Hydronephrosis Predicts Successful Catheter Removal after Painful Urinary Retention - Preliminary Results of a Prospective Single Center Study.

INTRODUCTION: The study aims to identify candidates who can be managed conservatively after the first episode of spontaneous painful acute urinary retention (AUR). METHODS: A total of 20 patients with primary spontaneous painful AUR were prospectively included in the study. Twenty-four hours after AUR, the catheter was removed. When residual urinary volume was <100 ml, patients were referred without catheter, when residual urinary volume was ≥100 ml, the catheter was replaced and removed again at day 4, 7 or 10 after AUR, respectively. Receiver operating characteristic curves, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to assess predictors for successful catheter removal. RESULTS: Thirteen out of 20 (65%) patients had a successful catheter removal until day 10 after AUR. Among them 12 of 13 (93.2%) had a successful catheter removal until day 4 of AUR. Hydronephrosis urinary volume and Qmax at the time of AUR were significant numeric predictors for failure of successful catheter removal. In addition, we calculated a prediction model combing age + prostate volume + urinary volume + Qmax that highly predicts successful catheter removal (sensitivity 100%, specificity 69%, PPV 64%, NPV 100%). CONCLUSION: We found for the first time a significant association between hydronephrosis and successful catheter removal. Successful catheter removal until day 4 after AUR can safely be managed without immediate transurethral resection of the prostate.

Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot.

PURPOSE: To clarify the role of human papillomavirus (HPV) in non-muscle invasive bladder cancer, HPV-DNA was scrutinized in formalin-fixed, paraffin-embedded (FFPE) bladder cancer tissue using single-step PCR (HPV L1) for HPV detection, followed by reverse line blot (RLB) for genotyping. METHODS: A total of 186 patients who underwent transurethral resection of the bladder due to primary, non-muscle invasive bladder cancer from 2006 to 2009 were reviewed. A positive control group of 22 cervical tissues with cervical carcinoma was included. RESULTS: Histology confirmed urothelial carcinoma in all patients: primary CIS, pTa, pT1 and pTa + pT1 in 14 (7.5 %), 134 (72 %), 36 (19.4 %) and two (1.1 %) patients, respectively. A total of 119 (63.9 %) of them were classified as low-risk, while 67 (36.1 %) were high-risk cancers. Tumor recurrence and progression (≥pT2) were seen in 79 and 11 patients (mean follow-up 45 months). The presence of HPV-DNA by single-step PCR was detected in four (2.2 %) patients. HPV 16 and HPV 6 were positive in two (1.1 %) and one (0.6 %) patient, respectively In one case, no HPV genotype listed on the RLB assay could be identified. In the control group, the HPV infection rate was 100 %: HPV 16 in 12 (54.6 %) patients, HPV 16/18 in four (18.3 %) patients, HPV 18 in two (9.1 %) patients, HPV 16/45 in one patient (4.5 %), HPV 18/33 in one (4.5 %) patient, HPV 16/33 in one (4.5 %) patient and HPV 33 in one (4.5 %) patient. CONCLUSIONS: Our study demonstrates low prevalence of HPV infection in FFPE bladder cancer tissue, arguing against the etiological role of HPV in non-muscle urothelial carcinogenesis.

De novo renal cell carcinoma in a kidney allograft with focus on contrast-enhanced ultrasound.

The development of de novo renal cell carcinoma (RCC) in a transplanted kidney is a rare condition. Currently, this is the second case report of a 41-year-old man in whom carcinoma of a renal allograft was detected by contrast-enhanced ultrasound (CEUS). An abdominal CT scan was not conclusive enough to differentiate between septal enhancement of a cyst and a low vascularized tumor. CEUS confirmed a solid, homogeneously enhancing but hypoechoic and hypovascular lesion compared to the surrounding kidney parenchyma without septal enhancement. Therefore, the patient underwent nephron-sparing surgery (NSS), affirming papillary RCC type 2. Graft function remained unchanged postoperatively; 12 months after NSS, no local recurrence or distant metastasis was described. CEUS seems to be a minimally invasive and efficient imaging option if other diagnostic tools cannot clearly exclude RCC, with the advantage of wide-ranging use, especially in cases of impaired renal function.

Organ preservation technique without ischemia in patients with testicular tumor.

