External validation of existing nomograms predicting lymph node metastases in cystectomized patients.

OBJECTIVES: Karakiewicz et al. and Green et al. created pre-cystectomy nomograms to predict lymph node involvement. The aim of the study was to externally validate these two nomograms in intermediate-volume institutions in Europe. PATIENTS AND METHODS: Data from a Serbian single-centre cystectomy series comprising 183 patients with bladder cancer were used for the validation of two US nomograms, which were originally based on data from 726 and 201 patients, respectively. A multivariate regression model assessed the value of the clinical parameters integrated in the two nomograms. The expected predictive accuracy, calibration and clinical utility according to the nomograms were calculated. RESULTS: Comparison of our dataset with the previously published data shows differences in nearly all underlying risk variables. Overall, 109 (59.6 %) patients had lymph node metastases. The analysis demonstrated that hydronephrosis and status of lymph nodes on computed tomography have independent prognostic value. The performance of the nomograms deteriorated from the development set, and the predictive accuracies for the two models showed moderate discriminatory ability (61.2-69.1 %). In the decision curve analysis, only the Green et al. model predicting lymph node positivity provided net benefit. CONCLUSIONS: The Green et al. nomogram seems applicable to patients from Europe, despite varying risk factors in the validation dataset. Acceptance of such a tool into daily clinical management may lead to more appropriate decision-making. Nevertheless, further improvement and implementation of novel statistical models with enhanced predictive accuracy is needed.

Calcitonin Gene-Related Peptide Receptor Blocker Inhibits Spontaneous Activity of Human Ureter.

Calcitonin gene-related peptide (CGRP) is present in nerve fibers that innervate the human ureter and may have important influence on the motility of this organ. The aim of our study was to investigate whether CGRP could affect the motility of an isolated human ureter. The tension and intraluminal pressure of the isolated ureteral segments were recorded and registered on a personal computer. Both phasic and tonic contractions of the isolated preparations were measured as area under the tension or pressure recordings. CGRP and CGRP fragment 8-37 were separately added to the organ baths in a cumulative way, thereby gradually increasing their concentration in the baths' solution. Alpha-CGRP did not affect either phasic, spontaneous activity or tone of isolated ureteral segments, as measured by both tension and intraluminal pressure. On the other hand, CGRP 8-37 caused concentration-dependent inhibition of spontaneous contractions of the isolated ureteral segments.

Improved predictive performance of prostate biopsy collaborative group risk calculator when based on automated machine learning.

BACKGROUND: The Prostate Biopsy Collaborative Group risk calculator (PBCG RC) has a moderate discriminatory capability. This study aimed to create automated machine learning (AutoML) PBCG RC for predicting the probability of any-grade and high-grade prostate cancer (PCa). METHODS: This retrospective, single-center study was carried out using the database with 832 patients who were subject to transrectal ultrasound-guided prostate biopsy with prostate-specific antigen (PSA) values from 2 to 50 ng/ml. Information about PBCG RC predictors was gathered for all patients. We used H2O, as an open-source platform for AutoML, where the set of 20 base learning algorithms were trained. The AutoML PBCG RC was compared in terms of discrimination, calibration, and clinical utility with the original PBCG RC. RESULTS: PCa was detected in 341 (41%) men, and 159 (19.1%) of them had high-grade PCa. Our AutoML models demonstrated better discriminative ability than the original PBCG RC for detection of PCa (area under the curve [AUC]: 0.703 vs 0.628; P = 0.023) and high-grade PCa (AUC: 0.990 vs 0.717; P < 0.001). The decision curve analyses showed that AutoML models performed better. For high-grade PCa the PSA was the most important feature. CONCLUSIONS: We applied ensemble techniques to create a freely available online PCa risk tool based on PBCG RC predictors and AutoML algorithms. The AutoML models drastically improved original model performance and the predictions of high-grade PCa were nearly perfect. However, new models should be used with a reserve, because external validation has not been performed yet.

Adaptation of the prostate biopsy collaborative group risk calculator in patients with PSA less than 10 ng/ml improves its performance.

