New treatment options for patients with metastatic prostate cancer.

Prostate cancer is one of the most common cancers in men. When metastasised (40% of patients), classic anti-androgen therapy is the first-line treatment. Usually, this treatment becomes ineffective when castration-resistant prostate cancer (CRPC) develops. Thus far, docetaxel was the only chemotherapeutic option that has shown to be able to extend overall survival and improve quality of life in these patients. Recently, cabazitaxel and abiraterone have shown significant survival benefits for patients progressive on or after docetaxel treatment, as did enzalutamide and radium-223. In North America, immune therapy (sipuleucel-T) became available for a subgroup of CRPC patients. These new treatment options will change the treatment paradigm of patients with metastatic castration resistant prostate cancer. A multidisciplinary approach by both medical oncologists and urologists seems mandatory.

Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Increasing antimicrobial resistance has stimulated interest in nonantibiotic prophylaxis of recurrent urinary tract infections. We assessed the effectiveness, tolerability and safety of nonantibiotic prophylaxis in adults with recurrent urinary tract infections. MATERIALS AND METHODS: MEDLINE®, EMBASE™, the Cochrane Library and reference lists of relevant reviews were searched to April 2013 for relevant English language citations. Two reviewers selected randomized controlled trials that met the predefined criteria for population, interventions and outcomes. The difference in the proportions of patients with at least 1 urinary tract infection was calculated for individual studies, and pooled risk ratios were calculated using random and fixed effects models. Adverse event rates were also extracted. The Jadad score was used to assess risk of bias (0 to 2-high risk and 3 to 5-low risk). RESULTS: We identified 5,413 records and included 17 studies with data for 2,165 patients. The oral immunostimulant OM-89 decreased the rate of urinary tract infection recurrence (4 trials, sample size 891, median Jadad score 3, RR 0.61, 95% CI 0.48-0.78) and had a good safety profile. The vaginal vaccine Urovac® slightly reduced urinary tract infection recurrence (3 trials, sample size 220, Jadad score 3, RR 0.81, 95% CI 0.68-0.96) and primary immunization followed by booster immunization increased the time to reinfection. Vaginal estrogens showed a trend toward preventing urinary tract infection recurrence (2 trials, sample size 201, Jadad score 2.5, RR 0.42, 95% CI 0.16-1.10) but vaginal irritation occurred in 6% to 20% of women. Cranberries decreased urinary tract infection recurrence (2 trials, sample size 250, Jadad score 4, RR 0.53, 95% CI 0.33-0.83) as did acupuncture (2 open label trials, sample size 165, Jadad score 2, RR 0.48, 95% CI 0.29-0.79). Oral estrogens and lactobacilli prophylaxis did not decrease the rate of urinary tract infection recurrence. CONCLUSIONS: The evidence of the effectiveness of the oral immunostimulant OM-89 is promising. Although sometimes statistically significant, pooled findings for the other interventions should be considered tentative until corroborated by more research. Large head-to-head trials should be performed to optimally inform clinical decision making.

Chronic pelvic pain: evaluation of the epidemiology, baseline demographics, and clinical variables via a prospective and multidisciplinary approach.

BACKGROUND: Chronic pelvic pain (CPP) is a common clinical condition with significant impact on quality of life. The etiology and pathogenesis of CPP is poorly understood. MATERIALS AND METHODS: To examine the epidemiology, base line demographics, and clinical variables, women with CPP were prospectively analysed by an integrated and synchronised approach. RESULTS: Of the 89 women with CPP analysed, the majority were assessed earlier, had a variety of surgical interventions and used pharmacological agents. Irritable bowel syndrome, dysfunction of the pelvic floor musculoskeletal system, and physical or sexual abuse were the most common diagnosed etiologies. Evaluation revealed an increased level of psychological impairment. DISCUSSION: CPP is a debilitating clinical condition and a result of complex interaction between different contributing factors. Patients will benefit from an orchestrated, multidisciplinary, and synchronized approach with attention paid to the different domains of pain. Treatment is mostly not curative; avoiding profound suffering despite persisting pain should be the goal.

Short-term outcome after cystectomy: comparison of two different perioperative protocols.

AIM: To compare the outcome of two perioperative protocols with respect to postoperative management of cystectomy patients. PATIENTS AND METHODS: Between June 2007 and November 2008, 85 consecutive patients with bladder cancer were treated with cystectomy and urinary diversion. Patients were operated in two hospitals by four urologic surgeons. In protocol A, patients were enterally fed via a postpyloric tube while the nasogastric tube (NGT) was removed directly after cystectomy and selective decontamination of the digestive tract was given until normal oral intake. In protocol B, postcystectomy management consisted of total parenteral nutrition by a central venous line and NGT removal after 24 h. Hospital stay and complications were compared between the two hospitals. RESULTS: More than half of all patients (52%) developed one or more complications within 30 days after surgery, 37% in protocol A and 71% in protocol B (p = 0.002). Higher ASA score and protocol type were the only factors significantly associated with early complications in both uni- and multivariate analyses. Length of stay was significantly shorter with protocol A as compared to protocol B, 13 days versus 19 days (p = 0.006). CONCLUSIONS: Cystectomy and urinary diversion is a procedure with considerable risk of complications. Enteral nutrition might be advantageous as compared to parenteral nutrition, showing fewer complications and shorter hospital stay. A high ASA score is associated with more early complications. Selective bowel decontamination may have an additional role in preventing infectious complications after cystectomy.

