Liposomal versus plain bupivacaine for pain control following vaginal reconstruction.

INTRODUCTION: Liposomal bupivacaine (LB) is a depot formulation of bupivacaine, which releases the drug over 72 hours to prolong local pain control. This retrospective study compares the effect of using LB versus plain bupivacaine on postoperative pain control, length of hospital stay and cost among patients undergoing vaginal reconstructive surgery. MATERIALS AND METHODS: Patients who underwent vaginal reconstructive surgery with levatorplasty and received an injection of 20 cc of either plain bupivacaine or LB for pudendal nerve block were included. The primary outcomes included postoperative narcotic use and subjective pain score. The secondary outcome was postoperative length of stay. Comparisons between groups were performed using the T test, Mann Whitney U and Chi-square tests with p < 0.05 considered significant. RESULTS: Between June 2016 and December 2021, 25 patients had received LB as a pudendal nerve block and 25 had received plain bupivacaine. Demographics between groups were similar. There was no difference between postoperative morphine equivalent dose (MED) for plain bupivacaine versus LB (25.3 ± 65.8 vs. 24.9 ± 31.7 MED; p = 0.159) or length of hospital stay (15.8 ± 12.0 hours vs. 23.8 ± 20.0; p = 0.094). Furthermore, subjective pain was also similar between groups (0 vs. 1.6 ± 2.6, p = 0.68), (4.6 ± 2.3 vs. 4.9 ± 2.0 average POD 1 pain, p = 0.534) and (4.3 ± 2.1 for vs. 4.9 ± 2.1 average POD 2 pain, p = 0.373). CONCLUSION: LB is not superior to plain bupivacaine for controlling pain following vaginal reconstructive surgery, and justification for the exponentially greater cost of LB is not supported. Prospective investigations with larger sample sizes are needed to determine the optimal pain management for levatorplasty in vaginal reconstructive surgery.

Evaluation of progression from first to second stage sacral neuromodulation and unplanned device removal.

OBJECTIVE: Sacral neuromodulation (SNM) is an advanced treatment option for patients with refractory overactive bladder (OAB) symptoms, urinary retention, and bowel disorders; it is usually performed in 2 separate procedures. This study aims to determine a cohort's progression rate from stage 1 to 2 and predict factors for progression and unplanned device removal or revision. MATERIAL AND METHODS: A retrospective review was conducted in patients who underwent SNM at a single institution between June 2012 and May 2019. Progression rates from stage 1 to 2, patient characteristics, and indications for unplanned SNM removal or revision were recorded. Chi-square, Mann-Whitney U, and Fisher's exact tests were used for data analysis. RESULTS: A total of 128 patients underwent SNM for 1 or more of the following diagnoses: OAB (n=103), urinary retention (n=15), neurogenic bladder dysfunction (n=4), fecal incontinence (n=2), and constipation (n=4). The progression rate to stage 2 was 92.2% (118/128). Patients who failed to progress to stage 2 had additional diagnoses other than OAB, such as urinary retention or bowel disorders (p=0.007). Fifteen patients (12.7%) required SNM removal or revision within 4 years of surgery. Among these patients, the body mass index was significantly lower (p=0.036). CONCLUSION: Most patients (92.2%) progressed to stage 2. Patients with only OAB symptoms had a higher progression rate to stage 2. Single full-stage procedures may be considered in select patients to reduce morbidity, time, and costs.

Comparing the vaginal wall sling with autologous rectus fascia and polypropylene sling: Short term outcomes and patient satisfaction.

