Phospholipase A2 expression in prostate cancer as a biomarker of good prognosis: A comprehensive study in patients with long follow-up.

BACKGROUND: Phospholipase A2 (PLA2) is a large family of enzymes involved in the inflammatory process that catalyzes the hydrolysis of membrane phospholipids, leading to the production of free fatty acids and lysophospholipids, starting the arachidonic acid cascade. Their expression has been related to the behavior of several cancers. Our objective is to search for PLA2 expression in prostate cancer (PCa) tissue that correlates with prognosis and survival. METHODS: Using qRT-PCR, we analyzed the expression levels of PLA2G1B, PLA2G2A, PLA2G2D, PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F, PLA2G6, PLA2G7, PLA2G16, PNPLA1, and PNPLA2 in PCa tissue from 108 patients submitted to radical prostatectomy, followed by a mean time of 163 months. RESULTS: All PLA2 was overexpressed in PCa compared to normal tissue. Interestingly, higher expression of some PLA2 was related to favorable prognostic factors: lower levels of PSA (PLA2G2A, PLA2G4D), lower rates of lymph node metastasis (PLA2G16 and PLA2G1B), and organ-confined disease (PLA2G4A). Most importantly, PLAG4B was independently related to longer disease-free survival. CONCLUSION: This is the first study exploring comprehensively the expression levels of PLA2 in PCa, showing that the higher expression of some PLA2 should be used as biomarkers of good prognosis and longer disease-free survival.

Tranexamic acid in patients with complex stones undergoing percutaneous nephrolithotomy: a randomised, double-blinded, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and safety of single-dose tranexamic acid on the blood transfusion rate and outcomes of patients with complex kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: In a randomised, double-blinded, placebo-controlled trial, 192 patients with complex kidney stone (Guy's Stone Scores III-IV) were prospectively enrolled and randomised (1:1 ratio) to receive either one dose of tranexamic acid (1 g) or a placebo at the time of anaesthetic induction for PCNL. The primary outcome measure was the occurrence rate of perioperative blood transfusion. The secondary outcome measures included blood loss, operative time, stone-free rate (SFR), and complications. ClinicalTrials.gov identifier: NCT02966236. RESULTS: The overall risk of receiving a blood transfusion was reduced in the tranexamic acid group (2.2% vs 10.4%; relative risk, 0.21, 95% confidence interval [CI] 0.03-0.76, P = 0.033; number-needed-to-treat: 12). Patients randomised to the tranexamic acid group had a higher immediate and 3-month SFR compared with those in the placebo group (29% vs 14.7%, odds ratio [OR] 2.37, 95% CI 1.15-4.87, P = 0.019, and 46.2% vs 28.1%, OR 2.20, 95% CI 1.20-4.02, P = 0.011, respectively). Faster haemoglobin recovery occurred in patients in the tranexamic acid group (mean, 21.3 days; P = 0.001). No statistical differences were found in operative time and complications between groups. CONCLUSIONS: Tranexamic acid administration is safe and reduces the need for blood transfusion by five-times in patients with complex kidney stones undergoing PCNL. Moreover, tranexamic acid may contribute to better stone clearance rate and faster haemoglobin recovery without increasing complications. A single dose of tranexamic acid at the time of anaesthetic induction could be considered standard clinical practice for patients with complex kidney stones undergoing PCNL.

Androgen deprivation therapy improves the in vitro capacity of high-density lipoprotein (HDL) to receive cholesterol and other lipids in patients with prostate carcinoma.

BACKGROUND: Androgen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters. METHODS: Sixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted. RESULTS: ADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55µg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged. CONCLUSION: Increase in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Postoperative Renal Function in Patients Undergoing Unilateral Nephrectomy: Development of a Prediction Model Using Preoperative Risk Factors and 51Cr-EDTA Clearance.

