Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer -what has gone wrong? A blueprint for the way forward in biomarker studies.

BACKGROUND: Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. METHODS: Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. RESULTS: Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. CONCLUSIONS: Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies.

Frequent PD-L1 expression in testicular germ cell tumors.

BACKGROUND: Many testicular germ cell cancers are curable despite metastatic disease, but about 10-15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies. METHODS: Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue. RESULTS: Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells. CONCLUSIONS: This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.

Brain metastasis in renal cancer patients: metastatic pattern, tumour-associated macrophages and chemokine/chemoreceptor expression.

BACKGROUND: The mechanisms of brain metastasis in renal cell cancer (RCC) patients are poorly understood. Chemokine and chemokine receptor expression may contribute to the predilection of RCC for brain metastasis by recruitment of monocytes/macrophages and by control or induction of vascular permeability of the blood-brain barrier. METHODS: Frequency and patterns of brain metastasis were determined in 246 patients with metastatic RCC at autopsy. Expression of CXCR4, CCL7 (MCP-3), CCR2 and CD68(+) tumour-associated macrophages (TAMs) were analysed in a separate series of 333 primary RCC and in 48 brain metastases using immunohistochemistry. RESULTS: Fifteen percent of 246 patients with metastasising RCC had brain metastasis. High CXCR4 expression levels were found in primary RCC and brain metastases (85.7% and 91.7%, respectively). CCR2 (52.1%) and CCL7 expression (75%) in cancer cells of brain metastases was more frequent compared with primary tumours (15.5% and 16.7%, respectively; P<0.0001 each). The density of CD68(+) TAMs was similar in primary RCC and brain metastases. However, TAMs were more frequently CCR2-positive in brain metastases than in primary RCC (P<0.001). CONCLUSION: Our data demonstrate that the monocyte-specific chemokine CCL7 and its receptor CCR2 are expressed in tumour cells of RCC. We conclude that monocyte recruitment by CCR2 contributes to brain metastasis of RCC.

Prospective multicentre study using high intensity focused ultrasound (HIFU) for the focal treatment of prostate cancer: Safety outcomes and complications.

PURPOSE: To investigate focal therapy using High Intensity Focused Ultrasound (HIFU) for the treatment of localized prostate cancer (CaP), we analyzed the safety and complications of this procedure. METHODS: Patients (pts) eligible for this multicenter prospective cohort study suffered from low to intermediate risk localized CaP with no prior treatment. After tumor identification on multiparametric MRI and in prostate biopsy, the lesions were treated with HIFU observing a safety margin of 8 to 10 mm. Adverse events (AE) after 30 and 90 days, as well as the required interventions were assessed and stratified for treatment localizations. RESULTS: Of the 98 men included in the study in two European centers, 35 (35.7%) experienced AEs in the first 30 days after HIFU intervention with Clavien-Dindo grade ≤ II: 15 pts (15.3%) had a postoperative urinary tract infection and 26 pts (26.5%) a urinary retention. Four pts (4.1%) underwent subsequent intervention (Clavien-Dindo grade IIIa/b). The number of late postoperative complications occurring between 30 and 90 days after intervention was low (2.0%). The highest complication rate was associated with tumors located at the anterior base (50.0%). The inclusion of the urethra in the ablation zone led to AEs in 20 out of 41 cases (48.8%) and represented a significant risk factor for complications within 30 days (odds ratio = 2.53; 95% confidence interval: 1.08-5.96; P = 0.033). CONCLUSIONS: Focal therapy of CaP lesions with a robotic HIFU-probe is safe and renders an acceptable rate of minor early AEs. The inclusion of the urethra in the ablation zone leads to an increase in early complications and should be avoided whenever possible.

Prospects and limitations of treatment with botulinum neurotoxin type A for patients with refractory idiopathic detrusor overactivity.

