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BONE ANCHORED SLING FOR THE TREATMENT OF POST-PROSTATECTOMY INCONTINENCE

PURPOSE This ongoing study evaluates the safety and efficacy of a new minimally invasive sling procedure for treating post-prostatectomy incontinence. MATERIALS AND METHODS A total of 16 men 56 to 74 years old (mean age 67) underwent the procedure using the Straight-In bone anchoring system. Time after prostatectomy was 1.5 to 5 years (mean 2.5). Of the 16 patients 14 had urodynamically confirmed stress urinary incontinence, while 2 had mixed incontinence with stress incontinence and detrusor instability. The procedure is performed with the patient in the lithotomy position using a perineal approach. Four miniature bone screws with pre-attached pairs of No. 1 polypropylene sutures are placed directly into the medial aspect of the inferior rami of the pubic bone. A pair of bone anchors is placed just below the symphysis on each side, and the second pair is inserted 3 to 4 cm. lower. To support the bulbar urethra a gelatin coated polyethylene terephthalate trapezoid shaped sling or cadaveric fascia lata is tied to the pubic bone using the 4 pairs of sutures attached to the bone anchors. Urethral resistance is increased to 30 to 50 cm. water above baseline pressure. RESULTS Followup was 4 to 20 months (mean 12.2). Of the 14 men with the preoperative urodynamic diagnosis of genuine stress incontinence 12 were cured of incontinence, defined as subjectively dry with no or only 1 pad used daily for security without any episode of leakage, while 2 were improved subjectively with a decrease of 50% or more in pads daily. Two other patients with the preoperative diagnosis of mixed urinary incontinence were improved. Postoperatively urodynamic study in these patients revealed resolved stress incontinence but persistent urge urinary incontinence. They responded to anticholinergics and are completely dry. Intraoperative and postoperative complications were minimal with no erosion, infection or osseous complications. CONCLUSIONS This new minimally invasive male sling procedure is safe and efficacious. Adjusting sling tension by measuring urethral resistance results in a low rate of over correction and failure. Further experience is needed to establish this procedure as treatment for post-prostatectomy incontinence.

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1.

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.

Heparanase: A Potential New Factor Involved in the Renal Epithelial Mesenchymal Transition (EMT) Induced by Ischemia/Reperfusion (I/R) Injury

Background Ischemia/reperfusion (I/R) is an important cause of acute renal failure and delayed graft function, and it may induce chronic renal damage by activating epithelial to mesenchymal transition (EMT) of renal tubular cells. Heparanase (HPSE), an endoglycosidase that regulates FGF-2 and TGFβ-induced EMT, may have an important role. Therefore, aim of this study was to evaluate its role in the I/R-induced renal pro-fibrotic machinery by employing in vitro and in vivo models. Methods Wild type (WT) and HPSE-silenced renal tubular cells were subjected to hypoxia and reoxygenation in the presence or absence of SST0001, an inhibitor of HPSE. In vivo, I/R injury was induced by bilateral clamping of renal arteries for 30 min in transgenic mice over-expressing HPSE (HPA-tg) and in their WT littermates. Mice were sacrificed 48 and 72 h after I/R. Gene and protein EMT markers (α-SMA, VIM and FN) were evaluated by bio-molecular and histological methodologies. Results In vitro: hypoxia/reoxygenation (H/R) significantly increased the expression of EMT-markers in WT, but not in HPSE-silenced tubular cells. Notably, EMT was prevented in WT cells by SST0001 treatment. In vivo: I/R induced a remarkable up-regulation of EMT markers in HPA-tg mice after 48–72 h. Noteworthy, these effects were absent in WT animals. Conclusions In conclusion, our results add new insights towards understanding the renal biological mechanisms activated by I/R and they demonstrate, for the first time, that HPSE is a pivotal factor involved in the onset and development of I/R-induced EMT. It is plausible that in future the inhibition of this endoglycosidase may represent a new therapeutic approach to minimize/prevent fibrosis and slow down chronic renal disease progression in native and transplanted kidneys.

Urinary NGAL and KIM-1: Biomarkers for Assessment of Acute Ischemic Kidney Injury Following Nephron Sparing Surgery

PURPOSE Nephron sparing surgery is considered the treatment of choice in most patients with confined renal cancer. Interrupting renal blood flow is often necessary during such surgery, which can induce significant renal injury. We explored the possibility of using urinary NGAL and KIM-1 excretion as novel biomarkers to assess the extent of acute kidney injury after nephron sparing surgery. MATERIALS AND METHODS The study group included 27 patients who underwent open nephron sparing surgery for enhancing solid renal tumors. During surgery the renal artery was clamped for between 6 and 47 minutes. Urine samples were collected before surgery, and 1, 3, 8, 24, 48 and 72 hours after renal pedicle clamp removal. Urinary levels of NGAL and KIM-1 were determined. RESULTS Renal artery clamping induced renal injury, as reflected by increased urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL excretion were evident after 1 hour of renal ischemia and lasted for 72 hours. Urinary NGAL correlated with the serum creatinine increase and ischemia duration. Compared with patients without significantly increased serum creatinine, those with significantly increased serum creatinine after nephron sparing surgery had a greater increase in urinary NGAL but not in KIM-1. CONCLUSIONS Renal injury severity after nephron sparing surgery could be quantitatively assessed by measuring urinary NGAL and KIM-1.

