Showing papers in "International Journal of Urology in 2010"

Male infertility in cancer patients: Review of the literature.

Abstract: The number of men surviving cancer at a young age has increased dramatically in the past 20 years as a result of early detection and improved cancer treatment protocols; more than 75% of young cancer patients nowadays are long-term survivors. Quality of life has become an important issue in childhood and adult cancer patients. The commonest cancers in patients of reproductive age are leukaemia, Hodgkin's lymphomas and testicular germ cell tumors. Fertility is often impaired after chemotherapy and radiation therapy. Cryopreservation of semen before cancer treatment starts is currently the only method to preserve future male fertility. In some malignancies, especially in germ cell tumors, sperm quality is already abnormal at the time of diagnosis. In approximately 12% of men, no viable spermatozoa are present for cryopreservation before the start of chemotherapy. Cytotoxic therapy influences spermatogenesis at least temporarily and in some cases permanently. The amount of damage inflicted by chemotherapy on spermatogenesis depends on the combination of drugs used and on the cumulative dose given for cancer treatment. Alkylating agents, such as cyclophosphamide and procarbazine, are most detrimental to germ cells. Radiation therapy, especially whole-body irradiation, is also associated with the risk of permanent sterility. Besides the cancer treatment, tumor type and pretreatment fertility are of prognostic value for future fertility in male cancer survivors. After cancer treatment, many men need artificial reproductive techniques to achieve fatherhood; usually in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is indicated for successful treatment. About 15% of men will use their cryopreserved semen because of persistent azoospermia after cancer treatment. Treatment results with cryopreserved semen are generally good and comparable to general IVF and ICSI results. So far, no studies have reported an increased rate of congenital abnormalities or malignancies in children born from fathers who had cancer treatment is the past, but close follow up is warranted, especially in children born after IVF/ICSI.

Real-time Virtual Sonography for navigation during targeted prostate biopsy using magnetic resonance imaging data.

Abstract: Objectives: To evaluate the effectiveness of the medical navigation technique, namely, Real-time Virtual Sonography (RVS), for targeted prostate biopsy. Methods: Eighty-five patients with suspected prostate cancer lesions using magnetic resonance imaging (MRI) were included in this study. All selected patients had at least one negative result on the previous transrectal biopsies. The acquired MRI volume data were loaded onto a personal computer installed with RVS software, which registers the volumes between MRI and real-time ultrasound data for real-time display. The registered MRI images were displayed adjacent to the ultrasonographic sagittal image on the same computer monitor. The suspected lesions on T2-weighted images were marked with a red circle. At first suspected lesions were biopsied transperineally under real-time navigation with RVS and then followed by the conventional transrectal and transperineal biopsy under spinal anesthesia. Results: The median age of the patients was 69 years (56–84 years), and the prostate-specific antigen level and prostate volume were 9.9 ng/mL (4.0–34.2) and 37.2 mL (18–141), respectively. Prostate cancer was detected in 52 patients (61%). The biopsy specimens obtained using RVS revealed 45/52 patients (87%) positive for prostate cancer. A total of 192 biopsy cores were obtained using RVS. Sixty-two of these (32%) were positive for prostate cancer, whereas conventional random biopsy revealed cancer only in 75/833 (9%) cores (P < 0.01). Conclusions: Targeted prostate biopsy with RVS is very effective to diagnose lesions detected with MRI. This technique only requires additional computer and RVS software and thus is cost-effective. Therefore, RVS-guided prostate biopsy has great potential for better management of prostate cancer patients.

Endothelial dysfunction and erectile dysfunction in the aging man

Abstract: Penile erection is a vascular event that requires an intact endothelium to occur. A dysfunctional endothelium is an early marker for the development of atherosclerotic changes and can also contribute to the occurrence of acute cardiovascular events. The pathogenesis of both endothelial and erectile dysfunction (ED) is intimately linked through decreased expression and activation of endothelial nitric oxide (NO) synthase, and the subsequent blunted physiological actions of NO naturally occurring with aging. It is now well-understood that ED is a symptom of underlying disease rather than a disease itself; for this reason in the near future both general practitioners, internal medicine practitioners and many specialists will have to interplay with sexual medicine. Aging in the man is also associated with several changes in arterial structure and function, part of them related to the decline of circulating levels of steroids, that is, testosterone and estradiol. These changes may be responsible, in part, for the lack of efficacy of ED treatments. The recent discovery that chronic administration of phosphodiesterase type 5 inhibitors may improve erectile and endothelial responsiveness of men previously non-responsive to on-demand regimes, and the knowledge that testosterone is one of the main modulators of the expression of penile phosphodiesterase type 5 isoenzyme, opens a new scenario in the treatment of men with ED and co-morbidities. The aim of this review is to discuss the pathophysiology of endothelial dysfunction and its relationship with ED in the aging male, and to suggest possible strategies to improve arterial function with regard to sexual dysfunctions.