PURPOSES: The prostate biopsy collaborative group risk calculator (PBCGRC) is a newly developed risk estimator for predicting prostate biopsy outcomes. However, its clinical usefulness is still unknown within the so-called gray area of PSA values. This study aimed to determine whether updating the PBCGRC improves its predictive performance for predicting any-grade and high-grade (HG), defined as biopsy Gleason score ≥ 7, prostate cancer (PCa) in patients with prostate-specific antigen (PSA) less than 10 ng/ml. METHODS: The risk of any-grade and HGPCa was calculated using the PBCG risk calculation formulas updated by recalibration in the large, logistic recalibration and model revision. Predictive performances of the PBCGRC and the updated models were compared using discrimination, calibration, and clinical utility. RESULTS: Within the study sample of 526 patients, PCa was detected in 193 (36.7%), and 78 (14.8%) of them had HGPCa. According to the calibration curves, the PBCGRC overestimated the risk of PCa. Predictive accuracy of the revised model was higher [the area under the receiver-operating characteristic curve (AUCs), 65.4% and 70.2%] than that of the PBCGRC (AUCs, 60.4% and 64.3%) for any-grade and HGPCa. The net benefit was greater for model revision in comparison with the original model. CONCLUSION: The performance accuracy of PBCGRC for the prediction of any and HGPC in men undergoing prostate biopsy with PSA levels below 10 ng/ml is suboptimal. The model revision resulted with significant improvement in model performance. However, external validation of the revised model is necessary before its routine use in clinical practice.

Optimal threshold of the prostate health index in predicting aggressive prostate cancer using predefined cost-benefit ratios and prevalence.

PURPOSES: The aim of the study was to determine optimal threshold of the Prostate Health Index (Phi) for predicting aggressive prostate cancer (PCa), taking into account misclassification costs, prevalence, and plausible risk factors. METHODS: This prospective cohort study analyzed patients undergoing prostate biopsy and Phi testing. The primary endpoint was aggressive PCa, defined as biopsy Gleason score ≥ 7. The data about age, total prostate-specific antigen (PSA), percentage of free PSA (%fPSA), and digital rectal examination (DRE) were extracted from the patient files. We divided the patients to the low- and high-risk group. The clinical usefulness of the Phi was assessed by the decision curve analysis. The predictive performance was assessed using the area under the receiver operating characteristic curve (AUC), per-class metrics, and the potential reduction in unnecessary biopsies. The uncertain interval of Phi values was also determined. RESULTS: There were 200 men included in the study, 35 (17.5%) of them having aggressive PCa. Important predictors of aggressive PCa were %fPSA, DRE, Phi, and belonging to the high-risk group. With optimal threshold of 30.7, about 32% unnecessary biopsies would be avoided. The optimal threshold of Phi was lower in the high-risk group than in the low-risk group. The AUC for detection of aggressive PCa was 0.791. Per-class metrics showed that the Phi has insufficient diagnostic accuracy. The lower and upper limits of the uncertain interval were 41.8 and 51.4, respectively. CONCLUSION: Different thresholds of the Phi could be optimal, depending on prevalence, patient characteristics, and misclassification costs. Further studies with a larger patient sample are necessary to confirm our conclusions.

Predictors of surgical site infection in dirty urological surgery.

