International Journal of Urology

The incidence of prostate cancer has been increasing worldwide in recent years. The GLOBOCAN project showed that prostate cancer was the second most frequently diagnosed cancer and the fifth leading cause of cancer mortality among men worldwide in 2012. This trend has been growing even in Asian countries, where the incidence had previously been low. However, the accuracy of data about incidence and mortality as a result of prostate cancer in some Asian countries is limited. The cause of this increasing trend is multifactorial. One possible explanation is changes in lifestyles due to more Westernized diets. The incidence is also statistically biased by the wide implementation of early detection systems and the accuracy of national cancer registration systems, which are still immature in most Asian countries. Mortality rate decreases in Australia, New Zealand and Japan since the 1990s are possibly due to the improvements in treatment and/or early detection efforts employed. However, this rate is increasing in the majority of other Asian countries. Studies of latent and incidental prostate cancer provide less biased information. The prevalence of latent and incidental prostate cancer in contemporary Japan and Korea is similar to those in Western countries, suggesting the influence of lifestyle changes on carcinogenesis. Many studies reported evidence of both congenital and acquired risk factors for carcinogenesis of prostate cancer. Recent changes in the acquired risk factors might be associated with the increasing occurrence of prostate cancer in Asian countries. This trend could continue, especially in developing Asian countries.

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.

Objectives:  Epithelial‐mesenchymal transition (EMT) is an important process in tumor development, and several studies suggest that the Wnt/β‐catenin signal pathway may play an important role in EMT. However, there is no direct evidence showing that the Wnt/β‐catenin pathway actually determines the EMT induced by an exogenous signal. Our previous research has successfully proved that overexpression of hypoxia‐inducible factor‐1α (HIF‐1α) could induce EMT in LNCaP cells, but not in PC‐3. The present study aims to determine whether the signal of HIF‐1α for inducing prostate cancer cells to undergo EMT might possibly pass through the Wnt/β‐catenin pathway.

Methods:  Epithelial‐mesenchymal transition associated proteins were detected in several human prostate carcinoma cell lines by Western blot, and then we distinguished the EMT positive cell lines from the EMT negative cell lines. Furthermore, we evaluated the possible correlation between potency of invasiveness and proliferation among these cell lines with different characteristics of EMT using Matrigel transwell and thiazolyl blue tetrazolium bromide (MTT) assays. Finally, the different expression of some critical proteins and genes in Wnt/β‐catenin signaling pathway were analyzed by Western blot and reverse transcription‐polymerase chain reaction (RT‐PCR) in these cells with different characteristics of EMT.

Results:  Among several prostate cancer cell lines, PC‐3, LNCaP and PC‐3/HIF‐1α are EMT negative cell lines, whereas LNCaP/HIF‐1α and IA8 have undergone the EMT process. EMT positive cells (LNCaP/HIF‐1α and IA8) exhibit much stronger potency of invasiveness and proliferation than those of PC‐3 and LNCaP, which belong to EMT negative cells. Interestingly, although PC‐3/HIF‐1α had not completed the EMT process, it still displayed stronger potency of invasion and proliferation, resembling EMT positive cells. The protein expression level of total glycogensynthase kinase 3β (GSK‐3β) and phospho‐GSK‐3β in LNCaP/HIF‐1α, IA8 and PC‐3/HIF‐1α cells significantly decreased; however, the relative ratios of p‐GSK3β/t‐GSK3β in LNCaP/HIF‐1α, IA8 and PC‐3/HIF‐1α cells were significantly higher than PC‐3 and LNCaP. Consistently, β‐catenin protein expression increased in LNCaP/HIF‐1α and IA8 cells, but not in PC‐3/HIF‐1α; RT‐PCR confirmed these results, except for the enhanced transcription activity of β‐catenin mRNA in PC‐3/HIF‐1α.

Conclusion:  Our data suggests that activation of the Wnt/β‐catenin signaling pathway correlates with the characteristic of EMT and potency of invasiveness and proliferation. This may be the critical factor that directly controls the process of EMT induced by HIF‐1α in prostate cancer cells.

Background: A filled bladder acts as an acoustic window for transabdominal ultrasound measurements of intravesical prostatic protrusion and volume. The aim of this study is to evaluate the effects of bladder volume on transabdominal ultrasound measurements of these parameters.

Methods: Twenty‐two patients undergoing transurethral resection of the prostate (TURP) were studied. Under general anesthesia just before TURP, a transrectal ultrasound measurement of prostate volume was obtained. The bladder was then filled in a stepwise manner with 100, 200, 300, 400 and 500 mL. At each volume, the intravesical prostatic protrusion and prostatic volume were measured transabdominally using ultrasound.

Results: There was an obvious trend of decreasing mean transabdominal intravesical prostatic protrusions with increasing bladder volume. The mean transabdominal intravesical prostatic protrusion at bladder volumes 100, 200, 300, 400 and 500 mL was 9.1, 8.8, 7.4, 5.8 and 4.6 mm, respectively. The bladder volume at which maximum prostatic protrusion occurred was between 100 and 200 mL. The mean transabdominal prostate volume at the five increasing bladder volumes was 50.6, 48.7, 49.2, 47.9 and 41.4 mL, and these were correlated to transrectal prostate volume, particularly when the bladder volume was less than 400 mL.