[Optimisation of the antibiotic policy in the Netherlands. X. The SWAB guideline for antimicrobial treatment of complicated urinary tract infections]. / Optimaliseren van het antibioticabeleid in Nederland. X. SWAB-richtlijn voor antimicrobiële therapie bij gecompliceerde urineweginfecties.

The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Policy) has developed an evidence-based guideline for the empirical antimicrobial treatment of complicated urinary tract infections (UTIs) in hospitalised adult patients. The choice of treatment is based on recent Dutch data on the resistance ofuropathogens to the most frequently used antibiotics. The first choice for empirical antibiotic treatment in a patient with a complicated UTI is a 2nd or 3rd generation cephalosporin or the combination of amoxicillin and gentamicin. Amoxicillin-clavulanic-acid intravenously is the second empirical choice. The treatment duration must be at least 10 days. The treatment must be adjusted after the results of the urine culture become known and made more specific if possible. Oral treatment can be given if the patient's clinical situation allows it. There are separate recommendations for the treatment ofUTIs in the following patient categories: men, pregnant women, patients with a urinary catheter, patients with diabetes mellitus and patients with renal diseases, congenital polycystic kidney disease or pyocystis.

The 24-h frequency-volume chart in adults reporting no voiding complaints: defining reference values and analysing variables.

OBJECTIVE: To determine the variables (e.g. voiding frequency, voided volumes, urine production) and their mutual relationships and differences between age groups and genders, using a frequency-volume chart (FVC) in an adult population (representing all age groups) who denied having any voiding complaints. SUBJECTS AND METHODS: In all, 1152 men and women aged > 20 years completed a 24-h FVC; registration started with the first voided volume in the morning and concluded with the first voided volume the next morning. The time of voiding and volume were both recorded, and bedtime hours noted. Each participant claimed to have no voiding complaints. The statistical analysis was aimed at discerning the relationships between the FVC variables, gender and age. RESULTS: There was a linear increase in mean 24-h voiding frequency and nocturia in men, from 6.0 and 0.5 in the third decade to 8.5 and 1.6 in those aged > 70 years. Contrary to men, in women the mean 24-h frequency declined slightly in the older decades; it increased from 6.9 in the third to 8.2 in the sixth, declining to 7.8 in those aged > 70 years. Nocturia in women increased linearly, although slower than in men, from 0.7 in the third decade to 1.4 in those aged > 70 years. The mean volume/void decreased significantly in both genders, from 313 to 209 mL in men, and from 274 to 240 mL in women. The mean 24-h volume was 1718 and 1762 mL in men and women, respectively. For both genders there was a strong linear association between 24-h urine production and voided volumes. CONCLUSION: The volume/void and maximum voided volume decreased significantly with age in both sexes, but more prominently in men. As a result, in men the frequency increased with age, probably reflecting subclinical changes associated with the development of prostatic enlargement. In contrast to men the frequency in women increased initially and decreased in the older groups. A higher 24-h urine production was associated with a higher mean volume/void.

Evaluation of the diagnostic workup in young women referred for recurrent lower urinary tract infections.

OBJECTIVES: To evaluate the current practice of the diagnostic workup in The Netherlands and the clinical relevancy of the outcome of various diagnostic procedures in young women referred for recurrent lower urinary tract infections (UTIs). METHODS: A questionnaire was sent to all urologic departments in The Netherlands (n = 104) inquiring about the diagnostic procedures used for recurrent lower UTIs. Furthermore, we performed a prospective study in 100 consecutive young female patients (18 to 40 years old) referred for evaluation of recurrent lower UTIs. All patients underwent a standardized workup: questionnaire, voiding diary, physical examination, urinalysis and culture, abdominal x-ray with ultrasound or intravenous urography, and cystoscopy. RESULTS: The response rate to the questionnaires was 92%. The standard procedures were laboratory blood tests in 56%, cystoscopy in 69%, plain abdominal x-ray in 91%, and abdominal ultrasound in 59%. Only 18% of the urologists asked every patient to make a voided urine frequency volume chart. In our group of patients, the radiologic procedures revealed only one relevant abnormality. Cystoscopy confirmed cystitis in 22 patients, but never revealed relevant findings. None of these diagnostic procedures ever contributed to the diagnosis. The 24-hour urine output was less than 1.5 L in 43 patients, which was considered insufficient. The individual self-reports of fluid intake were unreliable. CONCLUSIONS: Many Dutch urologists perform an extensive routine workup in patients referred for recurrent lower UTIs. The results of our study revealed that the yield of most diagnostic procedures in these patients is low. The focus in evaluating these patients should be directed toward the behavioral aspects. Thus, the routine workup can be restricted to a voiding diary, urinalysis, and urine culture.

