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Purpose: Current immunomagnetic enrichment method can only detect general epithelial antigens of circulating tumor cells (CTC). Further characterization of the CTCs to provide specific information on the tumor type is not possible. We attempted to overcome this drawback by developing the methodology for using a gastrointestinal-specific anti-cytokeratin (CK) 20 antibody to detect CTCs in colorectal cancer patients' blood.Experimental Design: The protocol was validated using a colorectal cancer SW480 cell line. The clinical significance of findings in colorectal cancer was investigated by detecting CK20-positive CTCs (pCTC) in patients with colorectal cancer, other common cancers, colorectal adenoma, benign colorectal diseases, and normal subjects. Moreover, the malignant nature of CK20 pCTCs was examined by comparing chromosome 17 aberration patterns with those from the corresponding primary tumors.Results: The assay successfully showed CK20-positive SW480 cells. When applied in patient samples, the detection rates were 62% (132 colorectal cancer patients; median number = 11 CTCs), 0% (120 patients with other common cancers), 6% (50 colorectal adenoma patients), 0% (120 patients with benign colorectal diseases), and 0% (40 normal subjects). Furthermore, statistical analysis showed that CK20 pCTC numbers were associated with tumor-node-metastasis stage and lymph node status. Using the median CK20 pCTC numbers as the cutoff points, stratified groups of colorectal cancer patients had significant differences in their recurrence, metastasis, and survival. Finally, chromosome 17 aneusomy in 90% of colorectal cancer patients with CK20 pCTCs matched with those from the primary tumors.Conclusions: Detection of CK20 pCTCs using the new protocol could generate clinically important information for colorectal cancer patients.

Supplementary Tables S1-S3 from Clinical Significance of Cytokeratin 20-Positive Circulating Tumor Cells Detected by a Refined Immunomagnetic Enrichment Assay in Colorectal Cancer Patients

Context Although percutaneous nephrolithotomy (PCNL) has been performed for decades and has gone through many refinements, there are still concerns regarding its more widespread utilization because of the long learning curve and the potential risk of severe complications. Many technical details are not included in the guidelines because of their nature and research protocol. Objective To achieve an expert consensus viewpoint on PCNL indications, preoperative patient preparation, surgical strategy, management and prevention of severe complications, postoperative management, and follow-up. Evidence acquisition An international panel of experts from the Urolithiasis Section of the European Association of Urology, International Alliance of Urolithiasis, and other urology associations was enrolled, and a prospectively conducted study, incorporating literature review, discussion on research gaps (RGs), and questionnaires and following data analysis, was performed to reach a consensus on PCNL. Evidence synthesis The expert panel consisted of 36 specialists in PCNL from 20 countries all around the world. A consensus on PCNL was developed. The expert panel was not as large as expected, and the discussion on RGs did not bring in more supportive evidence in the present consensus. Conclusions Adequate preoperative preparation, especially elimination of urinary tract infection prior to PCNL, accurate puncture with guidance of fluoroscopy and/or ultrasonography or a combination, keeping a low intrarenal pressure, and shortening of operation time during PCNL are important technical requirements to ensure safety and efficiency in PCNL. Patient summary Percutaneous nephrolithotomy (PCNL) has been a well-established procedure for the management of upper urinary tract stones. However, according to an expert panel consensus, core technical aspects, as well as the urologist’s experience, are critical to the safety and effectiveness of PCNL.

Picture archiving and communication system (PACS) is a medical imaging system for sharing, storage, retrieval, and access of medical images stored. Our study aimed to identify ophthalmologists' views on PACS, with the comparison between 3 platforms, namely electronic patient record (ePR), HEYEX (Heidelberg Engineering, Switzerland), and FORUM (Zeiss, US), following their implementation in an eye hospital for common ophthalmic investigations [visual field, optical coherence tomography (OCT) of retinal nerve fiber layer and macula, and fluorescein/indocyanine green angiography (FA/ICG)].An online survey was distributed among ophthalmologists in a single center. Primary outcome included comparison of PACS with paper-based system. Secondary outcomes included pattern of use and comparison of different PACS platforms.Survey response rate was 28/37 (75.7%). Images were most commonly accessed through ePR (median: 80% of time, interquartile range: 50 to 90%).All systems scored highly in information display items (median scores ≥7.5 out of 10) and in reducing patient identification error in investigation filing and retrieval during consultation compared to paper (score ≥7.0). However, ePR was inferior to paper in "facilitating comparison with previous results" in all investigation types (scores 3.0 to 4.5). ePR scored significantly higher in all system quality items than HEYEX ( P 0.001) and FORUM ( P 0.022), except login response time ( P = 0.081). HEYEX scored significantly higher among vitreoretinaluveitis members (VRU) for information quality items for OCT macula and FA/ICG [VRU: 10.0 (8.0 to 10.0), non-VRU: 8.0 (6.75 to 9.25), P = 0.042].Overall feedback for PACS among ophthalmologists was positive, with limitations of inefficiency in use of information, for example, comparison with previous results. Subspecialty played an important role in evaluating PACS.

