Deletion of protein tyrosine phosphatase SHP-1 restores SUMOylation of podocin and reverses the progression of diabetic kidney disease.

Both clinical and experimental data suggest that podocyte injury is involved in the onset and progression of diabetic kidney disease (DKD). Although the mechanisms underlying the development of podocyte loss are not completely understood, critical structural proteins such as podocin play a major role in podocyte survival and function. We have reported that the protein tyrosine phosphatase SHP-1 expression increased in podocytes of diabetic mice and glomeruli of patients with diabetes. However, the in vivo contribution of SHP-1 in podocytes is unknown. Conditional podocyte-specific SHP-1-deficient mice (Podo-SHP-1-/-) were generated to evaluate the impact of SHP-1 deletion at four weeks of age (early) prior to the onset of diabetes and after 20 weeks (late) of diabetes (DM; Ins2+/C96Y) on kidney function (albuminuria and glomerular filtration rate) and kidney pathology. Ablation of the SHP-1 gene specifically in podocytes prevented and even reversed the elevated albumin/creatinine ratio, glomerular filtration rate progression, mesangial cell expansion, glomerular hypertrophy, glomerular basement membrane thickening and podocyte foot process effacement induced by diabetes. Moreover, podocyte-specific deletion of SHP-1 at an early and late stage prevented diabetes-induced expression of collagen IV, fibronectin, transforming growth factor-ß, transforming protein RhoA, and serine/threonine kinase ROCK1, whereas it restored nephrin, podocin and cation channel TRPC6 expression. Mass spectrometry analysis revealed that SHP-1 reduced SUMO2 post-translational modification of podocin while podocyte-specific deletion of SHP-1 preserved slit diaphragm protein complexes in the diabetic context. Thus, our data uncovered a new role of SHP-1 in the regulation of cytoskeleton dynamics and slit diaphragm protein expression/stability, and its inhibition preserved podocyte function preventing DKD progression.

Upregulation of PACE4 in prostate cancer is not dependent on E2F transcription factors.

Recent studies in prostate cancer have identified PACE4, a proprotein convertase enzyme, as an emerging therapeutic target. Inhibition of PACE4-altCT, an oncogenic isoform of PACE4, using molecular or pharmacological approaches results in decreased cell proliferation and tumor progression in xenograft models. Although several validations have confirmed PACE4-altCT as a novel therapeutic target, the transcriptional regulation of PACE4 isoforms and mechanism of action remain a challenge. Previously, it has been reported that the human PACE4 promoter possesses potential binding sites for the E2F family of transcription factors, all of which are involved in cell cycle regulation and synthesis of DNA in mammalian cells. Therefore, we attempted to conduct in-depth evaluation of E2Fs on PACE4 and PACE4 isoform expression in prostate cancer. We conducted in vitro molecular silencing studies in various prostate cancer cell lines and determined the change in PACE4 expression levels. The results clearly show that the E2Fs alone do not alter PACE4 expression.

Apelin-13 Regulates Vasopressin-Induced Aquaporin-2 Expression and Trafficking in Kidney Collecting Duct Cells.

BACKGROUND/AIMS: Apelin and its G protein-coupled receptor APJ (gene symbol Aplnr) are strongly expressed in magnocellular vasopressinergic neurons suggesting that the apelin/APJ system plays a key role at the central level in regulating salt and water balance by counteracting the antiduretic action of vasopressin (AVP). Likewise, recent studies revealed that apelin exerts opposite effects to those of vasopressin induced on water reabsorption via a direct action on the kidney collecting duct. However, the underlying mechanisms of the peripheral action of apelin are not clearly understood. Here, we thus investigated the role of the apelin/APJ system in the regulation of water balance in the kidney, and more specifically its involvement in modulating the function of aquaporin-2 (AQP2) in the collecting duct. METHODS: Mouse cortical collecting duct cells (mpkCCD) were incubated in the presence of dDAVP and treated with or without apelin-13. Changes in AQP2 expression and localization were determined by immunoblotting and confocal immunofluorescence staining. RESULTS: Herein, we showed that the APJ was present in mpkCCD cells. Treatment of mpkCCD with apelin-13 reduced the cAMP production and antagonized the AVP-induced increase in AQP2 mRNA and protein expressions. Immunofluorescent experiments also revealed that the AVP-induced apical cell surface expression of AQP2, and notably its phosphorylated isoform AQP2-pS269, was considerably reduced following apelin-13 application to mpkCCD cells. CONCLUSION: Our data reinforce the aquaretic role of the apelin/APJ system in the fine regulation of body fluid homeostasis at the kidney level and its physiological opposite action to the antiduretic activity of AVP.

