Fabrication of Adipose-Derived Stem Cell-Based Self-Assembled Scaffold under Hypoxia and Mechanical Stimulation for Urethral Tissue Engineering.

Long urethral strictures are often treated with autologous genital skin and buccal mucosa grafts; however, risk of hair ingrowth and donor site morbidity, restrict their application. To overcome this, we introduced a tissue-engineered human urethra comprising adipose-derived stem cell (ASC)-based self-assembled scaffold, human urothelial cells (UCs) and smooth muscle cells (SMCs). ASCs were cultured with ascorbic acid to stimulate extracellular matrix (ECM) production. The scaffold (ECM) was stained with collagen type-I antibody and the thickness was measured under a confocal microscope. Results showed that the thickest scaffold (28.06 ± 0.59 µm) was achieved with 3 × 104 cells/cm2 seeding density, 100 µg/mL ascorbic acid concentration under hypoxic and dynamic culture condition. The biocompatibility assessment showed that UCs and SMCs seeded on the scaffold could proliferate and maintain the expression of their markers (CK7, CK20, UPIa, and UPII) and (α-SMA, MHC and Smootheline), respectively, after 14 days of in vitro culture. ECM gene expression analysis showed that the ASC and dermal fibroblast-based scaffolds (control) were comparable. The ASC-based scaffold can be handled and removed from the plate. This suggests that multiple layers of scaffold can be stacked to form the urothelium (seeded with UCs), submucosal layer (ASCs only), and smooth muscle layer (seeded with SMCs) and has the potential to be developed into a fully functional human urethra for urethral reconstructive surgeries.

Incorporation of Smooth Muscle Cells Derived from Human Adipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffold for the Reconstruction of Subtotally Resected Urinary Bladder in Athymic Rats.

BACKGROUND: The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction. METHODS: Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 ("sham") underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected. RESULTS: All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers. CONCLUSION: Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.

Overview of Urethral Reconstruction by Tissue Engineering: Current Strategies, Clinical Status and Future Direction.

BACKGROUND: Urinary tract is subjected to a variety of disorders such as urethral stricture, which often develops as a result of scarring process. Urethral stricture can be treated by urethral dilation and urethrotomy; but in cases of long urethral strictures, substitution urethroplasty with genital skin and buccal mucosa grafts is the only option. However a number of complications such as infection as a result of hair growth in neo-urethra, and stone formation restrict the application of those grafts. Therefore, tissue engineering techniques recently emerged as an alternative approach, aiming to overcome those restrictions. The aim of this review is to provide a comprehensive coverage on the strategies employed and the translational status of urethral tissue engineering over the past years and to propose a combinatory strategy for the future of urethral tissue engineering. METHODs: Data collection was based on the key articles published in English language in years between 2006 and 2018 using the searching terms of urethral stricture and tissue engineering on PubMed database. RESULTS: Differentiation of mesenchymal stem cells into urothelial and smooth muscle cells to be used for urologic application does not offer any advantage over autologous urothelial and smooth muscle cells. Among studied scaffolds, synthetic scaffolds with proper porosity and mechanical strength is the best option to be used for urethral tissue engineering. CONCLUSION: Hypoxia-preconditioned mesenchymal stem cells in combination with autologous cells seeded on a pre-vascularized synthetic and biodegradable scaffold can be said to be the best combinatory strategy in engineering of human urethra.

Science and society: Development of the Asian Men's Health Report: challenges and opportunities.

Men have shorter life expectancy and higher mortality than women; however, only a few countries have dedicated men's health policies. Men's health reports can support the development of men's health policies. The 2013 Asian Men's Health Report (AMHR) systematically documents and compares the status of men's health across countries in Asia. The AMHR can be used as an exemplar to guide future men's health reports. The main challenges during creation of the AMHR were the lack of comprehensive health databases and the variety of data quality between countries. The AMHR revealed variations in mortality and morbidity across diseases, regions, and income groups, prompting a Delphi survey among men's health stakeholders to determine whether any dedicated men's health policies in Asia existed and to reach a consensus on the recommendations of men's health policies. The AMHR helped to promote men's health in Asia and across the world, generated research questions and collaborations, provided evidence to support development of men's health policies, identified the need to improve existing health databases, and developed a framework for the creation of other men's health reports.

Urethral strictures after bipolar transurethral resection of prostate may be linked to slow resection rate.

