A cross-sectional analysis of paediatric urologists' current practices, opinions and areas of perceived importance in the delivery of adolescent & transitional care.

INTRODUCTION: Complex urological anomalies often require continued care as patients reach adulthood. Adequate transition for adolescents with ongoing urological care needs is critical to allow for seamless care in adult hospitals. Studies have shown that this can lead to improved patient and parental satisfaction, and lower utilisation of unplanned inpatient beds and emergency department visits. There is currently no ESPU-EAU consensus on the adequate mechanism and very few individual papers examining the role of urological transition for these patients in a European setting. This study aimed to identify current practice patterns in paediatric urologists providing adolescent/transitional care, to assess their opinions towards formal transition and to look for variations in care. This has implications for long-term patient health and specialist care. METHODS: An 18-item cross-sectional survey was compiled and pre-approved through the EAU-EWPU and ESPU board offices prior to dissemination to all registered ordinary members affiliated with the ESPU. This was created using a mini-Delphi method through the EWPU research meetings to provide current semi-quantitative data relating to current opinions and attitudes of this cohort. RESULTS: A total of 172 respondents (55% paediatric general surgery; 45% urology) across 28 countries completed the survey. The majority of respondents were in practice >10 years and spent >80% time in paediatric urology. There was no formal transition process according to 50% respondents and over half of those that did have less than 1/month, with <10% using validated questionnaires. More than two-thirds respondents continued to provide care after transition, as >70% units had no designated corresponding adult service. Furthermore, 93% paediatric believe a formal transition service to be very important, using a multidisciplinary framework. A pareto chart demonstrated 10 specific conditions to be of most interest in transition to adulthood. CONCLUSION: This is the first study to assess the requirements of paediatric urologists for adequate transitional care, however due to the nature of the survey's distribution, this was a non-scientific poll based on a convenience sample of respondents. It is critical that dual-trained or adult-trained urologists with a specific interest in paediatric urology work with current paediatric urologists in a multidisciplinary fashion to facilitate early transition based on the adolescent's developmental and biopsychosocial requirements. National urological and paediatric surgical societies need to make transitional urology a priority. The ESPU and EAU should collaboratively consider developing transitional urology guidelines to allow a framework by which this can occur.

Long-term biochemical evaluation of the androgen receptor pathway in males with disorders of sex development.

PURPOSE: Disorders of sex (DSD) development represent a serious condition. Most of the underlying mechanisms remain unclear. Disturbances within the androgen receptor (AR) pathway frequently account for 46 XY-DSDs. The individual gender-related outcome often is unsatisfactory. We present a long-term AR gene-mutation-associated follow-up in a group of 46 XY-DSD patients. METHODS: Twenty patients (46 XY) who underwent genitoplasty in infancy or early childhood were retrospectively identified. Median follow-up after surgery was 16 years. All were undervirilized at initial presentation. Thirteen had female gender assignment, and 7 were raised as males. A genital skin biopsy and subsequent fibroblast cultures were done. The specific binding of dihydrotestosterone, the thermostability of the receptor hormone complex, and 5-α-reductase activity were measured. AR gene mutations were detected by direct sequencing. The individual outcome was correlated with specific AR mutations. RESULTS: AR point mutations were detected in 12, 7 were previously unknown. There was no specific androgen binding in 3, reduced affinity in 9, and normal binding in 8 patients. 5-α-Reductase activity was normal in 15, reduced in 4 and completely absent in 1 patient. CONCLUSIONS: Retrospective evaluation revealed previously unknown and established AR gene mutations being associated with a distinct long-term outcome. Identification of the molecular mechanisms causing DSD will likely improve timely diagnosis and therapy. Exact characterization of AR activation and function may offer a treatment modality in affected patients. These data may allow us to give prognostic estimations on the individual outcome adding objective criteria for gender assignment in 46 XY-DSD patients.

Extracellular microenvironment and cytokine profile of the ureterovesical junction in children with vesicoureteral reflux.

