A randomised study of TURP after intraprostatic injection of mepicacaine/adrenaline versus regular TURP in patients with LUTS/BPO.

INTRODUCTION: During transurethral resection of the prostate (TURP), the most established surgical treatment of lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO), the prostate can bleed profusely, bringing about anaemia and compromised oxygen delivery to the entire body. OBJECTIVE: The primary objective of this study was to assess the efficacy of mepivacaine and adrenaline (MA) injected into the prostate on bleeding. The primary endpoint was to measure blood loss per resected weight of prostate tissue. MATERIAL AND METHODS: This randomised controlled trial evaluated 81 patients with LUTS/BPO. Patients were randomly allocated to regular TURP or TURP with intraprostatic injections of MA. RESULTS: On univariable analyses there was a significant difference in resection weight in favour of the experimental group, not reflected by a statistically significant difference in the other studied outcome parameters. Nevertheless, in multivariable analyses, blood loss per resection weight, which was the primary outcome, showed a significant decrease in favour of the experimental group. Clavien-Dindo complication classification showed three men with a grade I complication and two men with grade II. CONCLUSIONS: The results obtained in this study showed that it is beneficial to apply intraprostatic injections of MA in immediate conjunction with TURP, in terms of blood loss per resected gram. The study is, however, small and corroboration of our results in more extensive prospective studies may therefore be warranted before embarking upon this technique.

A randomised trial comparing two protocols for transrectal prostate repeat biopsy: six lateral posterior plus six anterior cores versus a standard posterior 12-core biopsy.

Objective: To test the hypothesis that a combination of 6 posterior and 6 anterior cores detects more cancer than 12 posterior cores at a repeat transrectal prostate biopsy in men who have had one previous benign systematic biopsy.Patients and methods: Three hundred and forty men with persistently raised serum PSA were randomly allocated 1:1 to either a standard 12-core biopsy (12 cores from the lateral peripheral zone through a side-fire biopsy canal) or an experimental 12-core biopsy protocol with 6 anterior cores through an end-fire biopsy canal and 6 cores from the lateral peripheral zone through a side-fire biopsy canal. All biopsies were obtained transrectally with ultrasound guidance. The primary endpoint was cancer detection. Secondary endpoints were detection of ISUP Grade Groups/Gleason Grade Group ≥2 cancer, total biopsy cancer length and complications leading to medical intervention.Results: Prostate cancer was detected in 42/168 men (25%) in the experimental biopsy group and in 36/172 (21%) in the standard biopsy group (p = 0.44). The corresponding proportions for Gleason score ≥7 were 12% and 7% (p = 0.14). Median total cancer length was 4 (inter quartile range [IQR] = 1.5 - 6) mm in the end-fire group and 3 (IQR = 1.3 - 7) mm in the side-fire group. Ten men in the end-fire group and three in the side-fire group had a medical intervention for biopsy-related complications (p = 0.05).Conclusion: The biopsy protocol that included six end-fire anterior cores did not detect more cancer and was associated with more complications.Trial registration: ClinicalTrials.gov identifier: NCT02761135.

Should all patients with non-muscle-invasive bladder cancer receive early intravesical chemotherapy after transurethral resection? The results of a prospective randomised multicentre study.

BACKGROUND: To decrease recurrences in non-muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours. OBJECTIVE: To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80 mg of epirubicin in 50 ml of saline intravesically within 24 h of TUR or no further treatment after TUR. MEASUREMENTS: The primary end point was time to first recurrence. RESULTS AND LIMITATIONS: A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0-2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of > or = 3 were 81% and 85%, respectively (p=0.35). CONCLUSIONS: A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.

Association between tobacco exposure and reproductive parameters in adolescent males.

Cigarette smoking is quite prevalent in the general population but our knowledge of its effect on male reproductive function is still very limited. Therefore, we investigated the impact of tobacco exposure on reproductive characteristics in young males. Military conscripts, 217 non-smokers and 85 smokers, with a median age of 18 years were enrolled. Physical examination and semen analysis, including measurement of accessory sex gland markers and reproductive hormone levels, were performed. Lifestyle-associated factors, including maternal smoking during pregnancy and snuffing, were recorded. Non-smokers had 49% higher total sperm number than smokers (95% CI 4.5-112%, p = 0.01). In addition, sperm concentration was 37% higher among non-smokers (95% CI -4% to 95%, p = 0.08). Serum levels of follicle-stimulating hormone (FSH) were 17% higher among non-smokers (95% CI 3-33%, p = 0.02), whereas no significant differences between smokers and non-smokers were found for inhibin B, testosterone, sex hormone binding globulin, luteinizing hormone and oestradiol. Those who smoked >10 cigarettes per day exhibited 37% lower (95% CI 10-69%, p = 0.005) FSH levels than those who smoked less. Maternal smoking during pregnancy had a negative impact on epididymal and seminal vesicle marker secretion. Smoking seems to impair sperm production and epididymal as well as accessory sex gland function and could be one of the factors contributing to regional differences in sperm parameters.

