Karen Bardossi

	A new study reports no statistically significant increase in the risk of bladder cancer among patients treated with the diabetes drug pioglitazone (Actos), despite 

	However, the authors, led by Assiamira Ferrara, MD, PhD, of Kaiser Permanente Northern California, Oakland, did find a possible link between pioglitazone and prostate and pancreatic cancer. They reported their findings in 

	To explore the relationship between pioglitazone and bladder cancer, the investigators performed a cohort analysis of 193,099 diabetic patients and a nested case-control analysis of 464 bladder cancer patients and 464 matched controls. The patients, who were all 40 years of age or older in 1997 through 2002 and from Kaiser Permanente Northern California, were followed until December 2012.

	A second cohort analysis of 236,507 patients, also from Kaiser Permanente and 40 years of age or older in 1997 through 2005, considered pioglitazone in relation to 10 additional cancers (prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma). It followed the patients until June 2012.

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	Of the 34,181 patients (18%) in the bladder cancer cohort who received pioglitazone for a median of 2.8 years (range, 0.2 to 13.2 years), 1,261 (0.65%) were diagnosed with bladder cancer during the study. The crude incidence of bladder cancer was 89.8 per 100,000 person-years in pioglitazone users and 75.9 in nonusers. The authors found no association between ever use of pioglitazone and bladder cancer (hazard ratio 1.06) after taking potential confounding factors into account.

	Case-control analyses also showed no significant association between pioglitazone and bladder cancer (odds ratio, 1.18) after adjusting for self-reported race and ethnicity, smoking history, occupations linked to bladder cancer, urinary tract infection, and glycosylated hemoglobin. The authors conclude that although pioglitazone use wasn’t associated with a statistically significant increased risk of bladder cancer, “a small increased risk, as previously observed, could not be excluded.”

	The second cohort analysis, of pioglitazone and 10 other cancers, found that 38,190 (16%) patients had ever used the drug and 15,992 (6.8%) had been diagnosed with cancer. Analysis revealed no significant relationship between pioglitazone and eight of the 10 cancers, but showed an increased risk of prostate and pancreatic cancer.

	For prostate cancer, the hazard ratio was 1.13 with a crude incidence of 453.3 per 100,000 person years for pioglitazone users and 449.3 for nonusers. For pancreatic cancer, the hazard ratio was 1.41 with a crude incidence of 81.1 for users compared with 48.4 for nonusers.

	“The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether the observed association are causal or due to chance, residual confounding, or reverse causality,” the authors noted.

	The study was funded by a grant from Takeda Development Center Americas, Inc.

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A new study reports no statistically significant increase in the risk of bladder cancer among patients treated with the diabetes drug pioglitazone (Actos), despite previous studies suggesting an association.

Study: No significant link between diabetes Tx, bladder Ca

	A recently published review expands understanding of the effectiveness and side effects of mid-urethral sling procedures for stress urinary incontinence, providing more information for women considering minimally invasive surgical treatment.

	For the study, which was published online in the 

 researchers considered data from a total of 81 trials (12,113 women), 55 of which (8,652 women) directly compared mid-urethral sling surgery by the transobturator route and retropubic route, according to a 

 from Cochrane. The quality of evidence from most of the trials was rated moderate, mainly because of bias or imprecision.

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	Rates of subjective cure over the short term (up to 1 year) were similar for the two procedures, ranging from 62% to 98% in the transobturator group and 71% to 97% in the retropubic group, as were objective cure rates. Subjective cure rates also were similar in the few trials that reported medium-term (1 to 5 years) and long-term (more than 5 years) results.

	Overall, both transobturator and retropubic procedures cured or significantly improved symptoms in more than 80% of women at 12 months. The cure rate decreased to around 70% in the few studies that reported 5-year results.

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	Adverse event rates for both procedures were low. Transobturator surgery had a lower rate of bladder perforation than the retropubic procedure (0.6% vs. 4.5%) as well as lower major vascular or visceral injury, operative blood loss, mean operating time, and length of hospital stay. Fewer women who underwent the transobturator operation experienced postoperative voiding dysfunction than women who had retropubic surgery (around 4% vs. 7%).

	Women in the transobturator group were more likely than women in the retropubic group to experience short-term groin pain (6.4% vs. 1.3%) but less likely to have suprapubic pain (0.8% vs. 2.9%). Limited data suggested that women who underwent transobturator surgery were more likely to need repeat surgery. For both procedures, the rate of tape erosion at 1 to 5 years post-op was low-around 2%-as was the rate of pain during sexual intercourse.

	“Overall, the rates of complication with both [procedures] are low, and women should be reassured by this. Importantly, for women considering surgery, quality of life has been found to be greatly improved following both operations and remains significantly improved even beyond 5 years following surgery,” lead author Abigail A. Ford, MD, of the Bradford Royal Infirmary, West Yorkshire, United Kingdom, told 

	The review illustrates the need to obtain longer-term follow-up data from existing trials, its authors emphasize, “to increase the evidence base and provide clarification regarding uncertainties about long-term effectiveness and adverse event profile.”