Objectives: To analyze the preoperative variables associated to the postoperative glomerular filtration rate (GFR) outcomes after nephrectomy for benign and malignant conditions, measured by the reference isotopic technique 51Cr-ethylene diamine tetra-acetic (51Cr-EDTA) and to create a model to predict the short-term postoperative GFR. Secondary aim was to evaluate which of the common equations for GFR estimation (Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) has the best correlation with the 51Cr-EDTA. Methods: Patients undergoing unilateral nephrectomy from 2014 to 2018 were selected. Pre- and postoperative variables were prospectively collected. Univariate and multivariate analyses were done to identify independent risk factors associated with renal function outcomes and to create a model to predict the postoperative GFR. Correlation analyses were performed to evaluate the performance of various serum creatinine-based equations for GFR estimation compared with 51Cr-EDTA. Results: In total, 107 patients were evaluated. After univariate and multivariate analyses, older age (p = 0.008), higher split function of the operated kidney on dimercaptosuccinic acid (DMSA) scintigraphy (p < 0.001), and lower preoperative 51Cr-EDTA (p < 0.001) were independent risk factors for higher GFR decline. Correlation analyses showed that GFR estimated by CKD-EPI equation had the best concordance to GFR measured by 51Cr-EDTA. Conclusions: Based on our findings age, DMSA and lower preoperative 51Cr-EDTA are predictors of postoperative renal function after unilateral nephrectomy. For the assessment of estimated GFR, CKD-EPI equation appears to have the best concordance with 51Cr-EDTA.

Endoscopic guided PCNL in the prone split-leg position versus supine PCNL: a comparative analysis stratified by Guy's stone score.

INTRODUCTION: The optimal patient positioning for percutaneous nephrolithotomy (PCNL) based on the complexity of stone burden is not yet defined. Thus, we aimed to evaluate the intraoperative parameters, effectiveness and complications of patients undergoing PCNL between the endoscopic-guided prone split-leg PCNL (ePSL) and the supine PCNL by stratifying patients according to Guy's stone score (GSS). MATERIALS AND METHODS: A retrospective chart review was conducted of patients undergoing PCNL at two high-volume tertiary referral centers. At one center, patients underwent PCNL using the ePSL technique, while at the second center, patients underwent PCNL in supine. Patient demographics and stone characteristics, operative details, complications and effectiveness were compared between groups. The impact of obesity was also investigated. RESULTS: Of 830 subjects, a total of 449 (54%) underwent PCNL in ePSL and 381 (46%) in supine. The ePSL group had a greater mean age and body mass index. No statistical differences were found in gender, serum chemistry and Charlson comorbidity index. After stratifying patients by GSS, the differences in baseline stone burden between PSL and supine lost significance and both groups could be compared. Complications were not statistically different between both groups. Univariate analysis demonstrated that multiple tracts and lower pole access were more prevalent in supine. In addition, for GSS1-3, ePSL was correlated with reduced operative time, radiation exposure, length of hospital stay and need for secondary procedure. Multivariate analysis correlated ePSL with lower radiation exposure and need for secondary procedures (p = 0.01). In comparison to the whole trial population, the same tendencies were appreciated for obese cohort. CONCLUSIONS: This is the first report focusing on the performance differences between ePSL and supine PCNL stratified by GSS. Both techniques are safe, with a low rate of complications. For GSS1-3, ePSL reduces radiation exposure and requires less need for both multiple access and secondary procedure.

The role of therapy with aminoglycoside in the outcomes of kidney transplant recipients infected with polymyxin- and carbapenem-resistant Enterobacteriaceae.

Kidney transplant recipients are at risk for infections due to carbapenem-resistant Enterobacteriaceae (CRE). Polymyxin-resistant CRE (PR-CRE) infections are especially difficult to treat. The aim of this study was to characterize PR-CRE infections among kidney transplant recipients and identify risk factors for treatment failure. This retrospective cohort study involved all kidney transplant recipients with PR-CRE infection between 2013 and 2017 at our center. Minimal inhibitory concentrations for polymyxin B were determined by broth microdilution. Carbapenem-resistant genes (blaKPC, blaNDM, and blaOXA-48), aminoglycoside-resistance genes, and polymyxin-resistant gene mcr-1 were identified by polymerase chain reaction. All but one of the 47PR-CRE infections identified were due to Klebsiella pneumoniae. The most common type of infection (in 54.3%) was urinary tract infection (UTI). Monotherapy was used in 10 cases. Combined treatment regimens included double-carbapenem therapy in 19 cases, oral fosfomycin in 19, and amikacin in 13. Treatment failure occurred in 21 cases (45.7%). Clinical success was achieved 78.9% of patients who used aminoglycosides versus 37.0% of those who not used this drug (p = 0.007). Multivariate analysis showed diabetes mellitus to be a risk factor for treatment failure; amikacin use and UTI were found to be protective. Nine strains were RmtB producers. Although aminoglycosides constitute an important therapeutic option for PR-CRE infection, the emergence of aminoglycoside resistance could have a major impact on the management of CRE infection.

