[Urachal Cancer: an update of current molecular findings]. / Das Urachuskarzinom: Ein Update aktueller molekularer Ergebnisse.

BACKGROUND: Urachal cancer is a rare type of cancer, often following a clinically aggressive course. Due to its rarity, knowledge about its molecular background is still limited. In addition, no sufficiently reliable diagnostic markers are available. OBJECTIVES: The aim of the present study is to give an overview of our recent molecular projects on urachal cancer and to connect it with current literature in the field. MATERIALS AND METHODS: Three projects are introduced. The first project identified and validated diagnostic biomarkers in urachal adenocarcinomas compared to colorectal adenocarcinomas and primary adenocarcinomas of the bladder using various proteomic methods. In the second project, the most relevant differential diagnostic markers between urachal adenocarcinomas and colorectal adenocarcinomas compared to normal tissue (urachal remnants) were determined by analyzing a miRNA panel. Sequence analyses were performed in the third project. The focus was on molecular differences to colorectal adenocarcinomas and urothelial carcinomas. RESULTS AND CONCLUSIONS: We detected potential biomarker candidates for the immunohistochemical differential-diagnosis and generated a miRNA-based diagnostic scoring system with a potentially high differential-diagnostic significance. The sequence analyses data confirm the molecular autonomy of the urachal adenocarcinomas compared to other entities.

The prognostic value of serum MMP-7 levels in prostate cancer patients who received docetaxel, abiraterone, or enzalutamide therapy.

OBJECTIVES: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. METHODS AND MATERIALS: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (n = 95), ABI (n = 140), or ENZA (n = 85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. RESULTS: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (P = 0.058 and P = 0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (P = 0.001) and ENZA (P = 0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. CONCLUSIONS: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.

STIP1 Tissue Expression Is Associated with Survival in Chemotherapy-Treated Bladder Cancer Patients.

To optimize treatment decisions in advanced bladder cancer (BC), we aimed to assess the therapy predictive value of STIP1 with regard to cisplatin therapy. Cisplatin-based chemotherapy represents the standard first-line systemic treatment of advanced bladder cancer. Since novel immunooncologic agents are already available for cisplatin-resistant or ineligible patients, biological markers are needed for the prediction of cisplatin resistance. STIP1 expression was analyzed in paraffin-embedded bladder cancer tissue samples of 98 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Furthermore, pre-chemotherapy serum STIP1 concentrations were determined in 48 BC patients by ELISA. Results were correlated with the clinicopathological and follow-up data. Stronger STIP1 nuclear staining was associated with worse OS in both the whole patient group (p = 0.034) and the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.043). These correlations remained significant also in the multivariable analyses (p = 0.035 and p = 0.040). Stronger STIP1 cytoplasmatic immunostaining correlated with shorter PFS both in the whole cohort (p = 0.045) and in the subgroup of patients who received at least 2 cycles of chemotherapy (p = 0.026). Elevated STIP1 serum levels were associated with older patient's age, but we found no correlation between STIP1 serum levels and patients' outcome. Our results suggest that tissue STIP1 analysis might be used for the prediction of cisplatin-resistance in BC. In contrast, pretreatment STIP1 serum levels showed no predictive value for chemotherapy response and survival.

High-soluble CGA levels are associated with poor survival in bladder cancer.

