Functions of epidermal growth factor-like growth factors during human urothelial reepithelialization in vitro and the role of erbB2.

Transitional epithelium of the urinary bladder can be damaged during, for example, catheterization, overstretching due to obstructed voiding, or partial resection. The subsequent repair process can be stimulated by specific proteins such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha). However, little is known about the role of EGF-like growth factors and their respective receptors in human urothelial repair. In this study, we examined the effects of EGF, TGFalpha, amphiregulin and heregulin-alpha (HRGalpha) on proliferation, wound closure, and the expression of their receptors c-erbB1-c-erbB4 in primary cultures of human urothelial cells in vitro. Under conditions representing intact urothelium, all EGF-like growth factors except HRGalpha induced proliferation. TGFalpha induced proliferation up to four times. Amphiregulin increased expression of c-erbB1. Treatment with either TGFalpha or amphiregulin resulted in higher c-erbB1 activation and c-erbB3 levels. None of the growth factors affected the constitutive expression of c-erbB2 and c-erbB4. In the repair model, both EGF and TGFalpha stimulated the wound closure most strongly. This was mainly achieved by increased cellular migration. Receptor expression was not affected by the addition of exogenous growth factor. The role of c-erbB2 in wound healing was further investigated with the use of antisense DNA. Wound closure could be delayed up to 50% by antisense c-erbB2 but not by mismatched or sense oligonucleotides. Excessive production (e.g. in bladder tumors) or application of EGF, TGFalpha or amphiregulin, but not HRGalpha may lead to either hyperplasia or a faster repair of damaged urothelium in vivo. These effects seem to be mediated not only via c-erbB1 but also via c-erbB2. Our results suggest that modified members of the EGF-EGFR family are potential targets for future therapies for bladder wound healing and malignancy.

[Treatment of ureteral calculi: report of 152 calculi]. / Traitement des calculs de l'uretère: à propos de 152 calculs.

OBJECTIVE: To define the therapeutic approach to ureteric stones. MATERIAL AND METHODS: 137 patients with 152 ureteric stones were treated between January 1990 and January 1997. Sixty seven stones (44%) were situated in the lumbar ureter, 16 stones (10%) were in the iliac ureter, 69 stones (46%) were in the pelvic ureter. These stones were treated by extracorporeal shock-wave lithotripsy (ESWL), ureteroscopy and, more rarely, ureterotomy. RESULTS: One hundred and three stones were treated in a single session, while 31 required two ESWL sessions. Treatment eliminated 82% of ureteric stones: 89% of lumbar ureteric stones, 31% of iliac stones and 85% of pelvic stones. Ureteroscopy was performed as first- or second-line treatment in 34 cases. It successfully treated 97% of ureteric stones: 100% of pelvic and lumbar stones and 91% of iliac stones. Three patients were successfully treated by ureterolithotomy for a lumbar ureteric stone and two for iliac ureteric stones. CONCLUSION: SWL is the reference treatment for stones of the lumbar ureter. Ureteroscopy is justified after failure of ESWL for stones of the pelvic and iliac ureter, as it gives excellent results.

Urinary continence following radical prostatectomy assessed by a self-administered questionnaire.

OBJECTIVES: A total aim of this study was to assess the incidence of urinary incontinence in patients following radical prostatectomy and determine the factors that may influence this incidence. METHODS: A total of 135 men underwent radical retropubic prostatectomy at our center between 1987 and 1997. 120 patients were sent a questionnaire regarding preoperative and postoperative voiding habits. Data collected included preoperative and postoperative continence status, interval to postoperative continence status, associated urinary symptoms, willingness to undergo radical prostatectomy again if need be and additional postoperative procedures. Patient age, date of surgery, number of neurovascular bundles resected at prostatectomy and duration of follow-up were also noted. RESULTS: Of the 120 patients, 116 (96.7%), a mean of 65.2 (range 48-76) years old, responded to the questionnaire. Mean follow-up was 4.3 years (range 1-10.8). Continence was defined as no regular use of pads. Our overall urinary incontinence rate was 14.4%. Of the respondents, 88. 8% (103/116) had achieved final continence status by 6 months postoperatively, and 95% (110/116) would undergo surgery again if need be. Of the patients considered incontinent postoperatively, 66. 6% had associated urgency. Age, year of surgery, number of neurovascular bundles resected at prostatectomy, preoperative urinary leakage of postvoiding dribbling, postoperative pelvic floor exercises, and anastomotic stricture had no significant impact on postoperative continence status. CONCLUSIONS: Using an anonymous self-administered questionnaire, we found a 14.4% incontinence rate after radical prostatectomy. These results allow patients to have realistic expectations when counseled prior to this operation.