PURPOSE: Vesicoureteral reflux is caused by a defective valve mechanism of the ureterovesical junction. Previous studies have revealed structural and metabolic changes in the intravesical ureter, impairing its contractile properties. Smooth musculature and nerves are replaced by collagen, while matrix degrading enzymes are over expressed. We investigated the presence of regulating cytokines and the extracellular matrix composition to elucidate further the pathophysiology of vesicoureteral reflux. MATERIALS AND METHODS: Ureteral endings were obtained from 28 children during antireflux surgery, and 14 age matched autopsy specimens served as controls. Routine histological sections were immunostained for insulin-like growth factor-1, nerve growth factor, transforming growth factor-beta1, tumor necrosis factor-alpha and vascular endothelial growth factor. Smooth muscle staining was supplemented by tenascin C, tetranectin and fibronectin detection. Staining patterns were investigated using computer assisted, high power field magnification analyses. RESULTS: Tumor necrosis factor-alpha and transforming growth factor-beta1 were significantly more abundant in vesicoureteral reflux samples, whereas insulin-like growth factor-1, nerve growth factor and vascular endothelial growth factor were more prevalent in healthy controls. Fibronectin was intensely expressed in refluxing ureters, while it was scarce in healthy children. Tenascin C was notable within the urothelium of both groups. Only vesicoureteral reflux samples displayed tenascin C in the musculature and connective tissue. Tetranectin staining was only detected in vesicoureteral reflux. CONCLUSIONS: Several cytokines are differentially expressed in primary refluxing ureters, indicating an ongoing tissue remodeling process in the ureterovesical junction region. Additionally, the smooth muscle coat is widely lacking, while extracellular matrix proteins typical for tissue shrinkage and reorganization are over expressed. These alterations are likely to contribute to the malfunctioning active ureteral valve mechanism in primary vesicoureteral reflux.

The efficacy of dihydrotestosterone transdermal gel before primary hypospadias surgery: a prospective, controlled, randomized study.

PURPOSE: We sought to evaluate the efficacy of transdermal dihydrotestosterone treatment based on the results of hypospadias repair in children with primary hypospadias. MATERIALS AND METHODS: A total of 75 randomized consecutive children who were a mean of 33.4 +/- 3.7 months old and had primary hypospadias were included in the study between September 2004 and April 2006. While 37 children were treated with 2.5% transdermal gel daily, applied directly onto the penile shaft and glans for 3 months (group 1), 38 children did not receive any treatment preoperatively (group 2). All children underwent hypospadias repair using tubularized incised plate urethroplasty. Postoperative complications were analyzed using the Mann-Whitney U test with respect to fistulas, urethral strictures, diverticula, meatal stenosis, glanular dehiscence and scar formation according to the results at 1-year followup. RESULTS: Mean ages of the children in groups 1 and 2 were similar (30.8 +/- 5.4 months and 35.1 +/- 5.1 months, respectively). The urethral meatus was coronal in 70%, penile in 24% and penoscrotal in 5% of the patients in group 1, while it was coronal in 84% and penile in 16% of the patients in group 2. Postoperative complications included urethrocutaneous fistula in 4 patients (11%) in group 2, compared to 1 patient (3%) in group 1 (p >0.05). While 3 patients (8%) in group 2 had glanular dehiscence, no patient in the dihydrotestosterone group had this complication (p <0.05). There were 2 patients with meatal stenosis in group 2 (5%), and no patient with meatal stenosis in group 1 (p >0.05). In addition, there were 16 patients (42%) with moderate to severe postoperative scar formation in group 2, compared to only 2 patients (5%) in the dihydrotestosterone group (p <0.05). Finally, there was a significant difference between the overall reoperation rates of group 2 (9 patients, 24%) and group 1 (1 patient, 3%, p <0.05). None of our patients had signs or symptoms of urethral stricture or urethral diverticulum. CONCLUSIONS: Pretreatment with dihydrotestosterone transdermal gel was effective in decreasing the complications and improving the cosmetic results after hypospadias repair.

Fetal distribution of 5alpha-reductase 1 and 5alpha-reductase 2, and their input on human prostate development.