Low-intensity shockwave therapy for erectile dysfunction in kidney transplant recipients. A prospective, randomized, double blinded, sham-controlled study with evaluation by penile Doppler ultrasonography.

OBJECTIVES: To study the efficacy of Low intensity Extracorporeal Shockwave Therapy (Li- ESWT) for the treatment of erectile dysfunction (ED) in kidney transplanted men. METHODS: Twenty men (mean age = 53.7 years) were selected. This was a double-blinded, prospective, randomized, sham-controlled trial. The ESWT protocol was based in a 2 treatment sessions per week for 3 weeks. The sham treatment was performed using the same device replacing the effective probe for one that emits zero energy. Baseline and follow-up assessment was performed with International Index of Erectile Function Questionnaire (IIEF) score and Erection Hardness Score (EHS) after 1, 4 and 12 months. Penile Doppler was performed before and after treatment. RESULTS: A total of 20 patients were recruited, 10 patients in each group. Baseline scores were similar. The mean EHS in after 1 month were 2.5 ± 0.85 (Li-EWST) and 2.4 ± 0.7 (Sham therapy), p = 0.724 . After 4 months it was 2.4 ± 0.7 and 2.6 ± 0.84, p = 0,0004 (between the moments) . The baseline IIEF score was 14.9 ± 3(Sham Theraphy) and 10.9 ± 5.1 (Li-EWST). The mean IIEF score after 1 month was 15.6 ± 6.1 (Li-EWST) and 16.6 ± 5.4 (Sham therapy). The mean IIEF score after 4 months was 17.2 ± 5.7 (Li-EWST) and 16.5 ± 5 (Sham therapy), p < 0.0001 (between the moments). IIEF score improvement was higher than 5 in 70% (ranged from 0-10) and in 10% (ranged from 1-14) in Li-ESWT and Sham groups, respectively. The mean change in IIEF score after 12 months was 4.8 in Li-ESWT group .Penile Doppler parameters were similar between groups and did not present improvements. CONCLUSIONS: Li-ESWT is a treatment with clinical efficacy. Despite evidences suggesting neoagiogenesis, our short protocol had no impact in penile Doppler parameters.

Does the urinary tract infection caused by carbapenem-resistant Gram-negative bacilli impact the outcome of kidney transplant recipients?

The incidence of urinary tract infection (UTI) after kidney transplantation (KT) caused by multidrug-resistant (MDR) bacteria is growing. The aim of this study was to analyze the impact of UTI caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) in the survival of graft and recipients following KT. This was a retrospective cohort study involving patients who underwent KT between 2013 and 2016. Patients were followed since the day of the KT until loss of graft, death or end of the follow-up period (31th December 2016). The outcomes measured were UTI by MDR following KT and graft and patient survival. Analyses were performed using Cox regression; for the graft and patient survival analysis, we used a propensity score for UTI by CR-GNB to matching a control group. UTI was diagnosed in 178 (23.9%) of 781 patients, who developed 352 UTI episodes. 44.6% of the UTI cases were caused by MDR bacteria. Identified risk factors for UTI by MDR bacteria were DM, urologic disease as the cause of end-stage renal failure, insertion of ureteral stent, carbapenem use, and delayed graft function (DGF). Risk factors for death during the follow-up period were female gender, patients over 60 years old at the time of KT, DM, body mass index over 31.8, UTI caused by CR-GNB. In conclusion, UTIs caused by CR-GNB have great impact on patients' survival after KT.

In Vitro Evaluation of Single-Use Digital Flexible Ureteroscopes: A Practical Comparison for a Patient-Centered Approach.

