Urokinase‐plasminogen‐activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer

OBJECTIVE

To evaluate the expression of urokinase‐plasminogen‐activator receptor (uPA‐R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis.

PATIENTS AND METHODS

In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA‐R expression was detected by dual‐immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow‐up was initiated to detect tumour relapse (defined as a prostate‐specific antigen (PSA) level of ≥0.2 ng/mL).

RESULTS

Overall, there was expression of ‘CK + uPA‐R’ in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high‐risk cancer (P = 0.005). The relative risk for CK + uPA‐R expression in the BM was 3.1 times higher in high‐risk than in low‐risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA‐R expression in BM or PB. The PSA‐recurrence free survival was significantly lower in patients with CK + uPA‐R‐positive BM cells (P = 0.01).

CONCLUSION

In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high‐risk disease. All patients with a later PSA relapse had had uPA‐R expression in their DTC from the BM. DTC with uPA‐R expression was an adverse prognostic factor for prostate cancer.     

Infected chronic hematoma mimicking soft tissue neoplasm

A rare case of an infected chronic hematoma in a patient with immunodeficiency syndrome mimicking a soft tissue neoplasm is presented. There are few reported cases of hematogenous infection of chronic hematomas, which be difficult to differentiate from soft tissue neoplasms.     

Membrane phosphoinositides control insulin secretion through their effects on ATP-sensitive K+ channel activity

ATP-sensitive K(+) channels (K(ATP) channels) of pancreatic beta-cells play key roles in glucose-stimulated insulin secretion by linking metabolic signals to cell excitability. Membrane phosphoinositides, in particular phosphatidylinositol 4,5-bisphosphates (PIP(2)), stimulate K(ATP) channels and decrease channel sensitivity to ATP inhibition; as such, they have been postulated as critical regulators of K(ATP) channels and hence of insulin secretion in beta-cells. Here, we tested this hypothesis by manipulating the interactions between K(ATP) channels and membrane phospholipids in a beta-cell line, INS-1, and assessing how the manipulations affect membrane excitability and insulin secretion. We demonstrate that disruption of channel interactions with PIP(2) by overexpressing PIP(2)-insensitive channel subunits leads to membrane depolarization and elevated basal level insulin secretion at low glucose concentrations. By contrast, facilitation of channel interactions with PIP(2) by upregulating PIP(2) levels via overexpression of a lipid kinase, phosphatidylinositol 4-phosphate 5 kinase, decreases the ATP sensitivity of endogenous K(ATP) channels by approximately 26-fold and renders INS-1 cells hyperpolarized, unable to secrete insulin properly in the face of high glucose. Our results establish an important role of the interaction between membrane phosphoinositides and K(ATP) channels in regulating insulin secretion.     

Penislike clitorises with megalourethras in nonvirilized female fetuses and a newborn. A histopathologic study and its bearing on their pathogenesis

Purpose

The aim of the study was to analyze the microstructure of penislike clitorises in female pseudohermaphroditism in relation to their pathogenesis.

Methods

Penislike clitorises from 2 fetuses and 1 newborn with anorectal malformations and multiple other caudal anomalies and 1 fetus with phallic urethra duplication were histologically examined in toto.

Results

The penislike clitorises revealed basically female features in the histogenesis of the corpora cavernosa and glans and in the absence of penile raphe, septum, fasciae, and periurethral glands. In 2 cases, the “phallic urethra” was completely surrounded by a single corpus cavernosum and in 3 cases by a circular glans. Labia minora and vestibular bulbs had not developed in 3 cases. The urethras had transformed into fusiform or scaphoid megalourethras with stenotic meatuses in 3 specimens and an extra orifice in the fourth specimen.

Conclusions

Penislike clitorises in female pseudohermaphroditism show a fundamental dysgenesis of major structural elements. The pattern favors the hypothesis of an early error in the formation of the cloacal membrane and adjacent cloaca in embryos between 26 and 29 days postovulation that may lead to dysregulation of molecular developmental interactions during the following formation of the genital tubercle.     

