Fast and accurate compensation of signal offset for T2 mapping.

OBJECTIVE: T2 maps are more vendor independent than other MRI protocols. Multi-echo spin-echo signal decays to a non-zero offset due to imperfect refocusing pulses and Rician noise, causing T2 overestimation by the vendor's 2-parameter algorithm. The accuracy of the T2 estimate is improved, if the non-zero offset is estimated as a third parameter. Three-parameter Levenberg-Marquardt (LM) T2 estimation takes several minutes to calculate, and it is sensitive to initial values. We aimed for a 3-parameter fitting algorithm that was comparably accurate, yet substantially faster. METHODS: Our approach gains speed by converting the 3-parameter minimisation problem into an empirically unimodal univariate problem, which is quickly minimised using the golden section line search (GS). RESULTS: To enable comparison, we propose a novel noise-masking algorithm. For clinical data, the agreement between the GS and the LM fit is excellent, yet the GS algorithm is two orders of magnitude faster. For synthetic data, the accuracy of the GS algorithm is on par with that of the LM fit, and the GS algorithm is significantly faster. The GS algorithm requires no parametrisation or initialisation by the user. DISCUSSION: The new GS T2 mapping algorithm offers a fast and much more accurate off-the-shelf replacement for the inaccurate 2-parameter fit in the vendor's software.

Mantle cell lymphoma diagnosed from radical prostatectomy for prostate adenocarcinoma: a case report.

We present a case of 64 - year - old man with mantle cell lymphoma (MCL) diagnosed in radical prostatectomy for adenocarcinoma. Lymphoma of the prostate, either primary or secondary, is a rare entity. The prognosis of lymphoma involving the prostate is usually poor. The most common form of leukemia/lymphoma involving the prostate is that of chronic lymphocytic leukemia/lymphoma (CLL/SLL). Mantle cell lymphoma of the prostate is an exceedingly rare entity. The association between MCL and urologic cancer was previously described, however the etiologic connection between these two conditions remains unknown. The pathologists should pay attention to all lymphoid infiltrates in the prostate, especially in cases when these are dense.

Genome-wide identification of urinary cell-free microRNAs for non-invasive detection of bladder cancer.

Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and non-invasive detection of various types of cancer including bladder cancer (BCA). In this study, 205 patients with BCA and 99 healthy controls were prospectively enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in independent cohorts using qRT-PCR. Whole-genome profiling identified 76 miRNAs with significantly different concentrations in urine of BCA compared to controls (P < 0.01). In the training and independent validation phase of the study, miR-31-5p, miR-93-5p and miR-191-5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls (P < 0.01). We further established 2-miRNA-based urinary DxScore (miR-93-5p, miR-31-5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post-operatively. In conclusion, we identified and independently validated cell-free urinary miRNAs as promising biomarkers enabling non-invasive detection of BCA.

MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition.

MicroRNAs (miRNAs) have been proven to be important oncogenes and tumor suppressors in wide range of cancers, including renal cell carcinoma (RCC). In our study, we evaluated miRNA-429 as potential diagnostic/prognostic biomarker in 172 clear cell RCC patients and as a potential regulator of epithelial-mesenchymal transition (EMT) in vitro. We demonstrated that miR-429 is down-regulated in tumor tissue samples (P < 0.0001) and is significantly associated with cancer metastasis (P < 0.0001), shorter disease-free (P = 0.0105), and overall survival (P = 0.0020). In addition, ectopic expression of miR-429 in 786-0 RCC cells followed by TGF-ß treatment led to increase in the levels of E-cadherin expression (P < 0.0001) and suppression of cellular migration (P < 0.0001) in comparison to TGF-ß-treated controls. Taken together, our findings suggest that miR-429 may serve as promising diagnostic and prognostic biomarker in RCC patients. We further suggest that miR-429 has a capacity to inhibit loss of E-cadherin in RCC cells undergoing EMT and consequently attenuate their motility.

Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer.