Template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract : Impact on patient survival

Abstract: Objectives: The benefit of lymphadenectomy (LND) in patients with urothelial carcinoma of the upper urinary tract (UCUUT) has remained controversial. The aim of this study was to examine the influence of the LND template and the total number of lymph nodes (LN) when increasing the number of patients undergoing complete dissection of regional nodes (CompLND). Methods: A total of 109 UCUUT patients with clinically negative nodes underwent nephroureterectomy with concomitant lymphadenectomy at our center. Patients' survival was examined according to the type of LND and the number of removed LN. Univariate analysis was performed to find the cut-off value of LN influencing survival. Results: Seventy-eight patients underwent CompLND. Incomplete lymphadenectomy was performed in an additional 41 patients. In the patients with pT2 or higher who were clinically negative for nodal metastasis, any cut-off value for the total number of LN removed showed no statistical significance. In contrast, CompLND had a significant impact on patient survival. The Cox proportional hazard model showed that CompLND was a significant factor after adjusting for adjuvant chemotherapy. The total number of removed LN was not significant. Conclusions: In patients with muscle-invasive clinical node-negative UCUUT, the number of LN removed shows minimal influence on their survival. In contrast, the influence of the particular type of lymphadenectomy is statistically significant. These findings suggest that the extent of lymphadenectomy should be determined by the template and not by the number of removed LN.

Intravesical prostatic protrusion predicts clinical progression of benign prostatic enlargement in patients receiving medical treatment.

Abstract: Objectives: To assess intravesical prostatic protrusion (IPP) as a novel predictor of clinical progression in patients with benign prostatic enlargement (BPE). Methods: All patients attending the outpatient clinic at our institution who were being treated for lower urinary tract symptoms (LUTS) secondary to BPE between January 1997 and December 2003 were recruited into the study. International Prostate Symptom Score (IPSS) scores, uroflowmetry parameters, post-void residual urine volume (PVR), IPP and serum prostate-specific antigen (PSA) were collected. IPP was classified into Grade 1, 2 or 3. Patients were stratified to different treatment options including watchful waiting, alpha blockers or 5-alpha reductase inhibitors. Those who developed high post-void residual urine volume (>100 mL), acute urinary retention or a deterioration of at least 4 points in IPSS score were considered to have disease progression. Using the Grade 1 IPP group as a reference, the odds ratio for clinical progression of Grade 2 and Grade 3 IPP were calculated by using multivariate analysis. Results: A total of 259 patients with a mean age of 63 years (range 50–90 years) and mean follow-up time of 32 months were available for analysis. Fifty-two patients were found to have clinical progression. Odds ratio for progression of a Grade 2 IPP was 5.1 (95% confidence interval [CI] 1.6–16.2) and that of a Grade 3 IPP was 10.4 (95% CI 3.3–33.4). Conclusion: A higher IPP grade is associated with a higher risk of clinical progression in BPE. IPP is a useful non-invasive predictor for clinical progression in BPE.

Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: report of two initial cases.

Abstract: Objectives: To report a novel cell therapy using autologous adipose tissue-derived stem cells (ADSC) for stress urinary incontinence caused by urethral sphincteric deficiency and the outcomes in two initial cases undergoing periurethral injection of stem cells for the treatment of urinary incontinence after radical prostatectomy. Methods: Two patients with moderate stress incontinence after radical prostatectomy were enrolled. After liposuction of 250 mL of adipose tissue from the abdomen, we isolated ADSC from this tissue by using the Celution system. Subsequently, the isolated ADSC and a mixture of stem cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short-term outcomes during a 12-week follow-up were assessed by a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography, and magnetic resonance imaging. Results: Urinary incontinence progressively improved after 2 weeks of injection up to 12 weeks in terms of decreased leakage volume in a 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life as per the questionnaire. In urethral pressure profile, both maximum urethral closing pressure and functional profile length increased. Ultrasonography and magnetic resonance imaging showed sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri- and postoperatively. Conclusion: This preliminary study showed that periurethral injection of the autologous ADSC is a safe and feasible treatment modality for stress urinary incontinence.

Autologous bone-marrow-derived mesenchymal stem cell transplantation into injured rat urethral sphincter.

