Purpose Imaging is routinely done preoperatively and postoperatively to assess patients treated with percutaneous nephrolithotomy. We developed a nomogram for percutaneous nephrolithotomy success. ...Materials and Methods From November 2007 to December 2009 the CROES (Clinical Research Office of the Endourological Society) collected data on consecutive patients at 96 centers globally. Patients were evaluated for stone-free status using plain x-ray of the kidneys, ureters and bladder. Treatment success was defined as no visible stones or residual fragments less than 4 mm. Multivariate regression was used to model the relationship between preoperative descriptors and the stone-free rate. Variables included case load, prior treatment, body mass index, staghorn stones, renal anomalies, and stone burden, location and count. Bootstrapping techniques were used to validate the model. Adjusted chi-square statistic values were used to rank the prognostic value of variables. A nomogram was developed using significant predictors from the model. We assessed the predictive accuracy of the nomogram using the ROC curve AUC. The nomogram was calibrated. Results Stone burden was the best predictor of the stone-free rate (chi-square = 30.27, p <0.001). Other factors associated with the stone-free rate were case volume (chi-square = 35.75, p <0.001), prior stone treatment (chi-square = 14.55, p <0.012), staghorn stone (adjusted chi-square = 4.73, p <0.029), stone location (chi-square = 14.74, p <0.001) and stone count (chi-square = 4.78, p <0.004). A nephrolithometric nomogram was developed with predictive accuracy (AUC 0.76). Conclusions The percutaneous nephrolithotomy stone-free rate can be predicted using preclinical data and radiological information. We present a nephrolithometric nomogram for percutaneous nephrolithotomy.
Propagation of human spermatogonial stem cells in vitro Sadri-Ardekani, Hooman; Mizrak, Sefika C; van Daalen, Saskia K M ...
JAMA : the journal of the American Medical Association,
11/2009, Letnik:
302, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Young boys treated with high-dose chemotherapy are often confronted with infertility once they reach adulthood. Cryopreserving testicular tissue before chemotherapy and autotransplantation of ...spermatogonial stem cells at a later stage could theoretically allow for restoration of fertility.
To establish in vitro propagation of human spermatogonial stem cells from small testicular biopsies to obtain an adequate number of cells for successful transplantation.
Study performed from April 2007 to July 2009 using testis material donated by 6 adult men who underwent orchidectomy as part of prostate cancer treatment. Testicular cells were isolated and cultured in supplemented StemPro medium; germline stem cell clusters that arose were subcultured on human placental laminin-coated dishes in the same medium. Presence of spermatogonia was determined by reverse transcriptase polymerase chain reaction and immunofluorescence for spermatogonial markers. To test for the presence of functional spermatogonial stem cells in culture, xenotransplantation to testes of immunodeficient mice was performed, and migrated human spermatogonial stem cells after transplantation were detected by COT-1 fluorescence in situ hybridization. The number of colonized spermatogonial stem cells transplanted at early and later points during culture were counted to determine propagation.
Propagation of spermatogonial stem cells over time.
Testicular cells could be cultured and propagated up to 15 weeks. Germline stem cell clusters arose in the testicular cell cultures from all 6 men and could be subcultured and propagated up to 28 weeks. Expression of spermatogonial markers on both the RNA and protein level was maintained throughout the entire culture period. In 4 of 6 men, xenotransplantation to mice demonstrated the presence of functional spermatogonial stem cells, even after prolonged in vitro culture. Spermatogonial stem cell numbers increased 53-fold within 19 days in the testicular cell culture and increased 18,450-fold within 64 days in the germline stem cell subculture.
Long-term culture and propagation of human spermatogonial stem cells in vitro is achievable.
What's known on the subject? and What does the study add?
Novel therapeutic methods have emerged in recent years as ‘focal’ treatment alternatives in which cancer foci can be eradicated and greatly ...reducing the associated side‐effects of radical treatment. High‐intensity focused ultrasound (HIFU) seems to result in a well fitted technology, which has proven short‐ to medium‐term cancer control, with a low rate of complications comparable with those of established therapies.
This is an up‐to‐date review of the available literature on HIFU as a definitive treatment of prostate cancer. It describes the technique in a comprehensive approach in terms of technical features, procedure, indications, and gives an overview of its historical background; finally, we present the future applications of HIFU and its development trend.
OBJECTIVES
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To provide an up‐to‐date review of the available literature on high‐intensity focused ultrasound (HIFU) as a definitive treatment of prostate cancer.
