Search

Enhanced recovery after surgery (ERAS) is a combination of multimodal pathways to improve surgical outcomes. Recommendations for radical cystectomy have been published by the ERAS society for the cystectomy but a lack of evidence is observed for urological procedures such as nephrectomy (Ne) and radical prostatectomy (RP). The aim of our study was to evaluate the impact of enhanced recovery protocol implementation for Ne ad RP at our academic institution.

•Benefit of colostomy on perineal Necrotizing Soft Tissue Infection survival remains uncertain.•Colostomy is associated with a high morbidity and risk of definitive stoma.•If mandatory, a damage control strategy using coelioscopic delayed loop left colostomy is advised.•Alternative minimally invasive fecal diversion should also be considered.

The present study was performed on frozen tissue samples from 50 patients treated for metastatic clear cell renal cell carcinoma. Using the quantitative multiplex polymerase chain reaction of short fluorescent fragment method, several gene copy number variations present in tumor tissue were found to be associated with worse prognostic factors. Specifically, loss of 9p (CDKN2A), 9q (ALDOB), and 6q (PLG) was associated with poor prognosis factors. In addition, these copy number variations were associated with the prognostic factors.

The objective of this study was to assess at 3 years bacillus Calmette–Guerin (BCG) maintenance treatment for NMIBC using one-third dose schedule and fewer instillations every 3 or 6 months. This was a phase III randomized study including patients with intermediate-risk or high-risk NMIBC, who received, after a full-dose induction schedule, three-weekly instillations of one-third dose BCG every 6 months (group I) and two-weekly instillations every 3 months (group II) during 3 years. We assessed oncological efficacy, BCG side effects, leukocyturia, and prostate-specific antigen. No tumor recurrence was reported at 36 months for 55 (82.09%) patients in group I versus 64 (90.14%) patients in group II (P=0.241). Muscle invasion was observed in six patients at 36 months (P=0.942). In terms of BCG toxicity, grade II and III local or systemic side effects were, respectively, reported in 8.7 and 23.9% of patients during the first year. Nevertheless, the adverse events (AEs) score at 36 months underlined a lower median value of 0.8 in group I versus 1.1 in group II (P=0.037). Furthermore, 9.9% major AEs occurred in group II versus 3% in group I (P=0.031). Leukocyturia and prostate-specific antigen level were not associated significantly with either tumor recurrence or muscle progression. We observed a significant difference in the AEs score at 36 months, suggesting less toxicity in patients who were treated with one-third dose of BCG for 3 consecutive weeks every 6 months.

Pelvic surgery for endometriosis is associated with a risk of bladder and digestive sequelae. Sacral neuromodulation (SNM) has been shown to be effective in the treatment of overactive bladder (OAB) and voiding dysfunction (VD). This study aimed to evaluate the efficacy of sacral neuromodulation (SNM) in treating voiding dysfunction (VD) following endometriosis surgery. A retrospective analysis was conducted on data from women who underwent SNM testing for persistent VD after endometriosis surgery. The study included 21 patients from a French tertiary referral center. Patient characteristics, lower urinary tract symptoms, urodynamic findings, SNM procedures, and outcomes were assessed. The primary outcome was the success of SNM treatment for VD. After a median follow-up of 55 months, 60% of patients achieved successful outcomes, with significant improvements of VD and quality of life. Moreover, more than half of patients who required clean intermittent self-catheterization (CISC) before SNM were able to wean off CISC. Complications such as infections and paraesthesia were observed, but overall, SNM was found to be effective and well tolerated. Age and the interval between endometriosis surgery and SNM testing were associated with treatment success. This study adds to the limited existing literature on SNM for VD after endometriosis surgery and suggests that SNM can be a valuable therapeutic option for these patients. Further research is needed to identify predictive factors and mechanisms underlying the effectiveness of SNM in this context. MRI-compatible and rechargeable devices, has improved the feasibility of SNM for these patients. In conclusion, SNM offers promise as a treatment option for persistent VD after endometriosis surgery, warranting further investigation.