OBJECTIVE: To determine the safety and efficacy of organ-sparing surgery (OSS) without ischemia in patients with testicular tumor. METHODS: From January 2003 to October 2010, marker-negative clinical stage I testicular tumors ≤ 30 mm and marker-positive tumors in case of a tumor in a singular testis were managed by an organ-sparing approach. After localization of the tumor by ultrasound and accurate staging, OSS was performed without ischemia. Frozen section analyses of the tumor and tumor bed biopsies were obtained. In cases of malignant germ cell tumor with a normal contralateral testis, an orchiectomy of the tumor-bearing testis was performed. In all other cases, the organ-preserving procedure was completed. RESULTS: A total of 65 patients underwent this approach. In 35 patients with a germ cell tumor on frozen section report (mean tumor size 1.4 cm; standard deviation ± 8.54 mm) and presence of a normal contralateral testis, a radical orchiectomy of the tumor-bearing testis was performed. Thirty-three organ-preserving procedures were completed in 30 patients without any complications (mean tumor size 0.9 cm; range, 0.2-2.0). No local or systemic recurrence was observed in all the 65 patients, and serum testosterone levels remained within normal limits in all but 2 patients. All patients are currently free of disease at a median follow-up of 52.5 months (range, 3-107). CONCLUSION: Our findings suggest that a "no-clamping" OSS technique is safe and feasible in selected tumor patients.

Unrecognized paraganglioma of the urinary bladder as a cause for basilar-type migraine.

Extra-adrenal paraganglioma with isolated localization in the urinary bladder is a rare neuroendocrine tumor. Although the typical symptoms like headache, nausea, weight loss, flushing, heart palpitation or paroxysmal hypertension during micturition are well established, we present an unusual case of bladder paraganglioma, 'misdiagnosed' with basilar-type migraine due to headache for the past 8 years. As urologists linked the presence of a tumor (by CT) and symptoms connected with micturition, no cystoscopy and no transurethral resection of the bladder was performed prior to detailed diagnostic workup. After diagnosis of an extra-adrenal paraganglioma, the patient was scheduled for open partial cystectomy. In consideration of the fact that bladder paraganglioma is an infrequent genitourinary cancer, this case report clearly points out the importance of an exact anamnesis and clinical examination to minimize the probability of misdiagnosis with possible fatal consequences in any case with clinical suspicion of bladder paraganglioma.

Organ-sparing surgery is the treatment of choice in benign testicular tumors.

PURPOSE: Ablation of the testis has been the reference standard for malignant and benign testicular tumors in the past. Nowadays, an organ-sparing surgery (OSS) can be attempted in special cases. Removal of a testis for a benign lesion should be avoided. In this retrospective survey, we analyze the results and long-term follow-up of OSS in benign testicular tumors. METHODS: Charts of all patients that underwent OSS because of a benign testicular tumor between 1999 and 2011 at our department were searched and the data from patients were collected. Before surgery, all patients underwent ultrasound (US) and complete staging. Surgery was performed under US or palpation guidance. Frozen-section examination of the tumor and tumor bed biopsies was obtained. All patients underwent postoperative follow-up. We retrospectively reviewed surgical technique, histology, epidemiology, and outcome in all patients. RESULTS: In the study period, 40 benign testicular tumors were surgically removed in 37 consecutive patients. Definitive histology did not report of any malignant histopathologic features in all patients. All patients are free of disease after a mean follow-up of 63 months (range 10-120). During this period, two patients developed a second leydig cell tumor (LCT) on the contralateral side; another patient had a second LCT within the same testicle, but on the opposite pole. All patients underwent a subsequent organ-sparing tumor resection. CONCLUSIONS: An overtreatment for benign testicular tumors should be avoided. Our initial results indicate that OSS in benign tumors is a safe, feasible treatment for patients.

The need for repeated urological evaluation in low-risk patients with microscopic hematuria after negative diagnostic work-up.