Conclusions: Transabdominal ultrasound measurement of prostatic protrusion is dependent on bladder volume. Transabdominal ultrasound measurement of prostatic volume correlates well with the transrectal measurement of the same parameter when the bladder volume is less than 400 mL.

As a result of significant improvements in current therapies, the life expectancy of cancer patients with bone metastases has dramatically improved. Unfortunately, these patients often experience skeletal complications that significantly impair their quality of life. The major skeletal complications associated with bone metastases include: cancer‐induced bone pain, hypercalcemia, pathological bone fractures, metastatic epidural spinal cord compression and cancer cachexia. Once cancer cells invade the bone, they perturb the normal physiology of the marrow microenvironment, resulting in bone destruction, which is believed to be a direct cause of skeletal complications. However, full understanding of the mechanisms responsible for these complications remains unknown. In the present review, we discuss the complications associated with bone metastases along with matched conventional therapeutic strategies. A better understanding of this topic is crucial, as targeting skeletal complications can improve both the morbidity and mortality of patients suffering from bone metastases.

Background: Elastography is a diagnostic imaging technique that evaluates the hardness of a lesion. It is expected to become a new diagnostic modality for prostate cancer. The aim of this study was to examine the usefulness of elastography in the diagnosis of prostate cancer.

Methods: A total of 29 patients with untreated, histologically proven prostate cancer were examined using an elastographic imaging technique. The patient was scanned in the dorsosacral position and the prostate was manually compressed with a transrectal ultrasonic probe. The echo signals from inside the tissue were measured before and after the tissue compression and an elastogram was generated by spatially differentiation of the displacement distribution.

Results: Elastography depicted the cancer lesion as a harder tissue than the surrounding normal prostatic tissue. Elastography successfully detected 93% (27 patients) of the untreated prostate cancer lesions. Detection of cancer lesions using elastography was significantly higher than by digital rectal examination (59%; 17 patients) and transrectal ultrasonography (55%; 16 patients).

Conclusion: Elastography has great potential as a useful modality for diagnosis of prostate cancer. Differentiation between cancerous and normal tissues can be expected to become more accurate as a result of technical advances in the quantification of tissue hardness.

Aim: The aims of this study were to define the relationship between intravesical prostatic protrusion (IPP), prostate‐specific antigen (PSA) and prostate volume (PV) and to determine which one of them is the best predictor of bladder outlet obstruction (BOO) due to benign prostatic enlargement.

Methods: A prospective study of 114 male patients older than 50 years examined between November 2001 and 2002 was performed. They were evaluated with digital rectal examination, International Prostate Symptoms Score, PSA, uroflowmetry, postvoid residual urine measurement, IPP and PV using transabdominal ultrasound scan. Statistical analysis included scatter plot with Spearman’s correlation coefficients and nominal logistic regression

Results: Prostate volume, IPP and PSA showed parallel correlation. Although all three indices had good correlation with BOO index, IPP was the best. The Spearman rho correlation coefficients were 0.314, 0.408 and 0.507 for PV, PSA and IPP, respectively. Using receiver‐operator characteristic curves, the areas under the curve for PV, PSA and IPP were 0.637, 0.703 and 0.772, respectively. The positive predictive values of PV, PSA and IPP were 65%, 68% and 72%, respectively. Using a nominal regression model, IPP remained the most significant independent index to determine BOO.

Conclusions: All three non‐invasive indices correlate with one another. The study showed that IPP is a better predictor for BOO than PSA or PV.

Gonadotropin‐releasing hormone agonists and antagonists provide androgen‐deprivation therapy for prostate cancer. Unlike agonists, gonadotropin‐releasing hormone antagonists have a direct mode of action to block pituitary gonadotropin‐releasing hormone receptors. There are two licensed gonadotropin‐releasing hormone antagonists, degarelix and abarelix. Of these, degarelix is the more extensively studied and has been documented to be more effective than the well‐established, first‐line agonist, leuprolide, in terms of substantially faster onset of castration, faster suppression of prostate‐specific antigen, no risk for testosterone surge or clinical flare, and improved prostate‐specific antigen progression‐free survival, suggesting a delay in castration resistance. Other than minor injection‐site reactions, degarelix is generally well tolerated, without systemic allergic reactions and with most adverse events consistent with androgen suppression or the underlying condition. In conclusion, degarelix provides a rational, first‐line androgen‐deprivation therapy suitable for the treatment of prostate cancer, with faster onset of castration than with agonists, and no testosterone surge. Furthermore, data suggest that degarelix improves disease control compared with leuprolide, and might delay the onset of castration‐resistant disease. In view of these clinical benefits and the lack of need for concomitant anti‐androgen treatment, gonadotropin‐releasing hormone antagonists might replace gonadotropin‐releasing hormone agonists as first‐line androgen‐deprivation therapy in the future.

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.