PURPOSE: Human prostate development starts in the tenth week of gestation. Initial interactions between the epithelium and mesenchyma are stimulated by androgens. The transformation of circulating testosterone to 5alpha-dihydrotestosterone by tissue linked 5alpha-reductase is a key event in androgen metabolism. The 5alpha-dihydrotestosterone mediates androgen effects in the urogenital sinus and external genitalia, leading to the formation of a male phenotype and androgen mediated prostate growth. Supposedly 5alpha-reductase 2 is the predominant isoenzyme in human accessory sex tissue, whereas the function of 5alpha-reductase 1 remains unclear. We focused on the detection, distribution and effects of the 2 isoenzymes during gestation and infancy. MATERIALS AND METHODS: Serial sections from fetuses and infants were immunostained using antibodies directed against 5alpha-reductase 1 and 2. Additionally, to detect the downstream products of androgen synthesis reverse transcriptase-polymerase chain reaction analyses were done for 17 beta-hydroxysteroid dehydrogenase types 2, 3 and 7. RESULTS: Immunohistochemistry revealed positive staining for each isoenzyme throughout fetal development. Moreover, reverse transcriptase-polymerase chain reaction for 5alpha-reductase 1 and 2 confirmed these findings on the transcription level. Additionally, the most relevant enzymatic downstream products of cellular androgen synthesis (17 beta-hydroxysteroid dehydrogenase 2, 3 and 7) were also detected by reverse transcriptase-polymerase chain reaction. CONCLUSIONS: To our knowledge this is the first study revealing the expression and distribution of each 5alpha-reductase isoenzyme as well as the potential contribution of 5alpha-reductase 1 during fetal human prostate development.

Structural changes of the intravesical ureter in children with vesicoureteral reflux-does ischemia have a role?

PURPOSE: Previous studies have revealed structural and metabolic changes in the distal most ureter, impairing its contractile properties, and, thus, having a role in the pathogenesis of vesicoureteral reflux. Musculature and nerves are replaced by interstitial collagen, while matrix degrading enzymes are over expressed. We investigated the microvessel architecture of the ureterovesical junction to elucidate further the pathophysiology of vesicoureteral reflux. MATERIALS AND METHODS: Ureteral endings were obtained from 28 children during antireflux surgery. Ureteral tissue from 14 age matched autopsy specimens served as control. Routine histological paraffin embedded sections were immunostained, detecting CD31 as an endothelial marker as well as vascular endothelial growth factor. Microvessel density and vascular endothelial growth factor expression were investigated based on computer assisted high power field magnification analyses. The t test and the Spearman rho test were applied for statistical evaluation. RESULTS: Overall, microvessel density was significantly reduced in cases of vesicoureteral reflux. While reflux grade and age were not correlated with microvessel density, it was particularly decreased in regions lacking smooth musculature. Vascular endothelial growth factor was observed in smooth muscle, endothelial and connective tissue cells. Additionally, cellular vascular endothelial growth factor expression was markedly abridged in cases of vesicoureteral reflux compared to healthy controls. CONCLUSIONS: Overall microperfusion is supposed to be impaired, leading to tissue ischemia due to reduction of vascular endothelial growth factor expression and subsequent microvessel density. Diminished ureteral perfusion is likely to induce and support smooth muscle dysfunction as well as subsequent extracellular matrix remodeling, including increased collagen deposition. These ongoing functional and structural alterations may further deteriorate the active valve mechanism of the ureterovesical junction, causing vesicoureteral reflux.

Interim outcome of the single stage dorsal inlay skin graft for complex hypospadias reoperations.

PURPOSE: Despite high success rates for primary hypospadias repair, some cases require multiple procedures for ultimate reconstruction. We report our experience with single stage dorsal inlay urethroplasty using skin grafts for complex reoperations. MATERIALS AND METHODS: A total of 31 patients (mean age 13.8 years) with failed previous hypospadias surgery were included in the study. Indications included fistulas, strictures, diverticula and repair breakdown. The urethral plate had been removed or was severely scarred in all patients. A free penile or groin skin graft was sutured and quilted to the corpora cavernosa, guaranteeing sufficient blood supply. The neourethra was tubularized and covered with a tunica vaginalis or dartos flap, followed by glanuloplasty. Outcome analysis included urethrograms, urethral ultrasound and flow measurements. RESULTS: Foreskin was used in 15 cases, penile skin in 12 and inguinal skin in 4. Average graft length was 3.92 cm. A total of 20 patients required glanuloplasty with a skin graft extended to the tip of the glans. After a mean followup of 30.71 months 5 patients underwent redo surgery, for a complication rate of 16.1%. Urethral stricture of the proximal anastomosis was the most frequent finding. CONCLUSIONS: This single stage approach using dorsal skin grafts is a reliable method to create a substitute urethral plate for tubularization. Complication rates are equivalent to those of staged procedures. Foreskin should be used as a graft donor site to optimize the outcome if available. This approach represents a safe option for reoperations even if the urethral plate or midline penile skin is grossly scarred.

Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children.

OBJECTIVES: To compare, in a prospective study, the efficacy of a single injection of polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux), a new biodegradable substance, and to assess the short-term and 1-year clinical effects concerning reflux resolution and the safety of these two bulking agents. Subureteral injection of bulking agents has recently demonstrated good success rates for endoscopic treatment of vesicoureteral reflux. Macroplastique has been one of the most popular bulking agents during the past years. Nevertheless, considering the synthetic property, new biodegradable substances have become more relevant. METHODS: From January 2000 to June 2001, 16 boys and 56 girls (total of 114 ureters) with a mean age of 34.5 months were treated endoscopically for vesicoureteral reflux. A single subureteral Macroplastique or Deflux injection was performed in 34 children (58 ureters) and 38 children (56 ureters), respectively. Both groups were comparable in terms of baseline parameters. Vesicoureteral reflux was grade II in 52, grade III in 57, and grade IV in 5 ureterorenal units. The procedure was performed on an outpatient basis, with the children under general anesthesia. In addition to the routine parameters, the follow-up evaluation consisted of renal ultrasonography and voiding cystourethrography at 3 and 12 months postoperatively. RESULTS: Endoscopic treatment was performed without any complications in all cases. At the 3-month follow-up visit, reflux was corrected in 50 (86.2%) of 58 refluxing ureters in the Macroplastique group and in 40 (71.4%) of 56 refluxing ureters in the Deflux group. At 1 year of follow-up, reflux correction was maintained in 80.9% of ureters in the Macroplastique group and in 67.6% of ureters in the Deflux group. No postoperative complications were observed in either group. CONCLUSIONS: A single subureteral injection of either polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux) is an effective treatment modality for children with vesicoureteral reflux. The procedure was well tolerated, safe, and associated with low morbidity. Deflux, a new biocompatible, biodegradable substance, seems to be an alternative modality to other bulking agents for treating vesicoureteral reflux in children, with acceptable short-term and 1-year results.

[Contrast-medium enhanced reflux ultrasound in children. A comparison with radiologic imaging up to now]. / Kontrastmittelverstärkte Refluxsonographie bei Kindern. Ein Vergleich zur herkömmlichen radiologischen Untersuchungstechnik.

Voiding cystourethrography (VCUG) has long been the method of choice for the diagnosis of vesicoureteral reflux (VUR). Especially in the course of conservative treatment, the radiation dose involved might become quite high over the years. Since the development of such ultrasound echo-enhancing agents as Levovist (Schering, Germany), we now have the ability to assess the diagnostic efficacy of this agent in the evaluation of VUR with a view to replacing VCUG with the radiation-free ultrasound methodology. A total of 104 children with a mean age of 5.4 years were examined using echo-enhancing ultrasound after informed consent had been obtained from their parents. For control purposes, all children were examined by standard VCUG as well. The diagnosis of VUR was judged to be positive when microbubbles appeared in the ureter or renal pelvis. Correlations were sought between the sonographic findings and those obtained by standard VCUG. In 76 (37%) of the 208 ureter-kidney units investigated, VUR was detected by both technologies. VUR was diagnosed by ultrasonography only in 5 units and by VCUG only only in 3 units. All reflux grades (I-V) were identified. The specificity and sensitivity of the contrast reflux ultrasound were significantly high. The long contrast time of up to 30 min combined with the high contrast effect resulted in convincing images with high levels of diagnostic confidence. Our results clearly demonstrate that the safety and accuracy of the diagnosis of VUR by means of contrast-enhanced ultrasound is statistically comparable to those of standard radiologic VCUG. Therefore, this methodology is an exceptional approach to reducing the number of children being exposed to ionising radiation especially during conservative follow-up of children with reflux.

Prospective randomized trial using laser acupuncture versus desmopressin in the treatment of nocturnal enuresis.

