Differences in Trial and Real-world Populations in the Dutch Castration-resistant Prostate Cancer Registry

__Background:__ Trials in castration-resistant prostate cancer (CRPC) treatment have shown improved outcomes, including survival. However, as trial populations are selected, results may not be representative for the real-world population. The aim of this study was to assess the differences between patients treated in a clinical trial versus standard care during the course of CRPC in a real-world CRPC population. __Design, setting, and participants:__ Castration-resistant Prostate Cancer Registry is a population-based, observational, retrospective registry. CRPC patients from 20 hospitals in the Netherlands have been included from 2010 to 2013. __Outcome measurements and statistical analysis:__ Baseline characteristics, systemic treatment, and overall survival were the main outcomes. Descriptive statistics, multivariate Cox regression, and multiple imputations with the Monte Carlo Markov Chain method were used. __Results and limitations:__ In total, 1524 patients were enrolled of which 203 patients had participated in trials at any time. The median follow-up period was 23 mo. Patients in the trial group were significantly younger and had less comorbidities. Docetaxel treatment was more freque

Activation of Hypoxia Inducible Factor 1 Is a General Phenomenon in Infections with Human Pathogens

Background: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. Methodology/Principal Findings: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. Conclusions/Significance: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections

Transanal endoscopic microsurgery for correction of rectourethral fistulae

Background: Rectourethral fistula is a rare complication of radical prostatectomy. Transanal endoscopic microsurgery (TEM) is a minimally invasive technique available for its surgical correction, although currently, TEM is used more commonly for excision of adenomas and stage T1 carcinomas of the rectum. Patients and Methods: We report two patients with rectourethral fistulae after laparoscopic radical prostatectomy in whom TEM was used for closure. The surgical procedure included microscopic full-thickness excision of the rectal wall around the fistula with a 1-cm margin and endoscopic suturing of the defect in the urethral and rectal walls. Results: In one case, the rectourethral fistula was closed using TEM. In the other patient, the procedure, performed after failure of a graciloplasty, was difficult because of extensive scar tissue, and the fistula persisted. Conclusions: The TEM procedure is a minimally invasive technique that may be considered for surgical repair of rectourethral fistulae. © Mary Ann Liebert, Inc

The AirSeal® insufflation device can entrain room air during routine operation

Background: Surgical procedures that use insufflation carry a risk of gas embolism, which is considered relatively harmless because of the high solubility of carbon dioxide. However, an in vitro study suggested that valveless insufflation devices may entrain non-medical room air into the surgical cavity. Our aim was to verify if this occurs in actual surgical procedures. Methods: The oxygen percentage in the pneumoperitoneum or pneumorectum/pneumopelvis of eight patients operated with use of the AirSeal® was continuously measured, to determine the percentage of air in the total volume of the surgical cavity. Results: Basal air percentage in the surgical cavity was 0–5%. During suctioning from the operative field air percentage increased to 45–65%. Conclusions: The AirSeal® valveless insufflation device maintains optimal distension of the surgical cavity not only by insufflating carbon dioxide, but also by entraining room air, especially during suctioning from the operative field. This may theoretically lead to air embolism in patients operated on with this device

Contrast-enhanced three-dimensional power Doppler angiography of the human prostate: correlation with biopsy outcome

OBJECTIVES: To determine the feasibility of contrast-enhanced three-dimensional (3D) imaging of the prostatic vasculature using power Doppler imaging and to analyze whether semiquantitative judgments of 3D images with respect to symmetry and distribution of vascular structures correlated with biopsy outcome. METHODS: 3D power Doppler images were obtained before and after intravenous administration of 2.5 g Levovist. Subsequently, random and/or directed transrectal ultrasound (TRUS)-guided biopsies were performed. Vascular images were analyzed by two experts. Prostate vasculature was judged with respect to symmetry and vessel distribution using a (scale) grading system. RESULTS: Eighteen patients with a suspicion of prostate cancer either because of an elevated prostate-specific antigen (greater than 4.0 ng/mL; Tandem-R-assay) or an abnormal digital rectal examination were included in the study. Prostate cancer was detected in 13 patients. Vascular anatomy was judged abnormal in unenhanced images in 6 cases, of which 5 proved malignant. Enhanced images were considered suspicious for malignancy in 12 cases, including 1 benign and 11 malignant biopsy results. Sensitivity of enhanced images was 85% (specificity 80%) compared with 38% for unenhanced images (specificity 80%) and 77% for conventional gray-scale TRUS (specificity 60%). Of 6 patients who showed no B-mode abnormalities, vascular patterns were judged abnormal in 4 cases, of which 3 were malignant. CONCLUSIONS: Contrast-enhanced 3D power Doppler angiography is feasible in patients with suspicion of prostate cancer who are scheduled for prostate biopsies. The sensitivity of power Doppler 3D imaging for the detection of prostate malignancy increased from 38% (5 of 13) to 85% (11 of 13) after administration of intravascular microbubble contrast (Levovist), and specificity was found to be 80% (4 of 5) for both imaging modalities. Thus, the use of Levovist when combined with the power Doppler display mode and 3D image reconstruction offers a promising new research area that might prove useful in prostate cancer detection in the futur