Best practices for enhancing surgical research: a perspective from the Canadian Association of Chairs of Surgical Research

Summary: The Canadian Association of Chairs of Surgical Research was created in 2014, with representation from every departmental surgical research committee across Canada, to establish Canadian surgical research as a beacon for health care innovation and to propose solutions for the daily challenges facing surgeon-researchers. Our key mandate has been to identify challenges for surgeons and scientists performing research to prevent further erosion of this vital area of activity that benefits patients, health care service providers and Canadian society. This article outlines the findings of a nationwide survey sent to all members of departments of surgery across Canada, seeking input on current threats and potential solutions. The results suggest that surgical research in Canada is experiencing a decline in funding and an increase in challenges affecting research productivity of academic surgeons, such as pressures to be clinically active, unpredictable surgical schedules, growing administrative demands, and increasing complexity of patient populations. Although surgeons are productive in their research endeavours, institutional changes and sharing of best practices are needed to ensure sustainable growth of research programs.

NLS-Cholic Acid Conjugation to IL-5Rα-Specific Antibody Improves Cellular Accumulation and In Vivo Tumor-Targeting Properties in a Bladder Cancer Model.

Receptor-mediated internalization followed by trafficking and degradation of antibody-conjugates (ACs) via the endosomal-lysosomal pathway is the major mechanism for delivering molecular payloads inside target tumor cells. Although a mainstay for delivering payloads with clinically approved ACs in cancer treatment and imaging, tumor cells are often able to decrease intracellular payload concentrations and thereby reduce the effectiveness of the desired application. Thus, increasing payload intracellular accumulation has become a focus of attention for designing next-generation ACs. We developed a composite compound (ChAcNLS) that enables ACs to escape endosome entrapment and route to the nucleus resulting in the increased intracellular accumulation as an interleukin-5 receptor α-subunit (IL-5Rα)-targeted agent for muscle invasive bladder cancer (MIBC). We constructed 64Cu-A14-ChAcNLS, 64Cu-A14-NLS, and 64Cu-A14 and evaluated their performance by employing mechanistic studies for endosome escape coupled to nuclear routing and determining whether this delivery system results in improved 64Cu cellular accumulation. ACs consisting of ∼20 ChAcNLS or NLS moieties per 64Cu-A14 were prepared in good yield, high monomer content, and maintaining high affinity for IL-5Rα. Confocal microscopy analysis demonstrated ChAcNLS mediated efficient endosome escape and nuclear localization. 64Cu-A14-ChAcNLS increased 64Cu cellular accumulation in HT-1376 and HT-B9 cells relative to 64Cu-A14 and 64Cu-A14-NLS. In addition, we tested 64Cu-A14-ChAcNLS in vivo to evaluate its tissue distribution properties and, ultimately, tumor uptake and targeting. A model of human IL-5Rα MIBC was developed by implanting NOD/SCID mice with subcutaneous HT-1376 or HT-B9MIBC tumors, which grow containing high and low IL-5Rα-positive tumor cell densities, respectively. ACs were intravenously injected, and daily blood sampling, biodistribution at 48 and 96 h, and positron emission tomography (PET) at 24 and 48 h were performed. Region of interest (ROI) analysis was also performed on reconstructed PET images. Pharmacokinetic analysis and biodistribution studies showed that 64Cu-A14-ChAcNLS had faster clearance rates from the blood and healthy organs relative to 64Cu-A14. However, 64Cu-A14-ChAcNLS maintained comparable tumor accumulation relative to 64Cu-A14. This resulted in 64Cu-A14-ChAcNLS having superior tumor/normal tissue ratios at both 48 and 96 h biodistribution time points. Visualization of AC distribution by PET and ROI analysis confirmed that 64Cu-A14-ChAcNLS had improved targeting of MIBC tumor relative to 64Cu-A14. In addition, 64Cu-A14 modified with only NLS had poor tumor targeting. This was a result of poor tumor uptake due to extremely rapid clearance. Thus, the overall findings in this model of human IL-5Rα-positive MIBC describe an endosome escape-nuclear localization cholic-acid-linked peptide that substantially enhances AC cellular accumulation and tumor targeting.