In this review we summarize the recent innovation of botulinum-A neurotoxin (BoNT-A) injections in the bladder as a potential new treatment option for idiopathic detrusor overactivity, refractory to conventional anticholinergic medication. BoNT-A is produced by Clostridium botulinum and consists of a 150-kDa neurotoxic protein that has the ability to cleave proteins within the nerve terminal. BoNT-A is thereby able to prevent acetylcholine release at the presynaptic membrane, resulting in a chemodenervation of the detrusor muscle after intravesical injection; this can reduce symptoms in patients with refractory idiopathic detrusor overactivity. BoNT-A intradetrusor injections might be an alternative to invasive surgery for patients in whom conservative measures and anticholinergic treatment have failed. Clinical studies with different dosages and injection protocols show success rates of 60-96% for neurogenic and non-neurogenic detrusor overactivity, with wide variations in the duration of response. The drug is still under development for the indication of idiopathic detrusor overactivity, and is under ongoing investigation for long-term efficacy and safety.

[GreenLight laser vaporisation of the prostate for treatment of benign prostatic hyperplasia. Development and significance]. / Die Greenlight-Laservaporisation der Prostata zur Therapie des benignen Prostatasyndroms. Entwicklung und Stellenwert.

GreenLight laser vaporisation has been successfully implemented in the treatment of benign prostatic hyperplasia in the last decade. Besides enhancement of the efficacy of the laser through increase of the power output to a maximum of 80 W and eventually 120 W, the encouraging clinical achievements resulted in a growing popularity of the laser system application. Swiss medical centres have been significantly involved in the evaluation of the clinical adoption of this surgical technique. Particularly the low peri- and post-operative morbidity as well as promising short- to medium-term functional results are noteworthy. In the present paper we present major results of the clinical evaluation of the technique. In addition to the important advantages of the technique, especially the virtually bloodless procedure, we also highlight the drawbacks and limitations of laser vaporisation, which possibly might entail adverse clinical effects. The future significance of this technique will thus have to be re-evaluated taking into account the yet unavailable long-term effects.

Transurethral injection therapy with dextranomer/hyaluronic acid copolymer (Deflux) for treatment of secondary vesicoureteral reflux after renal transplantation.

BACKGROUND AND PURPOSE: Secondary vesicoureteral reflux (SVUR) after renal transplantation may cause recurrent urinary-tract infections (UTI) and loss of renal function. There are only a few reports on the endoscopic treatment of SVUR by transurethral injection therapy. This is the first report of transurethral injection of dextranomer/hyaluronic acid copolymer (Deflux; Q-Med Scandinavia, Uppsala, Sweden) to relieve SVUR after renal transplantation. PATIENTS AND METHODS: Between November 2003 and October 2005, four women were treated for SVUR with transurethral injections of dextranomer/hyaluronic acid copolymer. All patients had deterioration of renal function attributable to SVUR, recurrent UTI, or both. The mean follow-up was 29 months (range 16-38 months). RESULTS: Initially, SVUR was corrected in all patients. Recurrent SVUR made a second treatment necessary in two patients. Three patients had no signs of SVUR 15, 27, and 36 months after the treatment. Renal function remained stable in these patients, and two were free of UTI. One of the patients who received two Deflux injections developed a filiform stenosis of the distal ureter, which was corrected by ureteropyeloplasty with the native ureter. CONCLUSION: Transurethral injection therapy with Deflux is a minimally invasive treatment option for patients with SVUR after renal transplantation. A second treatment seems to be necessary in some cases. Complications such as ureteral obstruction may occur.

Reluctance over right-sided retroperitoneoscopic living donor nephrectomy: justified or not?

