pain were recruited from 8 centers, located in the Dutch-speaking part of Belgium. Patients completed a questionnaire booklet including the validated Dutch version of the Roland Morris disability questionnaire, EQ-5D, the WHOQoL-Bref, the Numeric Rating Scale (NRS) for pain, and the Dutch translation of the COMI. Two weeks later, patients completed the Dutch COMI translation again, with a transition scale assessing changes in their condition. RESULTS: The patterns of correlations between the individual COMI items and the validated reference questionnaires were comparable to those reported for other validated language versions of the COMI. The intraclass correlation for the COMI summary score was 0.90 (95% CI 0.84-0.94). It was 0.75 and 0.70 for the back and leg pain score, respectively. The minimum detectable change for the COMI summary score was 1.74. No significant differences were observed between repeated scores of individual COMI items or for the summary score. CONCLUSION: The reproducibility of the Dutch translation of the COMI is comparable to that of other validated spine outcome measures. The COMI items correlate well with the established item-specific scores. The Dutch translation of the COMI, validated by this work, is a reliable and valuable tool for spine centers treating Dutch-speaking patients and can be used in registries and outcome studies.

Communication in healthcare: a narrative review of the literature and practical recommendations.

OBJECTIVES: Effective and efficient communication is crucial in healthcare. Written communication remains the most prevalent form of communication between specialised and primary care. We aimed at reviewing the literature on the quality of written communication, the impact of communication inefficiencies and recommendations to improve written communication in healthcare. DESIGN: Narrative literature review. METHODS: A search was carried out on the databases PubMed, Web of Science and The Cochrane Library by means of the (MeSH)terms 'communication', 'primary health care', 'correspondence', 'patient safety', 'patient handoff' and 'continuity of patient care'. Reviewers screened 4609 records and 462 full texts were checked according following inclusion criteria: (1) publication between January 1985 and March 2014, (2) availability as full text in English, (3) categorisation as original research, reviews, meta-analyses or letters to the editor. RESULTS: A total of 69 articles were included in this review. It was found that poor communication can lead to various negative outcomes: discontinuity of care, compromise of patient safety, patient dissatisfaction and inefficient use of valuable resources, both in unnecessary investigations and physician worktime as well as economic consequences. CONCLUSION: There is room for improvement of both content and timeliness of written communication. The delineation of ownership of the communication process should be clear. Peer review, process indicators and follow-up tools are required to measure the impact of quality improvement initiatives. Communication between caregivers should feature more prominently in graduate and postgraduate training, to become engraved as an essential skill and quality characteristic of each caregiver.

Sex-based survival differences in IDH-wildtype glioblastoma: Results from a retrospective cohort study.

A female survival benefit has been described for glioblastoma patients. Recent studies report that the effect of 06-methylguanine-DNA-methyltransferase gene promoter (MGMTp) methylation is only present in female patients. We retrospectively studied sex-based survival, including MGMTp-methylation, in a cohort of 159 uniformly treated isocitrate dehydrogenase wildtype (IDHwt) patients. All patients were treated with temozolomide-based chemoradiotherapy after surgery. Kaplan-Meier survival curves and Cox regression models were used to evaluate overall survival. The study included 59 female (37.1%) and 100 male patients (62.9%). There were no statistically significant differences between sexes concerning demographic, surgical or radiological characteristics. Female patients harbored MGMTp-methylated tumors in 45.8% of cases and males in 33% (P = 0.129). Median overall survival was 13.4 months for men and women alike. After adjustment of survival for age, Karnofsky Performance Score, extent of resection and MGMTp-methylation, sex did not have a significant survival impact. However, MGMTp-methylation proved to be an independent beneficial prognosticator for both sexes, contradicting earlier reports. Several sex-based molecular subtypes of glioblastoma with different response to current treatment may exist explaining conflicting survival results in different patient cohorts. Further research on sex-based differences in IDHwt glioblastoma patients is needed.

Subarachnoidal-pleural fistula (SAPF) as an unusual cause of persistent pleural effusion. Beta-trace protein as a marker for SAPF. Case report and review of the literature.

BACKGROUND: We describe a case of a 56-year-old woman who developed a recurrent pleural effusion after a thoracoscopic resection of an anterior bulging thoracic disc hernia (level D9-D10). Despite several evacuating pleural punctions, dyspnea reoccurred due to recurrent pleural effusion, the same side as the disc resection. Because of increasing headache after each punction, a subarachnoidal pleural fistula (SAPF) was suspected. Although magnetic resonance imaging (MRI) showed features suggestive of SAPF, there was not enough evidence to justify a new thorascopy. METHODS: Cerebrospinal fluid (CSF) leakage into the thoracic and abdominal cavity has been described as a result of trauma or surgery. Detection of beta-trace protein (BTP, a brain-specific protein) has been described to detect CSF fistulae causing rhino- and otoliquorrhea. Similarly, BTP determination could be used to identify the presence of CSF at other anatomical sites such as the thoracic cavity. Therefore, we decided to determine the concentration of BTP in the pleural effusion of this patient. BTP was assayed using immunonephelometry. RESULTS: The patient's BTP pleural fluid concentration was 14·0 mg/l, which was a 25-fold increase compared with the BTP serum concentration. After insertion of a subarachnoidal lumbal catheter, a video-assisted thorascopy was performed. Leakage of liquor through the parietal pleura into the thoracic cavity was observed. The SAPF was closed using a durasis patch and DuraSeal®. Postoperatively, there was no reoccurrence of pleural fluid. CONCLUSIONS: SAPF has to be included to the differential diagnosis of patients with persistent pleural effusion after spinal surgery. This case illustrates the importance of BTP in diagnosing SAPF, especially in cases where major therapeutic consequences may need to be drawn.

Frameless neuronavigation-guided endoscopic total en-bloc removal of a third ventricular colloid cyst: a case report on surgical technique.

A 26-year-old man was referred to our department with recurrent episodes of loss of consciousness. The radiological evaluation of the patient's cranium showed a third ventricular colloid cyst with only a slight degree of obstructive hydrocephalus. The complete, en-bloc removal of the cyst was achieved by a frameless neuronavigation-guided endoscopic resection technique. The patient had an uneventful post-operative period and was discharged home on the fourth post-operative day without any neurological or psychological deficit. The surgical technique and pertinent literature are discussed with emphasis on factors that contribute to our successful total en-bloc removal of the third ventricular colloid cyst.