Successful Sorafenib Treatment for Metastatic Renal Cell Carcinoma in a Case with Chronic Renal Failure

Treatment options for patients with end-stage renal disease (ESRD) and metastatic renal cell carcinoma (mRCC) are limited. We report the case of a 69-yr-old male who was treated with sorafenib after failure of immunotherapy. The treatment has resulted in remission with stable disease for 13 mo so far. Sorafenib seems to be a safe treatment option for patients with ESRD and mRCC, but further studies are required.     

Accuracy of Right and Left Ventricular Functional Assessment by Short-Axis vs Axial Cine Steady-State Free-Precession Magnetic Resonance Imaging: Intrapatient Correlation With Main Pulmonary Artery and Ascending Aorta Phase-Contrast Flow Measurements

Objective

The left ventricle (LV) is routinely assessed with cardiac magnetic resonance imaging (MRI) by using short-axis orientation; it remains unclear whether the right ventricle (RV) can also be adequately assessed in this orientation or whether dedicated axial orientation is required. We used phase-contrast (PC) flow measurements in the main pulmonary artery (MPA) and the ascending aorta (Aorta) as nonvolumetric standard of reference and compared RV and LV volumes in short-axis and axial orientations.

Methods

A retrospective analysis identified 30 patients with cardiac MRI data sets. Patients underwent MRI (1.5 T or 3 T), with retrospectively gated cine steady-state free-precession in axial and short-axis orientations. PC flow analyses of MPA and Aorta were used as the reference measure of RV and LV output.

Results

There was a high linear correlation between MPA-PC flow and RV–stroke volume (SV) short axis (r = 0.9) and RV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 1.4 mL for RV axial and –2.3 mL for RV–short-axis vs MPA-PC flow. There was a high linear correlation between Aorta-PC flow and LV-SV short-axis (r = 0.9) and LV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 4.8 m for LV short axis and 7.0 mL for LV axial vs Aorta-PC flow. There was no significant difference (P = .6) between short-axis–LV SV and short-axis–RV SV.

Conclusion

No significant impact of the slice acquisition orientation for determination of RV and LV stroke volumes was found. Therefore, cardiac magnetic resonance workflow does not need to be extended by an axial data set for patients without complex cardiac disease for assessment of biventricular function and volumes.     

Improved fat water separation with water selective inversion pulse for inversion recovery imaging in cardiac MRI

Purpose:

To develop an improved chemical shift‐based water‐fat separation sequence using a water‐selective inversion pulse for inversion recovery 3D contrast‐enhanced cardiac magnetic resonance imaging (MRI).

Materials and Methods:

In inversion recovery sequences the fat signal is substantially reduced due to the application of a nonselective inversion pulse. Therefore, for simultaneous visualization of water, fat, and myocardial enhancement in inversion recovery‐based sequences such as late gadolinium enhancement imaging, two separate scans are used. To overcome this, the nonselective inversion pulse is replaced with a water‐selective inversion pulse. Imaging was performed in phantoms, nine healthy subjects, and nine patients with suspected arrhythmogenic right ventricular cardiomyopathy plus one patient for tumor/mass imaging. In patients, images with conventional turbo‐spin echo (TSE) with and without fat saturation were acquired prior to contrast injection for fat assessment. Subjective image scores (1 = poor, 4 = excellent) were used for image assessment.

Results:

Phantom experiments showed a fat signal‐to‐noise ratio (SNR) increase between 1.7 to 5.9 times for inversion times of 150 and 300 msec, respectively. The water‐selective inversion pulse retains the fat signal in contrast‐enhanced cardiac MR, allowing improved visualization of fat in the water‐fat separated images of healthy subjects with a score of 3.7 ± 0.6. Patient images acquired with the proposed sequence were scored higher when compared with a TSE sequence (3.5 ± 0.7 vs. 2.2 ± 0.5, P < 0.05).