AIM: To evaluate the role of repeated urological evaluation after negative initial diagnostic work-up of asymptomatic microhematuria (AMH) in low-risk patients. PATIENTS AND METHODS: Criteria for patient inclusion were a complete negative initial diagnostic assessment including ultrasound (US), cystoscopy, upper urinary tract (UUT) imaging using intravenous urography (IVU) or multiphasic computed tomography (CT), absence of risk factors and a follow-up period of at least three years. Based on our institutional practice, urinalysis was repeated yearly; cystoscopy with US was repeated three years after initial work-up. The oncological outcome was evaluated across a mean follow-up of 8 (range: 3.7-10.2) years. RESULTS: A case series of 87 (32.2% of 270) low-risk patients, 56 women and 31 men, with a mean age of 52.4 (range: 19-87) years was studied. Three years after initial work-up, cystoscopy confirmed no bladder carcinoma in any of these 87 patients. Prostate cancer was diagnosed in one (1.1%) patient. In five (5.6%) patients, nephrological evaluation due to concomitant proteinuria on follow-up demonstrated chronic renal insufficiency (n=3), IgA nephropathy (n=1) and papillary necrosis of the kidney (n=1). CONCLUSION: Low-risk patients with persistent AMH after negative urological evaluation have a neglectable risk of developing bladder cancer on follow-up. Newly-discovered proteinuria on follow-up should be clarified by a nephrologist, as proteinuria could be a sign of significant glomerular disease.

Novel RHD alleles with weak hemagglutination and genetic Exon 9 diversity: weak D Types 45.1, 75, and 76.

BACKGROUND: Molecular variant RHD allele analysis is best complemented by detailed characterization of the associated D phenotype. STUDY DESIGN AND METHODS: Variant D types were characterized using molecular typing, RHD sequencing, extended serologic D antigen investigations, and flow cytometric D antigen quantification. RESULTS: We discovered three novel weak D types termed weak D Types 45.1, 75, and 76 with RHD nucleotide substitutions coding for amino acid exchanges in predicted intracellular RhD polypeptide stretches; antigen densities of approximately 1.990, 900, and 240 D sites per red blood cell were found, respectively. Adsorption-elution technique-supported D epitope mapping of these three weak D types demonstrated the expression of all tested D epitopes. Initial molecular typing of the three investigated samples by RHD gene exon scanning polymerase chain reaction using sequence-specific priming yielded a negative reaction for A1193 located in RHD Exon 9 and could be explained by specific mutations for weak D Types 45.1 (C818T, G1195A), 75 (G1194C), and 76 (A1215C). CONCLUSION: All novel weak D types expressed all tested D epitopes. It is of interest that for weak D Types 45.1, 75, and 76, similar alleles with a maximal divergence of one amino acid only, that is, weak D Types 45, 41, and 68, respectively, have been reported so far.

Orthotopic bladder replacement in women: focus on functional results of a retrospective, single-centre study.

OBJECTIVE: The aim of this study was to investigate the functional and oncological outcomes of orthotopic neobladders in women with urothelial cancer. MATERIAL AND METHODS: From 1993 to 2007, 61 women underwent radical cystectomy and orthotopic ileal neobladder using the hemi-Kock pouch or Skinner T pouch. Sixteen of them were excluded owing to a lack of available follow-up data. Finally, 39 women with diagnosed TCC were included in this retrospective study. Demographic data, functional outcome including micturition characteristics such as voided volume, continence situation, use of clean intermittent catheterization (CIC), residual urine volume and recurrence rate were collected 3, 6 and >12 months after surgery. RESULTS: Tumours were non-muscle-invasive in 13 patients (pT1; 32.8%) with isolated carcinoma in situ (after failure of bacillus Calmette-Guérin) in five patients (13.0%) and muscle-invasive in 19 patients (pT2-3; 49.0%), extensive superficial bladder cancer was shown in one patient (2.6%), and remaining dysplasia after transurethral resection of the bladder for T1 G2 in one patient (2.6%). Median follow-up was 37 (range 3-165) months. Day-time (71.4%) and night-time (67.8%) continence (0-1 pad/24 h) 3 months postoperatively increased to 83.8% on long-term follow-up. Clean intermittent self-catheterization was required by 20%. At a mean follow-up of 39.5 (8-86) months, two women experienced local recurrence (septum rectovaginale, pelvic floor), urethral recurrence was seen in 5.2% and distant metastasis (pulmonary, peritoneal carcinosis) also in 5.2%. CONCLUSIONS: Orthotopic bladder replacement is an efficient option in appropriately selected women undergoing radical cystectomy, with encouraging functional outcome and low urethral recurrence rates, similar to published literature in men.

Cross-cultural development of an EORTC questionnaire to assess health-related quality of life in patients with testicular cancer: the EORTC QLQ-TC26.

