The BET-inhibitor PFI-1 diminishes AR/AR-V7 signaling in prostate cancer cells.

OBJECTIVE: The bromodomain and extra-terminal (BET) family of proteins provides a scaffolding platform for the recruitment and tethering of transcription factors to acetylated chromatin, thereby modulating gene expression. In this study, we evaluated the efficacy of the BET-inhibitor PFI-1 to diminish AR/AR-V7 signaling and proliferation in castration-resistant prostate cancer cells. METHODS: Prostate-specific antigen and androgen receptor (AR) protein were quantified by means of two commercial ELISAs. Transactivation of the AR, AR-V7 and Q641X was determined by reporter gene assays. Cell proliferation was measured using a colorimetric MTT-assay. RESULTS: PFI-1 dose-dependently inhibited transactivation of full-length AR (non- mutated, i.e., wild-type or point-mutated/promiscuous forms) without affecting their cellular protein levels. Moreover, PFI-1 was active against C-terminally truncated constitutively active ARs like AR-V7 and Q641X. Prostate cancer cells exhibiting a transcriptionally active AR-signaling complex (LNCaP, 22Rv1) were more susceptible to the growth-inhibitory effects than the AR-negative PC-3 cells. CONCLUSION: The quinazolinone PFI-1 is a highly efficient inhibitor of AR-signaling-competent prostate cancer cells in vitro. PFI-1 could serve as a lead compound for the development of new therapeutics able to block AR/AR-V7 signaling in advanced prostate cancer.

C-terminally truncated constitutively active androgen receptor variants and their biologic and clinical significance in castration-resistant prostate cancer.

A mechanism allowing castration resistant prostate cancer cells to escape the effects of conventional anti-hormonal treatments is the synthesis of constitutively active, C-terminally truncated androgen receptor (AR)-variants. Lacking the entire or vast parts of the ligand binding domain, the intended target of traditional endocrine therapies, these AR-variants (termed ARΔLBD) are insensitive to all traditional treatments including second generation compounds like abiraterone, enzalutamide or ARN-509. Although ARΔLBD are predominantly products of alternative splicing, they can also be products of nonsense mutations or proteolytic cleavage. In this review, we will discuss the etiology and function of c-terminally truncated AR-variants and their clinical significance as markers/targets for the treatment of castration resistant prostate cancer.

Androgen deprivation therapy with Leuprolide acetate for treatment of advanced prostate cancer.

INTRODUCTION: Hormone sensitive advanced prostate cancer (PCa) is an incurable disease that is treated with a variety of hormonal therapies targeting the androgen/androgen receptor signaling axis. For decades androgen deprivation therapy (ADT) by surgical or chemical castration is the gold standard for the treatment of advanced PCa. Areas covered: This review discusses the pharmacological features of Leuprolide, a luteinizing hormone-releasing hormone (LHRH) agonists/analog and the most commonly used drug in ADT. Expert opinion: Although Leuprolide has been on the market for more than 30 years it is still the leading option for ADT and serves as a basis for most multimodal therapy concepts. The fact that with the onset of castration-resistance in late stage metastatic disease, a prolongation of ADT in combination with a second line hormonal manipulation is recommended supports the importance of the compound for daily clinical practice.

Laparoscopic vs open partial nephrectomy for T1 renal tumours: evaluation of long-term oncological and functional outcomes in 340 patients.