OBJECTIVES: Many women are affected by stress urinary incontinence (SUI). Due to investigations of the safety of synthetic mesh slings, there has been renewed interest in autologous slings. The aim of this study is to evaluate whether different sling material affects outcomes and patient satisfaction. METHODS: A retrospective review was performed of patients who underwent sling placement between May 2011 and April 2017 for SUI or stress-predominant mixed urinary incontinence. Patients were divided based on the sling material used: vaginal wall sling (VWS), rectus fascia sling (RFS), and soft polypropylene sling (SPS). Outcomes were compared using a Likert scale, the validated SEAPI score system, Incontinence Impact Questionnaire 7 (IIQ-7), and Incontinence Symptom Severity Index (ISSI). RESULTS: There were 228 patients that underwent sling placement with 94 receiving VWS, 62 RFS, and 72 SPS. Mean follow-up was 14 months. There was no statistical difference in postoperative pad usage or satisfaction score between the groups. All three groups had a statistically significant postoperative improvement in subjective SEAPI scores and daily pad use. The VWS and RFS groups had significant improvement in their ISSI. The VWS group also had postoperative improvement in IIQ-7 score. Complication rates were rare and similar between all three groups. CONCLUSIONS: Patient satisfaction and outcomes were overall similar between all three sling materials. Based on our outcomes, we continue to use the VWS as a treatment option for patients with SUI and redundant vaginal wall tissue that are opposed to synthetic mesh slings.

Translabial Ultrasound Evaluation of Pelvic Floor Structures and Mesh in the Urology Office and Intraoperative Setting.

BACKGROUND: Translabial ultrasound (TUS) can provide an inexpensive alternative imaging modality for evaluating pelvic floor structures and synthetic slings as mesh can be difficult to identify on pelvic exam or cystoscopy, patients may be unable to provide an accurate history of previous pelvic surgery, and cross-sectional imaging with computed tomography and magnetic resonance imaging can be inadequate for evaluating synthetic slings. OBJECTIVE: To demonstrate the use of TUS in the evaluation of female pelvic floor structures and mesh. METHODS: Translabial ultrasound can be used in the Urology clinic or intraoperative setting using a curvilinear transducer. Following identification of anatomic landmarks in the various planes of the pelvic floor, TUS can evaluate for pelvic floor disorders and the type and location of synthetic mesh material. Artifacts, such as air pockets in the vagina or rectum and the hypoechoic pubic symphysis, are also considered. RESULTS: Real-time imaging allows for dynamic examination of pelvic organ prolapse and urethral hypermobility that can contribute to pelvic exam findings. Bladder ultrasound can help evaluate for lesions, calculi, and even mesh erosion. Translabial ultrasound can also be used to differentiate hyperechoic retropubic and transobturator slings by identifying the position of sling arms and the appearance of the sling at different planes. Evaluation with TUS can demonstrate sling disruption, folding, urethral impingement, and erosion into pelvic floor structures. This can be particularly useful in patients presenting with pain, recurrent infections, or voiding dysfunction in which problems with mesh may not be easily identified on pelvic exam or cystoscopy. This imaging modality can complement a patient's history, aid in preoperative planning, and enable intraoperative identification of mesh slings. CONCLUSION: Translabial ultrasound provides a quick, readily available, and easy-to-learn imaging modality for evaluating pelvic floor structures and mesh in the office or intraoperative setting.

Dextrose Instillation as an Alternative Agent to Observe Ureteral Efflux During Pelvic Reconstructive Surgery.

OBJECTIVE: To evaluate the use, cost, postoperative urinary tract infection (UTI) rates, and complications of dextrose instillation during cystoscopy. METHODS: The medical records of patients who underwent cystoscopy during pelvic reconstructive surgery between June 2016 and June 2017 were reviewed. Patients were divided into two groups: patients who had one ampule of dextrose 50% (D50) directly instilled and patients who did not have D50 instilled during cystoscopy. Preoperative demographics, UTI rates, and postoperative complications were compared. Pharmaceutical cost and availability were reported by the pharmacy at our institution. RESULTS: Out of 63 patients identified, dextrose instillation was used in 20 patients and no dextrose was used in 43 patients. Each ampule of D50 cost $2.18 and there were no problems with supply shortage. As D50 was directly instilled into the bladder, there was immediate visualization of ureteral efflux at the time of surgery. Three patients (15%) in the dextrose group and 10 patients (23%) in the nondextrose group developed postoperative UTIs. There was no statistically significant difference in postoperative UTI rates between the two groups (p = 0.43) and there were no differences in postoperative complications. CONCLUSION: Dextrose is a safe, cost-effective, readily available agent that provides instantaneous visualization of ureteral efflux without an increased risk of postoperative UTI.

