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.

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.

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.

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.

Chronic scrotal pain syndrome (CSPS): the widespread use of antibiotics is not justified.

Data supporting the widespread use of antibiotics in patients with chronic scrotal pain syndrome (CSPS) are not available. Therefore, the aim of this study was to investigate the presence of bacteria in the genitourinary tract in patients presenting with CSPS. From July 2005 to July 2007 we prospectively enrolled patients presenting with CSPS in our outpatient clinic. The evaluation consisted of a detailed patient's history, physical examination and ultrasound examination of the scrotum. A blood and urinalysis, a Meares-Stamey four-glass test for bacterial cultures and PCR testing for Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis and Neisseria gonorrhoeae as well as a semen culture were performed. We assessed the symptom severity with the chronic epididymitis symptom index (CESI) score according to Nickel et al. (J Urol 2002, 167:1701; based on the NIH-CPSI). A total of 55 eligible men (median age 34 years) with CSPS were enrolled in the study. The median CESI score was 17 (range 4-26). The majority of patients (n = 39; 71%) were seen by a general practitioner or an urologist before. Of these, 25 patients (64%) were treated with antibiotics and 26 (67%) with non-steroidal anti-inflammatory drugs, respectively. A significant bacterial colony count in at least one specimen was detected in 21 of 55 patients (38%). The predominantly detected microorganisms were an Alpha-haemolytic Streptococcus (11 patients) and coagulase-negative staphylococci (10 patients). Thus, only in 12 of 55 (22%) patients isolated bacteria were considered to be of clinical relevance. No factor or condition predictive for a bacterial aetiology for CSPS could be identified. In our microbiological assessment of patients presenting with CSPS we found no evidence for the widely held belief that CSPS is predominantly the result of a chronic bacterial infection. We therefore conclude that the widespread use of antibiotic agents in the treatment of patients with CSPS is not justified.

[Urological treatment of renal calculi]. / Urologische Nierensteinbehandlung.

As a disease, nephrolithiasis can not only be exceedingly bothersome for the respective patients, it is also very expensive for our public health system. Indications for an active treatment of renal calculi go mainly according to the stone size as well as the clinical symptoms. The goal of modern nephrolithiasis treatment is the complete removal of all stones from the pelvi-calyceal system with the lowest possible morbidity. Extracorporeal shockwave lithotripsy, percutaneous nephrolitholapaxy and flexible ureterorenoscopy are the main options for treatment. According to the stonesize, -localisation and -composition these options are given different priorities. However, due to significant technical progress in the field of endourology there is a clear trend towards flexible ureterorenoscopy, which is a promising modality for the treatment of kidney stones for a number of reasons.

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.

Surgical management of renal cell carcinoma during the second trimester of pregnancy.

Renal cell carcinoma is rarely diagnosed during pregnancy and its management represents a real challenge. Pregnancy demands special consideration in terms of diagnostic evaluation and management, particularly during the second trimester. We report a patient undergoing left radical nephrectomy using a thoracoretroperitoneal approach at 22 weeks' gestation. Histological analysis revealed a pT2R0G2 chromophobic renal cell carcinoma. Furthermore, we review the sparse literature available.

Retroperitoneoscopic pyeloplasty for ureteropelvic junction obstruction (UPJO): solving the technical difficulties.

OBJECTIVES: To evaluate our current practice in retroperitoneoscopic pyeloplasty in patients with ureteropelvic junction obstruction (UPJO). Special interest was paid to technical difficulties associated with the retroperitoneoscopic approach. METHODS: Our retroperitoneoscopic approach for pyeloplasty is explained step for step including the most technically challenging part: the ureteropelvic anastomosis. RESULTS: Within 49 months a total of 47 retroperitoneoscopic pyeloplasties we performed at our institution. Before pyeloplasty an endopyelotomy had failed in five patients (11%). We did not necessarily perform a ventral transposition of the anastomosis in cases with a crossing vessel. Two (4%) conversions to open surgery were required because of scarring after previous endopyelotomy and massive obesity resulting in a limited working space. There were no intraoperative complications. A recurrence of UPJO was observed in 2% (n = 1). CONCLUSION: Functional results after retroperitoneoscopic pyeloplasty are excellent and comparable to those of open surgery. However, special knowledge of retroperitoneoscopy is necessary to provide the patient with a safe and effective minimally invasive alternative to open pyeloplasty.

A Vitex agnus-castus extract inhibits cell growth and induces apoptosis in prostate epithelial cell lines.