10-year single-center experience of combined intravesical chemohyperthermia for nonmuscle invasive bladder cancer

AIM Owing to the limited efficacy and significant toxicity of most topical intravesical agents for the management of nonmuscle invasive bladder cancer (NMIBC), a search for new therapeutic modalities continues. This study evaluates the safety and efficacy of a relatively new modality, combined intravesical chemotherapy and hyperthermia, using the intravesical chemohyperthermia system. METHODS The data summarize our 10 years of experience in the Department of Urology at Bnai Zion Medical Center, Israel. Ninety two patients with NMIBC (88 evaluable) were treated according to the adjuvant (66 patients) and the neoadjuvant (26 patients) protocols, with up to 7 years follow-up. RESULTS Over the follow-up period, 56 out of 64 patients (72%) treated according to the adjuvant protocol remained free from recurrences. The progression rate was 4.7% (three out of 64 patients). An initial complete response was documented in 19 out of 24 patients (79%) treated according to the neoadjuvant protocol. During the follow-up period, 16 out of these 19 patients (84%) remained free from recurrences. All of the recurrences in this group had stage Ta grade 1 tumors. CONCLUSION Microwave-induced chemohyperthermia is a safe and effective treatment option for patients with NMIBC, both in the adjuvant and neoadjuvant settings. The use of this treatment modality did not expose the patients to an increased risk of progression.

Oral fluconazole for Candida urinary tract infection.

Fungal urinary tract infections are increasingly prevalent in hospitalized patients. This trial compares the efficacy of oral fluconazole along with catheter replacement to that of catheter replacement alone for treatment of funguria. The study group patients (n = 30) were given 100 mg of fluconazole followed by 50 mg/day for 14 days and had their catheters replaced on day one. The control group, randomized on a 1:1 basis (n = 30) had only a catheter replacement. Seventeen and 21 patients in the study and control groups, respectively, had Candida albicans, 8 and 5 had Candida tropicalis, and 5 and 4 had Candida glabrata. The MICs of the organisms were determined by the E test. The MIC90 of the C. albicans, C. tropicalis, and C. glabrata were 12, 16, and 64 micrograms/ml, respectively. Funguria disappeared in all study group patients within a week but recurred in only 1 patient 8 weeks after enrollment in the study. Although fluconazole caused a more rapid and an almost complete eradication of funguria and urinary WBCs, catheter replacement alone was followed by an 87-93% clearance of urinary findings at 8 weeks of follow-up. These results suggest that in patients with funguria low-dose fluconazole induces a more rapid clearance of urinary findings than does catheter replacement alone.

Involvement of heparanase in the pathogenesis of acute kidney injury: nephroprotective effect of PG545

Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor. I/R induced tubular damage and elevation in serum creatinine and blood urea nitrogen to a higher extent in heparanase over-expressing transgenic mice vs. wild type mice. Moreover, TGF-β, vimentin, fibronectin and α-smooth muscle actin, biomarkers of fibrosis, and TNFα, IL6 and endothelin-1, biomarkers of inflammation, were upregulated in I/R induced AKI, primarily in heparanase transgenic mice, suggesting an adverse role of heparanase in the pathogenesis of AKI. Remarkably, pretreatment of mice with PG545 abolished kidney dysfunction and the up-regulation of heparanase, pro-inflammatory (i.e., IL-6) and pro-fibrotic (i.e., TGF-β) genes induced by I/R. The present study provides new insights into the involvement of heparanase in the pathogenesis of ischemic AKI. Our results demonstrate that heparanase plays a deleterious role in the development of renal injury and kidney dysfunction, attesting heparanase inhibition as a promising therapeutic approach for AKI.

Method Used for Tumor Bed Closure (Suture vs. Sealant), Ischemia Time and Duration of Surgery are Independent Predictors of Post-Nephron Sparing Surgery Acute Kidney Injury

Introduction: The aim of our study was to examine the influence of tumor complexity and operative variables on the degree and rate of post-nephron sparing surgery (NSS) acute kidney injury (AKI). Methods: We retrospectively reviewed the records of 477 patients who underwent NSS for enhancing renal masses in our institution. AKI was determined using the latest definition by AKIN and RIFLE criteria. Serum creatinine was assessed daily starting from day 1 post-surgery and until discharge (usually on postoperative day 3). Estimated glomerular filtration was determined using the Modification of Diet in Renal Disease equation. Results: Overall, 191 patients (40%) developed postoperative AKI, and most of them (88%) were grade 1. Multivariate analysis revealed that the most significant and independent variables associated with AKI were operation time (p = 0.02), ischemia time (p = 0.02), and the use of tissue adhesive for tumor bed closure (p = 0.02). Other important factors (by univariate analysis) were the need for blood transfusion (p = 0.003) and estimated blood loss (p = 0.007). Conclusions: Operative time, ischemia, and tumor bed closure method are independent predictors of post-NSS AKI. Efforts should be made to limit prolonged ischemia and to reduce viable parenchymal loss. Further studies concerning the functional impact of AKI in these patients will be required.

Transthoracal Approach for the Removal of Adrenal Tumors. Early Experience With 10 Cases

OBJECTIVES To evaluate the early results of a transthoracal approach for the removal of various adrenal tumors. METHODS Between May 1994 and March 1995, 10 patients with adrenal masses underwent transthoracal adrenalectomy. Operation time, blood loss, the use of parenteral analgesia, duration of thoracal drainage, time to oral intake, ambulation and hospitalization period were assessed. RESULTS All tumors were excised successfully, with a short operation time (mean 91.5 min), minimal blood loss (mean 35 ml), limited use of parenteral analgesics (mean 1.4 days), early ambulation (mean 1.9 days to ambulation) and shorter period of parenteral nutrition (mean 2 days) leading to a reduced hospital stay (mean 6.7 days). CONCLUSIONS The transthoracal approach provided excellent exposure and is a quick and safe procedure even for large, malignant and hormone-producing tumors. At present this is our preferred method for the removal of adrenal masses.