OBJECTIVES: Risk factors for surgical site infection (SSI) following urologic dirty operations have not been clearly identified. This study was conducted to describe incidence, potential risk factors and common causative pathogens of the SSI in such operations. METHODS: Medical records of patients who had undergone simple nephrectomy or lumbotomy for suppurative renal infection at our institutions from 1999 to 2006 were retrospectively evaluated. The following data were retrieved: presence of SSI, demographic data, laboratory findings, comorbidities, microbiological data, type of renal suppuration, type of urological surgery and antibiotic regimen. Risk factors for SSI were evaluated using the multiple logistic regression model. RESULTS: Sixty-five patients (mean age 55.6 +/- 13.1 years) were eligible for data analysis. In 20 of them (30.8%) a SSI was identified. The most common isolated pathogens were gram-negative bacteria. At univariate logistic regression analysis risk factors significantly associated with SSI included: presence of emphysematous infection, hypoalbuminemia, number of predisposing conditions, emergency operations, isolation of Enterobacteriaceae, positive pus culture. The use of trimethoprim/sulfamethoxazole was associated with a decreased risk for SSI. Multiple logistic model identified only the emergency operations and isolated Enterobacteriaceae as independent predictors of SSI (odds ratio [OR] = 11.1) (95% confidence interval [CI] = 3.0-40.8) and OR = 3.9 (1.0-14.8), respectively. CONCLUSIONS: Patients with suppurative renal infections are submitted to life-saving emergency surgery. Urological surgeons should keep in mind that this carries a high risk for subsequent SSI. Effective preventive measures in these circumstance cannot be identified. Further research in this area is necessary to clarify this issue.

Angiotensin Receptor Blocker Losartan Inhibits Spontaneous Motility of Isolated Human Ureter.

BACKGROUND AND OBJECTIVES: Ureteral motility is essential for elimination of intraluminal stones, and it may be adversely affected by cardiovascular drugs that a patient is taking chronically. The aim of our study was to test whether ACE inhibitors and an angiotensin receptor blocker may influence spontaneous contractions of isolated human ureter. METHODS: Both phasic and tonic contractions of the isolated ureteral segments taken from 10 patients were measured as changes of the longitudinal tension or pressure recordings. Captopril, enalapril and losartan were separately added to the organ baths cumulatively. RESULTS: While enalapril (2.7 × 10-7-3.9 × 10-4 M) and captopril (6.1 × 10-7-2.7 × 10-3 M) did not affect either spontaneous activity or tone of isolated ureteral segments, losartan (2.9 × 10-7-4.2 × 10-4 M) caused concentration-dependent inhibition of spontaneous contractions of the segments (50 % effective concentration (EC50) = 13.46 ± 1.80 × 10-6 M; F = 10.72, r = 0.79, p < 0.001). CONCLUSIONS: Due to differences in molecular mechanism of action, angiotensin receptor blocker losartan does and ACE inhibitors captopril and enalapril do not inhibit spontaneous contractions of isolated human ureter.

Automated development of artificial neural networks for clinical purposes: Application for predicting the outcome of choledocholithiasis surgery.

Among various expert systems (ES), Artificial Neural Network (ANN) has shown to be suitable for the diagnosis of concurrent common bile duct stones (CBDS) in patients undergoing elective cholecystectomy. However, their application in practice remains limited since the development of ANNs represents a slow process that requires additional expertize from potential users. The aim of this study was to propose an ES for automated development of ANNs and validate its performances on the problem of prediction of CBDS. Automated development of the ANN was achieved by applying the evolutionary assembling approach, which assumes optimal configuring of the ANN parameters by using Genetic algorithm. Automated selection of optimal features for the ANN training was performed using a Backward sequential feature selection algorithm. The assessment of the developed ANN included the evaluation of predictive ability and clinical utility. For these purposes, we collected data from 303 patients who underwent surgery in the period from 2008 to 2014. The results showed that the total bilirubin, alanine aminotransferase, common bile duct diameter, number of stones, size of the smallest calculus, biliary colic, acute cholecystitis and pancreatitis had the best prognostic value of CBDS. Compared to the alternative approaches, the ANN obtained by the proposed ES had better sensitivity and clinical utility, which are considered to be the most important for the particular problem. Besides the fact that it enabled the development of ANNs with better performances, the proposed ES significantly reduced the complexity of ANNs' development compared to previous studies that required manual selection of optimal features and/or ANN configuration. Therefore, it is concluded that the proposed ES represents a robust and user-friendly framework that, apart from the prediction of CBDS, could advance and simplify the application of ANNs for solving a wider range of problems.

Scoring System Development and Validation for Prediction Choledocholithiasis before Open Cholecystectomy.