OBJECTIVE: Testicular cancer (TC) is the most common cancer in young men, and its incidence is increasing. The low mortality rate makes quality of life (QOL) an important issue in this patient group. This study aimed to develop a supplementary module of the EORTC QLQ-C30 questionnaire to assess TC-specific aspects of QOL. METHODS: Questionnaire development was conducted according to guidelines from the EORTC Quality of Life Group. Phase I comprised generation of QOL issues relevant to TC patients through a literature search and interviews with patients and experts. Phase II included operationalization and assessment of item relevance. In phase III, items were pre-tested in a cross-cultural sample to assess issues such as understandability and intrusiveness of items. RESULTS: In phase I and II, an initial list of 69 QOL issues possibly relevant to TC patients was refined through patient and expert interviews. The remaining 37 issues were operationalized into items and assessed for relevance and priority in an expert sample (n = 28) and a patient sample (n = 62) from Austria, Canada and the Netherlands. After revision of the item list, 26 items were considered eligible for pre-testing in phase III, in which 156 patients from Australia, Austria, Italy and Spain participated. All items passed criteria for pre-testing, thus forming the new EORTC QLQ-TC26. CONCLUSION: The newly developed EORTC QLQ-TC26 is now available in several languages to assess QOL in TC patients receiving treatment and in TC survivors. Phase IV of questionnaire development will comprise international field testing, including extensive analysis of psychometric characteristics of the EORTC QLQ-TC26.

Postchemotherapy laparoscopic retroperitoneal lymph node dissection for low-volume, stage II, nonseminomatous germ cell tumor: first 100 patients.

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) is indicated after chemotherapy in case of radiologic incomplete remission or teratomatous elements in orchiectomy specimens. Open RPLND is associated with considerable morbidity, but technical difficulty of postchemotherapy laparoscopic RPLND (L-RPLND) can be significant; therefore, literature concerning pc L-RPLND is sparse. OBJECTIVE: To evaluate feasibility and long-term oncologic outcome of postchemotherapy L-RPLND for clinical stage II disease at a single institution. DESIGN, SETTING, AND PARTICIPANTS: Records of patients with nonseminomatous germ cell tumor who underwent postchemotherapy L-RPLND between 1993 and 2010 were retrospectively reviewed. Unilateral template resection was used until a bilateral nerve-sparing approach was introduced in 2004. Follow-up investigations were performed at 3-mo intervals for the first 3 yr, every 6 mo for the next 2 yr, and annually thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: This was a descriptive analysis. RESULTS AND LIMITATIONS: The study cohort comprised 100 patients with stage II retroperitoneal disease (stage IIC: n=16; IIB: n=68; IIA with persisting tumor marker: n=16). Mean diameter of retroperitoneal masses before and after chemotherapy was 3.5 cm and 1.4 cm, respectively. Unilateral and bilateral templates were resected in 71 and 29 patients, respectively. Surgery was successfully completed in all but one patient, whose procedure was converted to open surgery due to bleeding. Mean operation time for unilateral and bilateral resection was 241 and 343 min, respectively. Mean blood loss was 84 ml. Postoperative complications were a large lymphocele in one patient and chylous ascites in another. Mean postoperative hospital stay was 3.9 d. L-RPLND specimens showed teratoma in 38 patients and active tumor in 2 patients. During a mean follow-up of 74 mo, one patient recurred. No recurrence was observed inside the applied surgical field. No patient died of tumor progression. After bilateral nerve-sparing postchemotherapy L-RPLND, 95.2% of patients reported antegrade ejaculation. CONCLUSIONS: Postchemotherapy L-RPLND performed by experienced hands is feasible and associated with low morbidity and high oncologic efficacy.

Influence of achieved paternity on quality of life in testicular cancer survivors.

