Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guérin immunotherapy for T1G3/HG bladder cancer.

PURPOSE: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC). MATERIALS AND METHODS: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. RESULTS: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55). CONCLUSION: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.

Correction to: Outcome of kidney function after ischaemic and zero-ischaemic laparoscopic and open nephron-sparing surgery for renal cell cancer.

Following publication.

Outcome of kidney function after ischaemic and zero-ischaemic laparoscopic and open nephron-sparing surgery for renal cell cancer.

BACKGROUND: Nephron-sparing surgery (NSS) remains gold standard for the treatment of localised renal cell cancer (RCC), even in case of a normal contralateral kidney. Compared to radical nephrectomy, kidney failure and cardiovascular events are less frequent with NSS. However, the effects of different surgical approaches and of zero ischaemia on the postoperative reduction in renal function remain controversial. We aimed to investigate the relative short- and long-term changes in estimated glomerular filtration rate (eGFR) after ischaemic or zero-ischaemic open (ONSS) and laparoscopic NSS (LNSS) for RCC, and to analyse prognostic factors for postoperative acute kidney injury (AKI) and chronic kidney disease (CKD) stage ≥3. METHODS: Data of 444 patients (211 LNSS, 233 ONSS), including 57 zero-ischaemic cases, were retrospectively analysed. Multiple regression models were used to predict relative changes in renal function. Natural cubic splines were used to demonstrate the association between ischaemia time (IT) and relative changes in renal function. RESULTS: IT was identified as significant risk factor for short-term relative changes in eGFR (ß = - 0.27) and development of AKI (OR, 1.02), but no effect was found on long-term relative changes in eGFR. Natural cubic splines revealed that IT had a greater effect on patients with baseline eGFR categories ≥G3 concerning short-term decrease in renal function and development of AKI. Unlike LNSS, ONSS was significantly associated with short-term decrease in renal function (ß = - 13.48) and development of AKI (OR, 3.87). Tumour diameter was associated with long-term decrease in renal function (ß = - 1.76), whereas baseline eGFR was a prognostic factor for both short- (ß = - 0.20) and long-term (ß = - 0.29) relative changes in eGFR and the development of CKD stage ≥3 (OR, 0.89). CONCLUSIONS: IT is a significant risk factor for AKI. The short-term effect of IT is not always linear, and the impact also depends on baseline eGFR. Unlike LNSS, ONSS is associated with the development of AKI. Our findings are helpful for surgical planning, and suggest either the application of a clampless NSS technique or at least the shortest possible IT to reduce the risk of short-time impairment of the renal function, which might prevent AKI, particularly regarding patients with baseline eGFR category ≥G3.

Oncological outcomes, quality of life outcomes and complications of partial cystectomy for selected cases of muscle-invasive bladder cancer.

To evaluate the oncological results, associated complications, and postoperative health-related quality of life (HR-QoL) in patients treated with partial cystectomy (PC) for muscle-invasive bladder cancer (MIBC). 27 patients who underwent open PC for cT2 MIBC were included. A simple Cox's proportional hazards regression model was used to assess the association of several potential prognostic factors with survival. Postoperative HR-QoL was assessed with the EORTC (European Organisation for the Research and Treatment of Cancer) QLQ-C30 questionnaire version 3.0. Final pathological tumour stages in PC specimen were: pT0: 18.5%, non-MIBC: 3.7%, MIBC: 74.1%, pCIS: 14.8%. Estimated 5-year overall- and progression-free survival rates were 53.7% and 62.1%. Five (18.5%) patients experienced local recurrence with MIBC. Overall, the salvage cystectomy rate was 18.5%. The 90-day mortality rate was 0%. Significant risk factors for progression-free survival were vascular invasion (HR 5.33) and tumour multilocularity (HR 4.5) in the PC specimen, and a ureteric reimplantation during PC (HR 4.53). The rates of intraoperative complications, 30- and 90-day major complications were 7.4%, respectively and 14.8% for overall long-term complications. Postoperatively, median (IQR) global health status and QoL in our PC cohort was 79.2 (52.1-97.9). Open PC can provide adequate cancer control of MIBC with good HR-QoL in highly selected cases. Open PC can lead to long-term bladder preservation and shows an acceptable rate of severe perioperative complications, even in highly comorbid patients.