Metastatic renal cell carcinoma initially presenting with hematochezia and subsequently with vaginal bleeding: a case report.

BACKGROUND: We report an unusual case of a synchronous rectal and metachronous vaginal metastatic renal cell carcinoma. CASE PRESENTATION: A 78-year-old woman presented with hematochezia and a colonoscopy revealed a metastatic clear-cell renal cell carcinoma rectal polyp biopsy-proven. Abdominal computed tomography identified a 9.0-cm left renal mass with renal vein thrombosis, for which she underwent a laparoscopic radical nephrectomy. Histopathological examination confirmed a pT3a clear-cell renal cell carcinoma. Seven months later, the patient presented with vaginal bleeding. Physical examination revealed a vaginal polypoid mass and biopsy confirmed a clear-cell renal cell carcinoma metastasis. CONCLUSIONS: This case represents unusual manifestations of metastatic renal cell carcinoma and is a reminder of the wide spectrum of clinical course of this disease.

Open cystolithotomy for very large calculi in a Studer ileal neobladder.

Orthotopic ileal neobladder has been frequently performed as urinary diversion after cystectomy over the last decades. We report an unusual complication of very large calculi in a Studer ileal neobladder. Due to its size, open cystolithotomy was performed.

Perioperative outcomes for laparoscopic radical nephrectomies performed on ≥ 10 cm tumors.

INTRODUCTION: The role of laparoscopic radical nephrectomy (LRN) in the management of very large renal masses has yet to be determined. Moreover, no studies have considered the total size of the specimen removed. We report our experience managing renal masses ≥ 10 cm with transperitoneal LRN. MATERIALS AND METHODS: We retrospectively reviewed cases of LRN performed in the context of renal masses from 2006 to 2012 at our institution. LRNs were divided into two groups; tumors 10 cm or larger (n = 24) and tumors smaller than 10 cm (n = 124). Patient demographics, tumor characteristics, operative and perioperative outcomes were compared. Complication rate was assessed in relation to tumor and specimen size. RESULTS: Mean pathologic tumor size was 11.8 cm (range 10.0 cm-17.0 cm) and 5.8 cm (range 2.1 cm-9.5 cm) for tumors ≥ 10 cm and < 10 cm, respectively. No difference was found in demographic characteristics, operative and perioperative outcomes (estimated blood loss, rate of conversion to open radical nephrectomy, length of postoperative stay and complication rate), between both groups, except higher surgical time in the ≥ 10 cm group (171 min versus 143 min, respectively, p = 0.005). There was no difference in tumor and total specimen size between patients with and without complications. Due to its retrospective nature, the major limitation of this study is missing data regarding specimen size. CONCLUSION: LRN can be performed safely with acceptable operative and perioperative outcomes by experienced laparoscopists for very large renal masses (≥ 10 cm). Complication rates were unrelated to tumor and total specimen size.

Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

BACKGROUND: Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. METHODS: AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. RESULTS: AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. CONCLUSIONS: AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance.

Adrenal lymphangioma: a rare cystic lesion of the adrenal.

We herein report the case of a left adrenal lymphangioma in a 52-year-old asymptomatic female and review the pertinent literature relatable to this rare, benign lesion.

The Burden of Uncontrolled Cardiovascular Risk Factors in Men With Prostate Cancer: A RADICAL-PC Analysis.