OBJECTIVE: To evaluate the long-term oncological and functional outcomes of laparoscopic partial nephrectomy (LPN) compared with open partial nephrectomy (OPN) for pT1 renal tumours. PATIENTS AND METHODS: In this retrospective single-centre study, 340 consecutive patients underwent LPN and OPN for localized, incidentally discovered, renal masses of <7 cm (cT1). The patients were matched for age, sex, body mass index, American Society of Anesthesiology score, tumour side (right or left kidney) and tumour characteristics (RENAL nephrometry score). Demographic data, peri- and postoperative variables, including operating time, estimated blood loss, complications, hospital stay, renal function, histological tumour staging and grading, and metastasis rates were collected and analysed. RESULTS: The median (SEM) operating time for LPN and OPN was 145.3 (45.4) min and 155.2 (35.6) min, respectively (P = 0.07). The median (SEM) warm ischaemia time was 11.7 (2.2) min in the LPN and 14.4 (1.9) min in the OPN group (P = 0.03). The median (SEM) RENAL nephrometry scores for LPN and OPN were 5.9 (1.6) and 6.1 (0.3), respectively (P = 0.11). During follow-up, the biochemical markers of glomerular filtration were completely normalized, showing the absence of renal injury and there was no significant difference in glomerular filtration rate between the groups, with median (SEM) rates of 79.8 (3.0) mL/min/1.72 m(2) for the LPN and 80.2 (2.7) mL/min/1.72 m(2) for the OPN group at 5-year follow-up. The 5-year overall survival and cancer-specific survival rates, calculated using the Kaplan-Meier method, were 94% and 91% in the LPN group, and 92% and 88% in the OPN group. CONCLUSION: LPN and OPN provide similar long-term oncological outcomes in the therapy of T1 renal cancer. With regard to renal function, no damage to the kidney was found after LPN and OPN, with a complete normalization of renal function at the 5-year follow-up in both groups.

Early results of a European multicentre experience with a new self-anchoring adjustable transobturator system for treatment of stress urinary incontinence in men.

OBJECTIVE: To report our experience with a new self-anchoring adjustable transobturator male system (ATOMS®; AMI, Vienna, Austria) for the treatment of stress urinary incontinence (SUI) in men. PATIENTS AND METHODS: A total of 99 men, in a number of centres, were treated for SUI with the new ATOMS® device. The device was implanted in all patients using an outside-in technique by passing the obturator foramen and anchoring the device to the inferior pubic ramus. The titanium port was placed s.c. on the left symphysis region. Adjustments were performed via port access. Postoperative evaluation consisted of physical examination, 24-h pad test, and 24 h-pad count. Preoperatively and at 6-month follow-up, patients completed a validated quality-of-life questionnaire. Two-way ANOVA was used to analyse changes over time. Within-group effects for time were tested using post hoc Dunnett's contrasts of baseline values vs subsequent measurements. RESULTS: The most common indication was SUI after radical prostatectomy (92.9%). Failure of previous surgeries was present in 34.3% patients and 31.3% patients had undergone secondary radiation. The mean (SD; range) surgery time was 47 (13.8; 29-112) min. Temporary urinary retention occurred in two patients (2%) and transient perineal/scrotal dysaesthesia or pain was reported by 68 patients (68.7%) and resolved after 3-4 weeks of non-opioid analgesics. There were four (4%) cases of wound infection at the site of the titanium port leading to explantation. No urethral or bladder injuries related to the device or erosions occurred. The mean (SD; range) number of adjustments to reach the desired result (dryness, improvement and/or patient satisfaction) was 3.8 (1.3; 1-6). After a mean (SD; range) follow-up time of 17.8 (1.6; 12-33) months, the overall success rate was 92% and the mean pad use decreased from 7.1 to 1.3 pads/24 h (P < 0.001). Overall, 63% were considered dry and 29% were improved. CONCLUSION: Treatment of male SUI with this self-anchored adjustable system is safe and effective.

The adipocyte-derived hormone leptin has proliferative actions on androgen-resistant prostate cancer cells linking obesity to advanced stages of prostate cancer.

Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK) signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 µM) was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin's proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

Laparoendoscopic single-site and conventional laparoscopic radical nephrectomy result in equivalent surgical trauma: preliminary results of a single-centre retrospective controlled study.