Conclusion:

The water‐selective inversion pulse retains the fat signal in inversion recovery‐based contrast‐enhanced cardiac MR, allowing simultaneous visualization of water and fat. J. Magn. Reson. Imaging 2013;37:484–490. © 2012 Wiley Periodicals, Inc.     

Measurement of vibration‐induced volumetric strain in the human lung

Noninvasive image‐based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase‐contrast MRI to measure three‐dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three‐dimensional vector fields of 50‐Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective‐medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression‐sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence‐sensitive MRI may serve as a noninvasive marker sensitive to disease‐related alterations of regional elastic recoil pressure in the lungs. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Improved reproducibility in measuring LV volumes and mass using multicoil breath-hold cine MR imaging

There is a generally recognized need for improvement in quality of fast cardiac MR images. Consequently, breath-hold cine MR images were obtained with multiple surface coils connected to phased array receivers, and C/N, intra-observer and inter-observer variabilities for LV volumes and mass were evaluated. Two sets of short-axis images of the LV, one with multiple surface coils and another with a body coil, were acquired in eight subjects with a fast cine MR sequence using k-space segmentation (TR/TE=7/2.2 msec, temporal resolution=56 msec). C/N with multicoil imaging was 32.2 ± 7.6 (mean ± SD), significantly higher than that with a body coil (11.0 ± 3.3, P < .01). The mean percentage differences in intra-observer and inter-observer measurements with multicoil imaging were significantly better than those with a body coil. In conclusion, multicoil imaging provides significant gain in C/N on breath-hold cine MRI of the heart. In addition, intra-observer and inter-observer reproducibilities are improved with multicoil imaging.     

Assessment of thoracic aortic dimensions in an experimental setting: comparison of different unenhanced magnetic resonance angiography techniques with electrocardiogram-gated computed tomography angiography for possible application in the pediatric population

PURPOSE: To compare different unenhanced magnetic resonance angiography (MRA) techniques for quantitative evaluation of vessel lumen in an experimental setting in young pigs whose dimensions allow for a comparison with a pediatric population. MATERIAL AND METHODS: Magnetic resonance imaging was performed in 5 healthy ventilated pigs at 1.5 T. Three different electrocardiogram (ECG)-triggered sequences were applied for MRA: [TSE-Db] T2-weighted dark-blood TurboSpinEcho (2.0 x 1.1 x 4 mm3); [trueFISP] 2D-steady-state-free-precession (2.2 x 1.8 x 2 mm3); [NAV] respiratory-gated, T2-prepared 3D-trueFISP (1.3 x 1.3 x 1.3 mm3). ECG-gated-CT angiography (CTA) (16-row CT, 1 mm collimation) served as the standard of reference. The vessel lumen was measured at 7 positions perpendicularly angulated to the vessel wall on multiplanar reformations: ascending aorta (P1), the aortic arch before (P2) and after (P3) the origin of the first supraaortic branch, the aortic arch after the origin of the second supraaortic branch (P4), the descending aorta at the level of the diaphragm (P5), and the first and second supraaortic branches (P6, P7). RESULTS: Percentage differences in the vessel area determined by MRA reformation compared with CTA-reformation were 10% +/- 20% and 35% +/- 27% (TSE-Db), -4% +/- 13% and 20% +/- 24% (trueFISP), and -3% +/- 13% and -10% +/- 19% (NAV), for positions P1 to P5 and P6 to P7, respectively. A significant difference from CTA was found for TSE-Db at all positions, and for trueFISP only at positions P6 and P7. CONCLUSIONS: Unenhanced MRA techniques allow for a reliable assessment of the dimensions of the thoracic aorta compared with CTA as the standard of reference. Using ECG-gating and navigator techniques, the free-breathing approach showed the best agreement with CTA. This technique may therefore be the most useful in the pediatric age group allowing for true 3D data acquisition with its inherent postprocessing possibilities.