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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. 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). 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. 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.

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

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

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

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.

Background: Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3% of adult malignancies. P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of naturally occurring, short non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. There were preliminary data published indicating that piR-823 expression is deregulated in circulating tumor cells and tumor tissue in gastric and kidney cancer, respectively. Patients and Methods: In our study, we analyzed piR-823 levels in 588 biological specimens: tumor tissue (N=153), adjacent renal parenchyma (N=121), blood serum (N=178) and urine (N=20) of patients undergoing nephrectomy for RCC; and in blood serum (N=101) and urine (N=15) of matched healthy controls. Expression levels of piR-823 were determined in all biological specimens by quantitative real-time polymerase chain reaction, compared in patients and controls, and correlated with clinicopathological features of RCC. Results: We identified a significant downregulation of piR-823 in tumor tissue [p

Christopher M Dixon,1 Edwin Rijo Cedano,2 Dalibor Pacik,3 Vítězslav Vit,3 Gabriel Varga,3 Lennart Wagrell,4 Thayne R Larson,5 Lance A Mynderse6 1Department of Urology, Phelps Memorial Hospital, Sleepy Hollow, New York, NY, USA; 2Department of Urology, Clinical Canela, La Romana, Dominican Republic; 3Department of Urology, Brno University Hospital, Brno, Czech Republic; 4Urologcentrum, Stockholm, Sweden; 5Institute of Medical Research, Scottsdale, AZ, 6Department of Urology, Mayo Clinic, Rochester, MN,USA Objective: The objective of this study was to assess the effectiveness and safety of convective radiofrequency (RF) water vapor thermal therapy in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH); a pilot study design with 2-year follow-up evaluations.Patients and methods: Men aged ≥45 years with an International Prostate Symptom Score ≥13, a maximum urinary flow rate (Qmax) ≤15 mL/s, and prostate volume 20–120 cc were enrolled in a prospective, open-label pilot study using convective RF water vapor energy with the RezÅ«m System. Patients were followed up for 2 years after transurethral thermal treatment at 3 international centers in the Dominican Republic, Czech Republic, and Sweden. The transurethral thermal therapy utilizes radiofrequency to generate wet thermal energy in the form of water vapor injected through a rigid endoscope into the lateral lobes and median lobe as needed. Urinary symptom relief, urinary flow, quality of life (QOL) impact, sexual function, and adverse events (AEs) were assessed at 1 week, 1, 3, 6, 12, and 24 months. Results: LUTS, flow rate, and QOL showed significant improvements from baseline; prostate volumes were appreciably reduced. Sexual function was maintained and no de novo erectile dysfunction occurred. The responses evident as early as 1 month after treatment remained consistent and durable over the 24 months of study. Early AEs were typically transient and mild to moderate; most were related to endoscopic instrumentation. No procedure related to late AEs were seen. Conclusion: The RezÅ«m System convective RF thermal therapy is a minimally invasive treatment for BPH/LUTS which can be performed in the office or as an outpatient procedure with minimal associated perioperative AEs. It has no discernable effect on sexual function and provides significant improvement of LUTS that remain durable at 2 years. Keywords: benign prostatic hyperplasia, lower urinary tract symptoms, convective RF, water vapor thermal therapy, minimally invasive&nbsp