Erosion of Polytetrafluoroethylene (Gore-tex) Sling Over 20 Years After Placement for Stress Urinary Incontinence.

As synthetic material has evolved to improve both the efficacy and biocompatibility of suburethral slings, soft polypropylene slings are currently the gold standard for treatment of stress urinary incontinence. However, reports of complications beyond 10 years are limited and patients can nevertheless present with erosion and other complications from other sling materials that have been used in the past. We present a case of synthetic sling erosion 21 years after placement of a polytetrafluoroethylene sling (Gore-tex).

Prospective study on the effects of regular and decaffeinated coffee on urinary symptoms in young and healthy volunteers.

AIMS: Coffee reduction has been a strategy to prevent urinary symptoms with conflicting evidence. We aimed to study the effects of regular and decaffeinated coffee on urinary symptoms among low and frequent coffee users, who were young and healthy. METHODS: We conducted a double-blinded parallel study on subjects, who were restricted from consuming caffeinated items outside the study. After subjects completed 5 days of caffeine abstinence they consumed regular coffee (450 mg/d caffeine content) or decaffeinated coffee (12 mg/d caffeine content) for 5 days. Previous caffeine use and urinary symptoms were assessed by a diet survey, urogenital distress inventory, and interstitial cystitis problem and symptom indices (ICPI, ICSI). RESULTS: Forty nine subjects completed the study. When assessing the submeasures "frequency" and "urgency" on ICPI and ICSI subjects drinking coffee reported a significant increase in urgency (P < 0.05) and frequency (P < 0.05), whereas subjects drinking decaffeinated coffee experienced no difference in those submeasures in comparison to no caffeine intake. However, previous "low coffee users" experienced the largest increase of urinary symptoms, whereas previous "frequent coffee users" showed fewer symptoms when exposed to regular coffee. CONCLUSIONS: The study suggests that avoiding high-dosage coffee consumption prevents urgency and frequency, which supports recommendations to limit caffeinated beverages. The study differentiates between subjects having a history of low and frequent coffee use. Subjects, who are not used to regular coffee consumption, seem to be more vulnerable to the effects of coffee on urinary symptoms. Better understanding of the effects of coffee on urinary symptoms may improve patients counseling. Neurourol. Neurourol. Urodynam. 36:432-437, 2017. © 2015 Wiley Periodicals, Inc.

Early pregnancy likely caused by an intravesical intrauterine device.

A 42-year-old female with remote history of intrauterine device (IUD) placement presented with gross hematuria, urinary urgency, and dyspareunia. Cystoscopy showed an encrusted, free-floating intravesical foreign body consistent with a heavily calcified IUD. It was removed endoscopically using holmium laser cystolitholapaxy. The patient remained symptom free postoperatively. While most intravesical IUDs are thought to be the result of migration after several months, this patient became pregnant within 4 weeks after initial insertion. Therefore this may represent a case either of early intravesical migration or of accidental IUD placement into the bladder at the time of initial insertion.

Transvaginal retropubic sling systems: efficacy and patient acceptability.