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Diet, urine pH may affect urinary tract bacterial growth

A recently published review expands understanding of the effectiveness and side effects of mid-urethral sling procedures for stress urinary incontinence, providing more information for women considering minimally invasive surgical treatment.

	Dietary metabolites and urine acidity may affect the growth of bacteria in the urinary tract, potentially opening new avenues for treating urinary tract infections, according to a new study published in 

	To investigate the body’s natural defenses against UTI, researchers at Washington University in St. Louis cultured 

bacteria in urine from healthy volunteers and compared how effectively the antimicrobial protein siderocalin (SCN) hampered bacterial growth in different samples. During UTIs, cells in the urinary tract secrete SCN to inhibit bacterial proliferation by interfering with uptake of iron that the bacteria need to grow. SCN activity varies widely from person to person.

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	The authors considered what characteristics in the urine of healthy volunteers might influence the antimicrobial effectiveness of SCN. They found that elevated urine pH and small molecules called aryl sulfates, produced when gut microbes metabolize food, exerted a strong effect on SCN’s antibacterial activity.

	Changing pH by itself promoted or inhibited bacterial growth in urine, the study showed, which could affect therapy for UTI. Acid urine has long been thought to reduce bacterial growth, but surprisingly, less acidic urine, with a pH closer to neutral, had a stronger effect on SCN activity than more acidic samples.

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	In addition to pH, certain metabolites, specifically aryl sulfates, are key to controlling SCN activity, the authors determined after evaluating thousands of compounds in the urine samples. These metabolites, which vary with diet, were more plentiful in samples with less bacterial growth.

	The authors surmise that SCN may work with aryl metabolites from dietary plant compounds to prevent 

 from using a compound called enterobactin to bind to iron in urine. Exploring methods of obstructing enterobactin’s iron-binding capacity could lead to eventual development of drugs with different antimicrobial properties than current antibiotics, they note.

	“Our study suggests that the body’s immune system harnesses dietary plant compounds to prevent bacterial growth,” said senior author Jonathan Henderson, MD, PhD, in a 

 from Washington University. “We identified a list of compounds of interest, and many of these are associated with specific dietary components and with gut microbes.”

	Finding new approaches to preventing and treating UTI by promoting the chemical characteristics of urine that restrict bacterial growth, thereby strengthening the body’s innate immune defenses, could help address the problem of growing resistance to the antibiotics used to treat UTI, the study suggests.

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	Bariatric weight-loss surgery significantly improved urinary incontinence in severely obese people over a 3-year period in a newly reported study.

	The findings extend previous research showing weight-loss-associated reductions in incontinence over shorter periods of about a year.

	The observational cohort study investigated incontinence in 1,987 patients who underwent bariatric surgery between 2005 and 2009 at 10 hospitals nationwide. Using a validated questionnaire, researchers assessed frequency and type of incontinence episodes during the previous 3 months at baseline (before surgery), then annually for 3 years. They defined prevalent incontinence as episodes occurring at least once a week and remission as a decline between baseline and follow-up from prevalent incontinence to episodes less often than weekly.

	Study participants, predominantly women (78.8%), ranged in age from 18 to 78 years with a median age of 47 years. Median body mass index at baseline was 47 kg/m

. Researchers controlled for age, race, smoking status, and recent pregnancy. Before surgery, 49.3% of women and 21.8% of men reported experiencing incontinence at least once a week.

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	At 1 year after surgery, women had lost a mean of 29.5% of body weight and men had lost 27%. The prevalence of incontinence had fallen markedly, to 18.3% among women and 9.8% among men. Three years after surgery, the prevalence was higher than at 1 year (24.8% for women, 12.2% for men) but still substantially below baseline.

	The odds of improved incontinence increased with the amount of weight lost. The risk of relapse increased with each 10-pound weight gain. Younger age and absence of severe walking limitations were associated with greater improvement; recent pregnancy was associated with less improvement.

	Although previous studies have shown reduced incontinence a year after weight loss by such methods as a low-calorie diet, behavioral modification, and bariatric surgery, “there wasn’t evidence on the longer-term effects of these changes,” said lead author Leslee L. Subak, MD, of the University of California, San Francisco. “Improvement in urinary incontinence may help motivate severely obese men and women with incontinence to undergo bariatric surgery or other weight-loss interventions and improve long-term weight maintenance,” he noted.

	The study, which was published online in 

 (June 22, 2015), was supported by the Longitudinal Assessment of Bariatric Surgery 2, a cooperative agreement funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Dr. Subak has received a grant from the NIDDK.

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Author | Karen Bardossi

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Study: No significant link between diabetes Tx, bladder Ca

Mid-urethral slings demonstrate efficacy, few adverse effects

Diet, urine pH may affect urinary tract bacterial growth

Weight-loss surgery may reduce incontinence