[Andropause]. / Andropause.

The terms andropause, partial androgen deficiency of the aging male (PADAM) or late-onset hypogonadism (LOH) describe a clinical entity which has been defined as a syndrome associated with advanced age. This syndrome is characterised by a deficiency in serum testosterone levels that may result in significant alterations in the quality of life and adversely affect the function of multiple organ systems. Whereas in classic primary and secondary hypogonadism, the clinical picture of testosterone deficiency is clearly defined, the clinical diagnosis of PADAM might escape detection for various reasons: not all signs and symptoms necessarily present together; they often progress slowly and are subtle in nature; the non-specific signs and symptoms might not be discernible from the unavoidable process of aging itself. However, PADAM features many potentially serious consequences that can be avoided or treated, and is, therefore, clinically relevant. Testosterone substitution may be an effective way to manage this condition. Once patients begin treatment with testosterone substitution, follow-up and monitoring are essential.

Influence of stent size on the success of antegrade endopyelotomy for primary ureteropelvic junction obstruction: results of 2 consecutive series.

PURPOSE: We evaluated the influence of stent size in 2 consecutive series of unselected patients in whom primary ureteropelvic junction obstruction was managed by antegrade endopyelotomy and stenting with a 14 or 27Fr stent at the level of the incision. MATERIALS AND METHODS: Antegrade endopyelotomy was performed in 132 patients with primary ureteropelvic junction obstruction. The endopyelotomy was stented for 6 weeks. In 77 patients (group 1) a 14/8.2Fr percutaneous endopyelotomy (Smith) catheter was used. In 55 patients (group 2) a modified 14/8.2Fr Smith catheter was over pulled with a 27Fr wound drain. The wound drain was removed after 2 to 3 weeks and the standard 14/8.2Fr stent remained in place for another 3 to 4 weeks. Success at 6 to 8 weeks, and 6 and 24 months postoperatively was based on clinical evaluation, and excretory urography and/or diuretic renography. Thereafter clinical and ultrasound followup was performed every 2 to 3 years. RESULTS: Preoperatively data on the risk factors of large pyelocaliceal volume and impaired renal function were similar in the 2 groups. The overall success rate was 70% in group 1 at a median followup of 67 months (range 2 to 118) and 94% in group 2 at a median followup of 23 months (range 2 to 52). The early success rate after 6 to 8 weeks in groups 1 and 2 was 83% and 94%, respectively. The long-term success rate after 2 years was 71% and 93%, respectively. Perioperatively and postoperatively the incidence of complications was 16% in group 1 and 24% in group 2. When group 2 complications due to a lack of experience with the new stent were excluded from analysis, the remaining 15% complication rate was comparable to that in group 1. Mean pyelocaliceal volume decreased significantly in each group and remained stable. Split renal function did not change preoperatively to postoperatively with no significant difference in the 2 groups. CONCLUSIONS: Stenting an antegrade endopyelotomy with a modified 27Fr instead of a 14Fr catheter seems to increase the early and, even more impressively, the long-term success rate to a level similar to that of open pyeloplasty.

Prostate stem cell antigen is a promising candidate for immunotherapy of advanced prostate cancer.