Long non-coding RNA TUG1 is involved in the development and progression of a variety of tumors. Little is known about TUG1 function in high-grade muscle-invasive bladder cancer (MIBC). The aims of our study were to determine expression levels of long non-coding RNA TUG1 in tumor tissue, to evaluate its relationship with clinico-pathological features of high-grade MIBC, and to describe its function in MIBC cells in vitro. TUG1 expression levels were determined in paired tumor and adjacent non-tumor bladder tissues of 47 patients with high-grade MIBC using real-time PCR. Cell line T-24 and siRNA silencing were used to study the TUG1 function in vitro. We observed significantly increased levels of TUG1 in tumor tissue in comparison to adjacent non-tumor bladder tissue (P < 0.0001). TUG1 levels were significantly increased in metastatic tumors (P = 0.0147) and were associated with shorter overall survival of MIBC patients (P = 0.0241). TUG1 silencing in vitro led to 34 % decrease in cancer cell proliferation (P = 0.0004) and 23 % reduction in migration capacity of cancer cells (P < 0.0001). We did not observe any significant effects of TUG1 silencing on cell cycle distribution and number of apoptotic cells. Our study confirmed overexpression of TUG1 in MIBC tumor tissue and described its association with worse overall survival in high-grade MIBC patients. Together with in vitro observations, these data suggest an oncogenic role of TUG1 and its potential usage as biomarker or therapeutic target in MIBC.

Combination of MiR-378 and MiR-210 Serum Levels Enables Sensitive Detection of Renal Cell Carcinoma.

Serum microRNAs are emerging as a clinically useful tool for early and non-invasive detection of various cancer types including renal cell carcinoma (RCC). Based on our previous results, we performed the study to analyze circulating serum miR-378 and miR-210 in patients with various histological subtypes of RCC. RNA was purified from blood serum samples of 195 RCC patients and 100 healthy controls. The levels of miR-378 and miR-210 in serum were determined absolutely using quantitative real-time PCR. Pre- and postoperative levels of both microRNAs were compared in 20 RCC patients. Significantly increased serum levels of both miR-378 and miR-210 enabled to clearly distinguish RCC patients and healthy controls with 80% sensitivity and 78% specificity if analyzed in combination (p<0.0001), and their levels significantly decreased in the time period of three months after radical nephrectomy (p<0.0001). Increased level of miR-378 positively correlates with disease-free survival (p=0.036) and clinical stage (p=0.0476). The analysis of serum miR-378 and miR-210 proved their potential to serve as powerful non-invasive diagnostic and prognostic biomarkers in RCC.

Detection and quantitation of glutamate carboxypeptidase II in human blood.

BACKGROUND: Glutamate carboxypeptidase II (GCPII) is a transmembrane enzyme that cleaves N-acetyl-L-aspartyl-L-glutamate (NAAG) in the brain. GCPII is highly expressed in the prostate and prostate cancer and might be associated with prostate cancer progression. Another exopeptidase, plasma glutamate carboxypeptidase (PGCP), was reported to be similar to GCPII and to share its NAAG-hydrolyzing activity. METHODS: We performed a radioenzymatic assay with [(3) H]NAAG as a substrate to detect and quantify the enzymatic activity of GCPII in plasma. Using a specific antibody raised against native GCPII (2G7), we immunoprecipitated GCPII from human plasma. We also cloned two PGCP constructs, expressed them in insect cells, and tested them for their NAAG-hydrolyzing activity. RESULTS: We detected GCPII protein in human plasma and found that its concentration ranges between 1.3 and 17.2 ng/ml in volunteers not diagnosed with prostate cancer. Recombinant PGCP was enzymatically active but exhibited no NAAG-hydrolyzing activity. CONCLUSION: GCPII is present in human blood, and its concentration within a healthy population varies. Recombinant PGCP does not hydrolyze NAAG, suggesting that GCPII alone is responsible for the NAAG-hydrolyzing activity observed in human blood. The potential correlation between GCPII serum levels and the disease status of prostate cancer patients will be further investigated.

Management of bone metastases in patients with castration-resistant prostate cancer.

Bone metastases are a very common problem in prostate cancer. They are associated with considerable morbidity, adversely affect quality of life and frequently lead to advanced bone events (so-called skeletal-related events, SREs); SREs include fractures, spinal cord compression and the requirement for bone surgery or bone radiation. The aim of this paper was to evaluate currently available treatment options in the prevention and management of SREs and bone metastases in men with castration-resistant prostate cancer and to outline the importance of interdisciplinary management strategies. It also discusses the diagnostic workup of osseous metastases and practical considerations for the utilization of bone-targeted therapies in accordance with current guidelines to provide a consensus for special and/or difficult clinical situations.

Management of single large nonstaghorn renal stones in the CROES PCNL global study.