Kidney stone cultures can be beneficial in identifying bacteria not detected in urine, yet how stone cultures are performed among endourologists, under what conditions, and by what laboratory methods remain largely unknown. Stone cultures are not addressed by current clinical guidelines. A comprehensive REDCap electronic survey sought responses from directed (n = 20) and listserv elicited (n = 108) endourologists specializing in kidney stone disease. Questions included which clinical scenarios prompt a stone culture order, how results influence post-operative antibiotics, and what microbiology lab protocols exist at each institution with respect to processing and resulting stone cultures. Logistic regression statistical analysis determined what factors were associated with performing stone cultures. Of 128 unique responses, 11% identified as female and the mean years of practicing was 16 (range 1-46). A specific 'stone culture' order was available to only 50% (64/128) of those surveyed, while 32% (41/128) reported culturing stone by placing a urine culture order. The duration of antibiotics given for a positive stone culture varied, with 4-7 days (46%) and 8-14 days (21%) the most reported. More years in practice was associated with fewer stone cultures ordered, while higher annual volume of percutaneous nephrolithotomy was associated with ordering more stone cultures (p 0.01). Endourologists have differing practice patterns with respect to ordering stone cultures and utilizing the results to guide post-operative antibiotics. With inconsistent microbiology lab stone culture protocols across multiple institutions, more uniform processing is needed for future studies to assess the clinical benefit of stone cultures and direct future guidelines.

Objective:To report the outcomes of percutaneous nephrolithotomy (PCNL) in horseshoe kidneys (HSK) in 12 institutions worldwide and evaluate the impact of patient position during operation. Methods:We carried out a retrospective analysis of PCNL procedures performed between 2008 and 2018 in patients with HSK. Pre-, peri-, and postoperative data were collected, and a subgroup analysis was performed according to patient position. Success was defined as an absence of >4-mm fragments. Values ofp < 0.05 were considered significant. Results:We analyzed 106 procedures. The transfusion, complication, and immediate success rates (ISRs) were 3.8%, 17.5%, and 54.7%, respectively. The final success rate (FSR) increased to 72.4% after a mean of 0.24 secondary procedures. Logistic regression showed that higher body mass index (BMI) and stone size were significantly associated with residual fragments >= 4 mm. Sixty-seven patients (63.2%) were treated in prone and 39 (36.8%) in supine position. The prone group had a significantly higher BMI than the supine group (30.1vs27.7,p = 0.024). The transfusion, complication, and ISRs between the prone and supine groups were 4.5%vs2.6% (p = 0.99), 16.9%vs18.4% (p = 0.99), and 52.5%vs69.2% (p = 0.151), respectively. Surgical time was significantly longer in the prone group (126.5vs100 minutes,p = 0.04). Upper pole was the preferred access in 80.3% of the prone group and 43.6% of the supine group (p < 0.001). The prone group had significantly more Clavien 2 complications than the supine (p = 0.013). The FSR in the prone and supine groups increased to 66.1% and 82.1% after 0.26 and 0.21 secondary procedures, respectively. No complications higher than Clavien 3 occurred. Conclusion:PCNL in patients with HSK is safe and effective with a low complication rate. Higher BMI and stone size negatively impacted outcomes. Supine PCNL may be an option for treating kidney stones in patients with HSK.