Abstract: Objectives: To evaluate the functional and histological recovery by autologous bone-marrow-derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters. Methods: BMSC were harvested from female Sprague–Dawley retired breeder rats for later transplantation. The cells were cultured, and transfected with the green fluorescence protein gene. The urethral sphincters were injured by combined urethrolysis and cardiotoxin injection. One week after injury, the cultured BMSC were injected autologously into the periurethral tissues. Controls included sham-operated rats and injured rats injected with cell-free medium (CFM). Abdominal leak point pressures (LPP) were measured before and after surgery during the following 13 weeks. The urethras were then retrieved for histological evaluation. The presence of green-fluorescence-protein-labeled cells and the regeneration of skeletal muscles, smooth muscles, and peripheral nerves were evaluated by immunohistochemical staining. Results: LPP was significantly reduced in the injured rats. It increased gradually after transplantation, but there was no significant difference between the BMSC and CFM groups. In the BMSC group, transplanted cells survived and differentiated into striated muscle cells and peripheral nerve cells. The proportions of skeletal muscle cells and peripheral nerves in the urethra were significantly greater in the BMSC group compared to the CFM group. Conclusions: Despite a clear trend towards recovery of LPP in BMSC-transplanted urethras, no significant effect was detected. Further study is required for clinical applications for the treatment of stress urinary incontinence.

Efficacy and safety of nephron-sparing surgery.

Abstract: To analyse the current evidence of efficacy and safety of nephron-sparing surgery (NSS) that encompasses open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN) and robotic partial nephrectomy in the management of localized renal cell carcinoma (RCC). Oncological data, complications and postoperative renal function were reviewed for the most important series of partial nephrectomy. Partial nephrectomy (PN) provides similar oncological control as radical nephrectomy (RN) and is superior to RN with respect to preserving renal function and preventing chronic kidney disease. OPN remains the first treatment option for T1 renal tumors in centers without advanced laparoscopic expertise. Indications for LPN have expanded as such that LPN is suited for most renal tumors provided that the procedure is carried out in selected patients by an experienced laparoscopic surgeon. Warm ischemia time should be kept within 20 min, which is currently recommended regardless of surgical approach. In experienced hands, LPN yields intermediate oncological efficacy and renal function outcome comparable to open surgery in the treatment of pT1 renal tumors. Positive surgical margin rates are comparable after LPN and OPN. In contemporary series, the morbidity of LPN is decreasing to become similar to that of OPN. Preliminary results with robotic PN are comparable to results obtained with LPN. Additional studies are required to validate these results and compare with other current methods, such as thermal ablation. NSS is effective and safe for the management of localized RCC and is the gold standard to which new ablative techniques need to be compared.

Current status and future perspectives in laparoendoscopic single-site and natural orifice transluminal endoscopic urological surgery

Abstract: Objective of this study is to provide an evidence-based analysis of the current status and future perspectives of scarless urological surgery. A PubMed search has been performed for all relevant urological literature regarding natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single-site surgery (LESS). In addition, experience with LESS and NOTES at our own institution has been considered. All clinical and investigative reports for LESS and NOTES procedures in the urological literature have been considered. A wide variety of clinical procedures in urology have been succesfully completed by using LESS techniques. Thus far, experience with NOTES has largely been investigational, although early clinical reports are emerging. Further development of instrumentation and platforms is necessary for both techniques to become more widely adopted throughout the urological community.

Tension-free vaginal mesh procedure for pelvic organ prolapse: a single-center experience of 310 cases with 1-year follow up

Abstract: Objective: To prospectively evaluate the efficacy of a tension-free vaginal mesh (TVM) procedure for pelvic organ prolapse (POP). Methods: Between December 2005 and April 2008, 310 female patients (mean age 67.2 years, range 42–84) with POP underwent TVM procedures at our institute. Fifty-six individuals were qualified as stage 2 according to the POP quantification system and 162 and 92 were stage 3 and 4, respectively. One hundred ninety-one patients underwent anterior TVM, and seven underwent posterior TVM. One hundred twelve cases underwent both anterior and posterior TVM procedures. Each patient was systematically assessed at 1, 3, 6 and 12 months after surgery. Quality of life (QOL) was also assessed by using the Short Form-36 and the prolapse-QOL questionnaires. Results: Perioperative complications were the following: five bladder injuries (1.6%), no rectal injuries and three hemorrhages greater than 400 mL (1.0%). The anatomical cure rate (% stage 0 cases) at 3, 6 and 12 months after surgery were 94.1%, 93.5%, and 92.3%, respectively. Short Form-36 and prolapse-QOL parameters were significantly improved, and maintained during the follow-up period. Postoperative complications were the following: five pelvic hematomas (1.6%), one wound infection (0.3%), 10 vaginal mesh extrusions (3.2%), and three cases of pelvic pain (1.0%). Complications concerning lower urinary tract function were: eight cases of postoperative stress urinary incontinence (2.6%), three cases of transient urinary retention (1.0%), and two cases of de novo overactive bladder (0.6%). Conclusions: The TVM procedure provides a good outcome at 1 year with a low incidence of surgical complications and recurrence. Further evaluation with a longer follow up is needed.

New generation of diagnostic tests for infertility: review of specialized semen tests.

Abstract: The initial evaluation of the subfertile male includes a through history and physical examination, semen analyses, and hormonal evaluation. However, a normal spermiogram does not necessarily correlate with fertility potential, because it does not assess sperm function. For this reason, specialized semen tests have been developed to test various aspects of spermatozoal function. This article reviews basic male reproductive physiology, as well as clinically utilized advanced seminal tests, including their methodology and implications for reproductive technology outcomes and fecundity.