PURPOSE: We compared stone characteristics and outcomes in patients with a single large nonstaghorn renal calculus treated with percutaneous nephrolithotomy in the Clinical Research Office of Endourological Society global study. MATERIALS AND METHODS: Two statistical analyses were done, including one comparing renal stone size (20 to 30, 31 to 40 and 41 to 60 mm) and the other comparing renal stone site (pelvis, or upper, mid or lower calyx). Surgical outcomes, including operative time, hospital stay, stone-free rate and postoperative fever, were compared between groups. Fitness for surgery was assessed using the American Society of Anesthesiologists scoring system. Severity of postoperative complications was graded with the modified Clavien classification. RESULTS: Of 1,448 stones 1,202 (83%) were 20 to 30 mm, 202 (14%) were 31 to 40 mm and 44 (3%) were 41 to 60 mm. Of the large stones 73% were located in the renal pelvis. A statistically significantly lower stone-free rate, and higher postoperative fever and blood transfusion rates were seen with increased calculous size. With increased American Society of Anesthesiologists score the proportion of large stones in the calyces increased. At a score of III the proportion of large stones in the calyces was more than twice that of stones in the renal pelvis (13.5% vs 5.7%). Generally more patients with large calyceal than large pelvic stones had postoperative complications across the range of Clavien scores from I to IIIB. CONCLUSIONS: Calyceal site was associated with decreased fitness for surgery and an increased risk of postoperative complications compared to renal site. An increase in stone size results in a lower stone-free rate, and higher rates of postoperative fever and blood transfusion.

Short-term Outcomes of Water Vapor Therapy (Rezum) for BPH/LUTS in the First Czech Cohort.

PURPOSE: To evaluate the short-term results of water vapor therapy (Rezum) for BPH/LUTS in the first cohort of Czech patients. MATERIALS AND METHODS: Patients with BPH and moderate to severe LUTS (N = 76) who underwent Rezum treatment from December 2019 to July 2020 were included in the prospective study. Prior to the procedure, they completed the IPSS and OABv8 questionnaires and underwent uroflowmetry, transrectal ultrasound of the prostate, and PSA sampling. The parameters before and 3 months after the procedure were compared and statistically evaluated. RESULTS: The study protocol was completed by 92% of patients (N = 70). We observed a significant increase in Qmax (median 17.7 vs. 8.8 mL/s, P < .001), Qave (9 vs. 4.5 mL/s, P = .001) and voided volume (241 vs. 171 mL, P < .001) and a significant reduction in post-void residual (average 17.5 vs. 67.7 mL), prostate volume (39.3 vs. 62.3 mL) and total PSA (median 1.9 vs. 2.5 ng/mL, resp. P values < .001). There was also a significant decrease in OABv8 score (average 7.6 vs. 16.6, P < .001) and IPSS QoL (1.6 vs. 4.0, P = .037). The improvement in the IPSS score was apparent, yet statistically insignificant (6.8 vs. 16, P = .079). CONCLUSION: Water vapor therapy is an effective and safe method of BPH/LUTS treatment in the short-term.

Long non-coding RNAs and renal cell carcinoma.

BACKGROUND: To provide an overview of the importance of long non-coding RNAs (lncRNAs) in the pathogenesis of renal cell carcinoma and their utility as bio-markers for dia-gnosis, prognosis and prediction of treatment response. MATERIALS AND METHODS: A literature search in the Pubmed and Web of Science databases using the keywords variations of “long non-coding RNA” (“lncRNA”, “long noncoding RNA”, “long non-coding RNA”) and “renal cell carcinoma” (“renal cancer”, “renal cell carcinoma”, “kidney cancer”) was performed. The results related to the pathogenesis, dia-gnosis, prognosis and use as therapeutic targets were separated. RESULTS: Long non-coding RNAs regulate gene expression at different levels. They act both as oncogenes and tumor suppressors. The mechanism of their action has not been fully elucidated, but they are actively involved in the regulation of hypoxia inducible factors pathway, epithelial-mesenchymal transition, cell proliferation, cell cycle regulation, apoptosis, local invasion and development of metastases. Aberrant expression in tumor tissue compared to healthy parenchyma and the correlation of expression levels with clinical-pathological features allow the potential use of many lncRNAs as bio-markers for early detection and prognosis of the disease, including the response to targeted therapy. In vitro assays indicate the potential use of lncRNAs as therapeutic targets. CONCLUSION: Our knowledge of long non-coding RNAs in relation to renal cell carcinoma is increasing rapidly. At present, some of them can be considered as promising bio-markers. Further research is needed before they can be introduced into routine clinical practice.

Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis.

DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N-demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl-donor S-adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5-azacytidine, which was able to inhibit sarcosine-induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role.

Multicentric transitional cell carcinoma of the vagina and the ureter.