Diagnosis and prediction of recurrence and progression in superficial bladder cancers with DNA image cytometry and urinary cytology.

OBJECTIVE: To investigate the roles of urinary cytology and image cytometric analysis of nuclear DNA ploidy pattern in the diagnosis and prediction of recurrence and/or progression of superficial bladder cancers. PATIENTS AND METHODS: Aliquots of catheterized urine from 92 patients with primary (23) or previous (69) superficial bladder cancers were assessed using urine cytology and image-analysis cytometry independently. RESULTS: Of the 23 primary superficial transitional cell carcinomas (TCCs), 11 (48%) were detected by urinary cytology while 12 (52%) were detected by image-analysis cytometry (P>0.05) and 13 (57%) were revealed by combined cytology and cytometry. Of 42 recurrent superficial TCCs, 29 (69%) were detected by urinary cytology, whilst 19 (45%) were diagnosed by cytometry (P<0.05) and 29 (69%) by combined cytology and cytometry. The degree of ploidy in relation to pathological stage and/or grade showed an increasing frequency of aneuploid pattern in more invasive and undifferentiated tumours, but with no statistical significance (P>0.05). The positivity of DNA image cytometry had no significant association (P>0.05) with tumour recurrence and/or progression. CONCLUSIONS: DNA image cytometry can provide a limited but not significant advantage over urinary cytology in the detection of primary superficial TCCs, but it does not seem to be indicated for the prediction of tumour recurrence and/or progression.

Diagnosis and prediction of recurrence and progression in superficial bladder cancers with DNA image cytometry and urinary cytology

OBJECTIVE: To investigate the roles of urinary cytology and image cytometric analysis of nuclear DNA ploidy pattern in the diagnosis and prediction of recurrence and/or progression of superficial bladder cancers. PATIENTS AND METHODS: Aliquots of catheterized urine from 92 patients with primary (23) or previous (69) superficial bladder cancers were assessed using urine cytology and image-analysis cytometry independently. RESULTS: Of the 23 primary superficial transitional cell carcinomas (TCCs), 11 (48%) were detected by urinary cytology while 12 (52%) were detected by image-analysis cytometry (P > 0.05) and 13 (57%) were revealed by combined cytology and cytometry. Of 42 recurrent superficial TCCs, 29 (69%) were detected by urinary cytology, whilst 19 (45%) were diagnosed by cytometry (P < 0.05) and 29 (69%) by combined cytology and cytometry. The degree of ploidy in relation to pathological stage and/or grade showed an increasing frequency of aneuploid pattern in more invasive and undifferentiated tumours, but with no statistical significance (P > 0.05). The positivity of DNA image cytometry had no significant association (P > 0.05) with tumour recurrence and/or progression. CONCLUSIONS: DNA image cytometry can provide a limited but not significant advantage over urinary cytology in the detection of primary superficial TCCs, but it does not seem to be indicated for the prediction of tumour recurrence and/or progression.

Expression of transforming growth factor beta1 and its receptors in normal human urothelium and human transitional cell carcinomas.