Renal tubular epithelial cell injury and oxidative stress induce calcium oxalate crystal formation in mouse kidney.

Abstract: Objectives: To clarify the role of renal tubular cell (RTC) injury and oxidative stress in the early stage of renal calcium oxalate crystal formation in a mouse model. Methods: Daily intra-abdominal injections of glyoxylate (1.35 mmol/kg/day) into 8-week-old mice were carried out over 6 days. Kidneys were extracted before and at 6, 12 and 24 h and 3 and 6 days after glyoxylate injection. Crystal formation was detected using Pizzolato staining and polarized light optical microscopy. Immunohistochemical staining and western blotting of superoxide dismutase, and 4-hydroxynonenal and malondialdehyde were carried out in order to observe oxidative stress and lipid peroxidation, respectively. RTC microstructural damage and crystal nuclei formation were observed using transmission electron microscopy. To ameliorate RTC injury, mice were treated with green tea 1 week before and 1 week after glyoxylate administration. The number of crystals and RTC damage were observed and comparisons were made between glyoxylate-treated mice with and without green tea administration. Results: Oxidative stress and lipid peroxidation were observed after 6 h. Crystal nuclei containing collapsed mitochondria and fallen microvilli appeared in the renal distal tubular lumen after 24 h. Crystals occupying the tubular lumen were detected on day 3. The number of crystals in mice receiving green tea was significantly lower than in those receiving glyoxylate alone. Conclusions: RTC injury, especially mitochondrial damage, and oxidative stress induce the early stage of calcium oxalate crystal formation in mice.

Updated Japanese Urological Association Guidelines on prostate-specific antigen-based screening for prostate cancer in 2010

Abstract: The exposure rate of screening for prostate cancer using prostate‐specific antigen (PSA) in Japan is still very low compared with that in the USA or western Europe. The mortality rate of prostate cancer will increase in the future and in 2020 it will be 2.8‐fold higher than in 2000. Therefore, there is an urgent need to determine the best available countermeasures to decrease the rate of prostate cancer death. PSA screening, which can reduce the risk of death as a result of prostate cancer, should be offered to all men at risk of developing prostate cancer with fact sheets showing updated benefits and drawbacks of screening for prostate cancer.

Is extended and saturation biopsy necessary

Abstract: Prostate biopsy (PBx) techniques have significantly changed since the original Hodge's 'sextant scheme', which should now be considered obsolete. The feasibility of carrying out a biopsy scheme with a high number of cores in an outpatient setting is a result of the great improvement and efficacy of local anesthesia. Peri-prostatic nerve block with lidocaine injection should be considered the 'gold standard' because it provides the best pain relief to patients undergoing PBx. The optimal extended protocol should now include the sextant template with an additional 4-6 cores directed laterally (anterior horn) to the base and medially to the apex. Saturation biopsies (i.e. template with > or = 20 cores, including transition zone) should be carried out only when biopsies are repeated in patients where there is a high suspicion of prostate cancer. Complementary imaging methods (such as color- and power-Doppler imaging, with or without contrast enhancement, and elastography) could be used in order to increase the accuracy of biopsy and reduce the number of unnecessary procedures. Nevertheless, the routine use of these methods is still under evaluation.

Health-related quality of life in men with localized prostate cancer.

Abstract: With the established effectiveness of diverse treatments for localized prostate cancer, the identification of the physical and psychological consequences of the disease and its various treatments has become critical. In the present review, we aim to familiarize the reader with the methodologies of health-related quality of life (HRQOL) research and to review the recent literature on HRQOL outcomes in patients with localized prostate cancer. Studies have shown that prostate cancer and its treatment affect both disease-specific HRQOL (i.e. urinary, sexual, and bowel function) as well as general HRQOL (i.e. energy/vitality and performance in physical and social roles). However, these effects appear to differ according to the type of treatment, stage of disease, age of the subjects, time after treatment, and, more importantly, race or ethnicity. By including HRQOL in clinical decision-making, we can help our patients make more informed treatment choices for localized prostate cancer.

Quality of life following high-intensity focused ultrasound for the treatment of localized prostate cancer: a prospective study.