OBJECTIVE: To compare the manufacturing and in vitro performance characteristics of two single-use flexible ureteroscopes with a permanent optical flexible ureteroscope. MATERIALS AND METHODS: Two single-use flexible ureteroscopes, LithoVue (Boston Scientific) and Pusen (1rs. generation; Zhuhai Pusen Medical Technology Company Limited, China), were tested and compared with a permanent Flex-X2 ureteroscope (Karl Storz, Germany) in terms of technical characteristics, optics, deflection mechanism, and additional parameters which could potentially affect surgical technique. RESULTS: Pusen was the lightest ureteroscope while the LithoVue had the longest working length. LithoVue had a higher resolution power than the other two ureteroscopes at all distances tested (p < 0.001). Pusen showed higher resolution than Flex-X2 (p < 0.01). Field of view was wider for LithoVue (87°), followed by Flex-X2 (85°) and Pusen (75°). Color representation was superior for Flex-X2 than LithoVue and then Pusen. LithoVue outperformed Pusen and Flex-X2 for all settings with instruments in terms of deflection loss (p < 0.01). Pusen had the highest irrigation flow (52 mL/min) with an empty working channel (p < 0.01). LithoVue and Pusen showed similar flow rates with a 200 µm (21 mL/min) and 365 µm laser fiber (7 mL/min) and 1.3F basket (18 mL/min), being superior to Flex-X2 (p < 0.01). With the 1.9F basket, LithoVue had superior flow rate (7 mL/min) than Pusen (3.5 mL/min) and Flex-X2 (4 mL/min; p = 0.01). CONCLUSION: LithoVue outperformed the other ureteroscopes in terms of optical resolution, field of view, deflection capacity, and irrigation flow with larger instruments. Pusen is the lighter scope and showed better results in terms of irrigation when no instruments are in place. Flex-X2 was superior in terms of color representation.

The Moreau Strain of Bacillus Calmette-Guerin (BCG) for High-Risk Non-Muscle Invasive Bladder Cancer: An Alternative during Worldwide BCG Shortage?

BACKGROUND: Bacillus Calmette-Guerin (BCG) is the standard of care for adjuvant intravesical instillation therapy for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection. Increasing evidence suggests that there are marked differences in outcomes according to BCG substrains. BCG-Moreau was recently introduced to the European market to cover the issue of BCG shortage, but there are little data regarding the oncologic efficacy. METHODS: We retrospectively analyzed 295 consecutive patients, who received adjuvant intravesical instillation therapy with BCG-Moreau for intermediate- and high-risk NMIBC between October 2007 and April 2013 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease. RESULTS: Median age was 66 years (interquartile range 59-74, mean 65.9 years). According to the EAU risk group, 76 patients presented with intermediate-risk and 219 patients with high-risk NMIBC. The 5-year recurrence-free survival and progression-free survival rate was 64.8% (95% CI 52.8-74.4) and 81.4% (95% CI 65.2-90.2), respectively. CONCLUSIONS: BCG-Moreau is an effective substrain for adjuvant instillation therapies of NMIBC, and outcomes appear to be comparable to series using other substrains. During worldwide shortage of BCG-TICE, Connaught and RIVM, BCG-Moreau may serve as an equally effective alternative.

Revascularization of living-donor kidney transplant with multiple arteries: long-term outcomes using the inferior epigastric artery.

OBJECTIVE: To study the safety and long-term outcomes of use of the inferior epigastric artery (IEA) for revascularization of small accessory kidney arteries (3 mm or less). MATERIALS AND METHODS: Data of 602 living-donor kidney transplants were reviewed. Age was 37.4 ± 15 years (range, 3-78 years). Multiple arteries were present in 98 kidneys (16.3%); of these, 83 (84.7%) had 2 and arteries and 15 (15.3%) had 3 arteries. In 21 kidneys (21.4%) with multiple arteries (group I [GI]), the IEA was used for reconstruction. Four (14.3%) had 3 arteries, and 17 (85.7%) had 2 arteries. In 77 patients (group II [GII]), the inferior accessory renal artery was reconstructed with a side-to-side or an end-to-side anastomosis to the main renal artery. Follow-up was 43.8 ± 38.1 months (range, 1-124 months). The Fisher exact test and the 2-tailed t test were used for statistical analysis. RESULTS: Delayed graft function occurred in 1 GI patient (4.8%) and in 5 GII patients (6.5%; P >.05). One partial renal infarction occurred in each group (4.8% vs 1.3%; P >.05). There was 1 urinary fistula in GI and 3 urinary fistulas and 1 ureteral stenosis in GII (P >.05). One graft (4.8%) lost function in GI and 5 (6.5%) in GII (P >.05). Eleven patients (53.4%) were hypertensive in GI and 53 (68.8%) in GII (P >.05). CONCLUSION: The use of the IEA for revascularization of a living-donor kidney transplant with multiple arteries is safe and effective, yielding similar long-term outcomes compared with the standard technique. Use of the IEA avoids the risks of manipulation of the main renal artery.

