Perioperative search for circulating tumor cells in patients undergoing radical cystectomy for bladder cancer

<p>Abstract</p> <p>Objective</p> <p>Despite having an organ confined tumor stage at the time of radical cystectomy, a certain number of bladder cancer patients will develop local or distant metastases over time. Currently there are no reliable serum markers for monitoring and evaluating risk profiles of urothelial cancers. Several studies suggest that detection of Circulating Tumor Cells (CTC) may correlate with disease status and prognosis at baseline and early in the treatment of cancers. The presence of CTCs in whole blood before and during radical cystectomy could provide further information on disease status, and could be used as an indicator to determine the need for adjuvant or even perioperative chemotherapy.</p> <p>Methods</p> <p>From 03/2009 to 05/2009, five patients with histologically proven transitional cell carcinoma of the urinary bladder participated in this study. All patients were admitted to the hospital for radical cystectomy (rCx). A standard or extended lymph node dissection was performed in all cases. Preoperative CT or MRI scans revealed no distant or local metastases. Median age was 66.8 years (55-81 yrs). After obtaining informed consent from each patient, approximately 30 mL of peripheral blood was taken immediately before rCx and again during surgical removal of the urinary bladder from the patients' body. As additional parameters, operation time (OR) for surgical removal of the bladder and the amount of blood volume that was used for the detection of CTCs were recorded. Obtained blood samples were processed using the Cell-Search System (Veridex^©) within 48 hours of collection. CTCs were identified and quantitated using the Cell-Search System, followed by re-evaluation of the provided results by specially trained and experienced personal. (CS, SH)</p> <p>Results</p> <p>CTCs were detected before and during surgical removal of the urinary bladder in one of five patients (20%). In the one patient positive for CTC, two CTCs were detected in the blood sample that was obtained before surgery (analyzed blood volume was 25 mL). There was one CTC detected in the blood sample that was obtained during surgical removal of the urinary bladder (analyzed blood volume was 27 mL). There was no rise in the amount of CTCs during surgical procedure. The final pathological report of this patient showed an advanced tumor stage (T3b, N0, R1). In the other patients, no CTCs were detected at all, neither before rCX nor right after surgical removal of the bladder. Pathological stage for these patients ranged from pT1m G3 -pT2b G3. None of these patients showed lymph node involvement. An average of 14.6 lymph nodes (5-40 LNs) were obtained. OR time to surgical removal of the urinary bladder ranged from 60 minutes to 150 minutes (mean 82 min.).</p> <p>Conclusions</p> <p>Although only a very small group of patients was analyzed in this study, the presence of CTCs seems to be correlated with an advanced tumor stage. Therefore the detection of CTCs could be used for an optimized assessment of a patient's disease status in urothelial cancer. A further aim of this study was to assess whether surgical manipulation during radical cystectomy is associated with a release of CTCs into the vascular system. None of the patients who were negative for CTCs before surgery showed CTCs during surgical removal of the bladder, suggesting that there was no release of CTCs during surgery. However, further study is needed to prove these findings and evaluate the significance of CTCs as an indicator for therapeutic decisions.</p

Stratification of sunspot umbral dots from inversion of Stokes profiles recorded by Hinode

This work aims to constrain the physical nature of umbral dots (UDs) using high-resolution spectropolarimetry. Full Stokes spectra recorded by the spectropolarimeter on Hinode of 51 UDs in a sunspot close to the disk center are analyzed. The height dependence of the temperature, magnetic field vector, and line-of-sight velocity across each UD is obtained from an inversion of the Stokes vectors of the two FeI lines at 630 nm. No difference is found at higher altitudes (-3 <= log(tau) <= -2) between the UDs and the diffuse umbral background. Below that level the difference rapidly increases, so that at the continuum formation level (log(tau) = 0) we find on average a temperature enhancement of 570 K, a magnetic field weakening of 510 G, and upflows of 800 m/s for peripheral UDs, whereas central UDs display an excess temperature of on average 550 K, a field weakening of 480 G, and no significant upflows. The results for, in particular, the peripheral UDs, including cuts of magnetic vector and velocity through them, look remarkably similar to the output of recent radiation MHD simulations. They strongly suggest that UDs are produced by convective upwellings

High-resolution imaging and near-infrared spectroscopy of penumbral decay

Combining high-resolution spectropolarimetric and imaging data is key to understanding the decay process of sunspots as it allows us scrutinizing the velocity and magnetic fields of sunspots and their surroundings. Active region NOAA 12597 was observed on 24/09/2016 with the 1.5-m GREGOR solar telescope using high-spatial resolution imaging as well as imaging spectroscopy and near-infrared (NIR) spectropolarimetry. Horizontal proper motions were estimated with LCT, whereas LOS velocities were computed with spectral line fitting methods. The magnetic field properties were inferred with the SIR code for the Si I and Ca I NIR lines. At the time of the GREGOR observations, the leading sunspot had two light-bridges indicating the onset of its decay. One of the light-bridges disappeared, and an elongated, dark umbral core at its edge appeared in a decaying penumbral sector facing the newly emerging flux. The flow and magnetic field properties of this penumbral sector exhibited weak Evershed flow, moat flow, and horizontal magnetic field. The penumbral gap adjacent to the elongated umbral core and the penumbra in that penumbral sector displayed LOS velocities similar to granulation. The separating polarities of a new flux system interacted with the leading and central part of the already established active region. As a consequence, the leading spot rotated 55-degree in clockwise direction over 12 hours. In the high-resolution observations of a decaying sunspot, the penumbral filaments facing flux emergence site contained a darkened area resembling an umbral core filled with umbral dots. This umbral core had velocity and magnetic field properties similar to the sunspot umbra. This implies that the horizontal magnetic fields in the decaying penumbra became vertical as observed in flare-induced rapid penumbral decay, but on a very different time-scale.Comment: 14 pages, 11 figures, Accepted to be published in Astronomy and Astrophysic

Association between computed tomography obstruction index and mortality in elderly patients with acute pulmonary embolism: A prospective validation study.