PURPOSE: This study aimed to determine the urethral stricture (US) rate and identify clinical and surgical risk factors associated with US occurrence after transurethral resection of the prostate using the bipolar Gyrus PlasmaKinetic Tissue Management System (PK-TURP). MATERIALS AND METHODS: This was an age-matched case-control study of US occurrence after PK-TURP. Retrospective data were collected from the hospital records of patients who had a minimum of 36 months of follow-up information. Among the data collected for analysis were prostate-specific antigen level, estimated prostate weight, the amount of prostate resected, operative time, history of urinary tract infection, previous transurethral resection of the prostate, and whether the PK-TURP was combined with other endourological procedures. The resection rate was calculated from the collected data. Univariate and multivariate analyses were performed to identify clinical and surgical risk factors related to US formation. RESULTS: A total of 373 patients underwent PK-TURP between 2003 and 2009. There were 13 cases of US (3.5%), and most of them (10 of 13, 76.9%) presented within 24 months of surgery. Most of the US cases (11 of 13, 84.6%) occurred at the bulbar urethra. Multivariable logistic regression analyses identified slow resection rate as the only risk factor significantly associated with US occurrence. CONCLUSIONS: The US rate of 3.5% after PK-TURP in this study is comparable to contemporary series. A slow resection rate seems to be related to US occurrence. This should be confirmed by further studies; meanwhile, we must be mindful of this possibility when operating with the PK-TURP system.

Ureteral stricture formation after ureteroscope treatment of impacted calculi: a prospective study.

PURPOSE: Urinary calculi is a familiar disease. A well-known complication of endourological treatment for impacted ureteral stones is the formation of ureteral strictures, which has been reported to occur in 14.2% to 24% of cases. MATERIALS AND METHODS: This was a prospective study. Ureterotripsy treatment was used on patients with impacted ureteral stones. Then, after 3 months and 6 months, the condition of these patients was assessed by means of a kidney-ureter-bladder (KUB) ultrasound. If the KUB ultrasound indicated moderate to serious hydronephrosis, the patient was further assessed by means of a computed tomography intravenous urogram or retrograde pyelogram to confirm the occurrence of ureteral strictures. RESULTS: Of the 77 patients who participated in the study, 5 developed ureteral strictures. Thus, the stricture rate was 7.8%. An analysis of the intraoperative risk factors including perforation of the ureter, damage to the mucous membrane, and residual stone impacted within the ureter mucosa revealed that none of these factors contributed significantly to the formation of the ureteric strictures. The stone-related risk factors that were taken into consideration were stone size, stone impaction site, and duration of impaction. These stone factors also did not contribute significantly to the formation of the ureteral strictures. CONCLUSIONS: This prospective study failed to identify any predictable factors for ureteral stricture formation. It is proposed that all patients undergo a simple postoperative KUB ultrasound screening 3 months after undergoing endoscopic treatment for impacted ureteral stones.

Men's Health Index: a pragmatic approach to stratifying and optimizing men's health.

PURPOSE: The proposed Men's Health Index (MHI) aims to provide a practical and systematic framework for comprehensively assessing and stratifying older men with the intention of optimising their health and functional status. MATERIALS AND METHODS: A literature search was conducted using PubMed from 1980 to 2012. We specifically looked for instruments which: assess men's health, frailty and fitness; predict life expectancy, mortality and morbidities. The instruments were assessed by the researchers who then agreed on the tools to be included in the MHI. When there was disagreements, the researchers discussed and reached a consensus guided by the principle that the MHI could be used in the primary care setting targetting men aged 55-65 years. RESULTS: The instruments chosen include the Charlson's Combined Comorbidity-Age Index; the International Index of Erectile Function-5; the International Prostate Symptom Score; the Androgen Deficiency in Aging Male; the Survey of Health, Ageing and Retirement in Europe Frailty Instrument; the Sitting-Rising Test; the Senior Fitness Test; the Fitness Assessment Score; and the Depression Anxiety Stress Scale-21. A pilot test on eight men was carried out and showed that the men's health index is viable. CONCLUSIONS: The concept of assessing, stratifying, and optimizing men's health should be incorporated into routine health care, and this can be implemented by using the MHI. This index is particularly useful to primary care physicians who are in a strategic position to engage men at the peri-retirement age in a conversation about their life goals based on their current and predicted health status.

The status of men's health in Asia.

OBJECTIVES: This study aims to compare health status and its risk factors between men and women who are from countries of different income status in Asia. METHOD: We have included 47 Asian countries and 2 regions in this study. Life expectancy, mortality rate from communicable disease, non-communicable disease and injuries, the prevalence of non-communicable diseases risk factors and their trends were extracted from the WHO and respective governmental database. Subgroup analysis was performed based on country income groups. RESULTS: Overall, men have shorter life expectancy and higher mortality rates compared to women. Men from higher-income countries lived longer compared to men from lower-income countries. There is a wide variation of male life expectancy in upper and lower middle income countries. The mean systolic blood pressure, fasting blood glucose and body mass index in Asia have also increased over the years. CONCLUSION: This study confirms that Asian men have poorer health compared to women besides the growing concerns on NCD risk factors. The findings from this study calls for a concerted effort to find solutions in addressing men's health problems in Asia.