BACKGROUND: Laparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the morbidity and scarring associated with surgical intervention, and it has been proposed to result in less induced surgical trauma than conventional laparoscopy. OBJECTIVE: Investigate the surgical trauma after LESS radical nephrectomy (LESS-RN) and laparoscopic radical nephrectomy (LRN). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective single-centre study including 66 patients: 31 patients underwent LESS-RN and 35 historical control patients who had undergone LRN. LRNs were performed between April 2008 and May 2009; LESS-RNs were performed between May 2009 and February 2011. INTERVENTION: LESS-RN and LRN were both performed via a transperitoneal access. Blood samples were collected pre- and intraoperatively at 6, 24, and 48h, and at 5 d postoperatively. MEASUREMENTS: Serum concentrations of acute-phase markers, C-reactive protein (CRP), serum amyloid A (SAA) antibody, and interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured at each time point by enzyme-linked immunosorbent assay. Clinical data were collected by reviewing the patient's records. RESULTS AND LIMITATIONS: There were no differences in serum CRP and SAA levels between the groups (CRP: p=0.12; SAA: p=0.09) at all time points. The changes in IL-6 levels in the LRN group were statistically significantly higher compared with the LESS-RN group at 6h after surgery (p=0.02), whereas the LESS-RN group showed statistically significantly higher IL-6 levels than the LRN group at 24h after surgery (p=0.02). Also, the serum levels of the anti-inflammatory cytokine IL-10 showed different kinetics in each group, being higher in the LESS-RN during the early postoperative phase (at 6h: p=0.01) and higher in the LRN group at 48h after surgery (p=0.01). The limitations of this study were its nonrandomized character and the small cohort of patients. CONCLUSIONS: LESS-RN is as effective as LRN without compromising surgical and postoperative outcomes, but it does not add any significant advantage in comparison with traditional LRN in terms of systemic stress response and surgical trauma.

Laparoendoscopic single-site radical nephrectomy for renal cancer: technique and surgical outcomes.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery has been developed in attempt to further reduce the morbidity and scarring associated with surgical intervention. OBJECTIVE: To describe the technique and report the surgical outcomes of LESS radical nephrectomy (RN) in the treatment of renal cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: LESS-RN was performed in 33 patients with renal tumours. The indications to perform a LESS-RN were represented by renal tumours not greater than T2 and without evidence of lymphadenopathy or renal vein involvement. SURGICAL PROCEDURE: The Endocone (Karl Storz, Tuttlingen, Germany) was inserted through a transumbilical incision. A combination of standard laparoscopic instruments and bent grasper and scissors was used. The sequence of steps of LESS-RN was comparable to standard laparoscopic RN. MEASUREMENTS: Demographic data and perioperative and postoperative variables were recorded and analysed. RESULTS AND LIMITATIONS: The mean operative time was 143.7±24.3 min, with a mean estimated blood loss of 122.3±34.1 ml and a mean hospital stay of 3.8±0.8 d. The mean length of skin incision was 4.1±0.6 cm and all patients were discharged from hospital with minimal discomfort, as demonstrated by their pain assessment scores (visual analogue scale: 1.9±0.8). The definitive pathologic results revealed a renal cell carcinoma in all cases and a stage distribution of four T1a, 27 T1b, and 2 T2 tumours. All patients were very satisfied with the appearance of the scars, and at a median follow-up period of 13.2±3.9 mo, all patients were alive without evidence of tumour recurrence or port-site metastasis. CONCLUSIONS: LESS is a safe and feasible surgical procedure for RN in the treatment of renal cell carcinoma and has excellent cosmetic results.

Is intensive multimodality therapy the best treatment for fournier gangrene? Evaluation of clinical outcome and survival rate of 41 patients.