OBJECTIVE: To investigate the influence of achieved/non-achieved paternity on quality of life (QoL) in testicular cancer (TC) survivors. PATIENTS AND METHODS: We invited TC survivors treated at our department between 1989 and 2006 to complete a QoL assessment, including the European Organisation for the Research and Treatment of Cancer QoL questionnaire, EORTC QLQ-C30 (version 3.0©)/+ TC26, and follow-up questions. A total of 311 TC survivors answered the questionnaire, of whom 207 patients who did not desire paternity were excluded. The remaining 104 patients who stated a desire for paternity after TC treatment were further divided in group A (TC survivors who achieved paternity; n = 51) and group B (TC survivors who did not achieve paternity; n = 53). The data obtained were statistically analysed. RESULTS: Significant differences between groups regarding QoL were detected for social functioning (P = 0.002), emotional functioning (P = 0.001), general QoL (P = 0.018), fatigue (P = 0.025), pain (P = 0.01), sleeping problems (P = 0.024), treatment satisfaction (P = 0.039), financial aspects (P = 0.006), sexual problems (P = 0.017), body image problems (P < 0.001), dyspnoea (P = 0.005) and cognitive functioning (P = 0.019). For all scales except 'sexual enjoyment', patients in group A were found to have a better long-term QoL than those in group B. CONCLUSIONS: Whilst acknowledging the shortcomings in retrospective analyses, we believe our data clearly underline the important impact on QoL for TC survivors of achieved paternity. Counselling patients early at diagnosis as well as using cryopreservation of semen in all potential patients before treatment (only excluding patients definitely claiming they do not wish to achieve paternity) should therefore be regarded as the standard of care.

In young adults with a low body mass index ultrasonography is sufficient as a diagnostic tool for ureteric stones.

OBJECTIVE: • To identify additional factors that might improve the diagnosis of ureteric stones using ultrasonography (US) as the primary diagnostic method. PATIENTS AND METHODS: • We performed a retrospective study of 228 patients who underwent rigid ureterorenoscopy (URS) for obstructive ureteric stones. • Patient age, sex, body mass index (BMI) and stone location and size were recorded. • All patients underwent US for stone detection before surgery. • If no cause of the flank pain was found by US, computer tomography (CT) was performed to confirm the absence of ureteric stones. RESULTS: • In 57 (25%), 15 (6.6%) and 156 (68.4%) patients a stone was localized on the proximal, mid- and distal ureter, respectively. • In 96 (42.1%), 122 (53.5%) and 10 (4.4%) patients the stone measured 0-5, 6-10 and >10 mm, respectively. • The mean (range) BMI of the patients was 24.7 (17.3-37.2) kg/m(2). • The overall stone detection rate using US was 86.4% overall, and 96.4% in adults ≤ 35 years. In 72/197 patients (36.5%) the stones found using US measured ≤ 5 mm and in 24/31 patients (77.4%) the stones found using CT measured ≤ 5 mm. • Age (P= 0.008), stone size (P < 0.001) and BMI (P= 0.013) were factors that independently affected ureteric stone diagnosis using US. CONCLUSION: • Although CT has served as the 'gold standard' for stone detection, its high costs and radiation dose, together with the high detection rate of US in the hands of experienced radiologists, lead us to conclude that US should be the first choice for primary diagnostic purposes, especially in young slim adults as no patient ≤ 35 years with a BMI ≤ 24 kg/m(2) needed unenhanced CT for ureteric stone diagnosis.

Two cycles of cisplatin-based chemotherapy for low-volume stage II seminoma: results of a retrospective, single-center case series.

BACKGROUND: To report on the oncological outcome and toxicity of patients treated with 2 cycles of cisplatin-based chemotherapy for low-volume metastatic stage II seminoma. METHODS: We retrospectively identified a case series of 15 patients with seminoma stage IIA (26.7%) and IIB (73.3%) who underwent chemotherapy consisting of 2 cycles of cisplatin, etoposide and bleomycin (PEB) (cisplatin 20 mg/m(2) on days 1-5, etoposide 100 mg/m(2) on days 1-5, bleomycin 30 mg on days 1, 8 and 15) according to patient preference (refusing a 3rd cycle of PEB) or institutional practice in the last decades. Complete staging before chemotherapy was available in all patients. Patient age, the side and diameter of the primary tumor, the size of the lymph nodes before and after chemotherapy, acute and late toxicity of chemotherapy, the incidence of second malignancies, the relapse-free rate and cancer-specific mortality were recorded. RESULTS: Chemotherapy was well tolerated and no episode of febrile neutropenia occurred. Thrombocytopenia grade 4 was not seen in any patient, while leukopenia grade 4 was observed in 4 (26.6%) patients. The mean (range) lymph node size decreased significantly from 2.54 cm (1.1-4.0) before chemotherapy to 0.75 cm (0.4-2.2) after chemotherapy (p < 0.001). After a median (range) follow-up of 60 (13-185) months, no patient had relapsed, no patient had died as a result of seminoma and second malignancy was seen in only 1 (6.6%) patient. CONCLUSIONS: These excellent long-term results from a retrospective case series of 2 cycles of PEB in stage IIA/IIB seminoma patients represent a hint for further research with a view to reducing treatment burden. However, these incidental findings should be studied in prospective trials prior to drawing any conclusions.