Introduction and Objectives: Lack of access to urologic specialists is approaching crisis levels as the number of urologists is decreasing, while the demand for urologic care is increasing. The financial implications of this have not been explored. The objective of this study is to examine the impact of access and other patient factors on cost to treat urolithiasis. We hypothesized that markers of poor access would associate with higher costs of surgical encounters for patients presenting with urolithiasis. Methods: A retrospective review of prospectively collected data from the Registry for Stones of the Kidney and Ureter (ReSKU) from September 2015 to July 2018 was conducted to investigate characteristics of surgical patients treated for urinary stone disease. Univariate analysis was performed using the Welch two-sample t-test. Multivariate analysis was performed using logistic regression. Statistical analysis was performed in R version 3.5. Results: When taking into account age, delayed presentation, procedure type, stone size >20 mm, American Society of Anesthesiologists (ASA) code, gender, race, income, distance, urologist density, body mass index, diabetes, infection, education, language, insurance, and stone complexity, patients undergoing percutaneous nephrolithotomy procedure (p

To evaluate the impact of chronic stone recurrence on an individual's quality of life using the validated Wisconsin Stone Quality of Life (WISQOL) questionnaire. We collected cross-sectional data on patients with kidney stones from 14 institutions in North America. A stone event was defined as renal colic, stone-related procedure or emergency department visit. The regression analyses using general linear models and pairwise comparison determined the impact of the number of stone events on quality of life. The median number of stone events among the 2205 patients who completed the questionnaire was 3 (IQR 1-6). The mean total score was 107.4 ± 28.7 (max 140 points). The number of lifetime stone events was an independent predictor of lower quality of life (p 0.001), specifically, score declined significantly beyond five events. Compared with patients who experienced a single stone event, there was a 0.4, 2.5, and 6.9 point decline in the adjusted mean WISQOL score after 2-5, 6-10, or 10 events, respectively. The cumulative number of lifetime stone events was associated with a lower quality of life when more than five stone events were occurred. These findings underscore the importance of efforts to determine the underlying metabolic etiology of urolithiasis in the recurrent stone former, and the institution of a regimen to place their stone disease in remission.

OBJECTIVE To build the Wisconsin Stone Quality of Life Machine-Learning Algorithm (WISQOL-MLA) to predict urolithiasis patients' health-related quality of life (HRQoL) based on demographic, symptomatic and clinical data collected for the validation of the Wisconsin Stone Quality-of-Life (WISQOL) questionnaire, an HRQoL measurement tool designed specifically for patients with kidney stones. MATERIAL AND METHODS We used data from 3206 stone patients from 16 centres. We used gradient-boosting and deep-learning models to predict HRQoL scores. We also stratified HRQoL scores by quintile. The dataset was split using a standard 70%/10%/20% training/validation/testing ratio. Regression performance was evaluated using Pearson's correlation. Classification was evaluated with an area under the receiver-operating characteristic curve (AUROC). RESULTS Gradient boosting obtained a test correlation of 0.62. Deep learning obtained a correlation of 0.59. Multivariate regression achieved a correlation of 0.44. Quintile stratification of all patients in the WISQOL dataset obtained an average test AUROC of 0.70 for the five classes. The model performed best in identifying the lowest (0.79) and highest quintiles (0.83) of HRQoL. Feature importance analysis showed that the model weighs in clinically relevant factors to estimate HRQoL, such as symptomatic status, body mass index and age. CONCLUSIONS Harnessing the power of the WISQOL questionnaire, our initial results indicate that the WISQOL-MLA can adequately predict a stone patient's HRQoL from readily available clinical information. The algorithm adequately relies on relevant clinical factors to make its HRQoL predictions. Future improvements to the model are needed for direct clinical applications.

Purpose: Metabolic syndrome (MetS) is a cluster of metabolic diseases that is linked to atherosclerotic cardiovascular disease. MetS has also been linked to increased nephrolithiasis. However, limi...