UNLABELLED: We retrospectively compared perioperative donor outcomes and early complication rate of right- and left-sided retroperitoneoscopic living donor nephrectomy (RLDN). METHODS: From November 2001 to April 2006, we performed 118 RLDN. Including 24% (n = 28) right-sided RLDN and 76% (n = 90) left-sided RLDN. Perioperative results and the rate of adverse events were compared for both sides. RESULTS: We observed no significant difference in operation time, blood loss, warm ischemia time, or postoperative creatinine levels between right- and left-sided kidney donors. RLDN was successfully performed in 116 of 118 donors. One donor in each group had to be converted to an open approach. We observed one graft loss due to renal artery kinking in one recipient after left-sided RLDN. Two right donations needed a saphenous venous patch due to a short right renal vein (<2 cm). Overall, intraoperative and postoperative complications were comparable between the two donor groups. CONCLUSION: Right-sided RLDN provides comparable perioperative and postoperative results to those of left-sided RLDN. Our results demonstrated that groups with significant experience in RLDN can perform right living donor nephrectomy safely and efficiently with minimal invasiveness.

[Photoselective vaporization of the prostate: experience with prostate adenomas >80 cm3]. / Photoselektive Vaporisation der Prostata: Erfahrungen mit Prostataadenomen >80 cm3.

BACKGROUND: We report about our experiences with photoselective vaporization of the prostate (PVP) in patients with symptomatic benign prostatic hyperplasia (BPH) and total prostate volume larger than 80 cm(3). PATIENTS AND METHODS: The study included 201 patients with BPH: 51 (25.4%) patients had a prostate volume larger than 80 cm(3) and 150 (74.6%) patients had a volume smaller than 80 cm(3) in the preoperative transrectal ultrasound. RESULTS: The mean operation time for patients with large prostates was 79 min. Neither TUR syndrome nor severe bleeding was observed. In patients with large adenomas peak urinary flow increased by 135, 136, and 132% after 6, 12, and 24 months, respectively. The overall complication rate was comparable in both groups. CONCLUSION: PVP is characterized by excellent perioperative safety and significant improvement of voiding parameters. PVP is feasible in patients with large prostates.

Retroperitoneoscopic living donor nephrectomy: a comparison with the open approach in respect of early postoperative pain management.

INTRODUCTION: We retrospectively compared perioperative donor outcomes and early postoperative pain control after retroperitoneoscopic (RLDN) and standard open (OLDN) living donor nephrectomy. METHODS: One hundred donors included fifty after RLDN (37 women/13 men) and 50 after OLDN (35 women/15 men) were retrospectively analyzed for basic analgesics, for opioid consumption, and for visual analog scale (VAS) to verify the experienced pain. The donors were questioned in the morning and evening of the first through fifth postoperative days. RESULTS: The mean age of both groups was equal. The mean operating time was 149.7 +/- 48.2 minutes (60 to 270) for RLDN and 164.1 +/- 30.3 minutes (60 to 240) for OLDN (P = NS). The mean warm ischemia time was 120 +/- 36 seconds (50 to 240) and 114 +/- 31 seconds (60 to 190) for the RLDN and OLDN groups, respectively (P = NS). The mean evening VAS for RLDN versus OLDN on postoperative days 1 to 5 was: 2.1 versus 2.2 (P = NS), 0.9 versus 1.8 (P = .009), 0.5 versus 1.3 (P = .016), 0.1 versus 0.7 (P = .013), and 0.1 versus 0.7 (P = .013), respectively. In both groups there was a tendency toward a higher VAS score in the morning than in the evening. RLDN donors showed significantly earlier period free of pain (VAS = 0) than those after OLDN. There was a significant difference of being free from any opiate between both groups after surgery. CONCLUSIONS: After RLDN donors experienced less postoperative pain than after OLDN over the early postoperative days. Therefore, postoperative regional anesthesia is not necessary for donors operated by a retroperitoneoscopic approach.

Free/total prostate-specific antigen ratio can prevent unnecessary prostate biopsies.