Five-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study.

OBJECTIVES: To compare the efficacy and safety of transurethral microwave thermotherapy (TUMT) with ProstaLund Feedback Treatment, using the CoreTherm device, with transurethral resection of the prostate (TURP) 5 years after treatment. METHODS: This prospective, randomized, multicenter study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to TUMT or TURP in a 2:1 ratio. Patients were followed up at 3, 6, 12, 24, 36, 48, and 60 months after treatment. The intermediate results at 12 and 36 months have been previously reported. The treatment outcome at 5 years was evaluated with the International Prostate Symptom Score (IPSS), quality of life question (QOL), peak urinary flow rate (Qmax), postvoid residual urine volume, and prostate volume. The CoreTherm device differs from other microwave devices in that the intraprostatic temperature is constantly measured during the procedure to guide the treatment. RESULTS: Of the 154 patients, 66% completed the 60 months of follow-up. Statistically significant improvements in the TUMT and TURP groups were observed for IPSS, QOL, and Qmax at 60 months. The average values for the TUMT group were an IPSS of 7.4, QOL score of 1.1, and Qmax of 11.4 mL/s. The values for the TURP group were IPSS of 6.0, QOL score of 1.1, and Qmax of 13.6 mL/s. No statistically significant differences were found in any of these variables between the two treatment groups. In the TUMT group, 10% needed additional treatment versus 4.3% in the TURP group. CONCLUSIONS: The clinical outcome 5 years after TUMT using the CoreTherm device was comparable to the results seen after TURP. The safety of TUMT using the CoreTherm device compared favorably with that of TURP.

Feedback microwave thermotherapy versus TURP/prostate enucleation surgery in patients with benign prostatic hyperplasia and persistent urinary retention: a prospective, randomized, controlled, multicenter study.

OBJECTIVES: To assess the clinical efficacy of ProstaLund Feedback Treatment (PLFT) using the CoreTherm device versus transurethral resection of the prostate (TURP) and prostate enucleation surgery. METHODS: We performed a prospective, randomized, controlled, multicenter study of 120 patients with symptomatic benign prostatic hyperplasia and persistent urinary retention requiring an indwelling catheter or clean intermittent catheterization. The primary efficacy variables were success in catheter removal and symptom improvement. RESULTS: Of the 120 patients, 79% and 88% were catheter free after PLFT and surgery, respectively. The bother score (quality-of-life question) decreased from 4.6 in both groups before treatment to 1.4 in the PLFT group and 0.8 in the surgery group at 6 months of follow-up. The peak urinary flow rate was 13.4 mL/s after PLFT and 18.0 mL/s after surgery. The mean catheterization time was 34 days in the PLFT group and 5 days in the surgery group. CONCLUSIONS: PLFT is an effective alternative to surgical treatment in this group of catheterized patients. The risk of severe complications is reduced using PLFT, and an excellent treatment option can thereby be offered to this high-risk patient group who earlier could be treated only with lifelong catheterization.

Urinary phthalate metabolites and biomarkers of reproductive function in young men.

BACKGROUND: High exposure to phthalates, which are ubiquitous contaminants, has been shown in animal studies to produce detrimental effects on male reproductive functions. A recent study in humans reported dose-response relations between low phthalate levels in urine and human semen parameters, which raises the question whether humans are more sensitive to phthalate exposure than animals. METHODS: Urine, serum, and semen samples were collected from 234 young Swedish men at the time of their medical conscript examination. Semen volume, sperm concentration, and motility were measured, together with sperm chromatin integrity (sperm chromatin structure assay) and biochemical markers of epididymal and prostatic function. We analyzed reproductive hormones in serum, and mono ethyl phthalate (MEP), mono ethylhexyl phthaltale (MEHP), mono benzyl phthalate (MBzP), mono butyl phthalate (MBP), and phthalic acid in urine. RESULTS: For MBP, MBzP, and MEHP, no clear pattern of associations were observed with any of the reproductive biomarkers. Subjects within the highest quartile for MEP had fewer motile sperm (mean difference = 8.8%; 95% confidence interval = 0.8-17), more immotile sperms (8.9%; 0.3-18), and lower luteinizing hormone values (0.7 IU/L; 0.1-1.2), but there was no suggestion of harmful effects for most other endpoints. Phthalic acid actually was associated with improved function, as measured by several markers. CONCLUSIONS: The observed weak associations between 1 phthalate biomarker and impairment of a few aspects of reproductive function biomarkers were not consistent with results from a recent U.S. study. It is not yet possible to conclude whether phthalate exposure may reflect a hazard for human male reproduction.