OBJECTIVES To evaluate the utility of kidney injury test (KIT) assay urinary biomarkers to detect kidney stones and quantify stone burden. PATIENTS AND METHODS A total of 136 spot urine samples from 98 individuals, with and without kidney stone disease, were processed in a predefined assay to measure six DNA and protein markers in order to generate a risk score for the non-invasive detection of nephrolithiasis. From this cohort, 56 individuals had spot, non-timed urine samples collected at the time of radiographically confirmed kidney stones, and 54 demographically matched, healthy controls without kidney stone disease also provided spot, non-timed urine samples. Sixteen individuals with persistent stone disease had more than one urine sample. Using a proprietary microwell-based KIT assay, we measured cell-free DNA (cfDNA), methylated cfDNA, clusterin, creatinine, protein and CXCL10. A KIT stone score was computed across all markers using the prior locked KIT algorithm. The KIT stone score, with a scale of 0 to 100, was then correlated with demographic variables, kidney stone burden, obstructive kidney stone disease, and urine solutes in 24-h urine collections. RESULTS The scaled KIT stone score, a composite of all six biomarkers, readily discriminated individuals with current or prior radiographically confirmed kidney stones from healthy controls without kidney stone disease (P < 0.001). In individuals with nephrolithiasis, KIT stone score also correlated with radiologically measured stone size (P = 0.017) and differentiated patients with a clinical radiological diagnosis of obstructive nephrolithiasis associated with upper renal tract dilatation (P = 0.001). Stone burden as assessed by KIT stone score, however, did not correlate with the any of the traditional measures of 24-h urine solutes or the 24-h urine supersaturation levels. In patients with persistent stone disease, where multiple urine samples were collected over time and after different interventions, the use of KIT stone score could non-invasively track stone burden over time through a spot urine, non-timed urine sample. CONCLUSIONS A random, spot urine-based assay, KIT stone score, can non-invasively detect, quantify and monitor current stone burden, and may thus minimize radiographic exposure for kidney stone detection. The KIT stone score assay may also help monitor stone recurrence risk for patients with nephrolithiasis, without the requirement for 24-h urine collections.

Background Ureteral obstruction after percutaneous nephrolithotomy (PCNL) may require prolonged drainage with a nephrostomy tube (NT) or ureteral stent, but it is not well understood how and why this occurs. The goal of this study was to identify risk factors associated with postoperative ureteral obstruction to help guide drainage tube selection. Methods Prospective data from adult patients enrolled in the Registry for Stones of the Kidney and Ureter (ReSKU) who underwent PCNL from 2016 to 2020 were used. Patients who had postoperative NTs with antegrade imaging-based flow assessment on postoperative day one (POD1) were included. Patients with transplanted kidneys or those without appropriate preoperative imaging were excluded. We assessed the association between patient demographics, stone characteristics, and intraoperative factors using POD1 antegrade flow, a proxy for ureteral patency, as the primary outcome. Stepwise selection was used to develop a multivariate logistic regression model controlling for BMI, stone location, stone burden, ipsilateral ureteroscopy (URS), access location, estimated blood loss, and operative time. Results We analyzed 241 cases for this study; 204 (84.6%) had a visual clearance of stone. Antegrade flow on POD1 was absent in 76 cases (31.5%). A multivariate logistic regression model found that stones located anywhere other than in the renal pelvis (OR 2.63, 95% CI 1.29–5.53; p = 0.01), non-lower pole access (OR 2.81, 95% CI 1.42–5.74; p p = 0.05) increased the likelihood of obstruction. BMI, pre-operative stone burden, EBL, and operative time did not affect antegrade flow outcomes. Conclusion Concurrent ipsilateral URS, absence of stones in the renal pelvis, and non-lower pole access are associated with increased likelihood of ureteral obstruction after PCNL. Access location appears to be the strongest predictor. Recognizing these risk factors can be helpful in guiding postoperative tube management.

ObjectiveTo raise awareness that patients with proximal ureteral stricture who elect for nephrectomy can consider donating the kidney. We present a series of patients undergoing therapeutic living donor nephrectomy (TLDN), a scenario in which a patient undergoing nephrectomy for an underlying medical problem donates the kidney to a person with end-stage renal disease. This practice is underutilized, and only a single TLDN with proximal ureteral stricture has been previously described. We aim to help define the indications, risks, and benefits for patients.MethodsThis is a retrospective case series of seven therapeutic donors with proximal ureteral pathology and stone disease. Patient characteristics, donor work up, operative details, and donor and recipient outcome were collected.ResultsAll seven donors had proximal ureteral pathology, and six of the seven had nephrolithiasis or ureterolithiasis. After electing for nephrectomy, the mean time to TLDN was 57.9 days. No recipients experienced delayed graft function . Mean follow up was 40.1 months (range 8-131), and the most recent follow-up mean creatinine was 1.08 (mg/dL). Graft and recipient survival is 100%. No recipients developed recurrence of ureteral stricture or stones.ConclusionThis is the first series demonstrating patients with proximal ureteral stricture, even with concomitant stone disease, may donate kidneys for transplantation. Recipient outcomes suggest this practice is safe, and appropriately selected patients that have already elected for nephrectomy should receive counseling about this opportunity. Importantly, patients who donate a kidney receive waiting list priority if they ever need a kidney transplant in the future.