Susan Birk

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks following treatment with botulinum neurotoxin type A in a randomized trial of 313 patients.

“Dose response was observed in main patient-reported measures, with Botox doses at or above 100 U consistently providing meaningful benefit as measured by improvements on these questionnaires,” reported Dr. David A. Ginsberg and his colleagues in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

“One of the issues I think we've always had is, What is the best way to evaluate the efficacy in our therapies for overactive bladder? … What's very important are quality of life data. We do this [informally] every day in our practice. We ask patients … 'Are you feeling better?' But when we're doing studies, we don't really quantify this with quality of life evaluations,” said Dr. Ginsberg, who disclosed that he is a consultant for Allergan Inc., which supported the multicenter, double-blind phase II study.

At baseline, participants (mean age, 58.8 years; 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50-U group to 39.7 in the 300-U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups, compared with the placebo group, except in the group receiving the lowest Botox dose. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the patients in the 100-U, 150-U, and 300-U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention (PVR) of more than 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U 100-U, 150-U, 200-U, and 300-U groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773-8) reported that more than two of five patients required clean intermittent self-catheterization following treatment and concluded that “all prospective patients should be informed about this.”

Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“In addition, retention was defined as a PVR greater than 100 mL. Patients may very well have a PVR that high or higher, show improvement in regard to their [overactive bladder] symptoms, and not require intermittent catheterization to help empty their bladder,” he said.

“I tell my patients there is about a 10%-20% risk that they might need [intermittent catheterization] to empty their bladder,” he said.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks following treatment with botulinum neurotoxin type A in a randomized trial of 313 patients.

“Dose response was observed in main patient-reported measures, with Botox doses at or above 100 U consistently providing meaningful benefit as measured by improvements on these questionnaires,” reported Dr. David A. Ginsberg and his colleagues in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

“One of the issues I think we've always had is, What is the best way to evaluate the efficacy in our therapies for overactive bladder? … What's very important are quality of life data. We do this [informally] every day in our practice. We ask patients … 'Are you feeling better?' But when we're doing studies, we don't really quantify this with quality of life evaluations,” said Dr. Ginsberg, who disclosed that he is a consultant for Allergan Inc., which supported the multicenter, double-blind phase II study.

At baseline, participants (mean age, 58.8 years; 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50-U group to 39.7 in the 300-U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups, compared with the placebo group, except in the group receiving the lowest Botox dose. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the patients in the 100-U, 150-U, and 300-U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention (PVR) of more than 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U 100-U, 150-U, 200-U, and 300-U groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773-8) reported that more than two of five patients required clean intermittent self-catheterization following treatment and concluded that “all prospective patients should be informed about this.”

Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“In addition, retention was defined as a PVR greater than 100 mL. Patients may very well have a PVR that high or higher, show improvement in regard to their [overactive bladder] symptoms, and not require intermittent catheterization to help empty their bladder,” he said.

“I tell my patients there is about a 10%-20% risk that they might need [intermittent catheterization] to empty their bladder,” he said.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks following treatment with botulinum neurotoxin type A in a randomized trial of 313 patients.

“Dose response was observed in main patient-reported measures, with Botox doses at or above 100 U consistently providing meaningful benefit as measured by improvements on these questionnaires,” reported Dr. David A. Ginsberg and his colleagues in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

“One of the issues I think we've always had is, What is the best way to evaluate the efficacy in our therapies for overactive bladder? … What's very important are quality of life data. We do this [informally] every day in our practice. We ask patients … 'Are you feeling better?' But when we're doing studies, we don't really quantify this with quality of life evaluations,” said Dr. Ginsberg, who disclosed that he is a consultant for Allergan Inc., which supported the multicenter, double-blind phase II study.

At baseline, participants (mean age, 58.8 years; 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50-U group to 39.7 in the 300-U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups, compared with the placebo group, except in the group receiving the lowest Botox dose. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the patients in the 100-U, 150-U, and 300-U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention (PVR) of more than 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U 100-U, 150-U, 200-U, and 300-U groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773-8) reported that more than two of five patients required clean intermittent self-catheterization following treatment and concluded that “all prospective patients should be informed about this.”

Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“In addition, retention was defined as a PVR greater than 100 mL. Patients may very well have a PVR that high or higher, show improvement in regard to their [overactive bladder] symptoms, and not require intermittent catheterization to help empty their bladder,” he said.

“I tell my patients there is about a 10%-20% risk that they might need [intermittent catheterization] to empty their bladder,” he said.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40-79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjustment for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40-79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjustment for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40-79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjustment for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40–79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjusting for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

A randomized, controlled trial is now needed, Dr. Hamilton said. He and his colleagues plan to analyze additional data on this group of patients to look at cholesterol levels, duration of statin use, and dose and statin use after surgery.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

Statins Improve Male Urologic Health

New studies add weight to the possibility of a connection between statins and various aspects of male urologic health.

In addition to studies showing decreased risk of prostate cancer in men taking statins, a Mayo Clinic study using data on 2,447 men aged 40–79 from the Rochester Epidemiology Project revealed an inverse relationship between erectile dysfunction and statin use. A total of 729 (30%) of the men reported taking statin medications. Starting with the sixth year of follow-up and biennially thereafter, patients were asked questions from the Brief Male Sexual Function Inventory. The inverse association was strongest in the oldest men in the study, according to Dr. Ajay Nehra, of the urology department at Mayo. The association was strengthened after adjustment for age at baseline, diabetes, hypertension, coronary heart disease, smoking status, and weight.

In another Mayo Clinic study of the same cohort, statins were associated with a decreased risk of lower urinary tract symptoms and benign prostatic enlargement, as well as a decreased peak urinary flow rate. The combined use of statins and NSAIDs lowered these risks further, Dr. Jennifer L. St. Sauver, also of the Mayo Clinic, and her colleagues reported in a poster.

Dr. St. Sauver had no financial disclosures related to the study. Dr. Nehra is a consultant for Pfizer, GlaxoSmithKline, and Sanofi-Aventis.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40–79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjusting for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

A randomized, controlled trial is now needed, Dr. Hamilton said. He and his colleagues plan to analyze additional data on this group of patients to look at cholesterol levels, duration of statin use, and dose and statin use after surgery.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

Statins Improve Male Urologic Health

New studies add weight to the possibility of a connection between statins and various aspects of male urologic health.

In addition to studies showing decreased risk of prostate cancer in men taking statins, a Mayo Clinic study using data on 2,447 men aged 40–79 from the Rochester Epidemiology Project revealed an inverse relationship between erectile dysfunction and statin use. A total of 729 (30%) of the men reported taking statin medications. Starting with the sixth year of follow-up and biennially thereafter, patients were asked questions from the Brief Male Sexual Function Inventory. The inverse association was strongest in the oldest men in the study, according to Dr. Ajay Nehra, of the urology department at Mayo. The association was strengthened after adjustment for age at baseline, diabetes, hypertension, coronary heart disease, smoking status, and weight.

In another Mayo Clinic study of the same cohort, statins were associated with a decreased risk of lower urinary tract symptoms and benign prostatic enlargement, as well as a decreased peak urinary flow rate. The combined use of statins and NSAIDs lowered these risks further, Dr. Jennifer L. St. Sauver, also of the Mayo Clinic, and her colleagues reported in a poster.

Dr. St. Sauver had no financial disclosures related to the study. Dr. Nehra is a consultant for Pfizer, GlaxoSmithKline, and Sanofi-Aventis.

CHICAGO — Statins may have a protective effect against prostate cancer, according to recent study findings.

The research, presented at the annual meeting of the American Urological Association, adds weight to a growing body of evidence that statins may do more than help to lower cholesterol.

In an observational study of 2,447 men followed for 15 years, patients taking statins had one-third the risk of developing prostate cancer, compared with nonusers.

“We also found that the men who were taking statin medications the longest … had the greatest reduction in prostate cancer risk,” Dr. Rodney H. Breau of the Mayo Clinic, Rochester, Minn., reported in a press briefing. The study analyzed prostate cancer risk in men aged 40–79 years, starting in 1990 using data from the Rochester Epidemiology Project.