Immunotherapy of prostate cancer (CaP) may be a promising novel treatment option for the management of advanced CaP. However, the lack of suitable tumor antigens remains a major obstacle for the rational design of vaccines. To characterize potential CaP antigens, we determined the mRNA expression of the prostate-specific genes C1, C2, C5, PAGE-1, and prostate stem cell antigen (PSCA) in hormone-refractory CaP, benign prostatic hyperplasia, CaP cell lines, and CaP specimens. Among these gene products, only expression of PSCA appears to be retained in the majority of advanced CaP samples, as shown by reverse transcription-PCR analyses. Peptide fragments of PSCA presented in the context of major histocompatibility molecules could serve as recognition targets for CD8 T cells, provided these lymphocytes were not clonally deleted or peripherally tolerized. Our goal was to determine whether the human T-cell repertoire could recognize PSCA-derived peptide epitopes in the context of a common class I allele, HLA-A0201. Of nine peptides that, according to HLA-A0201 binding motifs, were candidate ligands of A0201 class I molecules, three peptides were able to stabilize HLA-A0201 molecules on the cell surface. One of the latter peptides, encompassing amino acid residues 14-22, was capable of generating a PSCA-specific T-cell response in a human lymphocyte culture from a patient with metastatic CaP. PSCA-specific CTLs recognized peptide-pulsed targets as well as three prostate carcinoma lines in cytotoxicity assays, indicating that this peptide could be endogenously processed. In conclusion, our findings establish PSCA as a potential target for antigen-specific, T cell-based immunotherapy of prostate carcinoma.

Current Status of Dendritic Cell-Based Tumor Vaccination.

For several decades, approaches utilizing nonspecific immune stimulants have provided evidence that the immune system, when properly activated, may eradicate cancer cells. However, it was only after the identification of the first human tumor-associated antigen, less than a decade ago, that development of specific vaccination procedures for cancer patients became feasible. Recent insights into the pivotal role of dendritic cells (DCs) for initiation and regulation of immune responses have allowed the design of DC-based tumor vaccination trials. In addition, the development of methods to raise large numbers of DCs from peripheral blood monocytes has paved the way for their clinical application. Tumor-specific vaccination utilizing antigen-loaded autologous DCs, has become practical and applicable to patients and may lead to vigorous antitumor responses. This review outlines recent progress, obstacles still to be overcome, and the future potential of DC-based vaccination. Copyright 2000 S. Karger GmbH, Freiburg

Endopyelotomy for primary ureteropelvic junction obstruction: risk factors determine the success rate.

PURPOSE: We prospectively assessed the feasibility, complications, and short-term and long-term results of endopyelotomy for primary ureteropelvic junction obstruction. MATERIALS AND METHODS: In 80 consecutive patients primary ureteropelvic junction obstruction was diagnosed by excretory urogram or nephrostomogram, retrograde pyelography, diuresis renography and the Whitaker test in ambiguous cases. In all patients antegrade endopyelotomy was performed with a cold knife and an indwelling stent was left for 6 weeks. At 6 and 24 months postoperatively results were assessed clinically by an excretory urogram and/or diuretic renography and later by questionnaire and ultrasound. RESULTS: The primary success rate was 89% (71 of 80 patients) after the first endopyelotomy and increased to 91% (73 of 80 patients) after 2 patients had a second endopyelotomy. After median followup of 26 months (range 1.5 to 72) 6 of the 73 initially successfully treated patients had relapse. Two were successfully re-treated by a second endopyelotomy, resulting in an overall success rate of 81% (65 of 80 patients) after 1 procedure and 86% (69 of 80 patients) after a second endopyelotomy in 4 patients. Mean preoperative pyelocaliceal volume decreased from 64 +/- 33 to 41 +/- 20 ml. (p = 0.0003) 6 months after endopyelotomy and did not change during the following 18 months. The probability of successful endopyelotomy was better in patients with a preoperative pyelocaliceal volume less than 50 ml. (87%) and worse in patients with a volume greater than 50 ml. (76%). A crossing vessel to the lower pole of the kidney causing persistent functional obstruction of the ureteropelvic junction was found in 6 of the 10 patients re-treated by open pyeloplasty (9) or nephrectomy (1). Preoperative mean renal function as determined by diuretic renography was significantly lower in patients with failed endopyelotomy than in successfully treated patients. Successfully treated patients showed no change in renal function 6 and 24 months postoperatively. CONCLUSIONS: Endopyelotomy in primary ureteropelvic junction obstruction is a safe, minimally invasive procedure with a high primary success rate and a low relapse rate. Open pyeloplasty could be avoided in 86% of our patients. Endopyelotomy is less invasive, has less functional and esthetic sequelae than open pyeloplasty and does not compromise open surgery if that becomes necessary. We recommend endopyelotomy as first line treatment for patients with primary ureteropelvic junction obstruction.