Background: Cardiovascular disease (CVD) incidence is higher in men with prostate cancer (PC) than without. Objectives: We describe the rate and correlates of poor cardiovascular risk factor control among men with PC. Methods: We prospectively characterized 2,811 consecutive men (mean age 68 ± 8 years) with PC from 24 sites in Canada, Israel, Brazil, and Australia. We defined poor overall risk factor control as ≥3 of the following: suboptimal low-density lipoprotein cholesterol (>2 mmol/L if Framingham Risk Score [FRS] ≥15 and ≥3.5 mmol/L if FRS <15), current smoker, physical inactivity (<600 MET min/wk), suboptimal blood pressure (BP) (≥140/90 mm Hg if no other risk factors, systolic BP ≥120 mm Hg if known CVD or FRS ≥15, and ≥130/80 mm Hg if diabetic), and waist:hip ratio >0.9. Results: Among participants (9% with metastatic PC and 23% with pre-existing CVD), 99% had ≥1 uncontrolled cardiovascular risk factor, and 51% had poor overall risk factor control. Not taking a statin (odds ratio [OR]: 2.55; 95% CI: 2.00-3.26), physical frailty (OR: 2.37; 95% CI: 1.51-3.71), need for BP drugs (OR: 2.36; 95% CI: 1.84-3.03), and age (OR per 10-year increase: 1.34; 95% CI: 1.14-1.59) were associated with poor overall risk factor control after adjustment for education, PC characteristics, androgen deprivation therapy, depression, and Eastern Cooperative Oncology Group functional status. Conclusions: Poor control of modifiable cardiovascular risk factors is common in men with PC, highlighting the large gap in care and the need for improved interventions to optimize cardiovascular risk management in this population.

Transfer of laparoscopic radical prostatectomy skills from bench model to animal model: a prospective, single-blind, randomized, controlled study.

PURPOSE: Learning laparoscopic urethrovesical anastomosis is a crucial step in laparoscopic radical prostatectomy. Previously we noted that practice on a low fidelity urethrovesical model was more effective for trainees than basic suturing drills on a foam pad when learning laparoscopic urethrovesical anastomosis skills. We evaluated learner transfer of skills, specifically whether skills learned on the urethrovesical model would transfer to a high fidelity, live animal model. MATERIALS AND METHODS: A total of 28 senior residents, fellows and staff surgeons in urology, general surgery and gynecology were randomized to 2 hours of laparoscopic urethrovesical anastomosis training on a urethrovesical model (group 1) or to basic laparoscopic suturing and knot tying on foam pads (group 2). All participants then performed timed laparoscopic urethrovesical anastomosis on anesthetized female pigs. A blinded urologist scored subject videotaped performance using checklist, global rating scale and end product rating scores. RESULTS: Group 1 was significantly more adept than group 2 at the laparoscopic urethrovesical anastomosis pig task when measured by the checklist, global rating scale and end product rating (each p <0.05). Time to completion was similar in the 2 groups. No statistically significant difference was noted in global rating scale and checklist scores for laparoscopic urethrovesical anastomosis performed on the urethrovesical model vs the pig. CONCLUSIONS: Training on a urethrovesical model is superior to training with basic laparoscopic suturing on a foam pad for performing laparoscopic urethrovesical anastomosis skills on an anesthetized female pig. Skills learned on a urethrovesical model transfer to a high fidelity, live animal model.

An unusual case of pancreatitis revealing a metachronous renal cell carcinoma metastasis to the gallbladder.

Clear-cell renal cell carcinoma (RCC) is a common urological tumor known for its potential to metastasize. Common sites of metastasis include the lungs, lymph nodes, liver and bones but rare sites of metastasis are described. Gallbladder metastasis from RCC is very rare and occurs mostly in men. It is admitted that most cases are asymptomatic. Cholecystectomy has been performed as the treatment for solitary lesion. We describe a case of RCC metastasis diagnosed after lithiasic pancreatitis in a 68-year-old male. To our knowledge, this is the first case of a metachronous RCC metastasis to the gallbladder presenting concurrently with lithiasic pancreatitis.

Transperitoneal laparoscopic radical nephrectomy after multiple previous abdominal surgeries and intraperitoneal hyperthermic chemotherapy: a case report.