BACKGROUND: To evaluate the effect of surgical wound debridement, antibiotics, and hyperbaric oxygen (HBO) in the treatment of Fournier gangrene (FG). METHODS: Forty-one patients with a mean age of 54.3±14.6 years were referred to our department with a diagnosis of FG. To calculate a Fourier Gangrene Severity Index (FGSI), nine factors were assessed (temperature; heart rate; ventilatory rate; serum sodium, potassium, creatinine, and bicarbonate concentrations; hematocrit; and leukocyte count). After clinical stabilization, extensive debridement of the necrotic tissue was performed, and a surgical vacuum-assisted closure (V.A.C.®) device was applied. Hyperbaric oxygen was administered; medical therapy consisted of intravenous antibiotics, electrolyte replacement, and parenteral nutrition. RESULTS: Intraoperative cultures revealed Escherichia coli in 27 patients (66%), Pseudomonas aeruginosa in 28 (68%), gram-positive cocci in 24 (59%), and mixed flora (aerobic and anaerobic bacteria) in 39 (95%). One month after primary debridement, wound granulation was sufficient for plastic surgical reconstruction in all patients. CONCLUSION: Because of the rapid worsening of FG, early diagnosis and immediate, aggressive multi-modality therapy with surgical debridement and broad-spectrum empiric antibiotics is crucial. The utility of HBO remains unproved.

Laparoscopic adrenalectomy in urological centres - the experience of the German Laparoscopic Working Group.

OBJECTIVE: To evaluate the safety and feasibility of laparoscopic adrenalectomy (LA) performed in several German centres with different laparoscopic experience, as LA has become the gold-standard approach for benign surgical adrenal disorders; however, for solitary metastasis or primary adrenal cancer its precise role is uncertain. PATIENTS AND METHODS: The data of 363 patients who underwent a LA were prospectively collected in 23 centres. All centres were stratified into three groups according to their experience: group A (<10 LAs/year), group B (10-20 LAs/year) and group C (>20 LAs/year). In all, 15 centres used a transperitoneal approach, four a retroperitoneal approach and four both approaches. Demographic data, perioperative and postoperative variables, including operating time, surgical approach, tumour size, estimated blood loss, complications, hospital stay and histological tumour staging, were collected and analysed. RESULTS: The transperitoneal approach was used in 281 cases (77.4%) and the retroperitoneal approach was used in 82 patients (22.6%). In all, 263 of 363 lesions (72.5%) were benign and 100 (27.5%) were malignant. The mean (sd) operating time was 127.22 (55.56) min and 130.16 (49.88) min after transperitoneal and retroperitoneal LA, respectively. The mean complication rates for transperitoneal and retroperitoneal LA were 5% and 10.9%, respectively. CONCLUSION: LAs performed by urologists experienced in laparoscopy is safe for the removal of benign and malignant adrenal masses. LA for malignant adrenal tumours should be performed only in high-volume centres by a surgeon performing at least >10 LAs/year.

Single-portal access laparoscopic radical nephrectomy for renal cell carcinoma in transplant patients: the first experience.

We present the details of the first three single-portal access laparoscopic radical nephrectomies (S-Portal-RN) performed in patients with a malignant renal tumour that developed after a renal transplant. The mean operative time was 171.6 ± 37.5 min, with a mean blood loss of 126.6 ± 25.1 ml. A single small skin incision (5 cm) was performed to remove the kidney. No significant difference in glomerular filtration rate was observed postoperatively. The postoperative recovery was uneventful with favourable short-term outcomes and high patient satisfaction at the 2-mo follow-up. We believe that S-Portal-RN for renal cancer after a renal transplant can be performed without increased risks for the patients or for the transplanted kidney.

Bilateral vs unilateral laparoscopic intrafascial nerve-sparing radical prostatectomy: evaluation of surgical and functional outcomes in 457 patients.

