[CEUS-diagnosis of solid renal tumors]. / CEUS ­ Diagnostik solider Nierentumoren.

CLINICAL ISSUE: Renal lesions are detected earlier, often as a result of ultrasound examinations. However, the imaging-based differential diagnosis of different tumour entities remains challenging STANDARD RADIOLOGICAL METHODS: All renal tumours >1 cm should be evaluated for malignancy by computed tomography (CT) or magnetic resonance imaging (MRI). If an angiomyolipoma diagnosis cannot be established with imaging, further diagnostics are appropriate or if malignant progression is suspected, then multidisciplinary discussion for TNM-staging based uro-oncologic therapy is usual. METHODICAL INNOVATIONS: Contrast-enhanced ultrasound (CEUS) gives clear information about the microperfusion of renal tumours. PERFORMANCE: CEUS is helpful for the differentiation of renal cysts and especially papillary renal cell carcinomas. Moreover, CEUS advances renal tumour detection compared to B­mode and Doppler ultrasound per se. Cortical pseudolesions may be confidently ruled out using CEUS. ACHIEVEMENTS: Clear differentiation of benign and malignant renal lesions >1 cm remains challenging, and only in rare cases is it possible with CEUS alone. Nevertheless CEUS is, in combination with other ultrasound techniques, eminently suitable for diagnosing focal pyelonephritis, renal abscesses and suspected renal lymphoma and supports the planning of ultrasound-assisted tumour biopsies. PRACTICAL RECOMMENDATIONS: Combining different imaging techniques is essential to accurately diagnose renal tumors. These imaging results (including the ultrasound/CEUS clips) should be viewed by the multidisciplinary cancer tumour board to facilitate individual treatment concepts for each patient.

The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer.

BACKGROUND: Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa). PATIENTS AND METHODS: The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters. RESULTS: Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values. CONCLUSIONS: A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.

Subwavelength microwave electric-field imaging using Rydberg atoms inside atomic vapor cells.

We have recently shown [Nat. Phys.8, 819 (2012)] that Alkali atoms contained in a vapor cell can serve as a highly accurate standard for microwave (MW) electric field strength as well as polarization. Here we show for the first time that Rydberg atom electromagnetically induced transparency can be used to image MW electric fields with unprecedented precision. The spatial resolution of the method is far into the subwavelength regime ∼λ/650 or 66 µm at 6.9 GHz. The electric field resolutions are similar to those we have already demonstrated ∼50 µV cm(-1). Our experimental results agree with finite element calculations of test electric-field patterns.

Atom-based vector microwave electrometry using rubidium Rydberg atoms in a vapor cell.

It is clearly important to pursue atomic standards for quantities like electromagnetic fields, time, length, and gravity. We have recently shown using Rydberg states that Rb atoms in a vapor cell can serve as a practical, compact standard for microwave electric field strength. Here we demonstrate for the first time that Rb atoms excited in a vapor cell can also be used for vector microwave electrometry by using Rydberg-atom electromagnetically induced transparency. We describe the measurements necessary to obtain an arbitrary microwave electric field polarization at a resolution of 0.5°. We compare the experiments to theory and find them to be in excellent agreement.

Electrical readout for coherent phenomena involving Rydberg atoms in thermal vapor cells.

We present a very sensitive and scalable method to measure the population of highly excited Rydberg states in a thermal vapor cell of rubidium atoms. We detect the Rydberg ionization current in a 5 mm electrically contacted cell. The measured current is found to be in qualitatively good agreement with a theory for the Rydberg population based on a master equation for the three-level problem, including an ionization channel and the full Doppler distributions at the corresponding temperatures. The signal-to-noise ratio of the current detection is substantially better than that of purely optical techniques.

Fabrication and characterization of an electrically contacted vapor cell.

We demonstrate the use of electrically contacted vapor cells to switch the transmission of a probe laser. The excitation scheme makes use of electromagnetically induced transparency involving a Rydberg state. The cell fabrication technique involves thin-film-based electric feedthroughs, which are well suited for scaling this concept to many addressable pixels like in flat panel displays.

GHz Rabi flopping to Rydberg states in hot atomic vapor cells.

We report on the observation of Rabi oscillations to a Rydberg state on a time scale below 1 ns in thermal rubidium vapor. We use a bandwidth-limited pulsed excitation and observe up to 6 full Rabi cycles within a pulse duration of ∼4 ns. We find good agreement between the experiment and numerical simulations based on a surprisingly simple model. This result shows that fully coherent dynamics with Rydberg states can be achieved even in thermal atomic vapor, thus suggesting small vapor cells as a platform for room-temperature quantum devices. Furthermore, the result implies that previous coherent dynamics in single-atom Rydberg gates can be accelerated by 3 orders of magnitude.

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer.

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.