Stress urinary incontinence is a common, disabling, and costly medical problem that affects approximately 50% of women with urinary incontinence. Suburethral retropubic slings have been developed as a minimally invasive and effective surgical option, and they have been used as a first-line treatment for stress urinary incontinence since 1995. However, complications including vaginal extrusion, erosion, pain, bleeding, infections, lower urinary tract symptoms, urinary retention, and incontinence have been reported with use of the slings. Several companies manufacture sling kits, and the sling kits vary with regard to the composition of the mesh and introducer needle. The aim of this review was to determine which sling kit was most effective for patients, had minimal reported side effects, and was best accepted by patients and surgeons. In a review of the literature, it was found that a total of 38 studies were published between 1995 and 2014 that reported on eight tension-free retropubic sling kits: SPARC, RetroArc, Align, Advantage, Lynx, Desara, Supris, and Gynecare TVT. The Gynecare TVT was the most cited sling kit; the second most cited was the SPARC. This review provides a summary of the studies that have examined positive and negative outcomes of the retropubic tension-free suburethral sling procedure using various sling kits. Overall, the results of the literature review indicated that data from comparisons of the available sling kits are insufficient to make an evidenced-based recommendation. Therefore, the decision regarding which sling kit is appropriate to use in surgery is determined by the medical provider's preference, training, and past experience, and not by the patient.

Stem cells for the treatment of urinary incontinence.

Stress urinary incontinence (SUI) is highly prevalent. As of now, there is no minimally invasive long-term treatment available. Adult stem cells are nonimmunogenic and have the ability to self-renew and to differentiate into multiple cell types. Over the past decade, in vivo studies have described periurethral injections of adult-derived stem cells for the treatment of SUI. The ultimate goal has been to achieve a permanent cure for SUI by restoration of the intrinsic and extrinsic urethral sphincter and the surrounding connective tissue, including peripheral nerves and blood vessels. For this purpose, future studies need to focus on delivery systems, cell survival, and functional improvement of the urethral closure mechanism, including improvement of innervation and vascularization.

Divergent effects of taurolidine as potential anti-neoplastic agent: inhibition of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo.

We investigated taurolidine (TRD) against various human bladder cell lines and the AY-27 rat bladder carcinoma cells. In vitro we tested the effect of TRD in ascending concentrations depending on different incubation times on cell proliferation by the XTT-test. Taurolidine had an inhibitory effect on all tested cell lines. Increasing concentrations and longer incubation times decreased the proliferation depending on the primary quantities of cells. For in vivo studies, an orthotopic rat bladder carcinoma was used. The animals were treated intravenously or intravesically and the tumors were harvested and weighted after the study. In contrast to other authors we could not find any anti-proliferative effect, we actually showed that instillation into the rat urinary bladder enhanced tumor growth.

Evaluation of normal prostate tissue, chronic prostatitis, and prostate cancer by quantitative perfusion analysis using a dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence.

OBJECTIVE: To quantify independent pharmacokinetic parameters for differentiation of prostate pathology. MATERIAL AND METHODS: Twenty-seven patients with biopsy-proven prostate cancer (PSA: 1.4-16.1 ng/mL) underwent magnetic resonance imaging with a new dynamic contrast-enhanced, inversion-prepared dual-contrast gradient echo sequence (T1/T2*-weighted, 1.65 seconds temporal resolution) using a combined endorectal/body phased-array coil at 1.5 Tesla. Perfusion, blood volume, mean transit time, delay, and dispersion were calculated using a sequential 3-compartment model. Twenty-three patients underwent prostatectomy. For histologic correlation a pathologist mapped areas of normal prostate tissue, chronic prostatitis, and prostate cancer (total of 63 areas) on histologic sections corresponding to the magnetic resonance imaging planes. RESULTS: Compared with normal prostate tissue, low-grade cancer (Gleason score

Diagnostic and prognostic validity of serum bone turnover markers in metastatic renal cell carcinoma.