Influence of hematuria and infection on diagnostic accuracy of urinary LASP1: a new biomarker for bladder carcinoma.

AIM: To further promote the clinical use of urinary LASP1 as biomarker for urothelial carcinoma of the bladder regarding limitations and alternative testing systems. PATIENTS & METHODS: Urine stabilization, alternative measurement systems and limitations by erythrocyte contamination and infection were investigated in 246 patients. RESULTS: Thimerosal allowed sufficient stabilization. Fluorescence-activated cell sorting analysis was not influenced by presence of erythrocytes or leukocytes and reliably urothelial carcinoma of the bladder but cell counts in specimen were low. Cut-off values of <25 leukocytes and <200 erythrocytes/µl resulted in sensitivity, specificity, positive and negative predictive values of 0.59, 0.80, 0.80 and 0.59, respectively. CONCLUSION: Hematuria up to 200 erythrocytes/µl but not presence of leukocytes may be tolerated for this promising marker.

The SIGHT questionnaire: A novel assessment tool for Satisfaction In Genital Hypospadias Treatment.

PURPOSE: Psychosexual development is currently underrepresented in hypospadias outcome research. The aim of this study was to develop and validate a questionnaire addressing psychosexual long-term satisfaction, specifically of adolescent patients, after hypospadias repair. MATERIALS AND METHODS: In a multistep participative design we identified key interests of adolescent patients with hypospadias. Next, a questionnaire addressing specifically the psychosexual satisfaction of adolescents after hypospadias repair was established. A population of 109 former patients with hypospadias was then assessed using this questionnaire. Furthermore, functional and cosmetic aspects, behavioural anomalies, and sexual activity were investigated. Age-matched patients undergoing circumcision served as control patients. Possible influence factors on patient satisfaction were investigated. Clinical trial registry site: German Registry of Clinical Trials DRKS, Freiburg, Germany (Reference: DRKS00003432). RESULTS: Key interests of adolescent patients were "normal appearance of the penis", "normal function of the penis regarding voiding and sexual activity", "no limitations regarding cosmetic appearance to others", "no limitations to sexual activity", and an "unimpaired masculine identity". The "Satisfaction In Genital Hypospadias Treatment" (SIGHT) questionnaire was developed using these items and using previously published evaluation systems. Nine questions address psychosexual aspects and two additional questions address current sexual activity. Internal consistency was high and retest reliability acceptable. The patient population showed a normal strength and difficulties score (SDQ). Overall satisfaction was high and similar to that of the control group. In a Spearman correlation a high SDQ value, erectile problems, and complications correlated negatively with satisfaction. CONCLUSION: To date, few studies have examined patients' satisfaction and psychosexuality. To our knowledge, the SIGHT questionnaire is the first to be developed participatively and in a stepwise fashion in collaboration with a paediatric psychologist and an open approach to determine items specifically important for adolescents. The SIGHT questionnaire can thus offer a relevant assessment of patients' psychosexual satisfaction. It is most suitable to supplement current strategies that so far mostly neglect the impact on psychosexual wellbeing.

The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer.

BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. RESULTS AND LIMITATIONS: Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. CONCLUSIONS: We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. PATIENT SUMMARY: As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given.

Dynamics of Urinary Calprotectin after Renal Ischaemia.

BACKGROUND: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. METHODS: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. RESULTS: Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). CONCLUSION: Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.

The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin.

OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS). PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups. RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints. CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

Urothelial Cancer in Renal Transplant Recipients: Incidence, Risk Factors, and Oncological Outcome.