Increased incidence of Leydig cell tumours of the testis in the era of improved imaging techniques.

OBJECTIVE: To report an observed high frequency of Leydig cell tumours (LCTs) diagnosed at our centre. PATIENTS AND METHODS: Charts of all patients who underwent surgery for a testicular tumour between 1999 and 2008 at our department were searched and data from patients with LCT were collected. Before surgery all patients underwent ultrasound and complete staging. In all but two patients with LCT an organ-sparing surgery was performed. Surgery was performed under ultrasound or palpation guidance. All patients underwent postoperative follow-up. We retrospectively reviewed surgical technique, histology, epidemiology and outcome in all LCT patients. RESULTS: In the study period, 197 testicular tumours were surgically removed of which 29 were diagnosed as LCT (14.7% of 197; further study group) in 25 patients. Mean age of patients with LCT was 45 years (range 21-68 years). Tumour size ranged from 1.2 to 80 mm (mean 10.23 mm). In two patients (8%) the lesion was palpable whereas incidental diagnosis was made in seven patients (28%). In the remaining patients diagnosis was made by ultrasound performed for testicular pain (six patients, 24%) or during infertility or erectile dysfunction evaluation (10 patients, 40%). Definitive histology reported no malignant histopathological features in all but one patient; this particular patient experienced tumour progression after 2 months and died from advanced disease 1 year later. All other patients are free of disease after a mean follow up of 56 months (range 7-93 months). During this period one patient developed a second LCT on the contralateral side; another patient had a recurrence within the same testicle, but on the opposite pole. Both underwent a subsequent organ-sparing tumour resection. CONCLUSION: The percentage of LCT (14.7% of all testicular tumours removed) was significantly higher than expected from the literature. One possible explanation for this phenomenon is the increasing use of better ultrasound technology and the subsequent increased detection of small nodules that have not been found in historical series. Use of 'observation-only' for very small lesions detected at infertility clinics is under debate.

Retrospective multicentre study of carboplatin monotherapy for clinical stage I seminoma.

OBJECTIVE: • To evaluate, in a retrospective multicentre study, the long-term oncological efficacy and morbidity of using carboplatin as an alternative treatment for patients with clinical stage I seminoma. PATIENTS AND METHODS: • Patients with clinical stage I seminoma treated with two cycles of adjuvant single-agent carboplatin (400 mg/m² body surface) from February 1990 until September 2008 were retrospectively identified. • A database was created (including information on patient characteristics, initial tumour staging, tumour marker levels, follow-up, oncological outcome, treatment side effects and long-term side effects), descriptive analyses were performed and the data were compared with those available in the literature. RESULTS: • Of 282 stage I seminomas identified in 276 patients, risk factors for progression (pT2/3, vessel invasion or tumour diameter ≥ 4 cm) were detected in 48.2% of tumours. • Chemotherapy was well tolerated, with patients experiencing only mild nausea. Bone marrow suppression was common (leucopaenia in 36.7% and thrombocytopaenia in 50.5% of patients, mainly grade 1/2). Neither neutropenic fever, nor any bleeding complication occurred. • During a mean follow-up of 75 months, three patients (1.06%) developed a retroperitoneal recurrence within the first 2 years after receiving adjuvant treatment and were salvaged by cisplatin-based chemotherapy. A contralateral second testicular germ cell tumour was diagnosed in five patients. CONCLUSIONS: • Two cycles of carboplatin monotherapy are highly effective and very well tolerated by all patients. The frequency of contralateral tumours appears to be reduced. • Despite the lack of a randomized trial, the available data in the literature suggest that the administration of two cycles instead of one cycle could lead to a reduction in recurrence rates of ≈50%.

The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study.