OBJECTIVES: Several treatment modalities for children suffering from monosymptomatic nocturnal enuresis are available, but desmopressin is a well-established option. On the other hand, alternative nonpharmacological therapies such as laser acupuncture are more frequently requested by the parents. To our knowledge, there is no prospective randomized trial which evaluated the efficacy of such an alternative approach in comparison with the widespread use of desmopressin. METHODS: Forty children aged over 5 years presenting with primary nocturnal enuresis underwent a previous evaluation of their voiding function to assure normal voiding patterns and a high nighttime urine production. Then the children were randomized into two groups: group A children were treated with desmopressin alone, and group B children underwent laser acupuncture. All children were investigated after a minimum follow-up period of 6 month to evaluate the duration of the response. RESULTS: The children of both groups had an initial mean frequency of 5.5 wet nights per week. After a minimum follow-up period of 6 months reevaluation revealed a complete success rate of 75% in the desmopressin-treated group. Additional 10% of the children had a reduction of their wet nights of more than 50%. On the other hand, 6 months after laser acupuncture, 65% of the randomized children were completely dry. Another 10% had a reduction of the enuresis frequency of more than 50% per week. 20% of the children in the desmopressin-treated group did not respond at all as compared with 15% in the acupuncture-treated group. Statistical evaluation revealed no significant differences among the response rates in both groups. CONCLUSION: Im comparison with pharmacological therapy using desmopressin, our study shows that laser acupuncture should be taken into account as an alternative, noninvasive, painless, cost-effective, and short-term therapy for children with primary nocturnal enuresis in case of a normal bladder function and high nighttime urine production. Success rates indicated no statistically significant differences between the well-established desmopressin therapy and the alternative laser acupuncture.

Renal cell carcinoma in a horseshoe kidney--superselective embolization of a vessel in a remaining calix after partial nephrectomy.

A 51-year-old patient underwent partial nephrectomy because of a renal cell carcinoma in a horseshoe kidney. Postoperatively a remaining calix led to persistent urinoma formation. By means of superselective embolization urine extravasation was stopped successfully. This demonstrates that superselective embolization can be an effective tool in the management of complications after open renal surgery.

Laparoscopic partial adrenalectomy for bilateral pheochromocytomas in a boy with von Hippel-Lindau disease.

OBJECTIVES: In adults, increasing numbers of adrenalectomies for pheochromocytomas are performed laparoscopically. We report for the first time laparoscopic bilateral subtotal adrenalectomy for pheochromocytomas in an 8-year-old boy with von Hippel-Lindau disease. METHODS: In July 1998, an 8-year-old boy with von Hippel-Lindau disease underwent laparoscopic adrenal-sparing surgery for bilateral pheochromocytomas. The boy presented with severe hypertension and two pheochromocytomas on both sides. RESULTS: The child could be solely treated with laparoscopic adrenal-sparing surgery. The procedure was completed as planned. There were absolutely no intraoperative or postoperative complications. Postoperatively, catecholamine levels and hypertension went back to normal. At follow-up no residual tumor could be detected and no steroid replacement therapy was necessary. CONCLUSIONS: In experienced hands, laparoscopic adrenal-sparing surgery for pheochromocytomas is feasible and safe. Moreover, this minimal invasive approach represents an exceptional improvement in life quality, especially in children with von Hippel-Lindau disease since surgery will probably be necessary again and again in their future life.

Effect of heat exposure on viability and contractility of cultured prostatic stromal cells.

OBJECTIVES: Different thermotherapeutic modalities such as transurethral microwave therapy or transurethral needle ablation have been developed to provide effective alternatives to surgical management of benign prostate hyperplasia (BPH). The mechanisms of thermotherapy, however, are not completely understood. We developed a model to investigate the effects of heat application on stromal cell viability and contractility. METHODS: Cells isolated from prostatectomy and cystoprostatectomy specimens were cultured in a selective medium. Temperatures ranging from 37 to 50 degrees C were applied for 1 h. Cell contraction was visualized by means of a cell culture microscope equipped with a time-lapse video system. For quantitative analysis, the percentage of contracting cells was evaluated; 10 microM of phenylephrine were applied for adrenergic stimulation of the cells. RESULTS: On immunohistochemistry and phase-contrast microscopy, these cells were identified as prostatic myofibroblasts. Incubation at 50 degrees C for 1 h in vitro induced immediate death of all cells, whereas at 45 degrees C all cells survived. At 37 degrees C 55% of the cells were seen to contract after addition of phenylephrine. Immediately after incubation at 45 degrees C contraction rate decreased to 29%, but returned to 46% 1 day later. CONCLUSIONS: With this model, it is possible to study the mechanisms of thermotherapy in vitro. The results suggest that the effects of thermotherapy are due to the induction of cell death rather than to reduced stromal cell contractility. Furthermore, the data show that treatment is probably only successful if temperatures in excess of 50 degrees C are maintained.