OBJECTIVE: To evaluate the incidence and risk factors for urothelial cancer (UC) as well as the oncological outcome and allograft function in renal transplant recipients. SUBJECTS/PATIENTS: We conducted a retrospective analysis of 1855 consecutive patients undergoing renal transplantation (TX) between February 1982 and May 2014 at a single center. UC incidence, overall and cancer-specific survival, recurrence and progression rates, risk factors for UC, and renal function were determined. Fisher's exact test and log-rank Mantel-Cox test were used as appropriate. RESULTS: In renal transplant recipients, incidence of de novo UC was 1.35% (25/1855). Deceased donor transplantation (P = .002), increased age at transplantation (P = .011), and analgesic abuse (P = .005) were significant risk factors for the development of UC post-TX. Progression rate and recurrence rate were doubled for post-TX-UC but stable for patients with pre-TX-UC compared with the general population. Analgesic abuse was associated with worse cancer specific and overall survival in post-TX patients. The overall survival status was significantly lower for post-TX patients at a median of 34 months vs 222 months in control patients. Adjuvant treatment was scarcely used. UC had no significant influence on graft function. CONCLUSION: A higher incidence of UC was identified in renal transplant recipients compared with that for the general population. These observations justify screening for UC in renal transplant patients, especially considering that in a large proportion, a tentative diagnosis was possible with noninvasive urine analysis. Prudent adjuvant treatment for UC should be used. Limitations of this study were the retrospective design and the single-center experience.

An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder.

BACKGROUND: To use combinatorial epitope mapping ("fingerprinting") of the antibody response to identify targets of the humoral immune response in patients with transitional cell carcinoma (TCC) of the bladder. METHODS: A combinatorial random peptide library was screened on the circulating pool of immunoglobulins purified from an index patient with a high risk TCC (pTa high grade plus carcinoma in situ) to identify corresponding target antigens. A patient cohort was investigated for antibody titers against ubiquitin. RESULTS: We selected, isolated, and validated an immunogenic peptide motif from ubiquitin as a dominant epitope of the humoral response. Patients with TCC had significantly higher antibody titers against ubiquitin than healthy donors (p<0.007), prostate cancer patients (p<0.0007), and all patients without TCC taken together (p<0.0001). Titers from superficial tumors were not significantly different from muscle invasive tumors (p = 0.0929). For antibody response against ubiquitin, sensitivity for detection of TCC was 0.44, specificity 0.96, positive predictive value 0.96 and negative predictive value 0.41. No significant titer changes were observed during the standard BCG induction immunotherapy. CONCLUSIONS: This is the first report to demonstrate an anti-ubiquitin antibody response in patients with TCC. Although sensitivity of antibody production was low, a high specificity and positive predictive value make ubiquitin an interesting candidate for further diagnostic and possibly immune modulating studies.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients.

BACKGROUND: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE: To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS: T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

The glandular resection and central embedding modification (GRACE) in Duckett and Barcat hypospadias repair.

INTRODUCTION: We recently reported a novel modification of the Barcat technique termed glandular resection and central embedding (GRACE). Here, we report results from a large patient population and apply this modification also to Duckett hypospadias repair. PATIENTS AND METHODS: We retrospectively evaluated 488 patients who had undergone primary or secondary hypospadias repair by Barcat or Duckett using the GRACE modification. RESULTS: For all GRACE repairs, cosmetic appearance was favorable regarding meatal position, shape and overall appearance. Maximum and average flow were above the 5th percentile in at least 95%. In Barcat and Duckett repairs, urethrocutaneous fistulas occurred in 5 and 30.7%, urethral strictures in 3 and 20.8%, and meatal strictures in 5 and 25.3%, respectively. CONCLUSIONS: The initially reported favorable cosmetic and functional results were confirmed both for Duckett and Barcat repair using the GRACE modification. Complication rates were favorably low for Barcat and higher, but consistent with published results, for Duckett repair.

LASP-1, a novel urinary marker for detection of bladder cancer.