Statin use was associated with a reduced likelihood of exceeding the prostate-specific antigen threshold for age and a reduced risk of prostate biopsy. In a randomly chosen subset of 618 patients who agreed to undergo PSA testing every other year, 11 (6.3%) statin users exceeded age-specific PSA thresholds, compared with 65 (14.7%) nonstatin users, for an age-adjusted hazard ratio of 0.35.

Among a group of 616 statin users, 75 (12.2%) underwent a prostate biopsy and 30 (4.9%) were diagnosed with prostate cancer. Age-adjusted hazard ratios for prostate biopsy and prostate cancer diagnosis were 0.39 and 0.38, respectively, compared with nonstatin users.

“We have to be very careful about looking at the data more closely to make sure we can't find some alternative explanation,” Dr. Breau said. “Our data indicate you probably need to be on these medications for a prolonged period of time and possibly starting at the right age to prevent cancer from developing.”

In another study presented at the meeting, there was a 30% reduction in the risk of a recurrence in PSA elevation following radical prostatectomy among statin users versus nonusers. “If these findings are confirmed in larger studies and/or randomized trials, it may be prudent to prescribe a statin to all men undergoing radical prostatectomy,” said Dr. Robert J. Hamilton of the University of Toronto.

The researchers analyzed the Shared Equal Access Regional Cancer Hospital (SEARCH) database to assess the risk of biochemical recurrence in 1,325 men who had undergone radical prostatectomy. At the time of surgery, 237 (18%) of the men were taking statins.

Statin users were 2 years older than nonusers and had undergone surgery more recently (median year of surgery, 2004 vs. 2002). At the time of the diagnosis, statin users also had lower clinical stages of disease (67% vs. 58% with T1 disease) and with lower PSA levels (6.2 vs. 6.9 ng/mL).

After adjusting for differences between the two groups, statin use appeared to reduce the risk of biochemical recurrence by 30%.

A randomized, controlled trial is now needed, Dr. Hamilton said. He and his colleagues plan to analyze additional data on this group of patients to look at cholesterol levels, duration of statin use, and dose and statin use after surgery.

Findings from a third study presented at the meeting suggest a potential mechanism of action. The study of 254 men examined levels of prostate tumor inflammation in statin users vs. nonusers who were undergoing radical prostatectomy. A single pathologist graded tumors based on levels of white blood cells. Statin use was associated with a 72% reduction in the risk of tumor inflammation, reported Dr. Lionel L. Bañez of Duke University, Durham, N.C. Although statin users were significantly more likely than nonusers to be overweight or obese, statin use was associated with a lower risk for any tumor inflammation.

Dr. Breau, Dr. Hamilton, and Dr. Bañez had no financial disclosures related to their studies.

Statins Improve Male Urologic Health

New studies add weight to the possibility of a connection between statins and various aspects of male urologic health.

In addition to studies showing decreased risk of prostate cancer in men taking statins, a Mayo Clinic study using data on 2,447 men aged 40–79 from the Rochester Epidemiology Project revealed an inverse relationship between erectile dysfunction and statin use. A total of 729 (30%) of the men reported taking statin medications. Starting with the sixth year of follow-up and biennially thereafter, patients were asked questions from the Brief Male Sexual Function Inventory. The inverse association was strongest in the oldest men in the study, according to Dr. Ajay Nehra, of the urology department at Mayo. The association was strengthened after adjustment for age at baseline, diabetes, hypertension, coronary heart disease, smoking status, and weight.

In another Mayo Clinic study of the same cohort, statins were associated with a decreased risk of lower urinary tract symptoms and benign prostatic enlargement, as well as a decreased peak urinary flow rate. The combined use of statins and NSAIDs lowered these risks further, Dr. Jennifer L. St. Sauver, also of the Mayo Clinic, and her colleagues reported in a poster.