To assess the impact of baseline chronic kidney disease on targeted therapy (TT)-induced toxicities and survival in patients treated for metastatic renal cell carcinoma (mRCC). Data from patients receiving first-line TT from January 2006 to June 2012 were collected retrospectively. TT side effects, time to treatment failure (TTF), and overall survival (OS) were analyzed according to the baseline glomerular filtration rate (GFR) calculated using the modification diet in renal disease formula. Hundred and two patients treated with sunitinib (N=67), sorafenib (N=24), or temsirolimus (N=11) were included. Forty-two patients (41%) had baseline chronic kidney disease with GFR less than 60 ml/min/1.73 m2. Patients with GFR less than 60 were more likely to encounter severe (grade 3–4) TT-induced toxicities (79 vs. 32%, P<0.0001). Moreover, renal function impairment was significantly associated with higher median TTF and OS (respectively, 12 vs. 6 months for TTF, P=0.003; and 33 vs. 13 months for OS, P=0.001). On multivariate analysis, GFR less than 60 was identified as the only factor associated with a higher rate of severe toxicity: odds ratio=4.74 (1.67–13.41), P=0.003. Severe toxicity (P=0.05) was identified as an independent prognostic factor for OS and TTF. Baseline chronic kidney disease was associated with higher TT-induced toxicities, which were identified as a prognostic factor of higher survival in mRCC treatment. These results suggest that GFR measurement could be used to optimize the efficacy of TT in patients treated for an mRCC.

Les instillations endovésicales du bacille de Calmette et Guerin (BCG) après résection endoscopique sont aujourd’hui le traitement de référence des TVNIM de risque intermédiaire et élevé. L’objectif est de prévenir la récidive tumorale et la progression au sein du muscle vésical. Pour une efficacité optimale, un traitement d’attaque suivi d’un traitement d’entretien est fortement recommandé. Le schéma de référence reste actuellement celui du SWOG, consistant en un cycle de trois instillations hebdomadaires à trois et six mois, puis tous les six mois pendant trois années. Cependant, moins de 20 % des patients sont en mesure de recevoir la totalité du traitement en raison des effets secondaires du BCG. Une prophylaxie par Ofloxacine permettrait de réduire de 18,5 % l’incidence des toxicités de grade II et III. De nouvelles modalités sont actuellement en cours d’évaluation, afin d’améliorer la tolérance du traitement d’entretien par instillations endovésicales de BCG. Ainsi, la diminution de dose du BCG (1/3 dose soit 27mg) lors du traitement d’entretien ne semble pas modifier le taux de survie sans récidive et/ou le risque de progression tumorale. En revanche, le nombre suffisant d’instillations endovésicales de BCG pour un traitement d’entretien efficace reste encore à définir.

Processes involved in the generation of hydrological winter drought within the Upper Rhine basin are investigated. Extremely low water stages were mainly documented through hydrological measurements (since 1808) at Basel, Switzerland. The effect of water released from Alpine reservoirs for power generation was estimated in order to obtain a quasi-homogenous series of “natural flows”. For the period prior to 1808, rocks emerging in rivers and lakes in the case of low water were used along with narrative evidence for assessing extreme events. 29 severe winter droughts are documented since 1540. Such events occurred after a succession of four months with below-average precipitation. A comparison with large-scale seasonal sea-level pressure (SLP) reconstructions revealed that they were often connected to persistent anticyclones centred over Western Europe. Severe winter droughts were relatively rare in the 20th century compared to the former period, which is due to increased winter temperature and precipitation.

The limitations of urinary cytology and the invasiveness of cystoscopy generate an increasing interest in noninvasive diagnostic tools for the management of transitional cell carcinoma. We assess the clinical performance of ImmunoCyt (DiagnoCure, Inc., Saint-Foy, Canada) in the detection of bladder cancer in a 10-center French trial.

Postprostatectomy incontinence remains a disabling condition. Sphincter injury, detrusor instability, and decreased bladder compliance have been previously reported as major factors. The aim of this study was to evaluate the urethral sphincter intrinsic component, which may provide passive continence. A urodynamic evaluation was performed in 20 patients undergoing a radical retropubic prostatectomy in the preoperative period and 3 months after surgery. Patients with disabled urinary incontinence underwent a new urodynamic evaluation 6 months later. The urethral pressure profile was measured just before, then 10, 20, and 30 minutes after the injection of 0.5 mg/kg moxisylyte chlorhydrate, an alpha adrenergic blocker. Three different pressure components were defined in urethral sphincter capacity: baseline, adrenergic, and voluntary. A postoperative intrinsic urethral sphincter pressure component was found in 17 patients and its value was under 6 cm H2O in five cases of severe incontinence. No significant difference was observed for these patients on urethral profile components 6 months later. In contrast, in cases of significant intrinsic component value, no incontinence was observed in most patients. Passive continence after radical prostatectomy should be a matter of concern and may also explain paradoxical incontinence, despite high voluntary urethral pressure obtained after reeducation. A follow‐up evaluation of the intrinsic sphincter component is suggested, by using an alpha receptor blockage test during urodynamic studies in the management of patients with postprostatectomy incontinence. Neurourol. Urodynam. 21:194–197, 2002. © 2002 Wiley‐Liss, Inc.

Letrozole (trademark Femara^®) is a new orally active, potent and selective aromatase inhibitor for the hormonal treatment of advanced breast cancer in postmenopausal women. The pharmacokinetics of letrozole and the suppression of peripheral estrogens were studied in 28 breast cancer patients after a single dose and at steady state. The pharmacokinetics of two distinct age groups (50, 65, N=15 and 70 years old, N=9) were compared. There were no significant differences in area under the curve (AUC) or terminal half-life between the two age groups neither after a single dose nor at steady state. However, when comparing steady state to single dose kinetics, half-life and AUC increased significantly by 42% (90% CI: 1.13, 1.78) and 28% (90% CI: 1.12, 1.47), respectively. This deviation from linearity was probably due to a partial saturation or auto-inhibition of the dominant metabolic clearance mechanism of letrozole. At steady state, approximately 70% of the administered dose was excreted in urine as unchanged letrozole (6.0±3.8%) or as the glucuronide of the major, pharmacologically inactive metabolite CGP44645 (64.2±22.7%). A single dose of letrozole caused suppression of serum estrogen levels close to the quantification limit of the assay. No difference between single dose suppression and suppression at steady state could be detected. Copyright © 2001 John Wiley & Sons, Ltd.

Letrozole (trademark Femara®) is a new orally active, potent and selective aromatase inhibitor for the hormonal treatment of advanced breast cancer in postmenopausal women. The pharmacokinetics of letrozole and the suppression of peripheral estrogens were studied in 28 breast cancer patients after a single dose and at steady state. The pharmacokinetics of two distinct age groups (⩾50, ⩽65, N=15 and ⩾70 years old, N=9) were compared. There were no significant differences in area under the curve (AUC) or terminal half‐life between the two age groups neither after a single dose nor at steady state. However, when comparing steady state to single dose kinetics, half‐life and AUC increased significantly by 42% (90% CI: 1.13, 1.78) and 28% (90% CI: 1.12, 1.47), respectively. This deviation from linearity was probably due to a partial saturation or auto‐inhibition of the dominant metabolic clearance mechanism of letrozole. At steady state, approximately 70% of the administered dose was excreted in urine as unchanged letrozole (6.0±3.8%) or as the glucuronide of the major, pharmacologically inactive metabolite CGP44645 (64.2±22.7%). A single dose of letrozole caused suppression of serum estrogen levels close to the quantification limit of the assay. No difference between single dose suppression and suppression at steady state could be detected. Copyright © 2001 John Wiley & Sons, Ltd.

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade 1, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21⁺/MDM2⁻/p53⁻ and p21⁺/MDM2⁺/p53⁻ observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21⁺/p53⁺ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins. Int. J. Cancer (Pred. Oncol.) 89:100–104, 2000. © 2000 Wiley-Liss, Inc.

Stenosing and calcified ureteritis occurring in Henoch–Schönlein purpura remains a rare urological complication. The authors describe their own experience of the diagnosis and treatment of this rare pathology along with a review of the literature. Recognition and early surgical management may prevent serious renal outcome. In cases of ureteral replacement, different procedures using ileal segment have been proposed. We report the results of the Cockett and Goodwin procedure with a follow–up of more than 25 years.

Sequencing of p53 exons 5–8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G→A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for ≥30 years and if former smokers, had stopped for ≤5 years. However, no correlation was found between the presence of p53 point mutations and the number of cigarettes smoked. The deletion mutation was the only one present in a tumor from a non-smoker. The data suggest that duration of exposure to carcinogens is the most critical factor in p53 mutagenesis in bladder cancer.

Background: with an increasing prevalence in industrialized countries, lithiasis represents a public health problem with significant economic cost. Ureteroscopy is nowadays the main treatment for kidney and ureteral stones with increasingly broad indications. While this treatment is relatively safe and effective, the complications can be severe.The aim of this study was to investigate the preoperative risk factors of complication in the 30 days following a rigid or flexible ureteroscopy in a large cohort of patients

Abstract: Background. In at least 15 % of dilated urinary tracts, diuresis renography fails to assess the presence or absence of urinary obstruction. Objective. To determine the shortcomings of 99 mTc-DTPA frusemide diuresis renography by reference to pressure flow studies. Materials and methods. Thirty-four patients, aged 1 month to 20 years, with questionable obstruction were evaluated by diuresis renography and pressure flow studies (the Whitaker test) as the reference method during the same short period of time. Discrepancies were analysed. Results. In patients with type I or IIIa renographic response, pressure flow studies never led to any change in management. Poor function, major dilatation and prior surgery were found to be risk factors of inaccurately obstructive pattern (type II) on renography (n = 6). In patients with type IIIb response, pressure flow studies could show low-grade (n = 3) or intermittent obstruction (n = 2). Intermittent obstruction was also demonstrated in two patients with type II response. Conclusion. In patients with risk factors, type II response was sometimes inaccurate, and urodynamic evaluation showed absence of obstruction and led to conservative management. Type IIIb response should be considered equivocal rather than partially obstructive, and pressure flow studies could be considered in such patients.

For the evaluation and interpretation of pharmacokinetic data reliable quantitative determinations are a requirement that can only be met by well-characterized and fully validated analytical methods. To cope with these requirements a method is being established that is based on an integrated and automated fiber-optic biospecific interaction analysis system (FOBIA) for immunoassays. Performance characteristics of this system used in monitoring of recombinant hirudin (CGP 39 393) are presented. Recombinant hirudin is a highly potent and selective inhibitor of human thrombin. Owing to its size and charge, recombinant hirudin is mainly eliminated by glomerular filtration. But only a fraction of the hirudin dose seems to be reabsorbed at the proximal tubule by luminal endocytosis and hydrolyzed by lysosomal enzymes, leaving 50% of the dose to be extracted in the urine. Thus, renal clearance of recombinant hirudin in the absence of renal insufficiency appears to depend primarily on the glomerular filtration rate. During a 3-month i.v. tolerability study in dogs, some of the dogs developed antibodies against recombinant hirudin. The hirudin-antibody complex accumulated in plasma and apparent hirudin plasma concentrations were therefore much higher than expected from single-dose kinetics. Hirudin captured by antibodies showed an extended half-life and the hirudin-antibody complex is still pharmacologically active, as demonstrated by the observed increase in thrombin time. In conclusion, only appropriate analytical methods allow adequate monitoring and pharmacokinetic characterization of biotechnology drugs in biological materials.

Pymetrozine (CGA 215 944) is a selective insecticide against plant sucking pests. Polyclonal antibodies were raised in rabbits against two pymetrozine related compounds conjugated to BSA. The antisera produced against one of the two compounds led to development of a competitive Enzyme Immuno Assay (EIA) against pymetrozine with high precision and accuracy and a detection limit of 50 ng of pymetrozine per g of plant fresh weight. Only a weak cross-reactivity was obtained with pymetrozine metabolites. Plant extracts produced a background corresponding to 10–30 ng equivalents of pymetrozine per g fresh weight. The detection limit was set above this background noise at 50 ng/g fresh weight. In other systems or following other extraction protocols the detection may yet be below this limit.

Instrumental and proxy data series from historical archives are compared over the period of the Maunder Minimum (AD 1645-1715) for western Europe (central England, Paris and Switzerland) and China. Winters became colder and drier over the late seventeenth century in western Europe. In China, however, winters were coldest around AD 1650 and became warmer and stormier over the subsequent decades. A significant warming of winters is observed around AD 1700, which, in Paris, corresponds to an increase in zonal wind frequency and a decrease in dust frequency in China. Summers during the late seventeenth century were rather dry in China and moderately wet in western Europe. These trends reversed around AD 1700, when summers became wetter in China and somewhat drier in western Europe. An approach to analysing seasonal anomalies is outlined based on a synoptic interpretation of historical weather charts derived from multi-proxy mapping.

We analyze the relationship among p53 mutations, p21 and Bax activation as well as their clinical implication in clinical response to intravesical bacillus Calmette-Guerin (BCG) therapy in high grade bladder tumors.

•Cisplatin-based combination chemotherapy before surgery is the standard of care for patients with muscle-invasive bladder cancer.•In the VESPER trial, patients received after randomization either gemcitabine and cisplatin (4 cycles) or methotrexate, vinblastine, doxorubicin and cisplatin (6 cycles).•A minimum number of 4 cycles is required to optimize the chances of pathological complete response at cystectomy.•Increasing the number beyond 4 cycles does not lead to a clinically significant deterioration in renal function without any obvious benefit on local control.

The main objective of the French GETUG/AFU V05 VESPER randomized phase III study was to assess the efficacy of dd-MVAC and GC in term of progression-free survival in patients for whom chemotherapy has been decided, before or after surgery.

No Abstract.

We report a new case of renal carcinoma in allograft kidney, 5 years after transplantation, which presented as a suspect allograft abscess in a complex history of recurrent urinary infection. Only surgical management with peroperative histological evaluation permitted us to confirm the diagnosis of malignancy.

Mutations in the p53 gene are implicated in the pathogenesis of half of all human tumors. In bladder tumors they are usually detected by immunohistochemistry. The assumption underlying protein analysis is that high level p53 expression is a consequence of mutations, but numerous exceptions have been reported. We describe the detection of p53 mutations in bladder cancer using a functional assay in yeast.