Extracts of Vitex agnus-castus fruits (VACF) are described to have beneficial effects on disorders related to hyperprolactinemia (cycle disorders, premenstrual syndrome). A VACF extract has recently been shown to exhibit antitumor activities in different human cancer cell lines. In the present study, we explored the antiproliferative effects of a VACF extract with a particular focus on apoptosis-inducing and potential cytotoxic effects. Three different human prostate epithelial cell lines (BPH-1, LNCaP, PC-3) representing different disease stages and androgen responsiveness were chosen. The action of VACF on cell viability was assessed using the WST-8-tetrazolium assay. Cell proliferation in cells receiving VACF alone or in combination with a pan-caspase inhibitor (Z-VAD-fmk) was quantified using a Crystal Violet assay. Flow cytometric cell cycle analysis and measurement of DNA fragmentation using an ELISA method were used for studying the induction of apoptosis. Lactate dehydrogenase (LDH) activity was determined as a marker of cytotoxicity. The extract inhibited proliferation of all three cell lines in a concentration-dependent manner with IC (50) values below 10 microg/mL after treatment for 48 h. Cell cycle analysis and DNA fragmentation assays suggest that part of the cells were undergoing apoptosis. The VACF-induced decrease in cell number was partially inhibited by Z-VAD-fmk, indicating a caspase-dependent apoptotic cell death. However, the concentration-dependent LDH activity of VACF treated cells indicated cytotoxic effects as well. These data suggest that VACF contains components that inhibit proliferation and induce apoptosis in human prostate epithelial cell lines. The extract may be useful for the prevention and/or treatment not only of benign prostatic hyperplasia but also of human prostate cancer.

Does the prostate really need androgens to grow? Transurethral resection of the prostate in a male-to-female transsexual 25 years after sex-changing operation.

We present the case of a male-to-female transsexual presenting with obstructive voiding symptoms due to benign prostatic hyperplasia 25 years after sex-changing operation and under continuous estrogen therapy.

Retroperitoneoscopic nephropexy for symptomatic nephroptosis using a modified three-point fixation technique.

INTRODUCTION: Laparoscopy has been reported as a minimally invasive approach for performing nephropexy in patients with nephroptosis. We evaluated our results after retroperitoneoscopic nephropexy using a modified three-point fixation technique. TECHNICAL CONSIDERATIONS: Twelve women presenting with flank pain and radiologically documented nephroptosis underwent retroperitoneoscopic nephropexy. After complete dissection of the perirenal fat from the kidney, three nonabsorbable (Ethibond-0) sutures were placed on the posterior renal capsule between the upper pole, middle part, and lower pole of the kidney and the psoas muscle. The average operative time was 91 minutes (range 50 to 180), and the mean estimated blood loss was less than 50 mL in all patients. Postoperative urography revealed complete resolution of nephroptosis in all cases. On a comparative pain analog score patients had 84% improvement (range 0% to 100%). Nine patients had complete resolution of their pain, and two had improvement of 70% to 80%. One patient did not have any improvement. The mean follow-up time was 3.4 years (range 0.5 to 5.5). CONCLUSIONS: Retroperitoneosopic nephropexy with a modified three-point fixation technique of the upper posterior pole, middle part, and lower pole of the kidney to the psoas muscle is a rapid and effective minimally invasive procedure for treating symptomatic nephroptosis with excellent intermediate-term results.

Primitive neuroectodermal tumor of the kidney with hyaline cells.

Primitive neuroectodermal tumor (PNET) of the kidney is a rare disease with high malignant potential. It affects young adults and has the tendency towards early metastasis. Relying on recently available immunohistochemistry and cytogenetic investigations, today most authors define PNET as part of the same nosologic entity as Ewing's sarcoma. We present the case of a 22-year-old man with a PNET arising from the kidney with, to our knowledge, a previously undescribed finding of hyaline cells within the tumor.

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.

Curative surgery for solitary adrenal metastasis of pT1 G3 transitional cell carcinoma of the bladder.

A preoperative computed tomography scan in a patient undergoing radical cystectomy for pT1N0 grade 3 transitional cell carcinoma revealed a tumor in the adrenal gland. Biopsy was negative, but 2 years later computed tomography showed progression, and adrenalectomy was performed, revealing transitional cell carcinoma. Four years after cystectomy, the patient had no evidence of other metastases. We discuss surgery for solitary metastasis of transitional cell carcinoma as a curative treatment option.