Dr. St. Sauver had no financial disclosures related to the study. Dr. Nehra is a consultant for Pfizer, GlaxoSmithKline, and Sanofi-Aventis.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

CHICAGO — A strategy of active surveillance was associated with low prostate cancer mortality in a long-term study of 453 men with a favorable disease risk profile at baseline.

The study offers evidence for the use of active surveillance, based on changes in disease risk over time, as a means of addressing the significant problem of overdetection and overtreatment of prostate cancer in patients with indolent disease, said Dr. Laurence H. Klotz of the University of Toronto.

Dr. Klotz presented the results of the prospective, single-arm study in a poster at the annual meeting of the American Urological Association.

The AUA's recently updated best practice guidelines for prostate-specific antigen (PSA) testing strongly support informing patients that active surveillance is an option “in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.” (The guidelines are available at www.auanet.org

In the present study, patients (median age 70 years; range, 45–86 years) with a PSA level of 10 ng/mL or less and a Gleason score of 6 or less were managed with active surveillance (median follow-up 7.2 years; range, 1–13 years). The surveillance consisted of a PSA test every 3 months for 2 years and then every 6 months, a confirmatory biopsy at 1 year to rule out higher-grade disease that may have been missed on the initial biopsy, and a biopsy every 3–4 years thereafter.

Patients were reclassified as higher risk and offered more aggressive treatment if they had a PSA doubling time of less than 3 years, progression to a Gleason score of 4 + 3 or greater, or unequivocal clinical progression.

The study began in 1995. Initially, men over the age of 70 with a Gleason score of 3 + 4 or a PSA of 10–15 ng/mL were included, but starting in 2000, the researchers limited enrollment to patients with a favorable risk profile.

To date, overall survival among the cohort is 83%. Prostate cancer survival is 99%; five patients (1%) have died of prostate cancer.

Also, 35% of patients have been reclassified as higher risk and offered definitive therapy. The biochemical failure rate was 52% (15% of the overall cohort) among the 137 patients who underwent surgery or radiation.

Follow-up has been completed in 95% of participants, “so we know what has happened with almost all of the patients,” Dr. Klotz said at a press briefing.

All five patients who died of prostate cancer progressed rapidly, were treated within 6–12 months of diagnosis, developed metastatic disease within 1 year of treatment, and died approximately 2 years later, Dr. Klotz noted. “It's safe to say, in looking back, that early treatment would have made no difference in these patients,” he said.

The fact that roughly half of the treated patients had biochemical failure indicates that using PSA doubling time and repeat biopsies as active surveillance parameters identifies patients at higher risk of disease progression, Dr. Klotz said. “The ones who are treated do represent a fairly high-risk cohort, and we're going to need longer follow-up to see what happens to those patients.”

Although about one-third of the patients eventually required definitive treatment, “roughly two-thirds remained untreated … and among these untreated patients, zero have gone on to metastatic disease or prostate cancer death,” he said.

Dr. Klotz stressed the distinction between active surveillance and the more passive approach of watchful waiting, which he noted was a common practice in the United Kingdom and Scandinavia before the development of PSA testing. Scandinavia had the highest prostate cancer mortality in the world, presumably related to this policy, he said.

With active surveillance, “we actively monitor, we read biopsies, we try to get as accurate a sense of the extent of disease and the risk of progression as possible, and treat the subset that looks as if they are actually at higher risk,” he said.

“It's all about risk assessment. … The moment we find a significant amount of Gleason 4 we say, 'This patient does not have the kind of indolent, very slow-growing disease we expected.'”

Funding for the study was provided by the Prostate Cancer Research Foundation of Canada. Dr. Klotz is a consultant for AstraZeneca and Sanofi-Aventis and has participated in research supported by GlaxoSmithKline.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks after treatment with botulinum neurotoxin type A (Botox) in a randomized trial of 313 patients.