Primary transitional cell carcinoma (TCC) of the vagina represents an extremely rare neoplasm and is associated with multicentric TCC of the urinary tract in all described cases. A case of multicentric TCC of the vagina and the left ureter in a 73-year-old woman is reported. Immunohistochemical analysis of cytokeratin expression was performed. Immunohistochemistry proved to play an important role in the differential diagnosis of vaginal TCC, supported the morphological diagnosis of TCC, and largely excluded the diagnosis of vaginal papillary carcinoma with transitional features as a morphological variant of squamous cell carcinoma. Subsequent urological examination revealed multicentric TCC of the left ureter. During the follow up, the metastases of the vaginal TCC into the regional inguinal lymph nodes were diagnosed, suggesting that indolent clinical course is not a rule in this type of tumor.

Identification of Sarcosine as a Target Molecule for the Canine Olfactory Detection of Prostate Carcinoma.

The hypothesis that dogs can detect malignant tumours through the identification of specific molecules is nearly 30 years old. To date, several reports have described the successful detection of distinct types of cancer. However, is still a lack of data regarding the specific molecules that can be recognized by a dog's olfactory apparatus. Hence, we performed a study with artificially prepared, well-characterized urinary specimens that were enriched with sarcosine, a widely reported urinary biomarker for prostate cancer (PCa). For the purposes of the study, a German shepherd dog was utilized for analyses of 60 positive and 120 negative samples. Our study provides the first evidence that a sniffer dog specially trained for the olfactory detection of PCa can recognize sarcosine in artificial urine with a performance [sensitivity of 90%, specificity of 95%, and precision of 90% for the highest amount of sarcosine (10 µmol/L)] that is comparable to the identification of PCa-diagnosed subjects (sensitivity of 93.5% and specificity of 91.6%). This study casts light on the unrevealed phenomenon of PCa olfactory detection and opens the door for further studies with canine olfactory detection and cancer diagnostics.

Post-treatment urinary sarcosine as a predictor of recurrent relapses in patients with prostate cancer.

To date, there has been no evidence regarding the association between urinary sarcosine content and prostate cancer survival. Our main objective was to investigate whether levels of post-treatment urinary sarcosine are associated with relapse. The inclusion criteria were (in accordance with EAU 2017) as follows: histopathologically verified adenocarcinoma in prostate biopsy cores or specimens from transurethral resection of the prostate (TURP) or prostatectomy for benign prostatic enlargement (BPE) with retained ability to urinate. The median follow-up was 53 months. In the study, we retrospectively evaluated a cohort of 511 patients with prostate cancer with various risk factors and treatment strategies. Post-treatment sarcosine levels were elevated in 266 (52%) patients and highly elevated (≥200 nmol/L) in 71 (13%) patients. Urinary sarcosine content was significantly associated with number of relapses that patients experienced, P = 0.002 for sarcosine ≥200 vs ≤30 nmol/L. Multivariate analysis revealed that sarcosine was an independent predictor of recurrent relapses (≥2 relapses with an intermediate period of remission), HR = 3.89 (95% CI 1.29-11.7) for sarcosine >200 vs <30 nmol/L. This trend was even more pronounced in a subgroup of patients who underwent radical prostatectomy, HR = 3.29 (95% CI 1.06-10.18), where (single) relapse-free survival could also be predicted by sarcosine levels, HR = 1.96 (1.05-3.66). Urinary sarcosine may become a possible predictor for patients' outcomes, because patients with elevated post-treatment sarcosine could be predicted to have recurrent relapses of the disease.

Worldwide Use of Antiretropulsive Techniques: Observations from the Clinical Research Office of the Endourological Society Ureteroscopy Global Study.

INTRODUCTION: Retropulsion, defined as unintended migration of a stone under the influence of the fragmentation device in ureteroscopy (URS) procedures, occurs in 2% to 60% of the cases. Antiretropulsive devices (ARDs) have been studied in experimental and small clinical studies. The current study aims at describing the worldwide usage of ARD and the outcomes related to their usage. METHODS: The Clinical Research Office of the Endourological Society URS Global Study enrolled 11,885 patients who underwent URS and stone fragmentation for ureteral and/or renal stones. Of the 11,885 treated patients, 9877 were treated for ureteral stones, and data were available on stone migration and ARD use. RESULTS: Of all procedures, 14.5% were performed with the use of an ARD. Less stone migration (-2.0%; p = 0.050), higher stone-free rates (SFRs) (2.8%; p < 0.001), and shorter length of stay (-4.7%; p = 0.001) were observed in the antiretropulsive group. CONCLUSIONS: When an ARD is used during URS, less migration, higher SFRs, and shorter length of hospital stay are observed. This effect is independent from baseline differences and corrected for other treatment characteristics.

Diagnosis of prostate cancer.