Three-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study.

OBJECTIVES: To compare, in a prospective randomized multicenter study, the efficacy and safety of transurethral microwave thermotherapy with ProstaLund Feedback Treatment (PLFT), using the CoreTherm device, with transurethral resection of the prostate (TURP) 36 months after treatment. METHODS: The study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to PLFT or TURP in a 2:1 ratio. The treatment outcome was evaluated on the basis of the International Prostate Symptom Score (IPSS), the quality-of-life question (QOL) of the IPSS, peak urinary flow rate (Qmax), urodynamics, and adverse events. The microwave power and treatment time were adjusted according to each patient's response to the supplied energy (ie, the intraprostatic temperature guided the PLFT). RESULTS: Statistically significant improvements in both the TURP and the PLFT groups were observed for IPSS, QOL, and Qmax at 36 months. The average value for the PLFT group was 8.2, 1.2, and 11.9 mL/s for IPSS, QOL, and Qmax, respectively. The corresponding values for the TURP group were IPSS 5.0, QOL 1.0, and Qmax 13.5 mL/s. The difference in IPSS outcome was statistically significant; however, no statistically significant differences were found in QOL or Qmax between the two treatment groups. The degree of improvement was in the same range as that observed after 12 and 24 months for both groups. During the 12 to 36-month period, the most frequent adverse events in the TURP group were impotence (15%), micturition urgency (13%), and urethral disorder (8%); in the PLFT group, impotence (8%), prostate-specific antigen increase (5%), and hematuria (4%) were the most common. CONCLUSIONS: The clinical outcome 3 years after microwave thermotherapy with PLFT was comparable to the results seen after TURP. The safety of PLFT compared favorably to that of TURP in this study.

Androgen receptor CAG repeat length correlates with semen PSA levels in adolescence.

BACKGROUND: Androgens exert their action through the androgen receptor (AR). The length of the AR CAG repeat is inversely correlated to receptor function and short CAG length might be a risk factor for development of prostate cancer. Our aim was to investigate whether CAG repeat number might have an impact on prostate function in adolescence. METHODS: AR genotyping was performed by direct sequencing of leukocyte DNA from 274 military conscripts. All men underwent endocrine evaluation and semen analysis. RESULTS: PSA in seminal plasma, total sperm count and motility all are inversely correlated with CAG numbers (rho = -0.128, P = 0.038; rho = -0.156, P = 0.010; rho = -0.158, P = 0.011), whereas serum levels of free testosterone (rho = 0.132; P = 0.029) and luteinizing hormone (rho = 0.126; P = 0.037) are positively correlated to CAG length. No correlation between seminal PSA and serum testosterone, neither free nor total, was found. CONCLUSIONS: In adolescence, AR genotype, but not serum testosterone, is associated with the level of seminal PSA.

A novel mutation in the D-box of the androgen receptor gene (S597R) in two unrelated individuals Is associated with both normal phenotype and severe PAIS.

BACKGROUND: An absent or dysfunctional androgen receptor (AR) in 46,XY individuals is the most common cause of various degrees of undermasculinization. Therefore, we routinely perform sequencing of the AR gene in all cases with suspected androgen insensitivity. METHODS: In a newborn 46,XY male diagnosed with partial androgen insensitivity syndrome and a phenotypically normal man, who in childhood had bilateral cryptorchidism, the AR was directly sequenced. Seven additional men with cryptorchidism in infancy were chosen as controls. RESULTS: An AR variant (S597R) was identified in both males. Treatment of the newborn with 1% dihydrotestosterone ointment locally, resulted in normal penile size for age. Sequencing of the region in 7 other men with cryptorchidism in infancy did not reveal any additional deviation from the normal reference sequence. CONCLUSION: The same mutation at this codon can cause significantly different phenotypes as shown by the variation in masculinization of these individuals, with 1 severely affected child and 1 normally developed man. However, the S597R mutation does not seem to be a common cause of undescended testes in boys. Despite the S597R mutation and severe undermasculinization, as seen in the baby, normal male phenotype for age could be achieved with treatment.

Correlation between sperm motility and sperm chromatin structure assay parameters.