Laparoscopic indications are still growing due to the acquisition and development of new skills and expertise in the laparoscopic field. We report the first case of a successful transperitoneal right radical nephrectomy after intraperitoneal hyperthermic chemotherapy in a 56-year-old female who previously underwent multiple abdominal surgeries for appendicular adenocarcinoma with pseudomyxoma peritonei. In patients with multiples previous abdominal surgeries and intraperitoneal chemotherapy, transperitoneal laparoscopic surgeries are feasible in experienced hands. However, patient safety is paramount and conversion to open surgery should always be considered in case of complications.

PACE4-altCT isoform of proprotein convertase PACE4 as tissue and plasmatic biomarker for prostate cancer.

The proprotein convertase PACE4 has demonstrated value as a viable therapeutic target in prostate cancer (PCa). A novel isoform named PACE4-altCT, which arises in neoplastic lesions, plays an important role in tumor progression and has been validated as a pharmacological target. With the discovery of its overexpression in PCa and the alternative splicing of its pre-RNA to generate an oncogenic C-terminally modified isoform named PACE4-altCT, understanding and validating its value as a potential biomarker is of great interest either from prognostic or targeted therapy intervention. Expression of ERG in LNCaP cells was used to investigate the relationship between ERG expression occurring in PCa cells and PACE4-altCT expression by Western blot and qPCR. Using immunohistochemistry, the expression levels of PACE4 isoforms in patient tissues were investigated and correlated with ERG tumor status and Gleason score. An ELISA method was developed using affinity purified recombinant protein and used for quantitative analysis of plasma concentrations of PACE4-altCT and used for correlation. In contrast with the consensual isoform, PACE4-altCT was only strongly overexpressed in prostate cancer patients, correlated with ERG expression levels. Despite its intracellular retention PACE4-altCT could be detected in the plasma of most patients with prostate cancer, whereas it was only found at low levels in normal patients whereas total plasmatic PACE4 levels did not vary significantly between groups. Our study demonstrates that PACE4-altCT is strongly overexpressed in prostate cancer using both immunohistochemical and ELISA techniques and may have some interesting potential as a biomarker.

Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with Diabetes.

Background: Diabetic kidney disease (DKD) remains the leading cause of end stage kidney disease worldwide. Despite significant advances in kidney care, there is a need to improve noninvasive techniques to predict the progression of kidney disease better for patients with diabetes. After injury, podocytes are shed in urine and may be used as a biologic tool. We previously reported that SHP-1 is upregulated in the kidney of diabetic mice, leading to podocyte dysfunction and loss. Our objective was to evaluate the expression levels of SHP-1 in urinary podocytes and kidney tissues of patients with diabetes. Methods: In this prospective study, patients with and without diabetes were recruited for the quantification of SHP-1 in kidney tissues, urinary podocytes, and peripheral blood monocytes. Immunochemistry and mass spectrometry techniques were applied for kidney tissues. Urinary podocytes were counted, and expression of SHP-1 and podocyte markers were measured by quantitative PCR. Results: A total of 66 participants (diabetic n=48, nondiabetic n=18) were included in the analyses. Diabetes was associated with increased SHP-1 expression in kidney tissues (P=0.03). Nephrin and podocin mRNA was not significantly increased in urinary podocytes from patients with diabetes compared with those without diabetes, whereas levels of SHP-1 mRNA expression significantly correlated with HbA1c and estimated glomerular filtration rate (eGFR). Additionally, follow-up (up to 2 years post recruitment) evaluation indicated that SHP-1 mRNA expression continued to increase with eGFR decline. Conclusions: Levels of SHP-1 in urinary podocytes may serve as an additional marker of glomerular disease progression in this population.

Fatal fast-growing renal cell carcinoma during pregnancy.