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To present the technique in a comprehensive approach, comparing the available devices according to the existing evidence in terms of technical features, procedure, indications, and to give an overview of its historical background; and finally, to discuss future applications of HIFU and its development trend.
MATERIALS AND METHODS
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A systematic literature search was conducted using MEDLINE and EMBASE via Ovid databases (January 2000 to December 2011), to identify studies on HIFU for treatment of prostate cancer.
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Only English‐language and human‐based full manuscripts that reported on case series studies with >50 participants, patient characteristics, efficacy and safety data were included.
RESULTS
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No randomised controlled trials were identified by the literature search. We identified 31 uncontrolled studies that examined the efficacy of HIFU as primary treatment and two studies that examined the efficacy of HIFU as salvage treatment.
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Most treated patients had localised prostate cancer (stage T1–T2); Gleason scores of 2–10 and mean prostate specific antigen (PSA) values of 4.6–12.7 ng/mL. The mean age range of the patients was 64.1–72 years. The mean follow‐up ranged from 6.4 to 76.8 months. Negative biopsy rates ranged from 35 to 95%. PSA nadirs ranged from 0.04 to 1.8 ng/mL. The 5‐year disease‐free survival rates ranged from 61.2 to 95%; 7‐ and 8‐year disease free survival rates ranged from 69 to 84%.
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The most common complications associated with the HIFU procedure as the primary treatment included: urinary retention (<1–20%); urinary tract infections (1.8–47.9%); stress or urinary incontinence (<1–34.3%); and erectile dysfunction (20–81.6%).
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Recto‐urethral fistula was reported in <2% of patients.
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Treatment‐related morbidity appeared to be reduced by the combination of transurethral resection (TURP) of the prostate and HIFU.
CONCLUSIONS
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Novel therapeutic methods have emerged in recent years as ‘focal’ treatment alternatives, in which cancer foci could be eradicated by greatly reducing the associated side‐effects of radical treatment.
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HIFU seems to result in short‐ to medium‐term cancer control, with a low rate of complications comparable with those of established therapies.
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However, longer‐term follow‐up studies are needed to evaluate cancer‐specific and overall survival. If available promising results on HIFU for definitive treatment of prostate cancer are confirmed in future prospective trials, focal therapy could start to challenge the current standard of care.
Abstract Context Incorporation of bipolar technology in transurethral resection (TUR) of the prostate (TURP) potentially offers advantages over monopolar TURP (M-TURP). Objective To evaluate the ...evidence by a meta-analysis, based on randomized controlled trials (RCTs) comparing bipolar TURP (B-TURP) with M-TURP for benign prostatic obstruction. Primary end points included efficacy (maximum flow rate Qmax , International Prostate Symptom Score) and safety (adverse events). Secondary end points included operation time and duration of irrigation, catheterization, and hospitalization. Evidence acquisition Based on a detailed, unrestricted strategy, the literature was searched up to February 19, 2009, using Medline, Embase, Science Citation Index, and the Cochrane Library to detect all relevant RCTs. Methodological quality assessment of the trials was based on the Dutch Cochrane Collaboration checklist. Meta-analysis was performed using Review Manager 5.0. Evidence synthesis Sixteen RCTs (1406 patients) were included. Overall trial quality was low (eg, allocation concealment and blinding of outcome assessors were poorly reported). No clinically relevant differences in short-term (12-mo) efficacy were detected (Qmax : weighted mean difference WMD: 0.72 ml/s; 95% confidence interval CI, 0.08–1.35; p = 0.03). Data on follow-up of >12 mo are scarce for B-TURP, precluding long-term efficacy evaluation. Treating 50 patients (95% CI, 33–111) and 20 patients (95% CI, 10–100) with B-TURP results in one fewer case of TUR syndrome (risk difference RD: 2.0%; 95% CI, 0.9–3.0%; p = 0.01) and one fewer case of clot retention (RD: 5.0%; 95% CI, 1.0–10%; p = 0.03), respectively. Operation times, transfusion rates, retention rates after catheter removal, and urethral complications did not differ significantly. Irrigation and catheterization duration was significantly longer with M-TURP (WMD: 8.75 h; 95% CI, 6.8–10.7 and WMD: 21.77 h; 95% CI, 19.22–24.32; p < 0.00001, respectively). Inferences for hospitalization duration could not be made. PlasmaKinetic TURP showed an improved safety profile. Data on TUR in saline (TURis) are not yet mature to permit safe conclusions. Conclusions No clinically relevant differences in short-term efficacy exist between the two techniques, but B-TURP is preferable due to a more favorable safety profile (lower TUR syndrome and clot retention rates) and shorter irrigation and catheterization duration. Well-designed multicentric/international RCTs with long-term follow-up and cost analysis are still needed.
BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-specific ultrasound molecular contrast agent (MCA), has shown promising results in multiple preclinical models regarding cancer imaging. ...In this first-in-human, phase 0, exploratory study, we investigated the feasibility and safety of the MCA for the detection of prostate cancer (PCa) in men using clinical standard technology.
Imaging with the MCA was performed in 24 patients with biopsy-proven PCa scheduled for radical prostatectomy using a clinical ultrasound scanner at low acoustic power. Safety monitoring was done by physical examination, blood pressure and heart rate measurements, electrocardiogram, and blood sampling. As first-in-human study, MCA dosing and imaging protocol were necessarily fine-tuned along the enrollment to improve visualization. Imaging data were correlated with radical prostatectomy histopathology to analyze the detection rate of ultrasound molecular imaging with the MCA.
Imaging with MCA doses of 0.03 and 0.05 mL/kg was adequate to obtain contrast enhancement images up to 30 minutes after administration. No serious adverse events or clinically meaningful changes in safety monitoring data were identified during or after administration. BR55 dosing and imaging were fine-tuned in the first 12 patients leading to 12 subsequent patients with an improved MCA dosing and imaging protocol. Twenty-three patients underwent radical prostatectomy. A total of 52 lesions were determined to be malignant by histopathology with 26 (50%) of them seen during BR55 imaging. In the 11 patients that were scanned with the improved protocol and underwent radical prostatectomy, a total of 28 malignant lesions were determined: 19 (68%) were seen during BR55 ultrasound molecular imaging, whereas 9 (32%) were not identified.
Ultrasound molecular imaging with BR55 is feasible with clinical standard technology and demonstrated a good safety profile. Detectable levels of the MCA can be reached in patients with PCa opening the way for further clinical trials.
Abstract Background Although widely used, the validity and reliability of the Clavien classification of postoperative complications have not been tested in urologic procedures, such as percutaneous ...nephrolithotomy (PCNL). Objective To validate the Clavien score and categorise complications of PCNL. Design, setting, and participants Data for 528 patients with complications after PCNL were used to create a set of 70 unique complication-management combinations. Clinical case summaries for each complication-management combination were compiled in a survey distributed to 98 urologists, who rated each combination using the Clavien classification. Outcome measurements and statistical analysis Interrater agreement for Clavien scores was estimated using Fleiss’ kappa (κ). The relationship between Clavien score and the duration of postoperative hospital stay was analysed using multivariate nonlinear regression models that adjusted for operating time, preoperative urine microbial culture, presence of staghorn stone, and use of postoperative nephrostomy tube. Results and limitations Overall interrater agreement in grading postoperative complications was moderate (κ = 0.457; p < 0.001). Agreement was highest for Clavien score 5 and decreased with lower Clavien scores. Higher agreement was found for Clavien scores 3 and 4 than in subcategories of these scores. Postoperative stay increased with higher Clavien scores and was unaffected by inherent differences between study centres. A standard list of post-PCNL complications and their corresponding Clavien scores was created. Conclusions Although the Clavien classification demonstrates high validity, interrater reliability is low for minor complications. To improve the reliability and consistency of reporting adverse outcomes of PCNL, we have assigned Clavien scores to complications of PCNL.
To evaluate accuracy and interobserver variability with the use of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 for detection of prostate cancer at multiparametric magnetic ...resonance (MR) imaging in a biopsy-naïve patient population.
This retrospective HIPAA-compliant study was approved by the local ethics committee, and written informed consent was obtained from all patients for use of their imaging and histopathologic data in future research studies. In 101 biopsy-naïve patients with elevated prostate-specific antigen levels who underwent multiparametric MR imaging of the prostate and subsequent transrectal ultrasonography (US)-MR imaging fusion-guided biopsy, suspicious lesions detected at multiparametric MR imaging were scored by five readers who were blinded to pathologic results by using to the newly revised PI-RADS and the scoring system developed in-house. Interobserver agreement was evaluated by using κ statistics, and the correlation of pathologic results with each of the two scoring systems was evaluated by using the Kendall τ correlation coefficient.