OBJECTIVES: To evaluate the ability of free/total prostate-specific antigen (PSA) ratio to improve specificity of prostate cancer detection, compare Diagnostic Products Corporation (DPC) Immulite and Ciba Corning ACS 180 total (t)PSA assay, and define an assay-specific cutoff point and reflex range for DPC PSA ratio (PSAR). METHODS: In a prospective study, 206 men were enrolled with measurement of both assays. Group 1 consisted of 173 men with a suspicion of prostate cancer (PCA). Thirteen men with known PCA (group 2) and 20 men younger than 32 years (group 3) were used as control groups. RESULTS: Our results in group 1 (115 with benign prostatic hyperplasia [BPH], 58 with PCA) revealed a sensitivity of 82.7%, a specificity of 45.2%, and an accuracy of 57.8% for the DPC tPSA assay (cutoff point more than 4.0 ng/mL) within the entire PSA range. tPSA values of the ACS 180 assay were 1.97-fold higher. Within the tPSA gray zone of 2.5 to 10 ng/mL (66 BPH, 23 PCA), specificity and accuracy of DPC tPSA can be improved by using the DPC PSAR (cutoff point less than 19%) from 33.3% to 71.2% and 42.7% to 70.8%, respectively, maintaining the same sensitivity level of 69.6%. CONCLUSIONS: By combining tPSA testing with PSAR within the gray zone, 39.7% (25 of 63) of unnecessary biopsies can be saved, without missing any additional cancers compared with tPSA testing alone. The optimal reflex range for DPC PSAR is 2.5 to 10 ng/mL and the best PSAR cutoff point for biopsy criterion is less than 19% in our high-risk population, with a cancer yield of 34%. Because we still do not have an international PSA standard, it is important to use assay-specific "normal values" and PSAR cutoff points.

Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome.

OBJECTIVES: To investigate the prepubertal prevalence of intratubular germ cell neoplasia of the unclassified type (ITGCNU) and its significance as a predictor of testicular cancer and to evaluate the effect of early orchiopexy (at younger than 2 years of age) on subsequent fertility of patients with bilateral cryptorchidism. METHODS: Testicular biopsies (n = 660) from 440 prepubertal patients with cryptorchidism who underwent orchiopexy between January 1, 1970 and December 31, 1979 were evaluated for ITGCNU using placental-like alkaline phosphatase (PLAP) antibody. The clinical outcome in 15 patients with PLAP-positive germ cells was evaluated in 1997. In addition, the effect of age at surgery on the fertility of patients with bilateral cryptorchidism was assessed by clinical follow-up until 1997 and was correlated with the histologic data at orchiopexy. RESULTS: PLAP-positive germ cells morphologically identical with adult ITGCNU were found in the biopsies of 22 patients (5%). After more than two decades, none of the 15 patients with successful follow-up developed testicular cancer. The fertility outcome in the patients with bilateral cryptorchidism correlated with the number of spermatogonia at orchiopexy (P = 0.018), but correlated inversely with age at orchiopexy (P = 0.021). CONCLUSIONS: PLAP-positive germ cells in prepubertal testicular biopsy specimens are not necessarily precursors of testicular cancer after orchiopexy. In addition, our data support the idea that early orchiopexy may be beneficial in preventing infertility.

Specific determination of germ cell alkaline phosphatase for early diagnosis and monitoring of seminoma: performance and limitations of different analytical techniques.

Two-dimensional electrophoresis, ion-exchange chromatography and immunoassay were evaluated in order to improve the diagnostic specificity of the germ cell specific isoenzyme of alkaline phosphatase (GCAP) for the detection of seminoma. Assessment of GCAP is hampered by its structural heterogeneity and low serum concentration. The structural heterogeneity of GCAP from seminoma tissue could be clearly visualized by two-dimensional electrophoresis. We inferred that it depended on allelic amino acid substitutions, varying sialylation and differential cleavage of the membrane anchor. The allelic variability of GCAP affects the accuracy of immunological measurements. However, immunoassay was found to be the only technique sensitive enough to assess GCAP in serum. The elevated GCAP levels in 15% of healthy blood donors were shown to be correlated with smoking. Further studies clarifying how to interpret the values measured in smokers are prerequisite for the introduction of GCAP as a serum marker for seminoma. In the future, GCAP might be utilized for the detection of carcinoma in situ (CIS) cells in ejaculate. Assessment of the enhanced expression of cellular GCAP by CIS cells exfoliated into ejaculate could be a means for noninvasive, early diagnosis that presumably will not be hampered by the patient's smoking habits.