Prospective therapeutic studies in nephrolithiasis.

Prospective randomized trials with respect to stone prophylaxis deal mainly with idiopathic calcium stone disease. There is a lot of evidence that alkali citrate, thiazides and allopurinol are effective in many patients. However, appropriate patient selection seems to be crucial. Alkali citrate and allopurinol have proven clinical efficacy in patients with hypocitraturia or hyperuricosuria, respectively. The correct method of patient selection for treatment with thiazides remains unclear. Despite the lack of prospective randomized trials, it is generally accepted that the first steps in the prophylaxis of idiopathic calcium stone disease are high fluid intake and a sensible diet.

Intravesical versus intravesical plus intradermal bacillus Calmette-Guerin: a prospective randomized study in patients with recurrent superficial bladder tumors.

PURPOSE: Intravesical instillation of bacillus Calmette-Guerin (BCG) induces various immunological reactions and decreases the recurrence rate of superficial bladder tumors. To determine whether additional immune stimulation with concomitant intradermal BCG applications could further lower the recurrence rate, 154 patients with superficial bladder tumors at high risk for recurrence were randomized to receive either 6 intravesical instillations of 120 mg. Pasteur strain BCG alone or combined with intradermal application. MATERIALS AND METHODS: A total of 76 patients received intravesical and intradermal BCG, while 78 received intravesical BCG only. Median followup was 41 months (range 2 to 89) and 36 months (range 2 to 86), respectively. Both treatment groups were comparable regarding patient age and number of previous transurethral bladder tumor resections, as well as tumor recurrence rate, stage and grade before BCG therapy. RESULTS: A highly significant decrease in the monthly tumor recurrence rate was observed in both arms after BCG compared to the pretreatment recurrence rates (p < 0.0001). Recurrence rate decreased from 0.73 +/- 1.07 (standard deviation) to 0.06 +/- 0.13 in the combined treatment group and from 0.71 +/- 0.90 to 0.074 +/- 0.17 in the intravesical treatment only group. However, we were unable to find any difference between the 2 groups regarding interval to initial recurrence or recurrence rates after BCG treatment. Changes in the purified protein derivative skin test performed before and after BCG therapy were not useful to predict response to treatment because 44% of our patients already had a positive test before treatment. Also, interpretation of the skin test was difficult and not always reliable. In the multivariate analysis, however, fever was an important prognostic factor. Patients with increased body temperature greater than 37.5C had a significantly lower recurrence rate than those without fever (37.5C or less) after BCG instillation (p = 0.009). Moreover, fever after BCG instillation was observed significantly more frequently in patients with a positive purified protein derivative skin test before treatment (p = 0.021). CONCLUSIONS: The therapeutic benefit from intravesical BCG apparently was not substantially improved by simultaneous intradermal BCG vaccination. Fever following intravesical BCG instillation is an important prognostic factor regarding superficial bladder tumor recurrence. Fever occurs predominantly in patients who were previously sensitized to mycobacteria (by BCG vaccination or infection) as shown by a positive pretreatment purified protein derivative skin test. This finding suggests that previously sensitized patients respond significantly better to a single course of intravesical BCG.

Analysis of early failures after intravesical instillation therapy with bacille Calmette-Guérin for carcinoma in situ of the bladder.