Recently, a neuroendocrine-like molecular subtype has been discovered in muscle-invasive urothelial bladder cancer (BC). Chromogranin A (CGA) is a widely used tissue and serum marker in neuroendocrine tumors. Our aim was to evaluate serum CGA (sCGA) concentrations and their associations with clinical and follow-up data in BC and renal cell carcinoma (RCC). sCGA concentrations were analyzed in the following cohorts: (1) BC training set (n = 188), (2) BC validation set (n = 125), (3) RCC patients (n = 77), (4) healthy controls (n = 97). CGA immunohistochemistry and RT-qPCR analyses were performed in 20 selected FFPE and 29 frozen BC tissue samples. Acquired data were correlated with clinicopathological parameters including comorbidities with known effect on sCGA as well as with patients' follow-up data. sCGA levels were significantly higher in BC but not in RCC patients compared to healthy controls. High sCGA levels were independently associated with poor overall and disease-specific survival both in the BC training (P < 0.001, P = 0.002) and validation set (P = 0.009, P = 0.017). sCGA levels were inversely correlated with glomerulus filtrating rate (GFR) and linearly correlated with creatinine clearance and urea concentrations. These correlations were not related to the prognostic value of sCGA. Tissue CGA levels were low to absent independently of sCGA concentrations. Our results demonstrate elevated levels and an independent prognostic value for sCGA in BC but not in RCC. Despite the significant correlation between sCGA and GFR, the prognostic relevance of sCGA seems not related to impaired renal function or other comorbidities.

Combined use of perimeatal-based flap urethroplasty (Mathieu) with midline incision or urethral plate in hypospadias repair.

Perimeatal-based flap urethroplasty is commonly used for the primary correction of distal hypospadias. The Mathieu repair provides excellent function and satisfactory cosmetic results, but the risk of devascularisation of the neourethral flap is an inherent problem of this technique. The midline incision of the urethral plate is part of the Snodgrass method, which offers good urethral calibre and tension-free closure. Our aim was to test the effectiveness of the use of the perimeatal-based flap combined with a midline incision of the urethral plate in hypospadias repair. 19 boys, aged 20 months to 5 years, with distal hypospadias, underwent a one-stage repair using the above-described modification of the Mathieu technique. The meatal-based flap with a midline incision of the urethral plate was similar in all cases. The hypospadias repair was successful in all patients, only one boy developed a urethrocutaneous fistula which required subsequent operation. There was no postoperative scarring, chordee or urethral stricture during follow-up. Hypospadias repair using a perimeatal-based skin flap and combined with an incision of the urethral plate reduces complication rates and offers good cosmetic results.

[Laparoscopic intervention in pediatric urology]. / Laparoszkópos beavatkozások a gyermekurológiában.

The authors summarise the short history of the laparoscopy, and main steps of its use in international and Hungarian practice of urological surgery. They evaluate the possibility of laparoscopy in paediatric urological practice. Finally, they present their experience with this minimally invasive technique from 1995. Between October 1995 and September 1998, 83 laparoscopic procedures were performed. In 59 patients the vena testicularis were ligated by laparoscopy and in 22 patients 24 non palpable testes were diagnosed and operated. In 9 of the cases laparoscopic orchidopexy was performed. The authors demonstrate their operative technique. All laparoscopic interventions were tolerated well by children and they were treated without any complication. Postoperative pain medication were given for 5 children. The operative time for varix ligation ranged from 15 and 20 minutes, and for laparoscopic orchidopexy from 30 and 40 minutes. The recurrence rate of varicocele was found to be 1.5%, and postoperative hydrocele developed in one patient (1.5%).

Ureteral motility.

The pyeloureteral function is to transport urine from the kidneys into the ureter toward the urinary bladder for storage until micturition. A set of mechanisms collaborates to achieve this purpose: the basic process regulating ureteral peristalsis is myogenic, initiated by active pacemaker cells located in the renal pelvis. Great emphasis has been given to hydrodynamic factors, such as urine flow rate in determining the size and pattern of urine boluses which, in turn, affect the mechanical aspects of peristaltic rhythm, rate, amplitude, and baseline pressure. Neurogenic contribution is thought to be limited to play a modulatory role in ureteral peristalsis. The myogenic theory of ureteral peristalsis can be traced back to Engelmann (1) who was able to localize the peristaltic pressure wave's origin in the renal pelvis and suggested that the ureteral contraction impulse passes from one ureteral cell to another, the whole ureter working as a functional syncitium. Recent studies of ureteral biomechanics, smooth muscle cell electrophysiology, membrane ionic currents, cytoskeletal components and pharmacophysiology much improved our understanding of the mechanism of how the urine bolus is propelled, how this process is disturbed in pathological states, and what could be done to improve it.