INTRODUCTION: Accurate precholecystectomy detection of concurrent asymptomatic common bile duct stones (CBDS) is key in the clinical decision-making process. The standard preoperative methods used to diagnose these patients are often not accurate enough. OBJECTIVE: The aim of the study was to develop a scoring model that would predict CBDS before open cholecystectomy. METHODS: We retrospectively collected preoperative (demographic, biochemical, ultrasonographic) and intraoperative (intraoperative cholangiography) data for 313 patients at the department of General Surgery at Gornji Milanovac from 2004 to 2007. The patients were divided into a derivation (213) and a validation set (100). Univariate and multivariate regression analysis was used to determine independent predictors of CBDS. These predictors were used to develop scoring model. Various measures for the assessment of risk prediction models were determined, such as predictive ability, accuracy, the area under the receiver operating characteristic curve (AUC), calibration and clinical utility using decision curve analysis. RESULTS: In a univariate analysis, seven risk factors displayed significant correlation with CBDS. Total bilirubin, alkaline phosphatase and bile duct dilation were identified as independent predictors of choledocholithiasis. The resultant total possible score in the derivation set ranged from 7.6 to 27.9. Scoring model shows good discriminatory ability in the derivation and validation set (AUC 94.3 and 89.9%, respectively), excellent accuracy (95.5%), satisfactory calibration in the derivation set, similar Brier scores and clinical utility in decision curve analysis. CONCLUSION: Developed scoring model might successfully estimate the presence of choledocholithiasis in patients planned for elective open cholecystectomy.

Finite element analysis of uncommonly large renal arteriovenous malformation--adjacent renal cyst complex.

BACKGROUND: Renal arteriovenous malformation (RAVM) represents abnormal communication between the intrarenal arterial and venous system. The purpose of this study was to investigate hemodynamics and biomechanics quantities which may influence the instability of RAVM and imply clinical complications. METHODS: A detailed 3D reconstruction of RAVM was obtained from the patient CT scans, aortic inlet flow was measured by color-flow Doppler ultrasound, while material characteristics were adopted from the literature. A numerical finite element analysis (FEA) of the blood flow was performed by solving the governing equations for the viscous incompressible flow. The physical quantities calculated at the systolic and diastolic peak moment were velocity, pressure, shear stress and drag forces. RESULTS: We reported a case of a 50-year-old patient with a large RAVM and adjacent renal cyst, who unsuccessfully underwent two attempts of embolization that resulted in the consequent nephrectomy. FEA showed that the cyst had a very low pressure intensity and velocity field (with unstable flow in diastolic peak). For both systolic and diastolic moments, increased values of wall shear stress were found on the places with intensive wall calcification. Unusually high values of drag force which would likely explain the presence of pressure in the cystic formation were found on the infero-medial side where the cyst wall was the thinnest and where the flow streamlines converged. CONCLUSIONS: FEA showed that the hemodynamics of the cyst-RAVM complex was unstable making it prone to rupture. Clinically established diagnosis of imminent rupture together with unfavorable hemodynamics of the lesion consequently made additional attempts of embolization risky and unsuccessful leading to total nephrectomy.

Scoring system for prediction of lymph node metastasis in radical cystectomy cohort.

OBJECTIVES: The objective of the study was to assess whether pretreatment clinical parameters combined with computed tomography can improve the prediction of lymph node metastasis in patients with bladder cancer treated with radical cystectomy. PATIENTS AND METHODS: In a single-center retrospective study, demographic and clinicopathological information (initial transurethral resection [grade, stage, multiplicity of tumors, lymphovascular invasion], hydronephrosis, abdominal and pelvic computed tomography) and the presence of lymph node disease on final pathology of 183 patients with bladder cancer undergoing radical cystectomy and pelvic lymph node dissection were reviewed. Logistic regression and bootstrap methods were used to create an integer score for estimating the risk of positive lymph nodes. Various measures for predictive ability and clinical utility were determined. RESULTS: On pathological examination, 59.6% of patients had positive lymph nodes. In a multivariable analysis, status lymph nodes on computed tomography and hydronephrosis were the most strongly associated predictors. The resultant total possible score ranged from 0 to 10, with a cut-off value of >4 points. The area under the receiver operating characteristic curve was 0.806. Relative integrated discrimination improvement was 14.3%. In the decision curve analysis, the model provided net benefit throughout the entire range of threshold probabilities. However, the final model was roughly equivalent to using the clinical exam. CONCLUSIONS: The pre-cystectomy scoring system improved the prediction of lymph node status in patients with bladder cancer. Our model represented a user-friendly staging aid, but a large multi-center study should be performed before widespread implementation.