Computed tomography pulmonary angiography (CTPA) has not only become the method of choice for diagnosing acute pulmonary embolism (PE), it also allows for risk stratification of patients with PE. To date, no study has specifically examined the predictive value of CTPA findings to assess short-term prognosis in elderly patients with acute PE who are particularly vulnerable to adverse outcomes. We studied 291 patients aged ≥65 years with acute symptomatic PE in a prospective multicenter cohort. Outcomes were 90-day overall and PE-related mortality, recurrent venous thromboembolism (VTE), and length of hospital stay (LOS). We examined associations of the computed tomography obstruction index (CTOI) and the right ventricular (RV) to left ventricular (LV) diameter ratio with mortality and VTE recurrence using survival analysis, adjusting for provoked VTE, Pulmonary Embolism Severity Index (PESI), and anticoagulation as a time-varying covariate. Overall, 15 patients died within 90 days. There was no association between the CTOI and 90-day overall mortality (adjusted hazard ratio per 10% CTOI increase 0.92; 95% confidence interval [CI] 0.70-1.21; P = 0.54), but between the CTOI and PE-related 90-day mortality (adjusted sub-hazard ratio per 10% CTOI increase 1.36; 95% CI 1.03-1.81; P = 0.03). The RV/LV diameter ratio was neither associated with overall nor PE-related 90-day mortality. The CTOI and the RV/LV diameter ratio were significantly associated with VTE recurrence and LOS. In elderly patients with acute PE, the CTOI was associated with PE-related 90-day mortality but not with overall 90-day mortality. The RV/LV diameter ratio did not predict mortality. Both measures predicted VTE recurrence and LOS. The evaluated CTPA findings do not appear to offer any advantage over the PESI in terms of mortality prediction

Optical coherence tomography for bladder cancer - ready as a surrogate for optical biopsy? - Results of a prospective mono-centre study

<p>Abstract</p> <p>Introduction</p> <p>New modalities like Optical Coherence Tomography (OCT) allow non-invasive examination of the internal structure of biological tissue in vivo. The potential benefits and limitations of this new technology for the detection and evaluation of bladder cancer were examined in this study.</p> <p>Materials and methods</p> <p>Between January 2007 and January 2008, 52 patients who underwent transurethral bladder biopsy or TUR-BT for surveillance or due to initial suspicion of urothelial carcinoma of the bladder were enrolled in this study. In total, 166 lesions were suspicious for malignancy according to standard white light cystoscopy. All suspicious lesions were scanned and interpreted during perioperative cystoscopy using OCT. Cold cup biopsies and/or TUR-B was performed for all these lesions. For this study we used an OCT-device (Niris^®, Imalux^®, Cleveland, US), that utilizes near-infrared light guided through a flexible fibre-based applicator, which is placed into the bladder via the working channel of the cystoscope. The technology provides high spatial resolution on the order of about 10-20 μm, and a visualization of tissue to a depth of about 2 mm across a lateral span of about 2 mm in width. The device used received market clearance from the FDA and CE approval in Germany. The diagnostic and surgical procedure was videotaped and analyzed afterwards for definitive matching of scanned and biopsied lesion. The primary aim of this study was to determine the level of correlation between OCT interpretation and final histological result.</p> <p>Results</p> <p>Of 166 scanned OCT images, 102 lesions (61.4%) matched to the same site where the biopsy/TUR-BT was taken according to videoanalysis. Only these video-verified lesions were used for further analysis. Of all analyzed lesions 88 were benign (inflammation, edema, hyperplasia etc.) and 14 were malignant (CIS, Ta, T1, T2) as shown by final histo pathology.</p> <p>All 14 malignant lesions were detected correctly by OCT. Furthermore all invasive tumors were staged correctly by OCT regarding tumor growth beyond the lamina propria. There were no false negative lesions detected by OCT. Sensitivity of OCT for detecting the presence of a malignant lesion was 100% and sensitivity for detection of tumor growth beyond the lamina propria was 100% as well. Specificity of OCT for presence of malignancy was 65%, due to the fact that a number of lesions were interpreted as false positive by OCT.</p> <p>Conclusion</p> <p>As a minimally invasive technique, OCT proved to have extremely high sensitivity for detection of malignant lesions as well as estimation of whether a tumor has invaded beyond the lamina propria. However, specificity of OCT within the bladder was impaired (65%), possibly due to a learning curve and/or the relatively low spatial resolution and visualization depth of the OCT technology. Further studies and technical development are needed to establish an adequate surrogate for optical biopsy.</p

The Fine-Structure of the Net-Circular Polarization in a Sunspot Penumbra

We present novel evidence for a fine structure observed in the net-circular polarization (NCP) of a sunspot penumbra based on spectropolarimetric measurements utilizing the Zeeman sensitive FeI 630.2 nm line. For the first time we detect a filamentary organized fine structure of the NCP on spatial scales that are similar to the inhomogeneities found in the penumbral flow field. We also observe an additional property of the visible NCP, a zero-crossing of the NCP in the outer parts of the center-side penumbra, which has not been recognized before. In order to interprete the observations we solve the radiative transfer equations for polarized light in a model penumbra with embedded magnetic flux tubes. We demonstrate that the observed zero-crossing of the NCP can be explained by an increased magnetic field strength inside magnetic flux tubes in the outer penumbra combined with a decreased magnetic field strength in the background field. Our results strongly support the concept of the uncombed penumbra