OBJECTIVES: The LIM and SH3 (LASP)-1 protein is a focal adhesion protein that has been linked to oncogenesis. The aim of this study was to evaluate the diagnostic use of the detection of LASP-1 in tumor specimens and in urine for noninvasive detection of transitional cell carcinoma (TCC). MATERIALS AND METHODS: Immunohistochemical staining for LASP-1 was performed on 72 archived bladder tumor specimens, and LASP-1 content was measured in 132 spontaneous urine sample sediments by Western blot analysis. RESULTS: In the histologic specimens, immunohistochemical staining for LASP-1 showed abundant expression throughout the urothelium of the bladder and ureter. However, modest overexpression of LASP-1 was observed in the TCC specimens. Measurement of the LASP-1 protein concentrations in urinary cell pellets from healthy donors and bladder cancer patients was highly sensitive for the presence of TCC. The cut-off value was determined by receiver operating characteristic (ROC) analysis. When a cut-off value of 1 ng LASP-1/500 µl of urine was used, the sensitivity, specificity, and positive and negative predictive values of the assay were 83.1%, 85.3%, 83.1%, and 80.6%, respectively.The increased urinary LASP-1 content in TCC patients was attributable in part to a specific increase in cell shedding presumably caused by changes in cell adhesion, as confirmed by LASP-1 knockdown. Contamination with erythrocytes above 250 cells/µl and urinary infection gave false positive results and are therefore sample exclusion criteria. CONCLUSIONS: In the absence of urinary infection or gross hematuria, urinary LASP-1 level is a promising marker for transitional cell carcinoma.

Standardized flexible ureteroscopic technique to improve stone-free rates.

OBJECTIVE: To present a unique completely standardized sequence of steps performed before, during, and after flexible ureteroscopy (FURS) that achieves superior results for FURS treatment of renal calculi. MATERIALS AND METHODS: The "Freiburg FURS technique" includes the following steps: (a) preoperative ureteral stenting; (b) placement of 2 hydrophilic wires; (c) semirigid ureteroscopy before FURS; (d) the use of a large access sheath (14F-16F) if multiple ureteral passages are expected; (e) the use of a 2-working channel flexible endoscope; (f) a modified active flushing system; and (g) an advanced holmium laser technique with complete stone extraction. We performed a prospective analysis of 153 consecutive FURS procedures for nephrolithiasis from August 2009 to July 2011. RESULTS: Data analysis revealed an "immediate" stone-free rate of 96.7% (as confirmed by endoscopy, fluoroscopy, and ultrasonography), a medium of 2.3 stones, and a cumulative stone size of 10.5 mm (range 3-43). The operative time was 67 minutes (range 20-160). The use of an access sheath was required in 71% of the patients and the postoperative use of a double-J stent in 57% of patients. Complications (Clavien grade II and III) developed in 9.1% of patients (including 7 with minimal perforation that required ureteral stenting for 1 month, 3 with secondary flank pain/hydronephrosis requiring double-J stenting and hospitalization, and 4 with fever or urinary tract infections requiring antibiotic therapy. Follow-up examinations after 3 months showed no late complications. CONCLUSION: The modified FURS technique provided clinically superior results with a low complication rate. However, the approach requires the use of considerable resources, both technical and surgical and financial.

Glandular resection and central embedding in hypospadias repair--a novel modification of the Barcat technique.

PURPOSE: Urethrocutaneous fistula and urethral or meatal stricture, to date, remain the commonest complications of hypospadias repair, with increased tissue tension being a major cause of failure. We developed a novel technique comprising glandular resection and central embedding of the neourethra to specifically address this critical issue. We report the results of the first 112 procedures, of which 7 cases were a secondary hypospadias repair. MATERIALS AND METHODS: All patients who underwent hypospadias repair using the glandular resection and central embedding technique over a period of 10 years were included into this retrospective single-surgeon case series. An independent third-party observer carried out follow-up examinations including urometric evaluation. RESULTS: The median follow-up was 37 months (range, 7-147 months). In the group of primary hypospadias repair, urethrocutaneous fistulas were observed in 4%, all requiring surgical revision, and meatal or urethral stricture were observed in 4% of the patients, treated either surgically or by dilatation. In 98% of the patients, the neomeatus was located at the tip of the glans. A cosmetically impeccable slitlike appearance of the meatus was achieved in 84%, and a cosmetically acceptable oval shape was achieved in 10% of the patients. Both maximum and average urinary flow rates were within the standard ranges for the respective age groups in 93.7% and 96%, respectively. There was no significant residual urine in 92% of the patients. In the group of secondary hypospadias repairs, both cosmetic and functional results were similar, and no complications were noted. CONCLUSIONS: Glandular resection and central embedding is a promising expansion of the repertoire of Barcat modifications. It allows safe embedding of the neourethra and glandular closure without detrimental tension. The cosmetic and functional results are encouraging.

Retrograde intrarenal surgery in treatment of nephrolithiasis: is a 100% stone-free rate achievable?

PURPOSE: To achieve an almost 100% stone-free rate by means of further developing and standardizing the procedure. PATIENTS AND METHODS: 100 consecutive patients with single or multiple renal calculi were prospectively enrolled in the study. Flexible ureterorenoscopy was performed as a completely standardized operation by the same two experienced surgeons. Primary outcome was an "endoscopic" (immediate) stone-free status as determined by endoscopic inspection at the end of surgery. In cases of residual fragments, a reevaluation by CT was performed after 3 months. RESULTS: The endoscopic stone-free rate was 97%. In three patients with a cumulative stone size >20 mm, a completely stone-free status could not be achieved in the primary procedure. In these patients, a CT scan after 3 months showed complete clearance from all residual fragments in two; this translates into a primary (after one procedure) stone-free rate after 3 months of 99%. Medium cumulative stone size was 9.8 mm (4-40 mm); in 44 patients, multiple calculi were extracted. Forty-nine patients received a ureteral stent at the end of the operation; two patients had to have stent placement for new onset hydronephrosis and/or colicky pain or fever. Overall complication rate was 7%. Results are limited, because no routine CT scan was used to evaluate stone clearance. CONCLUSION: By means of a standardized surgical approach and use of technical equipment of the newest generation, it is possible to achieve very high stone-free rates without compromising safety. This approach, however, necessitates use of considerable resources, both technical/surgical and financial.

Reactive antibodies against bacillus Calmette-Guerin heat-shock protein-65 potentially predict the outcome of immunotherapy for high-grade transitional cell carcinoma of the bladder.

BACKGROUND: Intravesical immunotherapy with Mycobacterium bovis (M. bovis) bacillus Calmette-Guerin (BCG) is the current standard of care against superficial, high-grade transitional cell carcinoma (TCC) of the urinary bladder (carcinoma in situ and pathologic T1, grade 3 disease). However, individual patient outcome is barely predictable because of the lack of serum markers. Consequently, progression to muscle-invasive bladder cancer and critical delay of treatments (such as neoadjuvant combination chemotherapy and/or radical cystectomy) often occur. The objectives of this study were to identify a marker for measuring the BCG-induced immune response and to predict the outcomes and potential improvements of BCG immunotherapy. METHODS: Because host immunoresponse mediates BCG activity, the authors screened a combinatorial random peptide library on the circulating pool of immunoglobulins (Igs) purified from an index patient after successful BCG immunotherapy to identify the corresponding target antigen(s). RESULTS: An immunogenic peptide motif was selected, isolated, and validated from M. bovis BCG heat-shock protein 65 (HSP-65) as a dominant epitope of the humoral response to treatment. Increasing IgA and IgG anti-HSP-65 titers specifically predicted a positive patient outcome in a cohort of patients with bladder cancer relative to several cohorts of control patients. CONCLUSIONS: The current results indicated that antibody production against M. bovis BCG HSP-65 can serve as a serologic marker for the predictive outcome of BCG immunotherapy. Subsequent studies will determine the value of this candidate marker to modify BCG-based treatment for individual patients with bladder cancer.

Design and validation of a bifunctional ligand display system for receptor targeting.

Here we developed a bacteriophage display particle designed to serve as a bifunctional entity that can target tumors while delivering an agent. We engineered a chimera phage vector containing a pIII-displayed alphav integrins-targeting moiety and a pVIII-displayed streptavidin binding adaptor moiety. By using the chimeric phage particle, targeting of alphav integrins on cells in culture and tumor-related blood vessels was shown through different applications, including luminescent quantum dots localization, surface plasmon resonance-based binding detection, and an in vivo tumor model. The strategy validated here will accelerate the discovery and characterization of receptor-ligand binding events in high throughput, and cell-specific delivery of diagnostics or therapeutics to organs of choice without the need for chemical conjugation.