Normal and abnormal development of the urogenital tract.

An understanding of the normal development of the urogenital tract, at both the structural and molecular level, gives an insight into the mechanisms involved in renal pathology. In this review we will outline embryology of normal and abnormal renal development and discuss the function of some of the key regulatory molecules which have been described recently.

The response of balanitis xerotica obliterans to local steroid application compared with placebo in children.

PURPOSE: We evaluated the clinical effectiveness of topical steroid application for balanitis xerotica obliterans in children and analyzed the association of any clinical response with histological findings. MATERIALS AND METHODS: Our double-blind, placebo controlled, randomized study included 40 boys in whom balanitis xerotica obliterans was diagnosed clinically by cicatricial phimosis. The severity of phimosis was graded into 4 groups. Patients were randomized to receive the topical application of 0.05% mometasone furoate or placebo. After 5 weeks phimosis severity was reevaluated and all patients underwent circumcision. Surgical specimens were histologically typed as an early, intermediate or late form of balanitis xerotica obliterans. RESULTS: Seven patients were withdrawn from the study. In the steroid group 7 boys had clinical improvement and 10 had no change. Histological study showed an early, intermediate and late form of balanitis xerotica obliterans in 5, 5 and 7 cases, respectively. Of cases with clinical improvement 5 were the early and 2 the intermediate type. In the placebo group 5 cases worsened clinically and 11 did not change. Histological evaluation revealed an early, intermediate and late form of balanitis xerotica obliterans in 3, 7 and 6 boys, respectively. Of the 5 cases with histological worsening, disease was the early, intermediate and late type in 2, 2 and 1, respectively. CONCLUSIONS: Applying a potent topical steroid affects improvement in balanitis xerotica obliterans in the histologically early and intermediate stages of disease, and may inhibit further worsening in the late stage.

Laparoscopic varicocele operation: a chance to prevent the recurrence.

There are recurrences and postoperative hydrocele of varicocele after any kind of surgical treatment. Laparoscopic clipping and dissection of internal spermatic vessels was performed without any complication in 73 children to treat varicocele in our department between 1995 and 1998. We have used a new method to detect etiological factors at laparoscopic surgery. The well-known Linton and Trendelenburg test was adapted to detect incidental collateral veins in 73 patients. Using these test, collateral veins were detected in 16 boys. The testicular artery identified in most of the cases as a pulsatile vessel. The operating time was 10-25 minutes. Laparoscopic varicocelectomy is a safe, effective treatment causing minimal discomfort and allowing patients an early to return to activity. These results suggest this technique a viable alternative to open ligation in paediatric urological practice.

Use of impedance cardiography to monitor haemodynamic changes during laparoscopy in children.

METHODS: Haemodynamic changes were measured noninvasively using impedance cardiography (ICG) in 30 ASA I children during laparoscopic varicocelectomy under general anaesthesia. After induction and intubation, mechanical ventilation was started, then pneumoperitoneum (PP) was created. During the course of anaesthesia, values of endtidal CO2 pressue (PECO2), peak inspiratory airway pressure (PIP), heart rate (HR), mean arterial blood pressure (MABP), stroke volume index (SVI), cardiac index (CI) and systemic vascular resistance index (SVRI) were recorded at 1 min intervals. We analysed four periods: T1, before induction; T2, after induction; T3, during PP; T4, after desufflation of PP until awake. RESULTS: After induction of anaesthesia a significant reduction of HR, MABP and CI was recorded. Creating PP together with the use of a 15 degrees head down tilt resulted in a further drop in CI, mainly caused by the reduction of SVI, and an elevation of MABP and SVRI. We measured a 25% total decrease of CI. CONCLUSION: Our patients tolerated this significant reduction of cardiac output well. We have demonstrated that ICG can be used to track the haemodynamic changes caused by PP in children, and suggest that this type of monitoring is useful in this group of age during laparoscopy.