BACKGROUND: Renal cell carcinoma (RCC) during pregnancy is rare. Volume doubling time for RCC is estimated to be 72 weeks. CASE: A 28-year-old woman was assessed for macroscopic hematuria at 21 weeks' gestation. A renal ultrasound revealed a 3.4 cm right renal mass. After MRI, the most likely diagnosis seemed to be angiomyolipoma. The patient opted for conservative management, and the pregnancy continued to almost 36 weeks, at which time the mass had tripled in size. Laparoscopic nephrectomy was performed four days after delivery, and pathological examination revealed a 9.3 cm renal cell carcinoma. Three months later, multiple metastases were identified, which were resistant to targeted therapies. The patient died 12 months postpartum. CONCLUSION: Although renal tumours during pregnancy have been reported, this is the first report of a fatal fast-growing renal tumour.

Inhibition of DHCR24/seladin-1 impairs cellular homeostasis in prostate cancer.

BACKGROUND: Seladin-1 belongs to a subgroup of androgen-dependent genes associated with anti-proliferative, pro-differentiation, and pro-apoptotic functions and plays a protective role against oncogenic stress. The present study aims to investigate the localization and expression of Seladin-1 protein in normal and tumoral human prostatic tissues as well as to explore its role in proliferation and steroid secretion in androgen-dependent (LnCaP) and androgen-independent (DU145) cell lines and in human prostate primary cell culture. METHODS: Seladin-1 protein localization and expression were assessed on whole tissue sections by tissue array/immunohistochemistry and following immunofluorescence and Western blotting. Proliferation (Ki67 fluorescence labeling and cell counts) and steroid secretion (ELISA) were assessed in cell lines and primary epithelial cell cultures. RESULTS: In human prostatic tissue and cells, Seladin-1 was mostly localized within epithelial and rarely within stromal cells and primarily present in secretory luminal cells of normal and tumoral prostate cells. Its expression was increased in low-risk prostate cancer but reduced in advanced prostate cancers when compared to normal tissues. Seladin-1 was highly expressed in LnCaP, whereas its expression level was lower in DU145 cells. Seladin-1 inhibition by treatment with its specific inhibitor, U18666A (75 nM), increased proliferation in LnCaP and primary cell culture, as well as testosterone and dihydrotestosterone levels in both LnCaP and DU145 cell lines. CONCLUSIONS: Seladin-1 involvement in proliferation and secretion suggests that its downregulation may be a major mechanism causing prostate cancer evolution. Seladin-1 may thus potentially decrease cell growth and steroid dependency in low-grade prostate cancer.

Long-term anatomical and functional results of laparoscopic promontofixation for pelvic organ prolapse.

OBJECTIVE: To assess the long-term anatomical and functional outcomes of laparoscopic promontofixation (LP) for pelvic organ prolapse (POP), and the long-term safety of LP, as POP is a common problem in women of all ages, with treatment including vaginal, abdominal, laparoscopic or robot-assisted surgical approaches. PATIENTS AND METHODS: This was a retrospective study of the first consecutive 186 women who underwent LP for POP, with or without stress urinary incontinence (SUI), from January 1998 to December 2002 in one centre. Those patients with concurrent SUI had LP with a Burch colposuspension or tension-free vaginal tape (TVT). The recurrence rate of POP was evaluated by physical examination at follow-up visits and by the patients, using a postal, unvalidated self-applied questionnaire (SAQ). Patients' urinary, sexual and digestive functions, overall satisfaction about surgery and quality of life, were evaluated with SAQ. RESULTS: All 186 patients had LP, with concomitant Burch (25) or TVT (100) procedures. The median (interquartile range) follow-up was 60 (48-71) months. In all, 71% of the patients attended their follow-up visits and the success rate was 92.4%. Eight patients were re-operated because of recurrent POP. The SAQ response rate was 95%; 91.1% and 79.8% of responders were satisfied or very satisfied after their surgery, and with their quality of life, respectively; women were unsatisfied or very unsatisfied because of recurrence of POP (seven), urinary symptoms (five) or constipation (two). Patients complained of recurrent POP (10.8%), persistent or recurrent UI (27.3% of the women treated with Burch and 21.1% with TVT), and transient constipation (20%). Over half of the women (50.6%) were not sexually active and 5.4% developed dyspareunia. The long-term complication rate was 6%; there were five vaginal mesh erosions. CONCLUSION: POP treated with LP offers excellent long-term results with low recurrence and morbidity rates, and a good quality of life.