Introduction: Renal cell carcinoma (RCC) is due to its asymptomatic nature usually diagnosed too late or incidentally during the examination for other indications. There is currently none sufficiently sensitive and reliable biomarker for diagnosis, prediction of the disease development or therapeutic outcome in RCC. Long non-coding RNAs (lncRNAs), RNA molecules regulating gene expression present a group of potential biomarkers as their specific expression profiles have been described in many types of tumors including RCC. Main aim of this study was to analyse global expression profiles of lncRNAs by RNA sequencing, compare them with clinical behaviour of the cancer and to characterize functions of the candidate lncRNAs in vitro. Material and methods: Using next-generation sequencing of RNA from the fresh frozen tissue of 22 patients with RCC we compared expression of lncRNAs in tumor and adjacent non-tumor renal parenchyma. Expression of candidate lncRNAs biomarkers (PVT1, LUCAT1, LINC00982 and SLC16A-AS1) has been validated using qPCR on an independent cohort of 30 patients, results have been statistically evaluated using Mann-Whitney U-test, ROC analysis and were correlated with the clinical stage and Fuhrman grade. Expression of PVT1 was silenced using siRNAs in RCC cell cultures (786-0) and functional characteristics of PVT1 have been studied using MTT test, cell counting and scratch-wound assay. Results: Using the DESeq tool, 1163 deregulated lncRNAs have been identified in patients with RCC when lncRNA profiles of tumors and paired renal parenchyma were compared (538 with increased and 625 with decreased expression levels in tumors). PVT1 (AUC 0,8567, sensitivity 86,67%, specificity 76,67%) and LUCAT1 (AUC 0,7756, sensitivity and specificity 90%) have significantly increased expression and LINC00982 (AUC 0,9578, sensitivity 76,67% and specificity 66,67%) has significantly decreased expression (p < 0,001) also in the validation phase. Statistically significant difference in expression of SLC16A-AS1 has not been observed. Partial effect on migration and proliferation has been observed in PVT1 after the transfection by short interfering RNA. Conclusion: PVT1, LUCAT1 and LINC00982 are a potential diagnostic biomarkers of RCC. Their prognostic potential has not been identified. PVT1 indicated oncogenic functioning in RCC cell lines. This work was supported by Ministry of Health of the Czech Republic, grant nr. NV18-03-00554 and by the Ministry of Education, Youth and Sports of the Czech Republic under the project CEITEC 2020 (LQ1601). All rights reserved. Citation Format: Adela Kubickova, Julia Bohosova, Karolina Trachtova, Jiri Sana, Alexandr Poprach, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Marek Svoboda, Ondrej Slaby. Long non-coding RNA PVT1 is a promising diagnostic biomarker with oncogenic functioning in renal cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3124.

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.

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.

Purpose To provide information about the role of microRNAs in the pathogenesis of renal cell carcinoma (RCC) and their diagnostic and prognostic utility as cancer biomarkers. Methods A literature search was performed in the PubMed and Web of Science databases using the keywords “renal cancer/renal cell carcinoma/kidney cancer” and “miR*/miRNA*/microRNA*”. Articles dealing with the role of miRNAs in the pathogenesis of RCC, diagnostic miRNAs and prognostic miRNAs were separated. Results MiRNAs act both as oncogenes and tumor suppressors. They regulate apoptosis, cell growth, migration, invasion, proliferation, colony formation and angiogenesis through target proteins involved in several signaling pathways, and they are involved in key pathogenetic mechanisms such as hypoxia (HIF/VHL dependent) and epithelial-to-mesenchymal transition. Differentially expressed miRNAs can discriminate either tumor tissue from healthy renal tissue or different RCC subtypes. Circulating miRNAs are promissing as diagnostic biomarkers of RCC. Information about urinary miRNAs associated with RCC is sparse. Detection of a relapse is another implication of diagnostic miRNAs. The expression profiles of several miRNAs correlate with the prognosis of RCC patients. Comparison between primary tumor tissue and metastasis may help identify high-risk primary tumors. Finally, response to target therapy can be estimated thanks to differences in miRNA expression in tissue and serum of therapy-resistant versus therapy-sensitive patients. Conclusions Our understanding of the role of microRNAs in RCC pathogenesis has been increasing dramatically. Identification and validation of their gene targets may have direct impact on developing microRNA-based anticancer therapy. Several microRNAs can serve as diagnostic and prognostic biomarkers.

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.

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

The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.

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

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 &lt, 0.0001), and their levels significantly decreased in the time period of three months after radical nephrectomy (p &lt, 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.

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.