Abstract: Objectives: To report our health-related quality of life (QOL) and functional outcomes following high-intensity focused ultrasound (HIFU) for localized prostate cancer. Methods: Data from prostate cancer patients undergoing HIFU at our institution between January 1999 and April 2007 were collected in our prospective database. Standard preoperative and surgical parameters, as well as baseline urinary function, QOL and sexual assessment were included. The Japanese version of the Functional Assessment of Cancer Therapy-general (FACT-G), the FACT-prostate (P) and the International Index of Erectile Function-5 (IIEF-5) were used for the functional assessment. These self-administered questionnaires were collected preoperatively and again at 6, 12 and 24 months postoperatively. Results: A total of 326 patients were included in the analysis. Maximum flow rate and residual urine volume were significantly impaired at 6 months (P = 0.010) after HIFU, even if they returned to baseline values at 12 or 24 months after HIFU. The total FACT-G score significantly improved at 24 months (P = 0.027) after HIFU. At 6, 12 and 24 months after HIFU, 52%, 63% and 78%, respectively, of the patients, not receiving neoadjuvant hormonal therapy, were potent. Conclusions: In our experience, functional and QOL outcomes after HIFU therapy for localized prostate cancer are better than those after other treatment modalities.

Maintenance intravesical bacillus Calmette‐Guérin instillation for Ta, T1 cancer and carcinoma in situ of the bladder: Randomized controlled trial by the BCG Tokyo Strain Study Group

Abstract: Objectives: We carried out a prospective, randomized, controlled trial to investigate the efficacy and safety of both induction and maintenance therapy with intravesical instillation of bacillus Calmette-Guerin (BCG) for high-risk non-muscle invasive bladder cancer (NMIBC). Methods: Intravesical instillation of 80 mg Tokyo strain was given to patients with high-risk NMIBC, including carcinoma in situ (CIS), once weekly for eight consecutive weeks as induction therapy. Patients who achieved complete response (CR) were randomly assigned to either the maintenance group or the observation group. Results: A total of 90 patients were enrolled. After induction therapy, 75% of the patients achieved CR and 53 of them were enrolled in the randomized comparative phase. A total of four maintenance instillations were given. Median follow-up was 26.5 and 28.7 months after randomization in the maintenance and the observation group, respectively. Although it was not statistically significant, the 2-year recurrence-free survival rate in the maintenance group (95.8%) was higher than that in the observation group (74.1%, P = 0.078). Univariate analysis identified maintenance therapy as a significant factor influencing recurrence. During induction therapy, 82.2% of patients experienced urination-related adverse drug reactions, but most events were not serious. There were fewer adverse drug reactions with maintenance therapy than with induction therapy. Neither induction therapy nor maintenance therapy reduced patients’ quality of life (QOL). Conclusions: These findings show high levels of efficacy and safety of BCG induction treatment for high-risk NMIBC, and suggest that the number of maintenance instillations could probably be reduced without reducing treatment efficacy or influencing QOL.

Technique for a hybrid system of real-time transrectal ultrasound with preoperative magnetic resonance imaging in the guidance of targeted prostate biopsy

Abstract: Diagnostic magnetic resonance imaging (MRI) for prostate has achieved increasingly higher levels of accuracy. Because real-time MR-guided targeted biopsy is still a complicated and expensive procedure, there is considerable interest in a technique of MR/transrectal ultrasound (TRUS) hybridized image-guided biopsy. However, because the 3-D shapes of the prostate at the time of image-acquisition at preoperative MRI are likely to be different from the intra-operative TRUS images, the precise registration of each 3-D volume data is critical. To reduce the potential errors in registration of TRUS with MRI, we introduce new procedural techniques in a rigid image fusion technique. First, preoperative MR images were obtained with a specifically-made plastic outer-frame, with exactly the same shape as the real TRUS probe, placed in the rectum, in order to simulate the deformation of the prostate caused by the absence or presence of a TRUS probe during the acquisition of MR or TRUS images. Second, instead of using a single plane of longitudinal image, we applied biplane TRUS images to be shown in parallel on a multiplanar display with corresponding reconstructed MRI, in order to register both horizontal and longitudinal images of the prostate simultaneously, thereby achieving improved 3-D anatomical matching.

Transurethral resection in one piece (TURBO) is an accurate tool for pathological staging of bladder tumor.

Abstract: Objectives: To demonstrate the usefulness of transurethral resection in one piece (TURBO) as an accurate pathological staging tool for bladder tumor. Methods: Ninety-seven patients with newly diagnosed bladder cancer underwent TURBO that was performed either in an en bloc or in a divisional manner. The histological quality of the resection specimens was evaluated and the pathological stage was assigned on the basis of the depth of invasion, which was histologically determined. Results: Specimens obtained by TURBO were well oriented and their 3-D architecture was maintained. This allowed a histological assessment of the entire specimen. Portions of muscularis propria were identified beneath the tumor base in the specimens of 80 (82%) patients. In only seven (7%) patients, the tumors had a deep resection margin positive for carcinoma and were ambiguously staged as “pT1 or higher” or “pT2 or higher”. Thus, definite pathological staging of TURBO specimens was possible in 90 (93%) patients (pTa, 30; pT1, 58; pT2, 2). Conclusions: An accurate pathological stage can be assigned to the TURBO specimen in most bladder cancer patients.