The contemporary challenge of prostate cancer diagnosis has been changed in the past decade from the endeavor to increase detection to that of detecting only those tumors that are clinically significant. Better interpretation of the role of prostate-specific antigen (PSA) and its kinetics as a diagnostic tool, the adoption of extended prostate biopsy schemes, and perhaps implementation of new transrectal ultrasound (TRUS) technologies promote the achievement of this clinical mission. This chapter reviews these issues as well as the change in practice of patient preparation for TRUS-biopsy and analgesia during it, the role of repeat and saturation prostate biopsies, and the interpretation of an incidental prostate cancer finding. Currently, the lifetime risk of a diagnosis of prostate cancer for North American men is 16%, compared to the lifetime risk of death from prostate cancer, which is 3% (Carter 2004). The advent of prostate-specific antigen (PSA) screening and transrectal ultrasonography (TRUS) has significantly impacted the detection of prostate cancer over the last 20 years. The mean age at diagnosis has decreased (Hankey et al. 1999; Stamey et al. 2004) and the most common stage at diagnosis is now localized disease (Newcomer et al. 1997; Stamey et al. 2004). The goal of prostate cancer screening is to detect only those men at risk for death from the disease at an early curable phase. The ambiguous natural history of this most common malignancy in men, being latent with questionable life-threatening potential in a large number of cases on the one hand, with only a relatively small number (though not negligible) of highly malignant cases on the other, propels many doubts about whether this is possible. This was famously phrased more than 20 years ago by Whitmore who asked: "Is cure possible for those in whom it is necessary; and is it necessary for those in whom it is possible?" This is probably even more relevant nowadays. During the past decade two factors influenced significantly the increased detection rate of prostate cancer in general and that of clinically insignificant prostate cancers in particular: the widespread use of serum PSA as a screening tool to a large extent and to a lesser though significant extent the application of extended multiple core biopsy schemes (Master et al. 2005). In fact, 75% of men in the United States aged 50 years and older have been screened with the PSA test (Sirovich et al. 2003). Outside of the screening context, which is dealt with in depth in Chap. 5, clinical suspicion of prostate cancer is raised usually by abnormal digital rectal examination (DRE) and/or by abnormal levels of serum PSA. Final diagnosis is achieved only based on positive prostate biopsies.

Literature review of factors affecting continence after radical prostatectomy.

Radical prostatectomy (RP) is the most common cause of stress urinary incontinence (UI) in men. Several anatomic structures affect or may affect urinary continence - urethral sphincter, levator ani muscle, puboprostatic ligaments, bladder neck, endopelvic fascia, neurovascular bundle - and understanding of the anatomy of pelvic floor and urethra is crucial for satisfactory functional outcome of the procedure. Surgical techniques implemented to improve continence rates include nerve-sparing procedure, bladder neck preservation/plication, urethral length preservation, musculofascial reconstruction, puboprostatic ligaments preservation or seminal vesicle preservation. Perioperative (preoperative and postoperative) pelvic floor muscle training (PFMT) aims to shorten the duration of postoperative UI and thus, improve early continence rates postoperatively. In the review, complex information regarding anatomical, intra- and perioperative factors affecting urinary continence after RP is provided, including description of important anatomical structures, possible implications for surgical technique and evaluation of different PFMT strategies in perioperative period.

Detection of let-7 miRNAs in urine supernatant as potential diagnostic approach in non-metastatic clear-cell renal cell carcinoma.

INTRODUCTION: Urinary microRNAs (miRNAs) are emerging as a clinically useful tool for early and non-invasive detection of various types of cancer. The aim of this study was to evaluate whether let-7 family miRNAs differ in their urinary concentrations between renal cell carcinoma (RCC) cases and healthy controls. MATERIALS AND METHODS: In the case-control study, 69 non-metastatic clear-cell RCC patients and 36 gender/age-matched healthy controls were prospectively enrolled. Total RNA was purified from cell-free supernatant of the 105 first morning urine specimens. Let-7 family miRNAs were determined in cell-free supernatant using quantitative miRNA real-time reverse-transcription PCR and absolute quantification approach. RESULTS: Concentrations of all let-7 miRNAs (let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in urine samples obtained from RCC patients compared to healthy controls (P < 0.001; P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively). Subsequent ROC analysis has shown that let-7a concentration possesses good ability to differentiate between cases and controls with area under curve being 0.8307 (sensitivity 71%, specificity 81%). CONCLUSIONS: We have shown that let-7 miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out of six let-7 family members, let-7a outperforms the others and presents promising non-invasive biomarker for the detection of RCC.