Value of diagnostic ultrasound in patients with chronic scrotal pain and normal findings on clinical examination.

OBJECTIVES: Chronic scrotal pain is a frequent complaint. In many patients with scrotal pain, scrotal ultrasound is performed when the physical examination reveals no abnormalities. We evaluated the yield of scrotal ultrasound in patients with chronic scrotal pain and a normal physical examination. METHODS: The study involved the findings in 111 patients with scrotal pain lasting longer than 2 weeks, in whom physical examinations and urinalyses were normal and who underwent ultrasound evaluation. Follow-up data were available. RESULTS: The median age at first presentation was 37 years. The median duration of pain at presentation was 5 months. The pain in the scrotum was localized to the right side in 37% of patients, to the left in 41 %, and bilaterally in 22%. Eighty-three percent had intermittent complaints, and 17% experienced continuous pain. In searching for a cause of the scrotal pain, 65% of patients were found to have a relevant medical history, such as regional surgery, infection, trauma, and low back pain, and 57% described provocative factors. Scrotal ultrasound revealed 12 epididymal cysts less than 0.5 cm and three subclinical varicoceles, but no clinically significant abnormalities. After a median follow-up of 12 months, the pain continued in 70%, although without the development of serious scrotal pathologic features. CONCLUSIONS: Scrotal ultrasound has no diagnostic value in patients with chronic scrotal pain in whom the physical examinations and urinalyses are normal. A patient's history may suggest an extrascrotal cause of his pain.

The efficacy of serial physical examination in penetrating abdominal trauma.

Over a 10-year period we reviewed the records of 370 consecutive patients with potentially penetrating abdominal wounds (48 gunshot and 322 stab wounds). Selective non-operative management for abdominal stab wounds was introduced, guided by serial physical examination. In our study the terms therapeutic and non-therapeutic laparotomies were used, the latter comprising negative as well as insignificant findings. Initially diagnostic peritoneal lavage and local wound exploration were used, but these methods were later abandoned. Mortality was 10.2% and morbidity 25% in the group of gunshot wounds and 1.2% and 8.6% in the group of stab wounds. During this period the rate of laparotomies for stab wounds decreased from 55% to 30%, while the rate of non-therapeutic laparotomies decreased from 24% to 0% in the last year. Delayed laparotomy did not cause death or increase morbidity. Our results support the concept of selective non-operative management of abdominal stab wounds using repeated physical examination. Peritoneal perforation and haemoperitoneum should not be an indication for routine laparotomy.

Neurotrophic factors in prostate and prostatic cancer.

Recent progress in growth factor research has led to a reexamination of the involvement of neurotrophic factors outside their classical domain of the nervous system. These last few years have seen a substantial accumulation of data concerning Nerve Growth Factor (NGF)'s prevalence within the prostate. NGF and its receptors were reported from the normal prostatic tissue, benign hyperplasia and prostatic cancer. Divergent ideas about the biological role of this factor, its specific distribution pattern within the tissue and its implication in the progression of carcinogenesis have been proposed. Especially the role of NGF in the metastatic process bears direct clinical relevance for research in this area. Many questions remain to be solved like the one on the prevalence of other neurotrophic factors. It is now increasingly becoming clear that neurotrophic factors do play a role in normal physiology and pathology of prostatic cells, opening up new prospects for diagnosis and treatment.

The development of valvular incompetence after deep vein thrombosis: a 7 year follow-up study with duplex scanning.

OBJECTIVES: To study the development and progression in time of deep venous valve incompetence with Duplex ultrasonography in combination with distal cuff deflation in patients with a history of deep venous thrombosis (DVT) and to evaluate symptoms of chronic venous insufficiency (CVI). DESIGN: Prospective cohort study. MATERIALS AND METHODS: In a long term follow-up study the deep venous system of 24 patients (7 men, 17 women, mean age 51 years) of an initial group of 27 with phlebographically documented deep venous thrombosis were examined with Duplex scanning at two intervals (mean 34 and 86 months) after DVT. RESULTS: All but one segments recanalised. Deep venous incompetence occurred exclusively in post-DVT segments. At first follow-up 48% of the post-thrombotic segments showed valve incompetence, while at second follow-up this had increased to 60% (p < 0.001). Venous segments of the upper leg mainly contributed to this increase. Our group of 24 patients was too small to find any significant correlation between symptoms, thrombosis and valvular incompetence. CONCLUSIONS: The development of deep vein valve incompetence after deep vein thrombosis is a progressive process over more than 5 years.