OBJECTIVE: To analyse the clinical and therapeutic consequences of early treatment failure after bacille Calmette-Guérin (BCG) instillation therapy for carcinoma in situ of the bladder. PATIENTS AND METHODS: A total of 115 patients with carcinoma in situ (Tis) of the bladder were treated by intravesical instillation of living BCG vaccine (Immun BCG Pasteur F). Twenty five patients had primary Tis and 90 had secondary Tis with synchronous or prior superficial papillary tumours. All papillary tumours were resected before instillation of BCG. All patients completed one series of 6 weekly instillations of 120 mg BCG. RESULTS: Twenty-two of 25 patients (88%) with primary Tis responded completely, with negative cytology and cystoscopy findings within a median follow-up period of 44 months. Three of the 25 (12%) had cytological evidence of disease within 9 months of therapy and were considered to be early treatment failures. One patient had muscle-invasive bladder cancer, one had Tis and invasive cancer of the prostatic urethra, and the last, in whom a second BCG course also failed, had Tis of both ureters. Seventy of 90 patients (78%) with secondary Tis had a complete response after treatment with BCG, with repeated negative cytology and cystoscopy examinations within a median follow-up time of 40 months. Twenty of the 90 (22%) with secondary Tis had positive cytology within 9 months after BCG therapy and were considered early treatment failures. Five of these 20 had a cystectomy, three for persistent Tis of the bladder and two for a solid urothelial carcinoma of the prostate. The remaining 15 early failures received a second course of BCG. Four of these 15 patients responded and the remaining 11 failed the second course. The 11 failures included two patients with multifocal T1 G3 bladder cancers. four with invasive bladder cancer, two with solid urothelial carcinomas of the prostatic urethra, and three with Tis of the upper urinary tract. CONCLUSIONS: According to these data, early treatment failure after 6 weekly instillations of 120 mg Immun BCG Pasteur F is an alarming signal which requires immediate re-assessment of the patient to exclude a muscle-invasive bladder cancer or an extravesical carcinoma in situ, either in the upper urinary tract or in the prostatic urethra.

Prognosis after extracorporeal shock wave lithotripsy of radiopaque renal calculi: a multivariate analysis.

To obtain a better understanding of the prognostic factors influencing treatment outcome after extracorporeal shock wave lithotripsy (ESWL), a multivariate logistic analysis of the data from 246 patients has been undertaken. All of the patients were treated with the Dornier lithotriptor HM-3 for radiopaque renal calculi. Treatment success was defined as stone-free within 3 months of one ESWL session and without adjuvant measures after ESWL. In a first analysis, 210 patients with solitary and multiple calculi without adjuvant measures before ESWL were studied. Of 210 patients, 141 (67%) were free from stones after 3 months). Significant influences on the success rate were body mass index and stone number. In a second analysis only those 160 patients with solitary calculi were considered. In this group, age, body mass index, stone location, stone burden and serum calcium significantly influenced the prognosis. When patients with adjuvant measures were added to the analysis an increasing prognostic importance of the stone burden was seen. In patients with a small to medium stone burden (< 4.0 cm3), the number of stones seemed to be more important than the stone burden. Patients appear to have the best chance for successful ESWL when their body mass index is between 20 and 28, their age is between 40 and 60 years, their stones are in the renal pelvis and solitary, the stone burden is < 1.0 cm3, and when their serum calcium is normal.

EQUIL93: a tool for experimental and clinical urolithiasis.

An extensively updated version of the EQUIL software is described. The former version, designated EQUIL2, is widely used to study urolithiasis and related areas of biomineralization. In this report, we discuss recent enhancements which give EQUIL93 an expanded scope of application. This program has been frequently used in studies of the physicochemical processes underlying stone salt crystallization, especially crystal growth and nucleation, but it has also been employed as an aid for in vivo research and as an evaluator of therapeutic measures. We illustrate several new applications, including some outside the urologic realm, and we discuss how the enhanced software can be helpful in stone risk assessments.

Extracorporeal shock wave lithotripsy in situ or after push-up for upper ureteral calculi: a prospective randomized trial.