PURPOSE: We assessed the diagnostic accuracy of bone markers in the serum of patients with renal cell carcinoma to detect bone metastases and evaluate the prognostic potential concerning renal cell carcinoma caused mortality. MATERIALS AND METHODS: The bone formation markers total and bone specific alkaline phosphatase, the bone resorption markers cross-linked N-terminal and tartrate-resistant acid phosphatase isoenzyme 5b, and the osteoclastogenesis markers osteoprotegerin and ligand of the receptor activator of nuclear factor-kappaB, were measured in the serum of 72 patients with renal cell carcinoma, including 28 with pN0M0, 8 with pN1M0 and 36 with M1, and in 32 female and 36 male controls by enzyme-linked immunosorbent assay techniques. Data were evaluated by receiver operating characteristics and survival analysis. RESULTS: Bone specific alkaline phosphatase, tartrate-resistant acid phosphatase isoenzyme 5b and ligand of the receptor activator of nuclear factor-kappaB did not significantly differ between patients with renal cell carcinoma and controls. Compared with controls tartrate-resistant acid phosphatase isoenzyme 5b, cross-linked N-terminal and osteoprotegerin showed increased concentrations in patients with nonbone metastases but not in those with bone metastases. No bone turnover marker led to differentiation between patients with nonbone and bone metastases. Increased osteoprotegerin above the upper 95% cutoff limit, tumor stage and distant metastatic spread were associated with renal cell carcinoma related survival on Kaplan-Meier analyses. A multivariate Cox proportional hazards regression model revealed that these 3 variables were independent prognostic factors for cancer related death. CONCLUSIONS: Bone turnover markers are hardly useful to diagnose bone metastases in patients with renal cell carcinoma. However, osteoprotegerin together with clinicopathological characteristics may be helpful as prognosticator of cancer specific death.

Combined determination of plasma MMP2, MMP9, and TIMP1 improves the non-invasive detection of transitional cell carcinoma of the bladder.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis and are involved in the process of tumour invasion and metastasis in several malignant tumour entities. The goal of this study is to evaluate the diagnostic value of various circulating MMPs and TIMPs in blood plasma for a non-invasive detection of transitional cell carcinoma of the bladder (TCC). METHODS: In this study the concentrations of MMP1, MMP2, MMP3, MMP9, their inhibitors TIMP1, TIMP2, and the MMP1/TIMP1-complex (MTC1) were quantified in blood plasma with the sandwich enzyme-linked immunosorbent assay (ELISA). Blood plasma samples were investigated from 68 patients (non-metastasized, n = 57 and metastasized, n = 11) with TCC of the bladder and from 79 healthy controls. The mROC program was used to calculate the best two- and three- marker combinations. The diagnostic values for all single markers and the marker combinations were estimated both by the overall diagnostic performance index area under the ROC curve (AUC) and the sensitivity and specificity at cutoff limits with the highest diagnostic accuracy and at the 90% and 95% limits of sensitivity and specificity, respectively. RESULTS: The median MMP2 concentration was elevated in blood plasma in all patient groups with TCC in comparison to the controls (p < 0.001). The concentrations of TIMP1, TIMP2, and MTC1 in plasma probes were significantly lower from patients with non-metastasized TCC compared to the controls. MMP2 tested alone reached the highest sensitivity and specificity at 75%, respectively. The sensitivity and specificity increased when tested in combination with MMP9 and TIMP1 (97%, 94%, respectively). The combination of MMP9 and TIMP1 also showed an improved sensitivity (80%) and specificity (99%) than tested alone. CONCLUSION: MMP2 is a statistically significant marker in blood plasma for bladder cancer detection with an increased diagnostic value in combination with MMP9 and TIMP1. This study showed that the highest sensitivities and specificities are not obtained by testing each marker alone. As shown by the best two-marker combination, which includes MMP9 and TIMP1, the optimized combination does not always include the best single markers.

Clinical value of vesical leukoplakia and evaluation of the neoplastic risk by mutation analyses of the tumor suppressor gene TP53.

