Stem Cell Therapy for Stress Urinary Incontinence (SUI)

Various bulking agents have been used since long for SUI treatment. Their low immediate and long term success rate associated with complications like particle migration, inflammatory reaction and urinary retention have made them not very popular for the clinical use. Lately, Incontinence researchers have been focusing on regenerative repair of damaged sphincter with stem cells. Muscle -derived stem cells (MDSC) and adipose- derived stem cells (ADSC) may become the future bulking agents for urinary incontinence treatment. They persist longer at the implanted site, cause less urinary retention and also improve the function of urethral sphincter.

A pilot study (Stem Cells Transl Med. 2014 Jul 1. pii: sctm.2013-0197) was recently conducted to find out whether transurethral injections (via cystoscope) of autologous adipose stem cells (ASCs) are an effective and a safe treatment for SUI. Five SUI patients were treated with ASCs combined with bovine collagen gel and saline. ASCs were isolated from subcutaneous fat and expanded for 3 weeks in laboratory. At 1 year, the cough test was negative in 3 patients. Validated questionnaires showed some subjective improvement in all five patients. In this small study, autologous adipose stem cells seems to be safe and well tolerated but larger studies are needed specially to know more about feasibility, safety and efficacy.

I am interested to see more and more trials coming out with stem cell therapy for SUI because they are unique for regenerating the sphincter, improved long term success rate and low surgical risk.

Changing Scenario in Prostate Cancer Prevention

Finasteride, a 5-alpha reductase inhibitor has been implicated a potential drug which can reduce the risk of developing prostate cancer. This was concluded (that there is about 25% less chance of developing Prostate cancer with Finasteride use) after PCPT (Prostate Cancer Prevention Trial) started almost 18 years ago and included about 18000 patients. However, this promising finding was overshadow by subsequent analysis which showed that high grade Prostate cancer (Gleason 7-10) were more common in patients who were taking Finasteride than Placebo (p=0.05).

Recently, the same group analyzed and published the long-term rates of survival among all study participants and among those with prostate cancer with 18 years follow up (Thompson et al. N Engl J Med 2013; 369:603-610). They concluded that Finasteride reduced the risk of prostate cancer by about one third. High-grade prostate cancer was more common in the Finasteride group than in the placebo group, but after 18 years of follow-up, there was no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer.

Prostate cancer prevention, screening and treatment guidelines have been continuously evolving based on many large studies from North America and Europe. This study is  certainly going to reignite the discussion on Prostate cancer prevention. It appears to me that use of Finateride can reduce the risk of developing low grade Prostate cancer and thereby can reduce the side effects associated with treatment of non life threatening Prostate cancer.

Prostate Cancer: Vegetable fat in the diet may be beneficial than Animal fat

Men with prostate cancer diagnosis may do better if they replace animal fat and carbohydrate with vegetable fat in their diet. It reduces their risk of developing lethal prostate cancer (progression into metastasis and prostate cancer specific death ) as well as all cause mortality. 4577 men with non-metastatic prostate cancer were studied prospectively between 1986 and 2010. There were 315 events of lethal prostate cancer and 1064 deaths with median follow up of 8.4 years. Replacing 10% energy intake from carbohydrate to vegetable diet caused lower risk of lethal prostate cancer (p=0.04) and all cause mortality (p=0.001). Saturated and trans fats after diagnosis were associated with higher incidence of all cause mortality (p=0.01). This report has been reported in JAMA Internal Medicine 2013; 173 (14):1318-1326. The examples of vegetable fats are olive oils, canola oils, nuts, seeds and avocados. Consumption of vegetable fat and oil increases antioxidants and reduces insulin and inflammations which may deter prostate cancer progression.

This study will play an important role in establishing association between diet and Prostate cancer and would encourage researcher to do further studies in this field.

A new drug (Mirabegron) for Overactive Bladder: That is it?

Traditionally, Overactive Bladder (OAB) symptoms are being treated mainly by anticholinergic medications. The side effect of anticholinergic medications (like dryness of mouth, constipation etc.) is one of the main reasons for their discontinuation. Recently, a new drug called Mirabegron is available for the treatment of OAB (J Urol. 2013 Apr;189(4):1388-95. doi: 10.1016/j.juro.2012.10.017. Epub 2012 Oct 16). Its mechanism of action is completely different from anticholinergic medications because it is β3-adrenoceptor agonist. A randomized, double blind, placebo controlled trial was conducted in USA and Canada in patients with symptoms of OAB for 3 months or more. They were randomized in placebo, 50 mg and 100 mg of Mirabegron once daily for 12 weeks. Primary end points were changes in number of incontinence episodes per 24 hours and micturitions per 24 hours and these were significantly less (p<0.05) in Mirabegron group. The incidence of side effects like dryness of mouth, constipation, hypertension, urinary infection etc were comparable to placebo. The Mirabegron was approved by US Food and Drug Administration (FDA) last year. In summary, this drug has same or better efficacy than placebo and older drugs and furthermore has almost no significant major side effects.

I hope Mirabegron will turn out to be a turning point for the OAB management and can confidently be prescribed in any group of patients without fear of significant side effects. The clinical data are strongly suggestive that it will be a wonderful drug. Hopefully, Mirabegron will be “that is it” for OAB treatment.

PSA and Prostate Cancer: What is new?

PSA and new guidelines for Prostate cancer screening by American Urological Association (AUA)

On May 03, 2013, AUA issued a new guideline for Prostate cancer screening. The purpose of this guideline is to reduce prostate cancer related mortality by addressing early detection of Prostate cancer.  The AUA panel recommend against PSA (Prostate Specific Antigen) screening in men < 40 years because there is low prevalence of clinically detectable Prostate cancer and there is no evidence showing benefit of PSA screening.  Furthermore, they also do not recommend routine PSA screening in men ages 40-54 years at average risk. If these men are at high risk (e.g. positive family history or African American race) then PSA screening should be individualized. The greatest benefits of screening seems to be for men ages 55 –69 years and panel strongly recommend for shared decision making for PSA screening in these age group. For men who decided for screening, screening interval of 2 years is preferred over annual screening in order to reduce harms of screening like overdiagnosis and false positives. Lastly, the AUA panel does not recommend routine PSA screening for men ages >70 years or for any men with life expectancy of less than 10-15 years. This new guideline is based on evidence from systemic literature reviews and replaces the previous AUA guidelines.

I think this new guideline is a fine balance between over and under screening. I hope that with these recommendations, more and more patients will be benefited from PSA screening and at the same time the potential harms from it can be minimised.

http://www.auanet.org/education/guidelines/prostate-cancer-detection.cfm