Scoring system development for prediction of extravesical bladder cancer.

BACKGROUND/AIM: Staging of bladder cancer is crucial for optimal management of the disease. However, clinical staging is not perfectly accurate. The aim of this study was to derive a simple scoring system in prediction of pathological advanced muscle-invasive bladder cancer (MIBC). METHODS: Logistic regression and bootstrap methods were used to create an integer score for estimating the risk in prediction of pathological advanced MIBC using precystectomy clinicopathological data: demographic, initial transurethral resection (TUR) [grade, stage, multiplicity of tumors, lymphovascular invasion (LVI)], hydronephrosis, abdominal and pelvic CT radiography (size of the tumor, tumor base width), and pathological stage after radical cystectomy (RC). Advanced MIBC in surgical specimen was defined as pT3-4 tumor. Receiving operating characteristic (ROC) curve quantified the area under curve (AUC) as predictive accuracy. Clinical usefulness was assessed by using decision curve analysis. RESULTS: This single-center retrospective study included 233 adult patients with BC undergoing RC at the Military Medical Academy, Belgrade. Organ confined disease was observed in 101 (43.3%) patients, and 132 (56.7%) had advanced MIBC. In multivariable analysis, 3 risk factors most strongly associated with advanced MIBC: grade of initial TUR [odds ratio (OR) = 4.7], LVI (OR = 2), and hydronephrosis (OR = 3.9). The resultant total possible score ranged from 0 to 15, with the cut-off value of > 8 points, the AUC was 0.795, showing good discriminatory ability. The model showed excellent calibration. Decision curve analysis showed a net benefit across all threshold probabilities and clinical usefulness of the model. CONCLUSION: We developed a unique scoring system which could assist in predicting advanced MIBC in patients before RC. The scoring system showed good performance characteristics and introducing of such a tool into daily clinical decision-making may lead to more appropriate integration of perioperative chemotherapy. Clinical value of this model needs to be further assessed in external validation cohorts.

Micropapillary carcinoma of the bladder presented with spontaneous intraperitoneal bladder rupture.

Spontaneous bladder perforation is a rare presenting feature of bladder malignancy. We describe an unusual case of a patient, admitted to emergency, with diffuse abdominal pain due to spontaneous bladder rupture in association with a micropapillary carcinoma. A diagnosis of an intraperitoneal bladder perforation was made during an emergency operation. Aspects of etiology, clinical presentation, diagnosis and management are described. Although cases of spontaneous carcinomatous bladder rupture are associated with high morbidity and mortality, prompt identification and treatment can lead to favourable outcomes.

Familial aggregation of bladder cancer.

UNLABELLED: Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son) and a family member related by marriage (the patient's wife). CASE REPORT: Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60), working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth--village, place of residence--village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer--carcinoma papillare transitiocellulare. CONCLUSION: The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.

Scoring system development and validation for initial treatment failure in suppurative kidney infections.