BACKGROUND: Interleukin-6 (IL-6) is associated with prostate cancer morbidity. In several experimental models, IL-6 has been reported to have anti-apoptotic and pro-angiogenic effects. Siltuximab (CNTO 328) is a monoclonal anti-IL-6 antibody which has been successfully applied in several models representing prostate cancer. This study was designed to assess preliminary safety of siltuximab in patients with early prostate cancer. PATIENTS AND METHODS: Twenty patients scheduled to undergo radical prostatectomy received either no drug or siltuximab (6 mg/kg, five patients per group with administration once, two times, and three times prior to surgery). Blood samples were collected for pharmacokinetic and pharmacodynamic analyses. Expression of elements of IL-6 signaling pathways was analyzed in tumor tissue by immunohistochemistry. Gene analysis in tumor specimens was performed with the DASL array. RESULTS: No adverse events related to siltuximab were observed. Patients treated with siltuximab presented with higher levels of proliferation and apoptosis markers. Following a single dose, serum concentrations of siltuximab declined in a biexponential manner. This study revealed a decrease in phosphorylation of Stat3 and p44/p42 mitogen-activated protein kinases. In addition, gene expression analyses indicate down-regulation of genes immediately downstream of the IL-6 signaling pathway and key enzymes of the androgen signaling pathway. CONCLUSIONS: Preliminary safety of siltuximab is favorable. Future studies in which siltuximab could be combined with androgen-deprivation therapy and experimental therapies in advanced prostate cancer are justified.

Long target droplet polymerase chain reaction with a microfluidic device for high-throughput detection of pathogenic bacteria at clinical sensitivity.

In this article we present a long target droplet polymerase chain reaction (PCR) microsystem for the amplification of the 16S ribosomal RNA gene. It is used for detecting Gram-positive and Gram-negative pathogens at high-throughput and is optimised for downstream species identification. The miniaturised device consists of three heating plates for denaturation, annealing and extension arranged to form a triangular prism. Around this prism a fluoropolymeric tubing is coiled, which represents the reactor. The source DNA was thermally isolated from bacterial cells without any purification, which proved the robustness of the system. Long target sequences up to 1.3 kbp from Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa have successfully been amplified, which is crucial for the successive species classification with DNA microarrays at high accuracy. In addition to the kilobase amplicon, detection limits down to DNA concentrations equivalent to 10(2) bacterial cells per reaction were achieved, which qualifies the microfluidic device for clinical applications. PCR efficiency could be increased up to 2-fold and the total processing time was accelerated 3-fold in comparison to a conventional thermocycler. Besides this speed-up, the device operates in continuous mode with consecutive droplets, offering a maximal throughput of 80 samples per hour in a single reactor. Therefore we have overcome the trade-off between target length, sensitivity and throughput, existing in present literature. This qualifies the device for the application in species identification by PCR and microarray technology with high sample numbers. Moreover early diagnosis of infectious diseases can be implemented, allowing immediate species specific antibiotic treatment. Finally this can improve patient convalescence significantly.

Endoscopic application of dextranomer/hyaluronic acid copolymer in the treatment of vesico-ureteric reflux after renal transplantation.

OBJECTIVE: • To evaluate the success of endoscopic dextranomer/hyaluronic acid copolymer (DHAC) application in the treatment of patients with recurrent urinary tract infections (UTIs) and vesico-ureteric reflux (VUR) into the transplanted graft after renal transplantation. PATIENTS AND METHODS: • Between January 2008 and April 2009, 19 patients with recurrent UTIs presented VUR proven by voiding cystourethrography. • To correct VUR of the transplanted ureter, DHAC was injected endoscopically using hydrodistention technique. • Pre- and postoperative serum creatinine levels, the number of pre- and postoperative UTIs, postoperative complications and reflux resolution rate were recorded. The mean follow-up was 6.5 months. RESULTS: • The average number of UTIs was reduced significantly from 4.89 (range 2-14) to 1.31 (range 0-4) on pre- and postoperative follow-up, respectively, of 6 months (P < 0.001). The success rate increased from 57.9% after the first injection to 78.9% after the second injection. • The remaining four patients with residual VUR received long-term low dose antibiotic prophylaxis. In total, two (10.5%) patients developed increasing creatinine levels postoperatively as a result of distal ureteral obstruction, and temporary urinary drainage was necessary in both patients. CONCLUSIONS: • DHAC appears to be an efficient and minimal invasive method for treating VUR after renal transplantation with respect to short-term success. • Further investigation with a larger group of patients and longer follow-up is needed to evaluate the prolonged effect, as well as any potential side effects.