UNLABELLED: Study Type - Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? Bilateral nerve-sparing radical prostatectomy still represents an issue for urologists as the indications to perform it depend oft from the personal clinical experience. Moreover, until now data concerning bilateral and unilateral laparoscopic nerve-sparing radical prostatectomy have been limited. This study states that bilateral laparoscopic intrafascial nerve-sparing technique results in superior functional outcomes when compared with unilateral nsLRP and it suggests to prefer a bilateral nerve-sparing technique in younger patients with low-risk, organ-confined prostate cancer. OBJECTIVE: To evaluate the surgical and functional outcomes in bilateral and unilateral nerve-sparing laparoscopic radical prostatectomy (nsLRP). PATIENTS AND METHODS: Between January 2005 and May 2009, 457 nsLRP were performed at our clinic. In all, 250 patients underwent a bilateral nsLRP and 207 patients underwent an unilateral nsLRP. One surgeon performed all the operations. All patients presented at biopsy a localized prostate cancer. Demographic data and perioperative and postoperative measurements and outcomes were compared. RESULTS: The operative times for bilateral nsLRP and unilateral nsLRP were 165 ± 45 min and 130 ± 25 min, respectively. The mean intra-operative blood loss was 450 ± 300 mL and 270 ± 160 mL in the bilateral and unilateral nsLRP groups with a transfusion rate of 3% and 1%, respectively (P = 0.013). Conversion to open surgery was never deemed necessary. Postoperatively, the mean Gleason Score after nsLRP and distribution of tumour stages was similar in the two groups, and the frequency of positive margins in both groups did not present any statistically significant difference. At 12 months, a complete continence was reported in 97% of patients who underwent a bilateral nsLRP and in 88% of patients of the unilateral nsLRP group. At that time, 69% in the bilateral nsLRP and 43% in the unilateral nsLRP groups reported the ability to engage in sexual intercourse. CONCLUSION: The bilateral laparoscopic intrafascial nerve-sparing technique results in superior functional outcomes with regard to urinary continence and sexual potency, when compared with unilateral nsLRP, reporting similar oncological outcomes.

Right-sided transperitoneal hand-assisted laparoscopic donor nephrectomy: is there an issue with the renal vessels?

OBJECTIVE: Short right renal vessels might complicate kidney transplantation, thus causing traction and difficulties during anastomosis. Single-center prospective comparison of right- and left-sided transperitoneal hand-assisted laparoscopic donor nephrectomy (HALDN) is presented. PATIENTS AND METHODS: Eighty-two living kidney donors underwent HALDN between 2003 and 2008. Right-sided HALDN was performed in 46 living kidney donors. The operative technique of right-sided HALDN was modified to obtain the maximum length of right renal vessels. Outcome data in donors including quality of life as well as graft outcome in recipients were prospectively collected. RESULTS: All procedures were laparoscopically completed with no conversion. Mean operative time was 127 minutes (vs. 138 minutes in left HALDN, p = 0.08). The mean warm ischemia time was 41 seconds (vs. 39 seconds in left HALDN, p = 0.23). There was no renal artery or vein thrombosis in any of the grafts. Mean blood loss was 81 mL (vs. 92 mL in left HALDN, p = 0.09). Hospital discharge was on an average of 3.6 days postoperative. Delayed graft function occurred in two recipients: one in the left group and the other in the right group. One-year graft survival rate was 95% in the left group versus 96.9% in the right group (p = 0.08). Further, no statistically significant difference in serum levels of creatinine was seen between the groups 1 year after the transplantation. CONCLUSIONS: Right HALDN is technically safe and feasible and results in convenient extension of right renal vessels to full length with no increased incidence of vascular thrombosis.

Adipocytokine: a new family of inflammatory and immunologic markers of invasiveness in major urologic surgery.

BACKGROUND: Laparoscopic surgery has been proposed to reduce surgical trauma and diminish patients' stress response. OBJECTIVE: To investigate the role of the adipocytokine, in combination with changes in other known inflammatory markers, in patients undergoing radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: A total of 580 patients were enrolled in this prospective study. Laparoscopic extraperitoneal radical prostatectomy (LRP) was performed in 286 patients, and open retropubic radical prostatectomy (RRP) in 294 patients. INTERVENTION: Blood samples were collected preoperatively and up to 5 d postoperatively. MEASUREMENTS: Serum concentrations of acute phase markers, interleukins (IL), and the adipocytokine leptin were measured at each time point by means of enzyme-linked immunosorbent assay. Clinical data were collected and analysed. RESULTS AND LIMITATIONS: Patients undergoing LRP had significantly lower IL-6 and adipocytokine levels at all measurement time points. However, biphasic kinetics of adipocytokine serum levels were observed during the postoperative course in all patients. LRP was associated with less adipocytokine and IL-6 release, indicating a smaller degree of surgical insult and the minimal invasive nature of this procedure. The limitation of this study was its nonrandomised design. CONCLUSIONS: Adipocytokines might serve as additional immunologic markers of invasiveness in major urologic surgery.

