Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

PURPOSE: Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. RESULTS: The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. CONCLUSIONS: Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information.

Reliability and validity of endoluminal sonography in a porcine model of ureteropelvic junction obstruction.

PURPOSE: The objective of this study was to evaluate the usefulness and reliability of endoluminal ultrasonography in ureteropelvic junction (UPJ) obstruction and to describe the changes in sonographic appearance that take place during obstruction and after treatment. MATERIALS AND METHODS: Twelve large healthy white female pigs were randomly divided into two groups: Group 1 (laparoscopic pyeloplasty) and group 2 (cutting balloon endopyelotomy). Percutaneous and endoluminal ultrasonographic and fluoroscopic studies were analyzed during the three phases of the study. The first phase included premodel documentation of a normal urinary tract and laparoscopic UPJ obstruction. During the second phase 6 weeks later, diagnosis and endourologic treatment were performed. Fifteen weeks after obstruction management, follow-up imaging studies and postmortem evaluation of all animals were performed. RESULTS: At the end of the study, group 1 had a lesser degree of fibrosis in the muscle-adventitia layers and periureteral repercussion, as well as a better peristaltic recovery. The animal study shows a positive correlation among the results of the pathologic and the endoluminal ultrasonographic studies in UPJ obstruction. CONCLUSIONS: Endoluminal ultrasonography provides excellent information regarding ureteral and periureteral anatomy. Among the two techniques evaluated in the study, laparoscopic pyeloplasty caused the lesser reaction at the reconstructed area. Fibrous replacement at the muscle-adventitia layers and periureteral area may be useful as indicators of the better therapeutic technique as well as for the assessment of post-therapeutic ureteral evolution and recurrences.

Endourologic techniques for ureteropelvic junction obstruction therapy. Comparative animal study.

PURPOSE: The aim of this work is to compare 3 endourologic techniques for treating a ureteropelvic junction (UPJ) obstruction. To accomplish this, we performed a study in a porcine animal specimen, in which we compared laparoscopic pyeloplasty that emerges as the future gold standard technique, with 2 endopyelotomy techniques. MATERIAL AND METHODS: Twenty-four healthy large white female pigs were randomly divided in 3 groups-group I (laparoscopic pyeloplasty), group II (endopyelotomy-Acucise, Applied Medical, Rancho Margarita, CA), and group III (endoballoon rupture endopyelotomy). Percutaneous and endoluminal ultrasonographic and fluoroscopic studies were analyzed during the different phases of the study. The study was divided in 3 phases. First one included premodel documentation of normal urinary tract and laparoscopic UPJ obstruction induction. During second phase at 6 weeks later, diagnosis and endourologic treatment were carried out. Fifteen weeks after obstruction treatment, follow-up imaging studies and postmortem evaluation of all animals were performed. RESULTS: After the sonographic and fluoroscopic assessment, we determined the percentage of success rate for each technique-with an 87.5% for groups I and II and 75% for group III. Significant statistical differences were found between the 2 pyelotomy groups and the pyeloplasty group regarding the duration of the intervention. Significant statistical differences are evident in the evolution of the UPJ's diameter between groups I and III. CONCLUSIONS: Laparoscopic pyeloplasty is the technique that produces fewer side effects in the reconstructed area, as well as a wider dilation of the UPJ. Nevertheless, as we show in this study, we found similar results between endopyelotomy in selected patients than pyeloplasty, and it is simpler and less invasive than the latter.

Evaluation of the duration of ureteral stenting following endopyelotomy: Animal study.

BACKGROUND: The purpose of the present paper was to evaluate whether it is possible to reduce the duration of ureteral stenting following endopyelotomy, and thus reduce side-effects. METHODS: Seventeen pigs were used. They were distributed at random into three groups. The study was divided as follows: phase I included baseline study of the urinary system and the creation of a ureteropelvic junction obstruction (UPJO) model. Phase II, 1 month later, consisted of diagnosing UPJO, Acucise endopyelotomy of the same, and the placement of a ureteral stent. Ureteral stents were left in situ for 1 week in group I, for 3 weeks in group II and 6 weeks in group III. Phase III, 3 months after treatment, consisted of follow up and post-mortem studies of the animals. The following procedures were carried out during each phase: ureteropelvic junction (UPJ) diameter measurement, ultrasound percutaneous and endoluminal studies, urine culture and determination of blood urea and creatinine levels. RESULTS: On removal of the stent, the presence of urinoma was observed in two animals in group I. There were statistically significant differences between group I and III with regard to evolution of the internal diameter of the UPJ. However, the least severe histological lesion at the UPJ level was found in group II. CONCLUSIONS: Ureteral stent placement for 1 week is insufficient in order to assure correct healing and evolution of the UPJ following endopyelotomy. Stenting for 3 weeks is effective, and it is not necessary to extend stenting time to 6 weeks. Endoluminal ultrasound is of great use in determining the effects of endourological techniques in the ureter and the retroperitoneal space. It is also useful for deciding which therapeutic technique to use, and for inserting the Acucise in order to prevent iatrogenic problems.