Fluorescence-in-situ-hybridization in the surveillance of urothelial cancers: can use of cystoscopy or ureteroscopy be deferred?

BACKGROUND: Fluorescence in situ hybridization (FISH) testing may be useful to screen for bladder carcinoma or dysplasia by detecting aneuploidy chromosomes 3, 7, 17 and deletion of the chromosome 9p21 locus in urine specimens. This study aimed to assess the sensitivity, specificity, positive and negative predictive value of FISH in a multi-ethnic population in Asia. MATERIALS AND METHODS: Patients with haematuria and/or past history of urothelial cancer on follow-up had their voided urine tested with FISH. Patients then underwent cystoscopy/ ureteroscopy and any lesions seen were biopsied. The histopathological reports of the bladder or ureteroscopic mucosal biopsies were then compared with the FISH test results. RESULTS: Two hundred sixty patients were recruited. The sensitivity and specificity of the FISH test was 89.2% and 83.4% respectively. The positive (PPV) and negative predictive values (NPV) were 47.1% and 97.9%. By excluding patients who had positive deletion of chromosome 9, the overall results of the screening test improved: sensitivity 84.6%; specificity 96.4%; PPV 75.9% and NPV 97.9%. CONCLUSIONS: UroVysion FISH has a high specificity of detecting urothelial cancer or dysplasia when deletion of chromosome 9 is excluded. Negative UroVysion FISH-tests may allow us to conserve health resources and minimize trauma by deferring cystoscopic or ureteroscopic examination.

Retrospective study of predictors of bone metastasis in prostate cancer cases.

INTRODUCTION: The purpose of this study was to identify clinical profiles of patients with low risk of having bone metastases, for which bone scanning could be safely eliminated. MATERIALS AND METHODS: This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed. RESULTS: 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was 69.2 ± 7.3 years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among those with a low PSA level less than 20 ng/ml, and less than 10 ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10 ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml) +1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=2.718 x/1+2.718 x. CONCLUSION: Newly diagnosed prostate cancer patients with a PSA level of 10 ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.

Treatment of the Hypogonadal Infertile Male-A Review.

INTRODUCTION: Testosterone treatment for hypogonadism is detrimental for men in reproductive age as it impairs spermatogenesis, and therefore affects fertility. It is, therefore, not indicated in men with hypogonadism and infertility. AIM: The aim of this review is to analyze current data regarding options of treatment for men with hypogonadism and infertility. MAIN OUTCOMES MEASURES: A comprehensive review of the current literature on management of infertility among hypogonadal men. METHODS: A literature search using PubMed from 1980 to 2012 was done on articles published in the English language. The following medical subject heading terms were used: "infertility," "infertile," "hypogonadism;" "testosterone deficiency" and "men" or "male;" and "treatment" or "management." RESULTS: The options for hypogonadal testicular failure are limited. Hormonal treatment is by and large ineffective. For secondary hypogonadism (hypogonadotropic/normogonadotropic hypogonadism), the options include gonadotropin-releasing hormone, human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), and anti-estrogens and aromatase inhibitors. Dopamine antagonist is indicated for prolactinoma. Artificial reproductive technique is indicated for primary testicular failure and also when medical therapy fails. CONCLUSION: The most suitable option with the current data available is hCG with or without hMG/FSH. Testosterone supplementation should be avoided, but if they are already on it, it is still possible for a return of normal sperm production within 1 year after discontinuing testosterone. Ho CCK and Tan HM. Treatment of the hypogonadal infertile male-A review. Sex Med Rev 2013;1:42-49.

Ketamine-associated ulcerative cystitis: a case report and literature review.

Ketamine can be abused as a recreational drug, and there has been a recent surge in its usage. The effects of ketamine on the urinary system were unknown until the recent publication of a few case reports. Many doctors are still unaware of this new clinical entity, termed ketamine-associated ulcerative cystitis. We report a case that we encountered and discuss the diagnosis and disease management in addition to a review of the literature.

Alum irrigation for the treatment of intractable haematuria.

Managing intractable haematuria is a daunting task. One cause of this condition is radiationinduced haemorrhagic cystitis. Several treatments for the condition have been proposed and one non-invasive option is alum irrigation. Here, we report on a 65-year-old woman with intractable haematuria secondary to radiation cystitis who was successfully treated with alum irrigation. Alum irrigation is safe, well tolerated and relatively cheap. A review of the literature and a comprehensive discussion on alum irrigation as treatment for haematuria is discussed here to create an awareness regarding this treatment option.