OBJECTIVE: To evaluate the association between chromatin structure and sperm motility. DESIGN: Cross-sectional prospective study. SETTING: Scanian Andrology Centre, Malmö, Sweden; ENEA Casaccia, Rome, Italy; and Department of Occupational Medicine, Aarhus University, Aarhus, Denmark. PATIENT(S): One hundred seventy-one males from Danish first pregnancy planner couples (group 1) and 278 Swedish military conscripts (group 2). MAIN OUTCOME MEASURE(S): Sperm chromatin structure assay (SCSA) parameters, DNA fragmentation index (DFI), high DNA stainable (HDS), and sperm motility, which was evaluated manually and by use of computer-aided sperm analysis (CASA). RESULT(S): A statistically significant negative correlation between DFI and the CASA percentage of motile sperms (group 1: r = -0.53; group 2: r = -0.38) was found. For the manual motility assessment, the correlation coefficients were slightly lower. Furthermore, HDS correlated negatively with CASA sperm motility (group 1: r = -0.39; group 2: r = -0.36) and percentage of World Health Organization category A motile sperm. In multiple linear regression analysis, concentration and SCSA parameters, but not the time of abstinence, were statistically significant predictors of sperm motility. CONCLUSION(S): There is a moderate correlation between sperm motility and SCSA parameters. The study supports the assumption that both SCSA and motility can be relatively independent predictors of male fertility.

Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population.

A time-related deterioration in male reproductive function caused by exposure to endocrine disrupters, including persistent organochlorines (POCs), has been hypothesized. In animal studies, POCs were found to have adverse effects on male reproductive function. However, little is known about the impact of POC exposure on reproductive parameters in men. In a study of 305 young Swedish men 18-21 years old from the general population, we correlated lipid-adjusted serum levels of 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153)--an index substance for POC exposure--to markers of male reproductive function: testis size assessed by ultrasound, sperm concentration, total sperm count, sperm motility assessed manually and with a computer-aided sperm analyzer (CASA), and serum levels of follicle-stimulating hormone, inhibin B, testosterone, sexual hormone-binding globulin (SHBG), luteinizing hormone, and estradiol. We found weak but statistically significant, negative correlations between CB-153 levels and both the testosterone:SHBG ratio (r = -0.25, p < 0.001)--a measure of the biologically active free testosterone fraction--and CASA sperm motility (r = -0.13, p = 0.02). No statistically significant association with other seminal, hormonal, or clinical markers of male reproductive function was found. In previous studies of more highly POC-exposed groups of adult men, the correlation between POC exposure, including CB-153, and free testosterone levels was not statistically significant. The present study gives some tentative support for weak negative effects of CB-153 exposure on sperm motility and free testosterone levels in young men, but further semen studies on more highly exposed groups may give more firm conclusions on the hazard for male reproductive function from dietary POC exposure.

Feedback microwave thermotherapy versus TURP for clinical BPH--a randomized controlled multicenter study.

OBJECTIVES: To compare the outcome of a microwave thermotherapy feedback system that is based on intraprostatic temperature measurement during treatment (ProstaLund Feedback Treatment or PLFT) with transurethral resection of the prostate (TURP) for clinical benign prostatic hyperplasia (BPH) in a randomized controlled multicenter study. The safety of the two methods was also investigated. METHODS: The study was performed at 10 centers in Scandinavia and the United States. A total of 154 patients with clinical BPH were randomized to PLFT or TURP (ratio 2:1); 133 of them completed the study and were evaluated at the end of the study 12 months after treatment. Outcome measures included the International Prostate Symptom Score (IPSS), urinary flow, detrusor pressure at maximal urinary flow (Qmax), prostate volume, and adverse events. Patients were seen at 3, 6, and 12 months. Responders were defined according to a combination of IPSS and Qmax: IPSS 7 or less, or a minimal 50% gain, and/or Qmax 15 mL/s or greater or a minimal 50% gain. RESULTS: No significant differences in outcome at 12 months were found between PLFT and TURP for IPSS, Qmax, or detrusor pressure. The prostate volume measured with transrectal ultrasonography was reduced by 30% after PLFT and 51% after TURP. Serious adverse events related to the given treatment were reported in 2% after PLFT and in 17% after TURP. Mild and moderate adverse events were more common in the PLFT group. With the criteria mentioned above, 82% and 86% of the patients were characterized as responders after 12 months in the PLFT and TURP groups, respectively. The post-treatment catheter time was 3 days in the TURP group and 14 days in the PLFT group. CONCLUSIONS: The outcome of microwave thermotherapy with intraprostatic temperature monitoring was comparable with that seen after TURP in this study. From both a simplicity and safety point of view, PLFT appears to have an advantage. Taken together, our findings make us conclude that within a 1-year perspective microwave thermotherapy with PLFT is an attractive alternative to TURP in the treatment of BPH.