Previous studies indicated that transforming growth factor beta1 (TGFbeta1) is expressed by normal urothelial cells and exerts regulatory autocrine functions in urothelial maintenance and wound healing. However, little is known about the expression patterns of TGFbeta1 and its receptors in bladder tumors. Therefore, we studied the protein and mRNA localization of TGFbeta1 and TGFbeta receptor types I and II (TGFbetaRI and TGFbetaRII) in normal human urothelium and transitional cell carcinomas (TCCs) of different grades and stages. Expression of TGFbeta1 and its receptors was examined by immunocytochemistry and mRNA in situ hybridization in normal urothelium and TCCs using a semiquantitative method. By immunocytochemistry, the expression of TGFbeta1 and TGFbetaRII was higher in superficial and basal cell layers of normal urothelium than in the intermediate layer. A similar localization was seen in superficial TCCs. TGFbetaRI was mainly present in basal and intermediate cell layers of normal urothelium and superficial TCCs. In contrast, in muscle invasive TCCs, all tumor cells stained intensely for all three proteins. No correlation was found between immunostaining and TCC grade. In situ hybridization pointed out that all cell layers in normal urothelium exhibit similar TGFbeta1 mRNA levels. Elevated TGFbeta1 mRNA levels were noted in TCCs irrespective of grade or stage. In conclusion, these data indicate that in normal urothelium TGFbeta1, TGFbetaRI, and TGFbetaRII expression depend on maturation and differentiation. This pattern is particularly lost in muscle invasive TCCs, in which the expression of the three proteins is enhanced. These data suggest autocrine TGFbeta1 mechanisms in human TCC cells that may be more pronounced in muscle invasive TCC cells.

[Urinary continence after retropubic radical prostatectomy: retrospective study with self-administered questionnaire]. / Continence urinaire après prostatectomie radicale rétro-pubienne: étude rétrospective par autoquestionnaire.

OBJECTIVES: To precisely evaluate the incidence of urinary incontinence after radical prostatectomy and its impact on quality of life. MATERIAL AND METHODS: A self-administered questionnaire was sent to 116 patients operated between 1987 and 1996. Preoperative and postoperative urinary continence, the time until urinary continence was achieved, the presence of urgent micturition, the degree of discomfort caused by urinary incontinence and associated voiding disorders were assessed. RESULTS: The questionnaire response rate was 96.6%. The urinary incontinence rate (continuous use of pads) was 13.4%. No predictive factor for postoperative urinary incontinence was identified. Urge incontinence was present in 31.3% of cases. 85% of patients claimed to be satisfied with the operation and 95.4% declared that they would be willing to undergo radical prostatectomy again. CONCLUSION: The incidence of urinary incontinence after radical prostatectomy is acceptable and the morbidity that it generates is well tolerated and has little impact on quality of life.

[Surgical aspects of renal transplantation in children]. / Aspects chirurgicaux de la transplantation rénale chez l'enfant.

Review of a series of 90 renal transplantations performed in 86 children revealed 3 cases of early or late mortality and 28 cases of major surgical complications, predominantly vascular (13 cases) and urological complications (12 cases). The time to onset, the diagnosis and the management of these complications are reviewed. This study again emphasizes the importance of graft selection (donor age) and the value of living related donor renal transplantation.

Expression and functions of EGF, FGF and TGFbeta-growth-factor family members and their receptors in invasive human transitional-cell-carcinoma cells.

Studies on epidermal-growth-factor-like-, fibroblast- and transforming growth factors suggested their implication in tumorigenesis involving effects on tumour-cell proliferation and migration. In human transitional-cell carcinomas (TCC), enhanced expression of TGF alpha and EGF receptors correlated with an aggressive phenotype. However, little is known about functions of these growth factors in invasive TCCs. In this study, we performed protein- and RNA-expression studies on a set of growth factors and their receptors on the newly established invasive human TCC cell line designated 1207. The data were correlated with functional proliferation and migration studies. Similar expression patterns of many cellular markers, growth factors and their receptors were noted both in the original TCC tissue and in its derivative cell line, indicating the relevance of this cell line to the investigation of growth factor functions on TCC cells. The proliferation induction by EGF, TGF alpha, amphiregulin, heregulin alpha, FGF-1 and FGF-7 correlated with the presence of EGF receptors, c-erbB4 and FGFR2 (IIIb), respectively. Amphiregulin and heregulin alpha induced the most proliferation. In conformity with the low expression of TGF beta receptors I and II, TGF beta1, barely inhibited proliferation, while TGF alpha induced invasion of 1207 cells into Matrigel. These data support the notion that notably EGF-like proteins mediate TCC growth and invasion through autocrine pathways which can be reinforced by loss of TGF beta1 regulation.