AIM: Leukoplakia has been found to be precancerous in organs covered with squamous epithelium. The present study was conducted to determine whether leukoplakia described in the female bladder is also a premalignant lesion. METHODS: Between 1973 and 1996, 77 female patients were diagnosed with vesical leukoplakia by cystoscopy and cytology and were followed-up until 2004 (mean follow-up time: 8.3 years). A survey was conducted to analyze exposure to cocarcinogens. Additionally, DNA was isolated from 36 urine sediments and analyzed for TP53 mutations. The results were compared to the mutation frequency of TP53 in urine sediments from patients diagnosed with transitional cell carcinoma (TCC) of the bladder and healthy controls. RESULTS: The whitish lesion was mostly located at the trigone and varied in size and location during the follow-up years. TP53 mutations were detected in 6 out of 36 urine samples in exons 5, 6 and 7 (mutation frequency: 16.7%). Among control patients with no leukoplakia or TCC of the bladder (n = 70), the spontaneous mutation frequency was similar (14.3%). In contrast, the mutation frequency in patients with TCC of the bladder (n = 148) revealed 39.9% in exons 5, 6, 7 and 8. The present study did not show any statistically significant correlations between chronic inflammations, TP53 mutations, exposure to carcinogens and vesical leukoplakia. CONCLUSIONS: Our data suggest that vesical leukoplakia does not necessarily hold neoplastic potential and needs to be clearly distinguished from leukoplakia in other localizations. Therefore, we suggest that a biopsy can be omitted, if follow-up controls by cystoscopy are performed regularly.

In situ gene expression and localization of metalloproteinases MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1 and TIMP2 in human renal cell carcinoma.

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis. Alterations of MMP and TIMP expressions have been found in several malignant tumour entities. In this study the expression pattern of MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1, and TIMP2 were investigated at mRNA and protein levels in human renal cell carcinoma (RCC). Formalin fixed paraffin embedded tumour samples of 10 patients and adjacent non-malignant controls were analysed by radioactive labelled riboprobe in situ hybridisation (isH) and immunohistochemistry. The slides were evaluated semiquantitatively. MMP1-antigen was strongly expressed in tumour epithelium with moderate stroma expression in one case. The gelatinases MMP2 and MMP9 showed moderate to strong signals in tumour epithelial cells at the mRNA and protein level, while the expression in tumour stroma was moderate. MMP3-mRNA and -antigen were expressed moderately to strong in tumour epithelium and focally in stroma cells. mRNA or TIMP1- and TIMP2-mRNA and -antigen were also predominantly expressed in tumour epithelium; only few samples showed positive expression in stroma cells. mRNA expression could be generally correlated to the protein expression in our study group, except for MMP1 (mRNA expression was only expressed in two cases). We found a pronounced expression for the gelatinases MMP2 and MMP9 and for MMP3 in RCC at the mRNA and protein level. The expression of TIMP1 and TIMP2 appears also to be relevant in RCC. Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters.

Matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine: tumor-reducing effects on hormone-sensitive prostate cancer in rats.

Therapeutic efficacy of the novel matrix metalloproteinase (MMP) inhibitor, Ro 28-2653 (5-biphenyl-4-yl-5-[4-(-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6-trione), has been shown in various models of different tumor entities. The tumor growth-reducing effect has been demonstrated in the orthotopic rat prostate Dunning model (subline MatLyLu). Based on these results we investigated Ro 28-2653 in combination with estramustine on the G subline of the Dunning tumor. This subline is characterized by a low metastatic ability and androgen sensitivity. Efficacy was determined by recording tumor growth in vivo by magnetic resonance imaging (MRI). Tumor cells were injected into the prostates of 81 Copenhagen rats. MRI was performed at day 100 and at day 126 after tumor cell injection. The duration of therapy was 17 days with daily oral application of Ro 28-2653 (100 mg/kg) and four i.p. injections of estramustine (7.5 mg/kg). Histological evaluations were conducted to provide further information about the effects on tumor morphology. Orthotopic tumor induction was successful in 100% of the animals. Tumor volume calculations with MRI showed a significant difference between the control groups, the animals treated with Ro 28-2653, and the animals treated with the combination of Ro 28-2653 and estramustine. The new MMP inhibitor Ro 28-2653 reduces tumor growth and provides a compatible therapeutic alternative for patients with prostate cancer.

Differential gene expression of urokinase-type plasminogen activator and its receptor in human renal cell carcinoma.