Pelvic organ prolapse management in female kidney transplant recipients.

PURPOSE: Pelvic organ prolapse in female postmenopausal kidney transplant recipients may be complicated by adverse events affecting graft function. We describe our experience with pelvic reconstructive surgery in renal transplant recipients. MATERIALS AND METHODS: Pelvic reconstructive surgery was done in 16 female renal transplant recipients with pelvic organ prolapse with or without stress urinary incontinence. Intraoperative and postoperative data were recorded prospectively, including medical and surgical history, pelvic organ prolapse quantification measurement, 24-hour pad count, quality of life measurements and graft outcome. Patients were followed up to 12 months. RESULTS: Mean +/- SD age at surgery was 58.3 +/- 7.7 years (range 50 to 66). Mean time to renal transplantation was 54.2 +/- 15.1 months (range 38 to 123). A total of 12 anterior and 4 combined anterior/posterior colporrhaphies were done. A concomitant suburethral single incision transobturator sling procedure was performed in 8 women. We noted no bladder or rectal injury, bleeding necessitating transfusion or infection. Pelvic floor testing at 12-month followup showed stage I vaginal wall prolapse in only 4 patients (25%). No patient had evidence of de novo incontinence, synthetic sling infection, erosion or rejection. All women reported improved quality of life on the SF-36 questionnaire. Renal graft function remained stable in all patients. CONCLUSIONS: Pelvic reconstructive surgery is feasible for pelvic organ prolapse in patients with a kidney allograft on immunosuppression. However, concern about impaired graft function, infection and wound healing remains important.

Management of localized prostate cancer by retropubic radical prostatectomy in patients after renal transplantation.

BACKGROUND: The study aimed to report our experience with retropubic radical prostatectomy (RRP) for treatment of localized prostate cancer in renal transplant recipients (RTR). METHODS: Data of 16 RTR who had an RRP between 2001 and 2007 were retrospectively analysed and compared to the data of 294 non-transplanted patients who were operated for RRP during the same period. Diagnostic work-up consisted of digital rectal examination, serum prostate specific antigene levels, as well as Transrectal Ultrasonography (TRUS)-guided prostate biopsy. Follow-up was obtained in all patients with a mean follow-up time of 2.1 years in RTR. RESULTS: Mean time distance to the renal transplantation at the time of RRP was 81.2 ± 19.1 months. RRP was successfully performed and tolerated in all RTR without pelvic lymph node dissection. No major complications occurred during or after the operation. There were two minor complications in transplant group (prolonged haematuria and urinary leakage). Mean operative time was 108.3 ± 3.9 min in transplant group, which was significantly longer as in non-transplanted group (89.1 ± 4.1, P < 0.05). Mean estimated intra-operative blood loss was significantly lower in transplant group (P < 0.05). In RTR, one case of positive surgical margins was present (R(1): 6.2 vs. 12.3% in non-transplanted group, P < 0.05). None of the RTR had impairment of graft function. At follow-up, no case of biochemical recurrence was observed in RTR. CONCLUSIONS: RRP is safe and feasible for management of localized prostate cancer in patients with kidney allograft being under immunosuppression. However, concern about impairment of graft function, infection and wound healing remains important.

Laparoscopic living-donor nephrectomy: analysis of the existing literature.