Cryptorchidism, open processus vaginalis, and associated hernia: laparoscopic approach to the internal inguinal ring.

OBJECTIVES: A nonpalpable testis was the first indication for laparoscopy in urology. This primarily diagnostic procedure has evolved to complete laparoscopic orchidopexy. An associated inguinal hernia due to an open processus vaginalis is reported in 26% of cryptorchidism cases. Simultaneous laparoscopic orchidopexy and herniorrhaphy are therefore the next logical step. METHODS: Between 1992 and 1998, 61 children underwent laparoscopy for pathology of the internal inguinal ring. In 48 boys the operation was performed for a nonpalpable testis and in 13 boys laparoscopic transection of the processus vaginalis was performed because of clinical hydrocele. RESULTS: In 25 of the 48 cases an intra-abdominal location was found with 18 existing and 7 vanishing testicles. Laparoscopic orchidopexy was performed either as a two-stage Fowler-Stephens technique (n = 6) or as a direct one-stage repair (n = 12). In 6 boys with cryptorchidism a direct inguinal hernia was associated, which received simultaneous laparoscopic herniorrhaphy. In 23 cases of cryptorchidism with an inguinal location of the testis, 3 vanishing testicles were found. In 20 cases with normal testicular vessels, an inguinal exploration followed. In 4 of the hydrocele cases additional herniorrhaphy had to be performed. In all cases the operation could be performed as planned without complications. After orchidopexy all testicles were in the normal position and well perfused as revealed by flow Doppler sonography. All hydroceles disappeared within several days. There was no inguinal hernia recurrence. CONCLUSIONS: Laparoscopic dissection of the internal inguinal ring allows perfect delineation of the anatomic structures and their relationship. Transection of the processus vaginalis can be performed without disturbance of the inguinal canal. Hernias can be closed with essentially the same technique as used in open surgery. Morbidity was minimal in all patients.

Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells.

PURPOSE: Dendritic cells are the most potent stimulators of immune responses including antitumor responses. We performed a pilot study of cultured antigen loaded dendritic cells in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Dendritic cells were obtained by culturing plastic adherent mononuclear cells from peripheral blood for 5 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. Day 5 dendritic cells were loaded with cell lysate from cultured autologous tumor cells and with the immunogenic protein keyhole-limpet hemocyanin (KLH) which serves as a helper antigen and as a tracer molecule. During the antigen pulse dendritic cells were activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Dendritic cells were administered by 3 intravenous infusions at monthly intervals. Cellular and humoral immune responses to KLH and cell lysate were measured in vitro before and after the vaccinations. RESULTS: Preparation of 12 dendritic cell vaccines from patients with advanced renal cell carcinoma was successful. Treatment with fully activated CD83+ dendritic cells was well tolerated with moderate fever as the only side effect. Potent immunological responses to KLH and, most importantly, against cell lysate could be measured in vitro after the vaccinations. CONCLUSIONS: Our data demonstrate that a dendritic cell based vaccine can induce antigen specific immunity in patients with metastatic renal cell carcinoma. Dendritic cell based immunotherapy represents a feasible, well tolerated and promising new approach for the treatment of advanced renal cell carcinoma.

Laparoscopic heminephroureterectomy in pediatric patients.