The urokinase-type plasminogen activator (uPA) system plays a central role in extracellular matrix degradation, cell migration, and invasion. uPA belongs to the family of serine proteases. It has been shown that its proteolytic activity is involved in the metastatic process by activation and binding to its receptor (uPAR). Previous studies in several organ systems have elucidated a higher uPA expression in malignant tissue in comparison to normal tissue. In this study uPA and uPAR gene expression were investigated in 18 human renal cell carcinoma (RCC) specimens in comparison with adjacent non-malignant renal tissues. mRNA in situ hybridisation and immunohistochemical staining were performed. mRNA of uPA and uPAR was significantly higher expressed in 56% (10/18) and 72% (13/18) of the RCC specimens in comparison to the adjacent non-malignant renal tissue (p<0.0001), respectively. uPA-mRNA and uPAR-mRNA were expressed predominantly in malignant renal cells and in very few surrounding stromal cells. The elevated expression of uPAR-protein in RCC reached statistical significance compared to adjacent normal tissue (p=0.007). uPAR genes were higher expressed in comparison to uPA alone. There was a statistical trend that higher expression of uPA and uPAR corresponded with TNM tumour stage and grade in RCC. Further investigations need to be done with larger sample sizes to prove a correlation of expression between uPA and uPAR to a more aggressive phenotype. We conclude that uPA- and uPAR are overexpressed in RCC and could function as tumour markers.

Phase II trial of weekly paclitaxel and carboplatin chemotherapy in patients with advanced transitional cell cancer.

OBJECTIVE: We investigated the efficacy and toxicity of a first-line combination chemotherapy using weekly paclitaxel and carboplatin in patients with metastatic transitional cell cancer (TCC). PATIENTS AND METHODS: Thirty-three patients with advanced measurable TCC of the urothelium were entered onto this trial. Patients were treated once weekly with a combination therapy of paclitaxel (100mg/m(2)) and carboplatin (AUC 2, according to the Calvert formula). Therapy courses were administered for six consecutive weeks. After two cycles, a re-staging was carried out to evaluate response. RESULTS: Objective response rate was 57.6% with 6 complete (18.2%) and 13 partial remissions (39.4%). Seven patients had stable disease (21.2%) and 7 patients had progressed at the first evaluation of response (21.2%). Median progression-free interval and median survival was 6.5 (1-35) and 12 (2.5-58) months, respectively. Toxicity was moderate and manageable with grade 3 and 4 neutropenia in 8 patients (24%), but no case of neutropenic fever. Other hematological grade 3 toxicities occurred in 9 patients (27%) and grade 3 peripheral neuropathy in 2 patients (6%). There was no treatment-related death. Dose reduction or short delay of treatment was necessary in 3 patients. CONCLUSIONS: Combination therapy using weekly paclitaxel and carboplatin was active in patients with advanced TCC and adverse prognostic features. The weekly dosing used in this trial warrants further investigation as an alternative first-line approach in patients with poor renal reserve and/or performance status or as a second-line management of advanced TCC.

Molecular, cellular and developmental biology of urothelium as a basis of bladder regeneration.

Urinary bladder malfunction and disorders are caused by congenital diseases, trauma, inflammation, radiation, and nerve injuries. Loss of normal bladder function results in urinary tract infection, incontinence, renal failure, and end-stage renal dysfunction. In severe cases, bladder augmentation is required using segments of the gastrointestinal tract. However, use of gastrointestinal mucosa can result in complications such as electrolyte imbalance, stone formation, urinary tract infection, mucous production, and malignancy. Recent tissue engineering techniques use acellular grafts, cultured cells combined with biodegradable scaffolds, and cell sheets. These techniques are not all currently applicable for human bladder reconstruction. However, new avenues for bladder reconstruction maybe facilitated by a better understanding of urogenital development, the cellular and molecular biology of urothelium, and cell-cell interactions, which modulate tissue repair, homeostasis, and disease progression.