Background Renal cell carcinoma (RCC) is characterized by its resistance to radiotherapy and/or chemotherapy. On the other hand, it is an immunogenic tumor - it is able to stimulate antitumor responses. A prognostic significance of HLA-G expression by neoplastic cells in RCC is not well characterized; significance HLA-E expression in RCC is not characterized at all. Methods In our study, we evaluated the expression of HLA-G and HLA-E specific mRNA transcripts produced by neoplastic cells in 38 cases of RCC and in 10 samples of normal kidney parenchyma. The results were statistically correlated with various clinico-pathological parameters. Results We confirmed that HLA-G is downregulated in normal kidney tissue; if it is up-regulated in RCC, then it is connected to worse prognosis. On the other hand, HLA-E mRNA transcripts were present in both normal kidney tissue and RCC and their increasing concentrations counterintuitively carried better prognosis, more favorable pT stage and lower nuclear Fuhrmann’s grade. Conclusion Considering the fact that there is known aberrant activation of HLA-G and HLA-E expression by interferons, identification of HLA-G and HLA-E status could contribute to better selection of RCC patients who could possibly benefit from more tailored neoadjuvant biological/immunological therapy. Thus, these molecules could represent useful prognostic biomarkers in RCC, and the expression of both these molecules in RCC deserves further study. The virtual Slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7383071387016614

Introduction: Piwi-interacting RNAs (piRNAs) consists a newly discovered class of non-coding RNA. PiRNAs were first identified in the germ cells of various animal species. They bind to Piwi proteins which are a subfamily of Argonaut proteins. In humans were identified four Ago genes and four Piwi genes. Human Piwi genes include PIWIL1, PIWIL2, PIWIL3 and PIWIL4. Recent studies suggest that deregulated expression of Piwi proteins is common to many types of tumors and also correlate with clinicopathologic features and worse prognosis in patients with breast, cervical, ovarian, colorectal and other cancers. PiRNAs are short single-stranded RNAs with 26-31 nucleotides in length. They are involved in silencing of transposable elements and it is assumed that also participate in sequence-specific chromatin modifications. The differential expression of piRNAs was found in gastric and breast cancer. In our pilot study we analyzed expression of Piwi genes and piR-651, which was previously found to be deregulated in various types of tumors. Patients and Methods: In our study, we have used the tumor tissue and the paired renal parenchyma tissue of 56 patients with renal cell carcinoma (RCC). From the tissue was isolated total RNA and by RT-qPCR were examined the expression of Piwi genes and piR-651. For the analysis of circulating piR-651, blood serum samples of 75 patients with RCC and 75 age, gender-matched healthy donors were used. We have compared expression levels of the studied genes in tumor and non-tumor tissues, serum samples, and also correlated them with clinicopathologic features of RCC patients (stage, grade, RFS, OS). Results: We found a significant down-regulation of PIWIL1 (p Conclusion: Accordingly to our pilot data expression of Piwi genes is altered in tumor tissue and is correlated to selected clinicopathologic features of RCC. We also suggest the potential of piR-651 in blood serum as novel non-invasive diagnostic biomarker in RCC. Acknowledgments: IGA MZCR No: NT/13860-4/2012, NT/13549-4/2012, NT/13547-4/2012, NT/13514-4/2012 Citation Format: Robert Iliev, Petra Vychytilova-Faltejskova, Jaroslav Juracek, Hana Mlcochova, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Marek Svoboda, Ondrej Slaby. Piwi genes and tissue/serum piR-651 are related to clinicopathologic features of renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 237. doi:10.1158/1538-7445.AM2015-237

The authors report on the treatment of lower-pole caliceal nephrolithiasis with extracorporeal shockwave lithotripsy (SWL) using the Czech-made Medilit M-5 lithotripter. In 310 patients, they have performed 452 treatments and evaluated the results 3 months after the last session using plain radiographs and ultrasound examination. The effectiveness of treatment and the success rate of SWL decreased with increasing size of stones: with stones20 mm, it declined to 30%. This poor success rate was attributable not only to the size of the concrement, but also to its location in a lower calix, which is unfavorable for the passage of fragments. For big lower-pole caliceal stones (20 mm in the longest diameter), the authors recommend percutaneous nephrolithotomy as the primary management method, the effectiveness of which does not depend on the size of the stone. The success rate achieved in treating the lower-pole caliceal lithiasis using the Medilit M-5 machine was 61.3%, similar to that achieved with other lithotripters.