Specimens of 162 lesions in 94 patients were sampled by means of transrectal US-MR imaging fusion biopsy. Results for 87 (54%) lesions were positive for prostate cancer. Kendall τ values with the PI-RADS and the in-house-developed scoring system, respectively, at T2-weighted MR imaging in the peripheral zone were 0.51 and 0.17 and in the transitional zone, 0.45 and -0.11; at diffusion-weighted MR imaging, 0.42 and 0.28; at dynamic contrast material-enhanced MR imaging, 0.23 and 0.24, and overall suspicion scores were 0.42 and 0.49. Median κ scores among all possible pairs of readers for PI-RADS and the in-house-developed scoring system, respectively, for T2-weighted MR images in the peripheral zone were 0.47 and 0.15; transitional zone, 0.37 and 0.07; diffusion-weighted MR imaging, 0.41 and 0.57; dynamic contrast-enhanced MR imaging, 0.48 and 0.41; and overall suspicion scores, 0.46 and 0.55.
Use of the revised PI-RADS provides moderately reproducible MR imaging scores for detection of clinically relevant disease.
To determine differences in patients' characteristics, operative time and procedures, and perioperative outcomes between prone and supine positioning in percutaneous nephrolithotomy (PCNL) using the ...Clinical Research Office of the Endourological Society (CROES) PCNL Global Study database.
Between November 2007 and December 2009, prospective data were collected on a total of 5803 consecutive patients who were treated over a 1-year period at each of 96 participating global centers. Patients with data on body position were dichotomized into prone or supine PCNL.
The majority of PCNL treatments were performed in the prone position (n=4637; 80.3% of sample). Differences in patient characteristics included in the prone group: A greater proportion of males (57.4% vs 52.2%); younger age (48.8 y vs 51.0 y); less frequent history of shockwave lithotripsy (19.5% vs 28.6%); greater frequency of American Society of Anesthesiologists score of 1 (54.7% vs 46.8%); and a Clavien grade of 2 or more (10.0% vs 7.2%). The mean operative time was significantly lower for prone vs supine PCNL (82.7 min vs 90.1 min) regardless of the method of tract dilation, while the stone-free rate was significantly higher (77.0% vs 70.2%). Compared with supine patients, prone patients exhibited higher rates of blood transfusions (6.1% vs 4.3%) and fever (11.1% vs 7.6%), but lower rates of failed procedures (1.5% vs 2.7%).
Since operative time and stone-free rates favor prone PCNL, but patient safety favors supine PCNL, the choice of patient position should be tailored to individual patient characteristics and the surgeon's preference.
Abstract Objective To present a summary of the 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS). Evidence ...acquisition We conducted a literature search in computer databases for relevant articles published between 1966 and 31 October 2012. The Oxford classification system (2001) was used to determine the level of evidence for each article and to assign the grade of recommendation for each treatment modality. Evidence synthesis Men with mild symptoms are suitable for watchful waiting. All men with bothersome LUTS should be offered lifestyle advice prior to or concurrent with any treatment. Men with bothersome moderate-to-severe LUTS quickly benefit from α1 -blockers. Men with enlarged prostates, especially those >40 ml, profit from 5α-reductase inhibitors (5-ARIs) that slowly reduce LUTS and the probability of urinary retention or the need for surgery. Antimuscarinics might be considered for patients who have predominant bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can quickly reduce LUTS to a similar extent as α1 -blockers, and it also improves erectile dysfunction. Desmopressin can be used in men with nocturia due to nocturnal polyuria. Treatment with an α1 -blocker and 5-ARI (in men with enlarged prostates) or antimuscarinics (with persistent storage symptoms) combines the positive effects of either drug class to achieve greater efficacy. Prostate surgery is indicated in men with absolute indications or drug treatment–resistant LUTS due to benign prostatic obstruction. Transurethral resection of the prostate (TURP) is the current standard operation for men with prostates 30–80 ml, whereas open surgery or transurethral holmium laser enucleation is appropriate for men with prostates >80 ml. Alternatives for monopolar TURP include bipolar TURP and transurethral incision of the prostate (for glands <30 ml) and laser treatments. Transurethral microwave therapy and transurethral needle ablation are effective minimally invasive treatments with higher retreatment rates compared with TURP. Prostate stents are an alternative to catheterisation for men unfit for surgery. Ethanol or botulinum toxin injections into the prostate are still experimental. Conclusions These symptom-oriented guidelines provide practical guidance for the management of men experiencing LUTS. The full version is available online ( www.uroweb.org/gls/pdf/12_Male_LUTS.pdf ).
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