PURPOSE: An increasing number of operative procedures in pediatric urology can be performed by laparoscopy. We report our experience with laparoscopic heminephroureterectomy, which is a typical operation in pediatric patients. MATERIALS AND METHODS: Laparoscopic heminephroureterectomy was performed in 14 consecutive children. In 12 cases 7 upper renal poles were removed for ectopic refluxing megaureter and obstructive ureterocele in 5 and 2, respectively. In 5 children lower poles were destroyed by reflux nephropathy. In 2 children laparoscopic upper pole heminephroureterectomy for obstructive ureterocele was combined with a Pfannenstiel incision for reimplantation of the refluxing lower pole ureter. RESULTS: All operations were completed as planned. Operative time was 180 to 330 minutes (mean 222) in group 1 and 345 to 510 (mean 427) in group 2. Blood loss was minimal (10 to 30 ml.) and there were no intraoperative or postoperative complications. Mean postoperative hospital stay in groups 1 and 2 was 4.4 and 7.5 days, respectively. CONCLUSIONS: Laparoscopic heminephroureterectomy in children is feasible and associated with minimal blood loss, low morbidity and a low complication rate. The disadvantage is the long operative time. This technically demanding procedure should be performed only at specialized centers.

Hyperactive androgen receptor in prostate cancer: what does it mean for new therapy concepts?

Investigations on androgen signaling alterations in the late stages of prostate cancer revealed new molecular mechanisms that may be in part responsible for failure of endocrine therapy. Both primary and metastatic lesions from prostate cancer express androgen receptor protein. Amplification of androgen receptor gene occurs in a subset of prostate cancer patients. Several point mutations of androgen receptor gene have been described; they generate receptors which are functionally activated by androgens, other steroids, and even by antihormones. The frequency of androgen receptor mutations may be high in tumor metastases. Functional activity of androgen receptor is influenced by nonsteroidal factors, such as peptide growth factors and second messengers. Thus, prostate cancer cells adapt to low androgen environment by various mechanisms utilizing androgen receptor. Therefore, new strategies for switching off the androgen receptor are needed.

Synergistic activation of androgen receptor by androgen and luteinizing hormone-releasing hormone in prostatic carcinoma cells.

BACKGROUND: We investigated modulation of androgen receptor (AR) activity in prostatic tumor cells by luteinizing hormone-releasing hormone (LHRH)-induced increase of the intracellular cyclic adenosine monophosphate (cAMP) level. METHODS: AR transactivation activity was assessed in transiently transfected DU-145 and in LNCaP cells. RESULTS: LHRH and cAMP derivative, respectively, induced reporter gene activity to about 15% of the maximal level in DU-145 cells transfected with an AR expression vector and an androgen-inducible reporter gene. LHRH or the cAMP analogue acted synergistically in combination with low concentrations of androgen thus lowering the androgen concentration required for maximal AR activation by a factor of 100. A similar activation of the AR by cAMP analogue was observed in LNCaP cells when enhancement of androgen-induced secretion of prostate-specific antigen was determined. The two nonsteroidal antiandrogens hydroxyflutamide and Casodex(R) inhibited reporter gene activity. CONCLUSIONS: The AR is synergistically activated by low doses of androgen and LHRH or the second messenger cAMP. This may have implications for the treatment of advanced prostate cancer.

Metastatic lesions from prostate cancer do not express oestrogen and progesterone receptors.

Oestrogen receptors (ER) and progesterone receptors (PR) have been reported by several authors in the stromal cells of the human prostate. Controversial results exist on the expression of ER and PR in epithelial cells of the prostate. Some recent publications, in contrast to previous findings, have suggested that these receptors are also present in human prostate cancer cell lines derived from metastatic lesions. The expression of ER and PR in these cell lines has been re-examined to determine their presence in lymph node metastases from patients who did not receive any kind of endocrine therapy and in distant metastases obtained from patients who failed endocrine treatment. ER and PR expression in LNCaP, PC-3, and DU-145 cells was assessed by means of the reverse transcriptase-polymerase chain reaction, ligand binding assays, and immunohistochemistry. With all the techniques applied, the three cell lines were found to be negative for both ER and PR. Immunohistochemical analyses were performed in four lymph node metastases obtained at radical prostatectomy from patients who did not receive endocrine therapy and in 17 distant metastases obtained at palliative surgery from patients who failed endocrine therapy. All 21 metastases were negative for ER and PR on immunohistochemistry. These results do not support the recently developed concept that receptors for oestrogenic and progestagenic steroids are present in metastases from human prostate cancer.