Vasopressin lowers renal epoxyeicosatrienoic acid levels by activating soluble epoxide hydrolase

Activation of the thick ascending limb (TAL) Na+-K+-2Cl--cotransporter (NKCC2) by the antidiuretic hormone arginine-vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5ng/h, 3d) significantly lowered renal EET levels (-56 +/- 3% for 5,6-EET, -50 +/- 3.4% for 11,12-EET, and -60 +/- 3.7% for 14,15-EET). The abundance of the principal EET-degrading enzyme soluble epoxide hydrolase (sEH) was increased at the mRNA (+160 +/- 37%) and protein levels (+120 +/- 26%). Immunohistochemistry revealed dDAVP-mediated induction of sEH in connecting tubules and cortical and medullary collecting ducts, suggesting a role of these segments in the regulation of local interstitial EET signals. Incubation of murine kidney cell suspensions with 1 {mu}M 14,15-EET for 30 min reduced phosphorylation of NKCC2 at the AVP-sensitive threonine residues T96 and T101 (-66 +/-5%; p<0.05) while 14,15-DHET had no effect. Concomitantly, isolated perfused cTAL pretreated with 14,15-EET showed a 30% lower transport current under high and a 70% lower transport current under low symetric chloride concentrations. In sum, we have shown that activation of AVP signaling stimulates renal sEH biosynthesis and enzyme activity. The resulting reduction of EET tissue levels may be instrumental for increased NKCC2 transport activity during AVP-induced antidiuresis

Effects of robotic-assisted laparoscopic prostatectomy on surgical pathology specimens

Background Robotic-assisted laparoscopic prostatectomy (RALP) has greatly changed clinical management of prostate cancer. It is important for pathologists and urologists to compare RALP with conventional open radical retropubic prostatectomy (RRP), and evaluate their effects on surgical pathology specimens. Methods We retrospectively reviewed and statistically analyzed 262 consecutive RALP (n = 182) and RRP (n = 80) procedures performed in our institution from 2007 to 2010. From these, 49 RALP and 33 RRP cases were randomly selected for additional microscopic examination to analyze the degree of capsular incision and the amount of residual prostate surface adipose tissue. Results Positive surgical margins were present in 28.6% RALP and 57.5% RRP cases, a statistically significant difference. In patients with stage T2c tumors, which represent 61.2% RALP and 63.8% RRP patients, the positive surgical margin rate was 24.1% in the RALP group and 58.8% in the RRP group (statistically significant difference). For other pathologic stages, the differences in positive margins between RALP and RRP groups were not statistically significant. The incidence of positive surgical margins after RALP was related to higher tumor stage, higher Gleason score, higher tumor volume and lower prostate weight, but was not related to the surgeons performing the procedure. When compared with RRP, RALP also caused less severe prostatic capsular incision and maintained larger amounts of residual surface adipose tissue in prostatectomy specimens. Conclusions In this study RALP showed a statistically significant lower positive surgical margin rate than RRP. Analysis of capsular incision and amount of prostatic surface residual adipose tissue suggested that RALP caused less prostatic capsular damage than RRP

Living with prostate cancer: randomised controlled trial of a multimodal supportive care intervention for men with prostate cancer

Background: Prostate cancer is the most common male cancer in developed countries and diagnosis and treatment carries with it substantial morbidity and related unmet supportive care needs. These difficulties may be amplified by physical inactivity and obesity. We propose to apply a multimodal intervention approach that targets both unmet supportive care needs and physical activity.Methods/design: A two arm randomised controlled trial will compare usual care to a multimodal supportive care intervention &ldquo;Living with Prostate Cancer&rdquo; that will combine self-management with tele-based group peer support. A series of previously validated and reliable self-report measures will be administered to men at four time points: baseline/recruitment (when men are approximately 3-6 months post-diagnosis) and at 3, 6, and 12 months after recruitment and intervention commencement. Social constraints, social support, self-efficacy, group cohesion and therapeutic alliance will be included as potential moderators/mediators of intervention effect. Primary outcomes are unmet supportive care needs and physical activity levels. Secondary outcomes are domain-specific and healthrelated quality of life (QoL); psychological distress; benefit finding; body mass index and waist circumference. Disease variables (e.g. cancer grade, stage) will be assessed through medical and cancer registry records. An economic evaluation will be conducted alongside the randomised trial.Discussion: This study will address a critical but as yet unanswered research question: to identify a populationbased way to reduce unmet supportive care needs; promote regular physical activity; and improve disease-specific and health-related QoL for prostate cancer survivors. The study will also determine the cost-effectiveness of the intervention.<br /