Molecular pathology of renal oncocytoma: A review

Abstract: Differentiating renal oncocytoma from its renal cell carcinoma (RCC) mimics, particularly chromophobe RCC, can be difficult, especially when limited tissue is available for evaluation and requires sophisticated microscopic, ultrastructural and immunohistochemical evaluation. In this review, the relevant literature has been reviewed, and supporting data obtained by applying modern microarray-based technologies are discussed with a focus on molecular pathology of renal oncocytoma. The high resolution whole-genome DNA-microarray based analyses excluded with all certainty the occurrence of small specific alterations. Renal oncocytomas are characterized by variable chromosomal patterns. The number of genes selected by global gene expression analyses and their usefulness in the diagnostic pathology based on immunohistochemical evaluation is far below the expectations. The conflicting staining patterns, together with the poor specificity of proposed antibodies, leads us to believe that these candidate immunomarkers might not help in the separation of these tumors. Applying DNA based tools might help in the diagnosis of renal oncocytoma with uncertain histology. However, only the combination of all available techniques could give reliable information.

Outcome of different post‐orchiectomy management for stage I seminoma: Japanese multi‐institutional study including 425 patients

Abstract: Objectives: To clarify the contemporary clinical outcome of stage I seminoma and to provide information on treatment options to patients. Methods: A retrospective analysis of 425 patients who underwent orchiectomy for stage I seminoma between 1985 and 2006 at 25 hospitals in Japan. Relapse-free survival rates were calculated using the Kaplan–Meier method and clinicopathological factors associated with relapse were examined by univariate and multivariate analyses using the Cox proportional hazards model. Results: A total of 30 out of 425 patients had relapsed. Relapse-free survival rates at 10 years were 79, 94 and 94% in the surveillance, chemotherapy and radiotherapy groups, respectively. Post-orchiectomy management and rete testis invasion were identified as independent predictive factors associated with relapse. Rete testis invasion remained to be an independent predictive factor, even if the cases with relapses in the contralateral testis were censored. Only one patient, who relapsed after adjuvant radiotherapy, died of the disease. Overall survival at 10 years was 100, 100 and 99% in the surveillance, chemotherapy and radiotherapy groups, respectively. More than half of the patients were lost to follow up within 5 years. Conclusions: The outcome of Japanese patients with stage I seminoma is similar to previously published Western reports. Surveillance policy is becoming a popular option in Japan, although the relapse rate in patients opting for surveillance policy is higher than those opting for adjuvant chemotherapy or radiotherapy. Rete testis invasion is an independent predictive factor associated with relapse regardless of the post-orchiectomy management. Long-term follow up is mandatory for detection of late relapse.

Prevalence of human papillomavirus infection in the urinary tract of men with urethritis.

Abstract: Objectives: To investigate the prevalence of human papillomavirus (HPV) in the genital and urinary tract of men with urethritis. Methods: Cell samples were collected from the penis, urethra and urine of 142 men with urethritis. A HPV test was performed on the samples using the modified GP5+/6+ polymerase chain reaction method, and the HPV genotype was determined using a HPV GenoArray test. Results: Out of 142 urethritis patients, HPV was detected in 48% (68 cases), and high-risk HPV was found in 32% (46 cases) of patients, on their penis or in the urinary tract (urethra or urine). HPV was detected in 31% in the penis, 20% in the urethra and 24% in the urine, while high-risk HPV was identified in 23% in the penis, 12% in the urethra and 11% in the urine. Among the HPV-positive men, 66% had HPV infection in the urinary tract where the most common HPV types were HPV6, HPV16, HPV18 and HPV58. Single HPV-type infection was more frequently found in the urinary tract (89%) than in the penis (65%) (P < 0.05). Conclusions: Similar to the penis, the urinary tract represents a common HPV infection site in men with urethritis.

Tissue engineering and stem cells : Basic principles and applications in urology

Abstract: To overcome problems of damaged urinary tract tissues and complications of current procedures, tissue engineering (TE) techniques and stem cell (SC) research have achieved great progress. Although diversity of techniques is used, urologists should know the basics. We carried out a literature review regarding the basic principles and applications of TE and SC technologies in the genitourinary tract. We carried out MEDLINE/PubMed searches for English articles until March 2010 using a combination of the following keywords: bladder, erectile dysfunction, kidney, prostate, Peyronie's disease, stem cells, stress urinary incontinence, testis, tissue engineering, ureter, urethra and urinary tract. Retrieved abstracts were checked, and full versions of relevant articles were obtained. Scientists have achieved great advances in basic science research. This is obvious by the tremendous increase in the number of publications. We divided this review in two topics; the first discusses basic science principles of TE and SC, whereas the second part delineates current clinical applications and advances in urological literature. TE and SC applications represent an alternative resource for treating complicated urological diseases. Despite the paucity of clinical trials, the promising results of animal models and continuous work represents the hope of treating various urological disorders with this technology.