Urothelial carcinoma transmission via kidney transplantation.

Transmission of urothelial carcinoma via solid organ transplant has never been reported in the literature to our knowledge. We report a case of transmission of this tumour to a kidney recipient. The donor was a 37-year-old woman, victim of a subarachnoid haemorrhage. The recipient was a 21-year-old girl, with a history of chronic kidney disease secondary to neurogenic bladder. This fatality has been rarely described in literature, but never with this histological type of cancer. Nowadays, with the expanded criteria for donation, older people are accepted as donor because of the shortage of organs. However, this may increase the likelihood of the number of cancer transmission.

Surgical complications after renal transplantation in grafts with multiple arteries.

INTRODUCTION: Renal transplantation with multiple arteries appears, in literature, associated to a major index of surgical complications. This study compared the surgical complications and short-term outcome renal transplants with multiple arteries and single artery grafts. MATERIALS AND METHODS: The data of 64 renal transplants with multiple arteries performed between January 1995 and December 1999 were compared to the ones of 292 transplants with single renal artery. The aspects analyzed were number of arteries of the graft, donor type, vascular reconstruction technique, the occurrence of surgical complications, the incidence of delayed graft function, graft function 1 month after transplantation, graft loss and the patients' deaths. RESULTS: The incidence of surgical complications in grafts with multiple arteries and single renal artery was respectively: vascular--3.1% and 3.1%; urological--6.3% and 2.7% and other surgical complications--15.6% and 10.6%, respectively. The incidence of lymphoceles was 3.1% in grafts with a single artery and 12.5% in grafts with more than 1 artery (p = 0.0015). The incidence of delayed graft function in grafts with multiple arteries and with a single renal artery was respectively 35.1 and 29.1% (p = 0.295). Mean serum creatinine at the 30th postoperative day was 2.46 and 1.81 in grafts with multiple and with 1 artery, respectively (p = 0.271). CONCLUSIONS: Kidney transplantation using grafts with single and multiple arteries present similar indexes of surgical complications and short-term outcome; lymphoceles were more frequent among grafts with multiple arteries.

Surgical complications after renal transplantation in grafts with multiple arteries

INTRODUCTION: Renal transplantation with multiple arteries appears, in literature, associated to a major index of surgical complications. This study compared the surgical complications and short-term outcome renal transplants with multiple arteries and single artery grafts. MATERIALS AND METHODS: The data of 64 renal transplants with multiple arteries performed between January 1995 and December 1999 were compared to the ones of 292 transplants with single renal artery. The aspects analyzed were number of arteries of the graft, donor type, vascular reconstruction technique, the occurrence of surgical complications, the incidence of delayed graft function, graft function 1 month after transplantation, graft loss and the patients' deaths. RESULTS: The incidence of surgical complications in grafts with multiple arteries and single renal artery was respectively: vascular - 3.1 percent and 3.1 percent; urological - 6.3 percent and 2.7 percent and other surgical complications - 15.6 percent and 10.6 percent, respectively. The incidence of lymphoceles was 3.1 percent in grafts with a single artery and 12.5 percent in grafts with more than 1 artery (p = 0.0015). The incidence of delayed graft function in grafts with multiple arteries and with a single renal artery was respectively 35.1 and 29.1 percent (p = 0.295). Mean serum creatinine at the 30th postoperative day was 2.46 and 1.81 in grafts with multiple and with 1 artery, respectively (p=0.271). CONCLUSIONS: Kidney transplantation using grafts with single and multiple arteries present similar indexes of surgical complications and short-term outcome; lymphoceles were more frequent among grafts with multiple arteries.