Contrast angiosonography: a technology to improve Doppler ultrasound examinations of the prostate

OBJECTIVES: A feasibility study to evaluate whether analysis techniques adapted from X-ray angiography can be used to analyze the transient enhancement of prostate blood flow patterns in color Doppler maps as obtained after administering ultrasound contrast agents. METHODS: Injections of ultrasound contrast agents were given to dogs and humans, and color Doppler blood flow patterns in fixed transverse sections through the prostate were recorded on video tape. Computer assistance of Doppler signals over time is used to evaluate the transient enhancement of flow patterns obtained with contrast-enhanced Doppler ultrasound. Results are compared to indicator dilution curve theory as used in, e.g., X-ray angiography. RESULTS: Administering a contrast agent to improve color Doppler evaluation of prostate blood flow resulted in clear enhancement of Doppler signal intensities without unwanted side effects. Using the computer, the perfused area of the prostate could be obtained quantitatively over time showing profiles of individual heartbeats. Averaging the perfused area over one heartbeat resulted in an indicator dilution curve, and correlation with dilution theory indicated the feasibility of applying wash-in and wash-out analysis of contrast agents in color Doppler images. CONCLUSION: Frame-by-frame interpretation by the computer indicated the feasibility of analyzing the transient enhancement of blood flow visibility in the Doppler image over time using techniques such as wash-in and wash-out time. This technology provides researchers in the field of ultrasound evaluation of the prostate the opportunity to apply a new diagnostic tool, contrast angiosonography, in their research. This method for analysis of prostatic blood flow can be helpful in any application that affects the blood supply of the prostate such as heat treatments and hormonal treatment

Transrectal ultrasound of the prostate: innovations and future applications

PURPOSE: We present a critical evaluation of the use of ultrasound for prostate disease examination in urological practice, and provide perspectives on ultrasound applications that may become important for the future evaluation of prostate problems. MATERIALS AND METHODS: Based on an evaluation of clinical data in cases suspicious for prostatic malignancy, we addressed the apparent shortcomings of transrectal ultrasound for accurately diagnosing prostate cancer. Future applications presented in the literature were noted. RESULTS: Evaluating the ultrasound data in cases suspicious for malignancy indicated that imaging has little advantage over digital rectal examination for detecting malignant areas. The new applications of ultrasound that hold great promise for use in the urology clinic include the injection of contrast agents to obtain information on blood supply, temperature estimation for the noninvasive assessment of temperature distributions during heat treatment and a therapeutic application for local treatment of prostate cancer. CONCLUSIONS: While differential diagnosis with ultrasound appears to result in disappointing sensitivity and specificity values, its use in volume measurement and biopsy guidance is unquestioned. The development of new applications may improve the clinical value of ultrasound in urological practice. The application of ultrasound contrast agents for the detection and clinical staging of prostate cancer is especially promising. Future research will indicate whether the promise evolves in clinical application

Transrectal ultrasound imaging of the prostate: review and perspectives of recent developments

We present a critical review of the recent literature and discuss the development and prospective view of the evaluations of transrectal ultrasound with regard to prostate malignancy. We illustrate this with personal experiences. Material and Methods: Based on a critical evaluation of clinical data we address the apparent shortcoming of greyscale transrectal ultrasonography in the assessment of prostate cancer. New developments and future possibilities are also discussed. Evaluation of the value of greyscale transrectal ultrasonography in the diagnosis of prostate cancer indicates a limited role, because of the non-uniform appearance of prostate cancer on the ultrasound images. Ameliorating of transrectal ultrasound, like the use of contrast ultrasonography, could improve the detection of prostate cancer. Although the use of greyscale transrectal ultrasonography lacks sensitivity and specificity for the diagnosis of prostate cancer, its use in volume measurement of the prostate and biopsy guidance is unquestionable. The first results of the application of contrast ultrasonography are promising, both in detection of prostate cancer as in treatment follow up. Other developments like improvement of transducer and computer technology could make the use of ultrasound more versatile. However, future research will indicate whether all these improvements will lead to clinical application

3D Navigo versus TRUS-guided prostate biopsy in prostate cancer detection

Item does not contain fulltextINTRODUCTION: To overcome the limitations regarding transrectal ultrasound (TRUS)-guided biopsies in prostate cancer (PCa) detection, there is a focus on new imaging technologies. The Navigo system (UC-care, Israel) uses regular TRUS images and electrospatial monitoring to generate a 3D model of the prostate. The aim of this study was to compare cancer detection rates between the Navigo system and conventional TRUS, in patients without a history of PCa. METHODS: We performed a retrospective study by collecting data from all patients who underwent 12-core prostate biopsies from lateral peripheral zones between September 2013 and February 2015 at the Jeroen Bosch Hospital in 's-Hertogenbosch (Netherlands). RESULTS: A total of 325 patients met our inclusion criteria. 77.8 % of biopsy sessions were performed using the Navigo system. There was no statistically significant difference in PCa detection (39.9 vs 46.2 % with Navigo system and TRUS, respectively). Using the Navigo system for taking prostate biopsies proved not to be associated with the presence of PCa at biopsy, likewise for clinically significant PCa and for both subgroups. LIMITATIONS: The limitations of the study include its retrospective design, the limited number of patients in the conventional TRUS group, the statistically significant different number of biopsy sessions and the ones performed by an advanced physician in both groups. CONCLUSION: In our study, there is no added value of 3D TRUS using Navigo system compared to conventional 2D TRUS regarding PCa detection in biopsy-naive men and men with prior negative biopsy

The application of three-dimensional contrast-enhanced ultrasound to measure volume of affected tissue after HIFU treatment for localized prostate cancer

INTRODUCTION: Adequate monitoring of volume and location of affected tissue might provide helpful information when performing localized ablative therapy for prostate cancer. We hypothesize that the change in blood flow patterns after therapy in comparison to the blood flow pattern prior to therapy can be used to locate and quantify the amount of affected tissue due to the therapy. We describe the use of three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) to determine its additive value to visualize the extent of tissue defects created by high-intensity focused ultrasound (HIFU) in correlation with the histopathology of the prostatectomy specimen. MATERIALS AND METHODS: Nine patients with biopsy-proven localized prostate cancer, who gave informed consent, were included in the protocol. HIFU treatment was performed 1 week in advance of radical retropubic prostatectomy (RRP) as part of a protocol to study the value of HIFU treatment as local ablative therapy for clinical T(1-2)N(0)M(0) prostate carcinoma. 3D-CE-PDU was performed 1 day prior to unilateral HIFU treatment of the affected lobe on biopsy indication and 1 day before RRP using 2.5 g Levovist((R)) (Schering AG, Germany) microbubble ultrasound contrast agent and a Kretz((R)) Voluson 530D ultrasound scanner (Kretztechnik AG, Austria). Ultrasound data and pathology whole-mount sections were stored digitally to allow off-line processing. Human interpretations of HIFU measurements in three-dimensional ultrasound data were based on gray-scale information (local increase in gray level) in combination with power Doppler mode (absence of blood flow). Histopathological analysis of the whole-mount section revealed a broad band of hemorrhagic necrosis in the HIFU-treated area. Using both the ultrasound data and the pathology sections, the total volume of the prostate and of the HIFU-treated area was measured, and relative volumes were obtained. RESULTS: Visual inspection of the three-dimensional reconstruction of contrast-enhanced Doppler measurements revealed the HIFU-affected prostate tissue by the absence of a blood flow pattern. Paired t tests of the relative HIFU volume indicated that Doppler results (mean 21.7%, SD +/-10.8%) differed from the pathology results (mean 32.6%, SD +/-16.0%), but a good correlation was found between the relative pathology HIFU volume (Pearson correlation r = 0.94, p <0.0015) and mean 3D-CE-PDU HIFU. Closer inspection of the pathology specimen revealed that the outer ring of the macroscopic hemorrhagic necrosis overestimated the actually dead tissue. On microscopy, the border of dead tissue appeared to be 1-2 mm inside the macroscopically identified red hemorrhagic band. 3D-CE-PDU HIFU volumes indicated by the single observers were not statistically different and correlated very well (Pearson correlation r = 0.98, p <0.001). CONCLUSION: The results illustrate that 3D-CE-PDU is a promising method to determine the size of the defect of HIFU ablative therapy for prostate carcinoma. The absence of blood flow indicated by three-dimensional power Doppler ultrasound images reflects affected tissue after HIFU treatment, and volume measurements of these areas can quantify the amount of affected tissu