P53 mutations and loss of heterozygosity on chromosomes 8p, 16q, 17p, and 18q are confined to advanced prostate cancer.

We analysed 39 prostatic carcinomas for loss of heterozygosity on chromosomal arms 8p, 10q, 16q, 17p and 18q and for mutations in the p53 anti-oncogene. Loss of heterozygosity (LOH) on 8p was detected in one out of 5 informative tumors, LOH on 16q in 3 out of 21 tumors, LOH on 17p in 2 out of 18 tumors, and LOH on 18q in 2 out of 17 tumors. No deletions were observed on 10q in 14 informative tumors. p53 alterations occurred in 3 out of 38 examined tumors, comprising two point mutations and a small deletion. Chromosomal deletions and p53 mutations were confined to locally invasive prostatic carcinomas, suggesting that they are associated with the progression of some prostate cancers rather than with tumor initiation.

Retroperitoneoscopic pyeloplasty for ureteropelvic junction obstruction.

BACKGROUND AND PURPOSE: Retroperitoneoscopy is an established procedure for renal surgery. We evaluated our results with retroperitoneoscopic pyeloplasty for ureteropelvic junction (UPJ) obstruction. PATIENTS AND METHODS: In 14 female and 10 male patients, a retroperitoneoscopic pyeloplasty was performed (13 right/11 left). Four patients had previously had an endopyelotomy. The operation was performed using standard retroperitoneoscopic technique with the patient in a flank position. After preparation of the ureter and renal pelvis, the UPJ was resected in 22 patients in an Anderson-Hynes pyeloplasty. Twenty of these patients had a crossing vessel. The other two patients, who had small renal pelves, were operated on with a Fenger pyeloplasty. In all patients a 7F double-J stent was placed. RESULTS: The mean operative time was 189 minutes (range 70-360 minutes), and the average blood loss was 110 mL (range 50-400 mL). There were no intraoperative complications, although one patient with adhesions and scarring after previous endopyelotomy had to be converted to open surgery. The transurethral catheter was left for 7 days in the first 10 cases and for 4 days in the 14 subsequent patients. The hospitalization time was 9.7 and 7.5 days, respectively. The only postoperative complication was a urinoma, which was punctured. The double-J catheter was removed after an average of 4.6 weeks (range 4-8 weeks). Intravenous urography 6 weeks later showed no obstruction. The mean follow-up time was 11.5 months (range 1-24 months) with no signs of obstruction on ultrasonography. CONCLUSIONS: Retroperitoneoscopic pyeloplasty for UPJ obstruction is a safe and effective procedure. Our short-term results are similar to those of open pyeloplasty with the advantage of a minimally invasive approach.

[Results of comprehensive data collection concerning urologic laparoscopy]. / Ergebnisse der bundesweiten Datenerhebung über die urologische Laparoskopie.

To evaluate the current status of laparoscopy, the "Working Group Laparoscopy" of the German Urological Association performed a questionnaire among urologists in Germany. Of 300 questionnaires 183 were returned and analyzed (61%): 54% of the departments already performed laparoscopy and another 50% are planning to introduce this technique. The major concerns are economical (70%), long learning curve (92%), investment (53%), and lack of scientific data (76%). Simple nephrectomy, cryptorchism, and varicoceles are treated by 66, 59, and 58 of the 96 departments laparoscopically (of 183 resp.). Laparoscopic surgery for radical prostatectomy and tumor nephrectomy is done by 32 and 34 of 96 departments. Only a minority of the centers performs more than 40 laparoscopies per year and indication. Compared to a survey conducted in 1995, the acceptance level of this technique has increased (100% vs 48%). Only a minority of the departments performs more than 40 laparoscopic interventions per year for one indication.

