Advanced imaging to extend the therapeutic time window of acute ischemic stroke

Reperfusion therapy for acute stroke has evolved from the initial use of intravenous tissue plasminogen activator (tPA) within 3 hours of symptom onset to more recent guideline‐recommended use up to 4.5 hours. In addition, endovascular therapy is increasingly utilized for stroke treatment and is typically initiated up to 8 hours after onset. Recent studies demonstrate that imaging of the ischemic penumbra with diffusion/perfusion magnetic resonance imaging (MRI) can identify subgroups of patients who are likely to improve following successful reperfusion (Target Mismatch profile) and others who are at increased risk for hemorrhage and poor clinical outcomes (Malignant profile). New data indicate that stent retriever devices provide better recanalization efficacy and clinical outcomes than the previously available mechanical thrombectomy devices. Going forward, we believe that the use of penumbral imaging with validated MRI techniques, as well as the currently less well‐validated computed tomography (CT) perfusion approach, will maximize benefit and reduce the risk of adverse events and poor outcomes when used both early after stroke onset and at later time points. New trials that feature diffusion/perfusion MRI or CT perfusion‐based patient selection for treatment with intravenous tPA and or endovascular therapies versus nonreperfused control groups are planned or in progress. We predict that these trials will confirm the hypothesis that penumbral imaging can enhance patient selection and extend the therapeutic time window for acute ischemic stroke. ANN NEUROL 2013.     

L-1-11C-tyrosine PET in patients with laryngeal carcinomas: comparison of standardized uptake value and protein synthesis rate.

PET with L-1-(11)C-tyrosine (TYR) can measure and quantify increased protein synthesis in tumor tissue in vivo. For quantification of the protein synthesis rate (PSR), arterial cannulation with repeated blood sampling to obtain the plasma input function and a dynamic TYR PET study to calculate a time-activity curve are necessary. In most PET studies the standardized uptake value (SUV) method is used to quantify tumor activity. The SUV can be calculated without repeated arterial blood sampling and prolonged scanning time, as required for determination of the PSR. The relationship between PSR and SUV is largely unknown and different factors can cause wide variability in the SUV. Therefore, the comparison of the absolute quantification method (PSR) with the SUV method is obligatory to determine the possible use of noninvasive PET in head and neck oncology. METHODS: Twenty-four patients with proven squamous cell carcinomas of the larynx (T1-T4) were studied using dynamic TYR PET. The PSRs of tumor and nontumor (background) regions were determined. Four different methods were used to calculate the SUV: uncorrected SUV (SUV(BW)); and SUVs corrected for body surface area (SUV(BSA)), for lean body mass (SUV(LBM)), and for the Quetelet index (SUV(QI)). Correlations between PSR values and SUVs were calculated. RESULTS: The PSR of all tumors was significantly higher (P < 0.001) than the PSR of nontumor tissue. The correlations of SUV(BW), SUV(BSA), SUV(LBM), and SUV(QI) with the quantitative values of the PSR were high (r = 0.84-0.90). The best correlation was observed with the SUV based on the LBM (SUV(LBM)). CONCLUSION: High correlation between the quantitative values (PSR) and the SUVs offers the possibility to use noninvasive TYR PET for detection and reliable quantification of primary head and neck tumors.     

Real-time diffusion-perfusion mismatch analysis in acute stroke

Diffusion-perfusion mismatch can be used to identify acute stroke patients that could benefit from reperfusion therapies. Early assessment of the mismatch facilitates necessary diagnosis and treatment decisions in acute stroke. We developed the RApid processing of PerfusIon and Diffusion (RAPID) for unsupervised, fully automated processing of perfusion and diffusion data for the purpose of expedited routine clinical assessment. The RAPID system computes quantitative perfusion maps (cerebral blood volume, CBV; cerebral blood flow, CBF; mean transit time, MTT; and the time until the residue function reaches its peak, T(max)) using deconvolution of tissue and arterial signals. Diffusion-weighted imaging/perfusion-weighted imaging (DWI/PWI) mismatch is automatically determined using infarct core segmentation of ADC maps and perfusion deficits segmented from T(max) maps. The performance of RAPID was evaluated on 63 acute stroke cases, in which diffusion and perfusion lesion volumes were outlined by both a human reader and the RAPID system. The correlation of outlined lesion volumes obtained from both methods was r(2) = 0.99 for DWI and r(2) = 0.96 for PWI. For mismatch identification, RAPID showed 100% sensitivity and 91% specificity. The mismatch information is made available on the hospital's PACS within 5-7 min. Results indicate that the automated system is sufficiently accurate and fast enough to be used for routine care as well as in clinical trials.     

Metastasiertes kastrationsresistentes Prostatakarzinom

Background

At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented.

Objectives

The focus is on the clinical impact of these data.

Materials and methods

A group of German experts in the field of urogenital–oncologic expertise discussed the clinical impact with respect to the current data.

Results

The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC.

Conclusions

Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20?mg/m² cabazitaxel.

     

Metastasiertes kastrationsresistentes Prostatakarzinom

Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life.     

Lack of correlation between serum lipoproteins and biliary cholesterol saturation in patients with gallstones

It has been suggested that elevated serum lipoprotein cholesterol levels may be a determinant of biliary cholesterol saturation and cholesterol gallstone disease. The aim of this study was to correlate serum lipoprotein cholesterol and apolipoprotein levels with biliary cholesterol saturation in patients with gallstones who participated in the National Cooperative Gallstone Study. Baseline serum lipoprotein and biliary lipid levels were studied in 181 of these patients before they received treatment for dissolution of their gallstones. Neither low-or high-density lipoprotein cholesterol nor apolipoprotein levels correlated with biliary cholesterol saturation. This study, therefore, does not support the concept that serum lipoproteins are a determinant of biliary cholesterol saturation. It is possible, however, that a significant effect of lipoprotein levels is obscured by the greater effects of more important determinants of biliary cholesterol saturation.This project was funded by the National Institute of Arthritis, Metabolism and Digestive Diseases of the Department of Health and Human Services under contract N01-AM-3-2216 and N01-AM-0-2205. The contents of this publication do not necessarily reflect the views or policies of the department nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.