Propensity Score Vergleich der verschiedenen radikalen Operationstechniken beim high risk Prostatakarzinom

ZusammenfassungAbstractEinleitung:Die Behandlung von Patienten mit einemhigh riskProstatakarzinom (PCa) bleibt hinsichtlich der Wahl des geeigneten operative Verfahrens der radikalen Prostatektomie (RP) kontrovers: offene retropubisch RP (RRP), laparoskopisch RP (LRP) oder Roboter-assistiert (RARP). Ziel dieser Arbeit war es, den Einfluss der unterschiedlichen Techniken auf das histopathologische Ergebnis sowie auf die biochemischen Rezidivraten zu untersuchen.Patienten und Methoden:Insgesamt wurden 805 Patienten mit einemhigh riskPCa (PSA >20 ng/mL, Gleason Score ≥8, oder klinisches Stadium ≥cT2c) identifiziert. Der Vergleich von 407 RRP Patienten mit 398 Fällen, die minimal invasiv operiert wurden (LRP+RARP) ergab deutliche Störgrößen. Dementsprechend wurden alle 110 RARP Fälle mit dem Propensity Score (PS) 1:1 gegen LRP und RRP Fälle gematched. Der PS beinhaltete Alter, klinisches Tumorstadium, präoperativer PSA, Gleason Score der Biopsie, die Erfahrung des Operateurs sowie die Anwendung einer nerverhaltenden Operationstechnik. Die Patientencharakteristika wurden mit geeigneten Testverfahren verglichen. Vergleich von Gesamtüberleben (OS) und Rezidiv-freiem Überleben (RFS) mit dem log rank Test. Die RFS Prädiktoranalyse erfolgte mithilfe von Cox Regressionsmodellen.Ergebnisse:Innerhalb der post-matching Kohorte von 330 Patienten lag der Anteil an Patienten mit einem pathologischen Gleason Score  7 bei 1,8, 55,5 und 42,7% für RARP, 8,2, 36,4, 55,5% für LRP sowie 0, 60,9 und 39,1% für RRP (p=0,004 für RARP vs. LRP und p=0,398 für RARP vs. RRP). Unterschiede bei den histopathologischen Stadien waren statistisch nicht signifikant. Die Gesamtrate an positiven Schnitträndern (PSM) sowie die PSM Rate für ≥pT3 waren nicht unterschiedlich. PSM bei pT2 betrug 15,7, 14,0 und 20,0% für RARP, LRP und RRP (statistisch nicht signifikant). Das mittlere 3-Jahres RFS lag bei jeweils 41,4, 77,9, 54,1% (p<0,0001 für RARP vs. LRP und p=0,686 für RARP vs. RRP). Das mittlere 3-Jahres OS wurde jeweils mit 95,4, 98,1 und 100% berechnet (statistisch nicht unterschiedlich).Schlussfolgerung:RARP kann beihigh riskPCa Patienten mit der LRP und RRP vergleichbaren pathologischen sowie onkologischen Ergebnissen angewendet werden

Risk prediction models for biochemical recurrence after radical prostatectomy using prostate-specific antigen and Gleason score

Many computer models for predicting the risk of prostate cancer have been developed including for prediction of biochemical recurrence (BCR). However, models for individual BCR free probability at individual time-points after a BCR free period are rare. Follow-up data from 1656 patients who underwent laparoscopic radical prostatectomy (LRP) were used to develop an artificial neural network (ANN) to predict BCR and to compare it with a logistic regression (LR) model using clinical and pathologic parameters, prostate-specific antigen (PSA), margin status (R0/1), pathological stage (pT), and Gleason Score (GS). For individual BCR prediction at any given time after operation, additional ANN, and LR models were calculated every 6 months for up to 7.5 years of follow-up. The areas under the receiver operating characteristic (ROC) curve (AUC) for the ANN (0.754) and LR models (0.755) calculated immediately following LRP, were larger than that for GS (AUC: 0.715; P = 0.0015 and 0.001), pT or PSA (AUC: 0.619; P always <0.0001) alone. The GS predicted the BCR better than PSA (P = 0.0001), but there was no difference between the ANN and LR models (P = 0.39). Our ANN and LR models predicted individual BCR risk from radical prostatectomy for up to 10 years postoperative. ANN and LR models equally and significantly improved the prediction of BCR compared with PSA and GS alone. When the GS and ANN output values are combined, a more accurate BCR prediction is possible, especially in high-risk patients with GS ≥7