[Angiosarcoma of the kidney. Case report and review of the literature]. / Angiosarkom der Niere. Fallbeispiel und Literaturübersicht.

The primary renal angiosarcoma is a rarely seen highly malignant tumor. Making a diagnosis based on histology may prove difficult. Because of hematogenous formation of metastases and bad prognosis in most cases we recommend that the surgical intervention be followed by the well tolerated systemic chemotherapy with Doxorubicin and Ifosfamid.

[Seminal vesicle cyst and ipsilateral kidney failure. Report of 2 cases and review of the literature]. / Samenblasenzyste und ipsilaterale Nierenagenesie. Bericht über 2 Fälle und Literaturübersicht.

The seminal vesicle cyst is a congenital malformation of the male urogenital tract, which seems to be more frequent than originally presumed. It is usually combined with an ipsilateral renal agenesis and an ectopic ureter. Two relevant cases are reported and embryology, major presenting symptoms, diagnostic procedures, differential diagnosis and therapy are extensively discussed.

[The 80 W potassium-titanium-phosphate (KTP) laser vaporization of the prostate. Technique and 6 month follow-up after 70 procedures]. / Die 80-Watt-Kalium-Titanyl-Phosphat- (KTP-)Laservaporisation der Prostata. Technik und 6-Monatsergebnisse nach 70 Eingriffen.

BACKGROUND: Despite good efficacy, even in our days, TURP remains a potentially difficult procedure to perform and is associated with significant risks for the patient. Several alternatives have been tried to reduce the known perioperative morbidity. We report our first experiences with 80 W potassium titanyl phosphate (KTP) laser vaporization of the prostate in patients with symptomatic BPH. PATIENTS AND METHODS: In 70 patients 80 W KTP laser vaporization was performed successfully. Mean age was 70.5 years (46-93 years) and mean transrectal prostate volume was 48.1 ml (10-250 ml). RESULTS: Mean operating time was 41 min ( n=22), 64 min ( n=33), and 80 min ( n=15) for a 26 ml, 46 ml, and a 91 ml prostate, respectively. At time of discharge, after 1 month, and 6 months the urinary peak flow increased by 75.4%, 166.8%, and 168.6%, respectively. CONCLUSION: The 80 W KTP laser vaporization of the prostate combines the tissue-debulking properties of transurethral resection of the prostate with the known good hemostatic properties of other laser procedures. It is a safe procedure for the patient and provides a virtually bloodless operation and immediate improvement of voiding.

[Ureteral stent placement in hydronephrosis during pregnancy]. / Die retrograde Ureterschienung bei Schwangerschafts-hydronephrose.

In this study we describe 22 cases of retrograde ureteral stent placement in pregnant women with therapy-resistant flank pain due to hydronephrosis. Eleven were primiparous and one patient expected twins. Eight of 22 patients presented symptoms of pyelonephritis. In 21 cases the hydronephrosis was located on the right and in 4 cases it was bilateral. Maximal lower calix diameter was 12 mm (range 9-22 mm). With the exception of two cases, sonographically controlled stent placement was performed under local anesthesia without sedation. All patients were painfree within 6 days and were given prophylactic low doses of antibiotic until the day of delivery. Renal function remained within the normal limits. Double-J stent displacement occurred in 3 patients - of which one underwent nephrostomy. Postnatal examination demonstrated urolithiasis in 4 of 19 patients. This study provides evidence for effectiveness of retrograde ureteral Double-J stent placement as a therapeutic option in cases of severe symptomatic hydronephrosis during pregnancy with a low morbidity rate.