BACKGROUND: Suppurative kidney infections (SKIs) have potentially lethal implications and a high incidence of treatment-related morbidity and death. Until this point, there has been no study that has derived a prognostic model for adverse early outcomes in SKI. Therefore, our aim was to derive and validate a simple scoring system of early treatment failure in SKI. METHODS: Logistic regression and bootstrap methods were used to create an integer score for estimating the risk of early treatment failure using patient characteristics, severity of disease, bacterial etiology, type of pathology, initial antibiotic therapy, and early urologic procedures. RESULTS: This study included 92 adult patients with 104 SKIs. Early treatment failure was observed in 57 patients (54.8%). The length of the hospital stay and the treatment complications were significantly longer and more common, respectively, in patients with early treatment failure. The factors associated most strongly with early treatment outcome were whether there had been an early complete urologic procedure, the adequacy of early antibiotic therapy, and the presence or absence of sepsis syndrome. The total possible score ranged from 0 to 22 points, with a cut-off value of 5 points. A score of ≤ 5 points identified early success correctly in 85.3% of patients, whereas a score > 5 points correctly identified early failure in 93.2%. The scoring system retained its predictive ability on the validation set. CONCLUSION: A scoring system was created to predict early treatment failure for a given patient with SKI. Although the system has good performance characteristics and provides a possible intervention measure, further studies should be performed before widespread implementation.

Risk factors for treatment failure in renal suppurative infections.

There are conflicting results of published studies about prognostic value of various factors in purulent renal infections. The purpose of this study was to identify and quantify potential risk factors for early and late treatment failure in such infections. A retrospective review of 75 renal suppurative infections, at three tertiary Serbian Clinics of Urology, was conducted. We considered numerous potential risk factors in a multivariate analysis. This series was comprised of 49 women and 26 men, with mean age of 56.7 years. There were 38 and 37 patients who experienced successful and unfavorable early treatment outcome, respectively. Overall mortality rate was 9.3%. Comorbidity [odds ratio (OR) = 1.6], complex suppurative pathological findings (OR = 3.6), presence of Pseudomonas spp. (OR = 6.7), multiple bacterial strains (OR = 2.7), and positive culture itself (OR = 3.6) were the predictors of poor early prognosis. A urological intervention and presence of pyonephrosis significantly increased the chance for good initial outcome (OR = 0.32 and 0.37, respectively). In the late treatment failure analysis presence of comorbidities (OR = 5.8) and treatment complications (OR = 7.5) significantly increased chance for fatal outcome. Patients' baseline health status and complexity of suppuration itself were the most important predictors of clinical outcomes. Surgical drainage dominated over antimicrobial therapy.

Effects of exogenous glutamate and kainate on electric field-stimulated contractions of isolated human ureter.

OBJECTIVES: A neurotransmitter role for glutamate in the autonomous nervous system was recently demonstrated in the gastrointestinal tract, and its stimulatory effect on spontaneous motility of human ureter was shown. The aim of our study was to investigate the effects of glutamate on the release of neurotransmitters from intramural nerves of the human ureter. METHODS: The effects of exogenous glutamate were tested on electric field-stimulated contractions of isolated human ureter, taken from 16 adult patients after nephrectomy. The longitudinal tension and intraluminal pressure of the isolated ureter were recorded simultaneously. The electric field stimulation was done with square wave pulses (20 V through electrodes, 400 mA, duration 1 ms, frequency 16 Hz). The pulse trains lasted for 30 s, a with 30-s pause. RESULTS: Glutamate (7.9 x 10(-6) M/L to 10.6 x 10(-3) M/L) and kainic acid (6.3 x 10(-8) M/L to 2.2 x 10(-5) M/L) produced a concentration-dependent decrease in the electric field-stimulated activity of the isolated preparations. However, N-methyl-D-aspartic acid (9.1 x 10(-8) M/L to 3.1 x 10(-5) M/L), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (7.2 x 10(-8) M/L to 3.2 x 10(-6) M/L) and (+/-)-1-Aminocyclopentane-trans-1,3-dicarboxylic acid (7.7 x 10(-8) M/L to 6.5 x 10(-5) M/L) were ineffective. The electric field-stimulated contractions of isolated ureter were also inhibited by lidocaine (3.70 x 10(-4)M/L) and atropine (1.00 x 10(-6)M/L). CONCLUSIONS: The results of our study suggest that glutamate inhibits electric field-stimulated release of acetylcholine in the human ureter through activation of kainate ionotropic receptors, located on the intramural nerve fibers.