[Natural orifices transluminal endoscopic surgery (NOTES) in Germany: summary of the working group reports of the "D-NOTES meeting 2009"]. / Endoskopisches Operieren über natürliche Körperöffnungen (NOTES) in Deutschland: Zusammenfassung der Arbeitsgruppensitzungen der "D-NOTES 2009"

The D-NOTES-group met in June 2009 for an evaluation of ongoing preclinical and clinical activities in natural orifice endoscopic surgery and the further coordination of research in Germany. Different working groups with various topics were formed. Consensus statements among various participants with different scientific and medical background were initiated. In summary, important topics were handled such as the correct handling of bacterial contamination and related complications, the question of the ideal entry point and a secure closure, interdisciplinary cooperation, and matters related to training and education. Furthermore, participants agreed on terminological basics. A to-do-list for medical engineering was formulated.

[Innovative ultrasound-based diagnosis of renal tumors]. / Innovative Ultraschalldiagnostik bei Nierentumoren.

BACKGROUND: In Germany, renal tumours are detected earlier also due to advancing technology within ultrasound devices and its more widespread application. Ultrasound diagnosis is usually the first imaging procedure available to urologists. For all renal lesions larger than 1 cm in diameter, fat content can be revealed by quantitative measurements within CT/MRI diagnostic modalities to confirm the suspected diagnosis of angiomyolipoma, or in patients with potentially malignant renal lesions referral (with all the their imaging data) to the multidisciplinary tumour team. As a further step, biopsy may be indicated, especially in the case of inflammatory lesions or suspected lymphoma; otherwise patients with a solid tumour are treated within a tumour stage-appropriate urological therapy regime. RESULTS: Contrast-enhanced ultrasonography (CEUS) is currently unable to distinguish between benign and malignant renal tumours. Nevertheless, this noninvasive method is useful in everyday clinical practice: in excluding renal pseudolesions, in inflammatory lesions, for follow-up of traumatic pseudolesions, and for the differential diagnosis of atypical renal cyst diagnosis versus renal cancer. Contrast-enhanced sonography also reveals the microperfusion of kidney tumors, providing clues for distinguishing between clear cell and papillary types of renal cell carcinoma. The method is also utilised in CEUS-controlled biopsy procedures of renal lesions. CONCLUSIONS: Contrast-enhanced sonography augments CT/MRI imaging with real-time information on the perfusion of the kidney tumour and can be a therapy-relevant aid for the multidisciplinary cancer conference with the ultrasound examinations being presented as video clips for comment thereon.

[Bilateral intrauterine testicular torsion in a mature newborn]. / Bilaterale intrauterine Hodentorsion bei einem reifen Neugeborenen.

Bilateral intrauterine testicular torsion is an extremely rare emergency and can be difficult to diagnose due to its diverse manifestation and potential differential diagnoses. In time surgical intervention is crucial for the retention of testicular function. We present a newborn with a bilateral testicular torsion, in which one testicle could be saved after detorsion. The contralateral side showed hemorrhagic infarction and was removed. Since organ preservation is rarely successful, the surgical therapy is discussed controversially.

Long-term outcome after grafting with small intestinal submucosa and collagen fleece in patients with Peyronie's disease: a matched pair analysis.

Advanced Peyronie's disease (PD) with severe penile curvature requires grafting following plaque incision or partial plaque excision. So far, the ideal graft material has not been identified although various grafts have been studied. In this first matched pair analysis we compared the outcome after grafting with small intestinal submucosa (SIS) and self-adhesive collagen fleece (CF). We retrospectively identified 43 patients after SIS grafting with complete follow-up data sets to be eligible for the present study. A total of 43 patients after CF grafting were matched case by case to the SIS group using the degree of preoperative penile curvature as the primary matching factor. Postoperative outcome was compared with the focus on penile straightening, penile length, potency, relapse rates and long-term complications. Median degree of curvature was 80° in each group. Mean follow-up periods were 31 months after SIS and 39 months after CF grafting. The CF grafting procedure was significantly faster than SIS grafting (80 vs. 104 min, p < 0.001). No major short-term complications were observed. Both techniques gained good long-term penile straightening rates. Relapse of penile curvature was observed after SIS grafting only. Postoperative penile shortening occurred more often after SIS grafting (28% vs. 5%, p = 0.007). With a mean preoperative IIEF-5 score of 16, the SIS cohort significantly differed from the CF cohort with a mean IIEF-5 score of 19 (p = 0.016). The median IIEF-5 score improvement was higher after SIS grafting (+4.5 vs. +1, p = 0.002). Diminished penile sensation was the main long-term side effect with low rates after both procedures (9% and 7% in the SIS and CF group respectively, p = 0.100). In this first matched pair analysis both techniques showed promising long-term results. CF seems to have advantages regarding duration of surgery and preserving penile length. More comparative studies with larger collectives are desirable.

[Active immunotherapy of urologic malignancies and tumor-mediated immunosuppression]. / Aktive Immuntherapie urologischer Tumoren und tumorbedingte Immunsuppression.

The absence of curative treatment strategies for metastatic prostate cancer requires further development of novel, more effective treatment regimens. Because of recent advances in immunologic and translational research, therapeutic vaccines are becoming important as promising treatment modalities against prostate cancer. Immunizing patients who have hormone-refractory prostate cancer with an allogenic IL-2 and IFN-gamma secreting tumor cell vaccine is safe and feasible with no dose-limiting toxicity; it has been shown to reduce the progression of prostate-specific antigen in treated subjects and to induce vaccine-specific immune responses. Despite these results, current vaccine strategies have shown only limited success in clinical settings. There is ample evidence that multiple immunosuppressive mechanisms, such as regulatory T cells and myeloid suppressor cells, exist that considerably dampen antitumor responses and weaken the activity of current immunotherapeutic regimens. Recent insights into the characteristics of the regulatory elements of the immune system have provided new opportunities to enhance vaccine-mediated antitumor immunity by reversing tumor-mediated immunosuppression before immunotherapies can be used successfully for cancer patients.

Apical soft tissue biopsies predict biochemical failure in radical perineal prostatectomy patients with apical cancer involvement.

The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radical perineal prostatectomy (RPP) patients with documented apical prostate cancer (PCA) involvement. Between June 1998 and May 1999, 77 consecutive men with localized PCA and documented invasion of the prostatic apex underwent RPP by a single surgeon. Soft tissue biopsies were systematically obtained from the prostatic fossa overlying the apex at the time of surgery. Time to biochemical failure was calculated using the Kaplan-Meier method. The rates of positive apical margins and positive apical soft tissue biopsies were 23.4% (18/77) and 15.6% (12/77). The sensitivity, specificity and positive predictive value of positive apical margins for residual apical disease as determined by apical soft tissue biopsy were 41.7, 80, and 28%, respectively. The overall biochemical failure rate was 28.6% (22/77) with a median follow-up of 51 months (range 3-73 months). The 36-month biochemical recurrence-free survival rate was 55.9+/-14.9% for patients with positive apical biopsies and 78.7+/-5.3% for those with negative biopsies (P=0.023). In conclusion, positive apical soft tissue biopsy is an independent predictor of biochemical failure in patients with apical PCA who undergo RPP. Positive apical surgical margins poorly predict residual apical disease that is frequently identifiable by apical soft tissue biopsy. Apical soft tissue biopsies should therefore be obtained in patients with known extensive apical cancer involvement at the time of RPP.

Two-frequency acousto-optic modulator driver to improve the beam pointing stability during intensity ramps.

We report on a scheme to improve the pointing stability of the first order beam diffracted by an acousto-optic modulator (AOM). Due to thermal effects inside the crystal, the angular position of the beam can change by as much as 1 mrad when the radio-frequency power in the AOM is reduced to decrease the first order beam intensity. This is done, for example, to perform forced evaporative cooling in ultracold atom experiments using far-off-resonant optical traps. We solve this problem by driving the AOM with two radio frequencies f(1) and f(2). The power of f(2) is adjusted relative to the power of f(1) to keep the total power constant. Using this, the beam displacement is decreased by a factor of 20. The method is simple to implement in existing experimental setups, without any modification of the optics.

[Corticosteroids in the management of advanced prostate cancer]. / Kortikoide im Management des fortgeschrittenen Prostatakarzinoms.

Corticosteroids have been widely used for decades in cancer therapy, predominantly due to their anti-inflammatory activity. In the treatment of metastatic castration-resistant prostate cancer (mCRPC), corticosteroids play an important role both in the management of tumor-related symptoms, especially bone metastasis-related pain, and as concomitant treatment to counteract side effects associated with approved active prostatic anticancer agents such as docetaxel, cabazitaxel, and abiraterone acetate. In association with abiraterone acetate, low-dose corticosteroids (prednisone or prednisolone) reduce the mineralocorticoid side effects of abiraterone. In addition, corticosteroids may exert direct antitumoral activities, resulting in PSA decline.

[When is surgical resection of the primary tumor indicated in metastatic urothelial carcinoma of the bladder and what is the scientific rationale?] / Wann ist bei eingetretener Metastasierung des Harnblasenkarzinoms die operative Entfernung des Primärtumors angezeigt und gibt es eine wissenschaftliche Grundlage dafür?

Cisplatin-based polychemotherapy is still the standard therapy for metastatic urothelial carcinoma, although disease progression is often noted at an early time point even in patients with response. In recent years, cytoreductive surgery has been gaining increasing interest in many tumor entities in the setting of metastatic disease to improve patients outcome, but urothelial carcinoma is not regarded as a candidate for such a multimodal therapy approach. However, several retrospective studies suggest a survival benefit of radical cystectomy and/or metastasectomy for well-selected patients with metastatic urothelial carcinoma. Prognostically relevant parameters for consolidative cystectomy/metastasectomy after chemotherapy seem to be a distinct response to inductive chemotherapy and limited metastatic spread (regional lymph node, single lung metastasis).