Decision making in the management of benign prostatic enlargement and the role of transabdominal ultrasound

Abstract: Benign prostate enlargement (BPE) is a common disease affecting elderly men. It can present clinically in many ways including, but not exclusively, lower urinary tract symptoms (LUTS) and acute urinary retention (AUR). There- fore, in managing men with BPE, a correct diagnosis in the outpatient setting is important. Diagnosis of BPE in the clinic can be aided by simple, non-invasive, transabdominal ultrasound (TAUS). In our practice, a normal prostate is generally defined as less than 20 mL, and shows no intravesical prostatic protrusion (IPP) to distort the normal funneling bladder neck on TAUS, with a maximum flow rate of more than 15 mL/s. The degree of IPP can be measured non-invasively in the midsagittal plane, and can be graded accordingly. Studies have shown that the grade of IPP correlates well with the degree of bladder outlet obstruction (BOO). In addition, TAUS can also be used to measure prostate volume (PV) and post-void residual urine (PVR). There is a good correlation between IPP and PV, but IPP is a better predictor for BOO. Patients with low-grade IPP, no significant PVR ( 100 mL) and bothersome symptoms (higher stage) will need more aggressive manage- ment. The final decision for management can then be tailored and individualized to achieve cost-effectiveness.

Urethroplasty for urethral strictures: quality assessment of an in-home algorithm.

Abstract: Objectives: To evaluate the outcome of different techniques of urethroplasty and to assess the quality of an in-home algorithm. Methods: Two hundred fifty-two male patients underwent urethroplasty. Mean patient's age was 48 years (range 1–85 years). Data were analyzed for the failure rate of the different techniques of urethroplasty. An additional analysis was done based on an in-home algorithm. Results: Median follow up was 37 months (range: 6–92 months). Global failure rate was 14.9%, with an individual failure rate of 11.7%, 16.0%, 20.7% and 20.8% for anastomotic repair, free graft urethroplasty, pedicled flap urethroplasty and combined urethroplasty, respectively. In free graft urethroplasty, results were significantly worse when extrapreputial skin was used. Anastomotic repair was the principle technique for short strictures (83.3%), at the bulbar and posterior urethra (respectively 50.8 and 100%). Free graft urethroplasty was mainly used for 3–10 cm strictures (58.6%). Anastomotic repair and free graft urethroplasty were more used in case of no previous interventions or after urethrotomy/dilation. Pedicled flap urethroplasty was the main technique at the penile urethra (40.7%). Combined urethroplasty was necessary in 41 and 47.1% in the treatment of, respectively, >10 cm or panurethral/multifocal anterior urethral strictures and was the most important technique in these circumstances. Two-stage urethroplasty or perineostomy were only used in 2% as first-line treatment but were already used in 14.9% after failed urethroplasty. Conclusion: Urethroplasty has good results at intermediate follow up. Different types of techniques must be used for different types of strictures.

Efficacy of low dose tamsulosin in medical expulsive therapy for ureteral stones in Japanese male patients: A randomized controlled study

Abstract: Objective: To evaluate the efficacy of low dose tamsulosin for facilitating spontaneous passage of ureteral stones in Japanese male patients. Methods: A total of 71 patients with symptomatic ureteral stones, 10 mm or smaller in size, were randomly allocated into groups 1 and 2. Group 1 received tamsulosin (0.2 mg/day) for a maximum of 4 weeks and group 2 received no medication. The primary endpoint was the stone expulsion rate and the secondary endpoints were stone expulsion time and analgesic use. Results: There were no significant differences between the groups in terms of age, stone size and location. The stone expulsion rate was significantly higher in group 1 than in group 2 (77% vs 50%, P = 0.002). No significant differences were noted in the stone expulsion time and analgesic use between the groups. Conclusion: Low dose tamsulosin can significantly facilitate spontaneous passage of ureteral stones without significant side-effects in Japanese male patients.

Molecular pathology of chromophobe renal cell carcinoma: a review.

Abstract: The recognition of chromophobe renal cell carcinoma (RCC) among other distinct types of renal cell tumors (RCT) based on light-microscopic features, such as cytoplasmic and nuclear characteristics, might pose a dilemma in some cases because of morphological pattern overlapping with renal oncocytoma or conventional RCC. The present article reviews chromophobe RCC with focus on aspects of its molecular pathology, which was shown using ancillary modern microarray-based technology that can distinguish it from its mimics and therefore be helpful for its correct diagnosis. Although the high resolution DNA-microarray analyses excluded with all certainty the occurrence of small specific alterations, the loss of entire chromosomes 2, 10, 13, 17 and 21 occurs exclusively in chromophobe RCC and therefore probes localized at these chromosomes might be used to establish the diagnosis of chromophobe RCC in cases with uncertain histology. The usefulness of proposed candidate genes selected by the global gene expression analyses in the diagnostic pathology is far below expectations. The conflicting staining patterns, together with the poor specificity of used antibodies, leads us to believe that these candidate immunomarkers might not help in the separation of chromophobe RCC, with the exception of CD82, which has recently been suggested to be used for routine histological diagnosis.