CONTEXT: Laparoscopic living-donor nephrectomy (LLDN) has achieved a permanent place in renal transplantation and in some centers has replaced open donor nephrectomy as the standard technique. OBJECTIVE: To evaluate the published literature regarding the relative results and complications of open LLDN and the hybrid technique of hand-assisted LLDN. EVIDENCE ACQUISITION: A systematic review of the literature was performed, searching PubMed and Web of Science. A "free text" protocol using the term living-donor nephrectomy was applied. Six hundred twenty-nine records were retrieved from the PubMed database and 686 records were retrieved from the Web of Science database. EVIDENCE SYNTHESIS: Fifty-seven comparative studies were identified in the literature search. The three techniques of open, laparoscopic, and hand-assisted laparoscopic donor nephrectomy were compared in terms of reported outcomes. With regard to the perioperative outcome parameters, laparoscopy was better than open surgery in terms of blood loss, analgesic requirements, and duration of hospital stay and convalescence. Postoperative graft function was not significantly different between the different forms of donor nephrectomy, although longer warm ischemia times are reported for laparoscopy. CONCLUSIONS: All three techniques of live-donor nephrectomy are standard of care. The laparoscopic techniques result in less postoperative pain and estimated blood loss with shorter hospital stay, while postoperative graft function is not inferior to that after open live-donor nephrectomy.

Apical leptin induces chloride secretion by intestinal epithelial cells and in a rat model of acute chemotherapy-induced colitis.

The purpose of this study was to investigate whether luminal leptin alters ion transport properties of the intestinal epithelium under acute inflammatory conditions. Monolayers of human intestinal T(84) epithelial cells and a rat model of chemotherapy-induced enterocolitis were used. Cells were treated with leptin and mounted in Ussing chambers to measure basal and secretagogue-induced changes in transepithelial short-circuit current (I(sc)). Furthermore, the role of MAPK and phosphatidylinositol 3-kinase (PI3K) signaling pathways in mediating responses to leptin was investigated. Acute colitis in Sprague-Dawley rats was induced by intraperitoneal injection of 40 mg/kg methotrexate. Leptin (100 ng/ml) induced a time-dependent increase in basal I(sc) in T(84) intestinal epithelial cells (P < 0.01). Moreover, pretreatment of T(84) cells with leptin for up to 1 h significantly potentiated carbachol- and forskolin-induced increases in I(sc). Pretreatment with an inhibitor of MAPK abolished the effect of leptin on basal, carbachol- and forskolin-induced chloride secretion (P < 0.05). However, the PI3K inhibitor, wortmannin, only blunted the effect of leptin on forskolin-induced increases in I(sc). Furthermore, leptin treatment evoked both ERK1/2 and Akt1 phosphorylation in T(84) cells. In the rat model, luminal leptin induced significant increases in I(sc) across segments of proximal and, to a lesser extent, distal colon (P < 0.05). We conclude that luminal leptin is likely an intestinal chloride secretagogue, particularly when present at elevated concentrations and/or in the setting of inflammation. Our findings may provide a mechanistic explanation, at least in part, for the clinical condition of secretory diarrhea both in hyperleptinemic obese patients and in patients with chemotherapy-induced intestinal inflammation.

Laparoscopic vs open retropubic intrafascial nerve-sparing radical prostatectomy: surgical and functional outcomes in 300 patients.

OBJECTIVE: To evaluate the surgical and functional outcomes in nerve-sparing laparoscopic radical prostatectomy (nsLRP) and retropubic nsRP (nsRRP). PATIENTS AND METHODS: Between January 2005 and November 2007, 150 nsLRP and 150 nsRRP were performed at our clinic. Demographic data, variables before and after surgery, and outcomes, were compared. RESULTS: The operative duration was 165 min for nsLRP and 120 min for nsRRP. Although the nsLRP group had a lower frequency of positive margins, the difference was not statistically significant. At 1 year after surgery, complete continence was reported in 97% of patients who had nsLRP and in 91% who had nsRRP (P= 0.03). At that time, 66% of patients in the nsLRP and 51% in the nsRRP group reported being able to engage in sexual intercourse (P < 0.05). There were no statistical differences in surgical trauma in both groups. CONCLUSION: Our study showed that nsLRP performed by expert surgeons results in better functional outcomes for continence and potency than for nsRRP. There was no significant difference between the surgical techniques in surgical trauma.