A total of 110 patients with upper ureteral calculi was admitted to a prospective trial and randomly allocated to 2 groups: 1 group treated with in situ extracorporeal shock wave lithotripsy (ESWL) and 1 group treated with ureteral manipulation before ESWL. All patients had solitary upper ureteral calculi without urinary infection. The stones had to be smaller than 1 cm. and located more than 2 cm. lateral to the spine. ESWL was performed with the Dornier HM3 lithotriptor. One patient in the in situ ESWL group had to be treated twice because disintegration of the stone was insufficient after the initial treatment session. All other patients underwent only 1 treatment session. Because 16 patients were lost to followup, 94 were evaluable for the analysis of immediate and long-term results. For disintegration of the stones in situ ESWL needed significantly more shock waves (1,844 +/- 639 versus 1,297 +/- 473, p < 0.001) and a higher voltage (19.5 +/- 1.4 versus 18.7 +/- 0.9 kv., p < 0.001). There were no severe complications in either treatment group. At 3 months 44 of 46 patients (96%) after in situ ESWL and 45 of 48 (94%) after ureteral manipulation before ESWL were free of stones. In view of these results it is suggested that uncomplicated upper ureteral calculi (as defined previously) should be treated first with in situ ESWL, thus, avoiding an invasive procedure.

[Urological emergencies]. / Der urologische Notfall.

Every general practitioner has to deal with urologic emergencies. The most frequent illnesses are urinary retention, acute scrotum, priapism, macrohematuria, nephritic colic, obstructive pyelonephritis and pyonephrosis. Whereas urinary retention, as well as acute ureteric stone colic must generally be treated by the practitioner, the urologist must often be consulted in case of an acute scrotum or for priapism. Testicular torsion is one situation, where surgical treatment needs to be performed within 6 hours. Of utmost importance is his timely assistance with the obstructive pyelonephritis and pyonephrosis. These are initially often not recognized, especially because the first ultrasound examination of the intrarenal pyelone may not show a dilatation of the collecting system despite obstruction. If the adequate treatment with drainage and antibiotics is applied too late, this can result in serious and potentially lethal consequences.

Ileal bladder substitute: antireflux nipple or afferent tubular segment?

Spheroidal bladder substitutes made from double-folded ileal segments, similar to Goodwin's cup-patch technique, are devoid of major coordinated wall contractions. This, together with the reservoir's direct anastomosis to the membranous urethra, prevents major intraluminal pressure peaks and assures a residue-free voiding of sterile urine. In order to determine whether, under these conditions, an afferent tubular isoperistaltic ileal segment of 20-cm length protects the upper urinary tract as efficiently as an antireflux nipple, 60 male patients who were subjected to radical cystectomy were prospectively randomised to groups in which a bladder substitute was formed together with either of these 2 antireflux devices. An analysis of the results obtained in 20 patients from each group who could be followed for more than 1 year (median observation time 30 and 36 months) showed no differences between the groups in metabolic disturbances, kidney size, reservoir capacity, diurnal and nocturnal urinary continence, the incidence of urinary tract infection or episodes of acute pyelonephritis. Later than 1 year postoperatively, intravenous urograms of the renoureteral units of 25% of the patients with antireflux nipples showed persistent but generally slight dilatation of the upper urinary tracts. This observation was significantly more frequent than it was in patients with afferent tubular segments. Urodynamic and radiographic studies showed that the competence of the antireflux nipples was secured by the raised surrounding intravesical pressure. This, however, also resulted in a transient functional obstruction, and a gradual rise of the basal pressure in the upper urinary tracts was recorded. In patients with afferent ileal tubular segments, contrast medium could be forced upwards into the renal pelvis when the bladder substitutes were overfilled. However, despite raised intravesical pressures, peristalsis in the isoperistaltic afferent tubular segment gradually returned contrast medium back to the reservoir. Our results suggest that the combination of an ileal low-pressure reservoir together with an afferent tubular isoperistaltic limb is at least as good as an antireflux nipple valve. Moreover, the use of the afferent ileal limb makes it possible to resect the distal and often diseased ureters together with the paraureteric lymphatics at a safe distance from the bladder tumor. This avoids also distal ischemic ureteric stenosis and makes possible a simple end-to-side ureterointestinal anastomosis with a small complication rate.