IgG4-related inflammatory pseudotumor of the kidney

Abstract: IgG4-related disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T lymphocyte infiltration of various organs, such as sclerotic sialadenitis, hypothyroidism, interstitial pneumonia, cholangitis, autoimmune pancreatitis, retroperitoneal fibrosis, tubulointerstitial nephritis, prostatitis, and inflammatory pseudotumor of lung, mammary gland and kidney. A 56-year-old woman was referred to Tokai University Hachioji Hospital with a renal tumor, which was found incidentally by abdominal ultrasonography during a medical examination. There was no history of previous illness. General blood tests and urinalysis showed normal values. Abdominal ultrasonography showed low echoic mass and computed tomography (CT) showed a renal tumor located at the lower pole of the left kidney in low-attenuation areas, compared with the normal renal cortex during the first phase of enhancement. The tumor was slightly enhanced during the second phase of enhancement (Fig. 1a). On T1-weighted magnetic resonance images (MRI), the tumor was isointense, and on T2-weighted images, the tumor was hypointense (Fig. 1b). We diagnosed the tumor as papillary renal cell carcinoma, and carried out laparoscopic radical nephrectomy. Macroscopically, the resected specimen of the renal tumor showed a 45 ¥ 35 ¥ 35 mm-sized white and jagged verge mass lesion (Fig. 1c). Microscopically, the tumor had no capsule and consisted of diffuse lymphoplasmacytic infiltration with fibrosis. Immunohistochemically, the IgG4 positive plasma cells infiltrated diffusely (mean of 42 cells/HPF per field of 0.62 mm) (Fig. 1d). Therefore, the final diagnosis was IgG4 related inflammatory pseudotumor of the kidney. Serum IgG4 levels were normal (68.9 mg/dL) at 1 month after operation and there was no suspicion of IgG4related disease from head to foot at 12 months after operation without any additional therapy. In an imaging study, 30 cases of IgG4-related kidney disease showed as renal masses or nodules (20 cases, 67%), nothing particular (6 cases, 20%), pelvic wall thickening (3 cases, 10%), kidney swelling (2 cases, 7%) and irregular patchy (1 case, 3%). The diagnostically important features in patients with IgG4-related systemic disease are elevated serum IgG4 levels and/or abundant infiltration of affected organs by IgG4-positive plasma cells. Cornell et al. suggested the criteria for immunohistological diagnosis of infiltrating IgG4-positive plasma cells in organs are more than 30 cells/high-power field per field of 0.62 mm. If the tumor had been diagnosed as an IgG4-related inflammatory pseudotumor of the kidney before operation, we might not have carried out surgery, and instead carried out needle biopsy and provided steroid therapy. So, it is important to consider a differential diagnosis with IgG4-related inflammatory pseudotumor of the kidney similar to imaging in our case and the presence of systemic inflammation disease. Zen et al. reported that T helper (Th) 2 cells and regulatory immune reactions, such as regulatory T cells (Tregs), IL-10 and TGF-b, are upregulated in cases of IgG4-related diseases. We found some Tregs (positive staining of CD4 and 25) with fibrosis in the present case. So, IgG4-related inflammatory pseudotumor of the kidney might be affected by Tregs; but it will be important in the future to study why Th2 cells and Tregs are upregulated in cases of IgG4-related disease.

Inverse expression of estrogen receptor‐β and nuclear factor‐κB in urinary bladder carcinogenesis

Abstract: Objectives: To investigate the expression of nuclear factor-κB (NF-κB) and estrogen receptor-β (ER-β) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis. Methods: Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-β and NF-κB, and tumor grade and T-stage were evaluated, along with demographic data, sex and age. Results: A significant decrease in ER-β expression in the nucleus of bladder cells during loss of cell differentiation (rs = −0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2–T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-κB was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-κB was shown. No correlation between NF-κB, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-β and nuclear p65 immunoreactivity was observed (rs = −0.45, P-value < 0.001). There was no correlation with demographic data. Conclusions: Our immunohistochemical study suggests the possible inverse regulation of NF-κB and ER-β transcription factor during bladder carcinogenesis. Selective ER-β agonists and agents, inhibitors of NF-κB, might represent a possible new treatment strategy for bladder urothelial tumors.

Intravesical Toll-like receptor 7 agonist R-837: optimization of its formulation in an orthotopic mouse model of bladder cancer.

Abstract: Objective: To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer Methods: Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-β-cyclodextrin (HPβCD) Induction of tumor necrosis factor α (TNFα) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells Results: Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFα and KC in a dose-dependent manner Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC Addition of HPβCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFα and KC Histological examination showed that poloxamer-HPβCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice Conclusion: The optimized poloxamer-HPβCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects