Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma.

BACKGROUND: Implementation of adjuvant therapies in non-metastatic melanoma improved treatment outcomes in some patients; however, adjuvant therapy can be associated with significant cost and risk of toxicity. Therefore, there is an unmet need to better identify patients at high risk of recurrence. PATIENTS AND METHODS: We carried out an ultrasensitive droplet digital PCR (ddPCR)-based detection of BRAFV600E-mutated circulating tumor DNA (ctDNA) from blood samples prospectively collected before surgery, 1 hour after surgery, and then serially during follow-up. RESULTS: In 80 patients (stages ≤III), BRAFV600E mutations were detected in 47.2% of tissue, in 37.7% of ctDNA samples collected before surgery, and in 25.9% of ctDNA samples collected 1 hour after surgery. Patients with detected ctDNA in blood collected 1 hour after surgery compared to patients without detected ctDNA had higher likelihood of melanoma recurrence (P < 0.001) and shorter median disease-free survival (P = 0.001) and overall survival (P = 0.003). CONCLUSIONS: Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical blood samples from patients with resectable melanoma. Detection of ctDNA in post-surgical samples is associated with inferior treatment outcomes.

Determination of the Middle Cerebral Artery Occlusion Length in Acute Stroke: Contribution of 4D CT Angiography and Importance for Thrombolytic Efficacy Prediction.

PURPOSE: To assess the benefit of 4D-CT angiography (4D-CTA) in determination and precise measurement of middle cerebral artery (MCA) occlusion in comparison to CTA. Possible relationship of measured occlusion lengths with recanalization after intravenous thrombolysis was analysed as a second objective. METHODS: Detailed evaluation of complete MCA occlusions in 80 patients before intravenous thrombolysis using temporal maximum intensity projection (tMIP) dataset, calculated from 4D-CTA and conventional single-phase CTA was performed. Further, manual measurement technique was compared to results of semiautomatic procedure (vessel analysis) as reference. Statistical analysis of correlation between MCA occlusion length and IVT efficacy (24 h recanalization rate according modified Thrombolysis In Myocardial Infarction criteria-mTIMI) was performed. RESULTS: The distal end of occlusion was identified in all patients using tMIP, but only in 48 patients (60%) using CTA. The manual measurement method was not statistically different and well correlated with reference tMIP-vessel analysis. (15.4 vs. 16.3 mm; p = 0.434; r = 97). In measurable occlusions by CTA, no significant difference was proved in manually measured lengths using tMIP and CTA (14.5 vs. 13.3 mm; p = 0.089). Favorable recanalization (mTIMI 2-3) was achieved in 37 patients (47%). Length of occlusion in M1 segment (p = 0.002) and M2 segment involvement (p = 0.017) were proved as independent negative predictors of recanalization. Using receiver operating characteristics analysis, the cutoff length of the M1 segment occlusion for favorable recanalization was found to be 12 mm. CONCLUSION: The feasibility of MCA occlusion assessment using tMIP datasets and benefit over conventional CTA were confirmed. The manual measurement method was proved as feasible and simple with good correlation to reference semiautomatic analysis. The significant correlation of the MCA occlusion length and early recanalization was found. The length of 12 mm was recognized as cut-off length for favorable recanalization.

Isocitrate dehydrogenase-1 mutations as prognostic biomarker in glioblastoma multiforme patients in West Bohemia.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. Recent whole-genome studies revealed novel GBM prognostic biomarkers such as mutations in metabolic enzyme IDH-isocitrate dehydrogenases (IDH1 and IDH2). The distinctive mutation IDH1 R132H was uncovered to be a strong prognostic biomarker for glioma patients. We investigated the prognostic role of IDH1 R132H mutation in GBM patients in West Bohemia. METHODS: The IDH1 R132H mutation was assessed by the RT-PCR in the tumor samples from 45 GBM patients treated in the Faculty Hospital in Pilsen and was correlated with the progression free and overall survival. RESULTS: The IDH1 R132H mutation was identified in 20 from 44 GBM tumor samples (45.4%). The majority of mutated tumors were secondary GBMs (16 in 18, 89.9%). Low frequency of IDH1 mutations was observed in primary GBMs (4 in 26, 15.3%). Patients with IDH R132H mutation had longer PFS, 136 versus 51 days (P < 0.021, Wilcoxon), and OS, 270 versus 130 days (P < 0.024, Wilcoxon test). SUMMARY: The prognostic value of IDH1 R132H mutation in GBM patients was verified. Patients with mutation had significantly longer PFS and OS than patients with wild-type IDH1 and suffered more likely from secondary GBMs.

[Social impact of cerebrovascular disorders in a large engineering plant 1982-1986]. / Spolecenská závaznost cerebrovaskulárních chorob ve velkém strojírenském podniku v letech 1982-1986.

The authors analyzed the incidence of cerebrovascular diseases (dg. 430-438) in an industrial population in 1982-1986. The morbidity from cerebrovascular diseases associated with temporary or permanent work incapacity had during the investigation period a slightly rising trend which was more marked in manual male workers above 50 years of age. Strokes are the cause for granting invalidity pensions in cca 4%. In general cardiovascular and cerebrovascular diseases account for cca 21% of invalidity pensions. In the register of cerebrovascular attacks the incidence of strokes was roughly double in men as compared with women; it was on average 30 patients per year per 36,000 employees, i.e. cca 0.8%. Cerebrovascular attacks are in cca 70% associated with hypertension and the basis of almost three quarters of strokes is cerebral ischaemia. The trend of cerebrovascular diseases is unfavourable and depends above all on the control of hypertension in the population.