“Botox doses at or above 100 U consistently [provided] meaningful benefit as measured by improvements on these questionnaires,” Dr. David A. Ginsberg and his colleagues reported in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

At baseline, participants (mean age 58.8 years, 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia, said Dr. Ginsberg, who disclosed that he is a consultant for Allergan, which supported the multicenter, double-blind, phase II study.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50 U group to 39.7 in the 300 U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups except those receiving the lowest dose, compared with the placebo group. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the 100 U, 150 U, and 300 U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention over 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U, 100-U, 150-U, 200-U, and 300-U dose groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773–8) reported that more than 2 of 5 patients required clean intermittent self-catheterization following treatment. Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“I tell my patients there is about a 10%–20% risk that they might need [intermittent catheterization] to empty their bladder,” Dr. Ginsberg said.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks after treatment with botulinum neurotoxin type A (Botox) in a randomized trial of 313 patients.

“Botox doses at or above 100 U consistently [provided] meaningful benefit as measured by improvements on these questionnaires,” Dr. David A. Ginsberg and his colleagues reported in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

At baseline, participants (mean age 58.8 years, 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia, said Dr. Ginsberg, who disclosed that he is a consultant for Allergan, which supported the multicenter, double-blind, phase II study.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50 U group to 39.7 in the 300 U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups except those receiving the lowest dose, compared with the placebo group. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the 100 U, 150 U, and 300 U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention over 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U, 100-U, 150-U, 200-U, and 300-U dose groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773–8) reported that more than 2 of 5 patients required clean intermittent self-catheterization following treatment. Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“I tell my patients there is about a 10%–20% risk that they might need [intermittent catheterization] to empty their bladder,” Dr. Ginsberg said.

CHICAGO — Patients with idiopathic overactive bladder refractory to anticholinergics reported significant improvements in health-related quality of life, symptom severity, and satisfaction for at least 24 weeks after treatment with botulinum neurotoxin type A (Botox) in a randomized trial of 313 patients.

“Botox doses at or above 100 U consistently [provided] meaningful benefit as measured by improvements on these questionnaires,” Dr. David A. Ginsberg and his colleagues reported in a poster at the annual meeting of the American Urological Association. “The benefit to patients was rapid, as early as 2 weeks, and was sustained for at least 24 weeks” at these doses.

Treatment with 100 U “may be the best dose in terms of balancing efficacy and safety” and lowering the risk of urinary retention as a possible side effect, Dr. Ginsberg of the University of Southern California in Los Angeles said in an interview.

Several earlier studies showed the drug's effectiveness in terms of urodynamics, but the present study offers some of the first objective data on changes in quality of life and patient satisfaction, he said. The use of Botox for overactive bladder is currently an off-label indication.

At baseline, participants (mean age 58.8 years, 91% female) were having eight or more episodes of urge urinary incontinence per week with no more than one incontinence-free day, and an average of eight micturitions daily based on a 7-day voiding diary. Patients were randomized to receive Botox 50 U, 100 U, 150 U, 200 U, or 300 U or placebo intradetrusor injections. Patients received a single treatment of 20 injections under local anesthesia, said Dr. Ginsberg, who disclosed that he is a consultant for Allergan, which supported the multicenter, double-blind, phase II study.

Health-related quality of life was assessed at baseline and at weeks 2, 6, 12, 18, 24, and 36 using the Incontinence Quality of Life questionnaire (I-QOL), the incontinence-specific King's Health Questionnaire (KHQ), and the Overactive Bladder-Urinary Incontinence Patient Satisfaction With Treatment Questionnaire (PSTQ). Global assessments of overall symptoms, activity limitations, and emotions related to overactive bladder since the last clinic visit were performed at the same intervals following treatment.

Significant improvements in incontinence-related QOL and urinary symptoms were found in all of the treatment groups, compared with the placebo group. “A clear dose-response relationship was observed for Botox at week 12, with mean increases from baseline in I-QOL total scores ranging from 29.8 in the Botox 50 U group to 39.7 in the 300 U group versus a mean increase from baseline of 17.9 in the placebo group,” Dr. Ginsberg said. “This dose-response relationship was evident at all subsequent time points.”

Global assessments of symptoms, QOL, activity limitations, and emotions were significantly more positive for up to 24 weeks in patients in all of the Botox treatment groups except those receiving the lowest dose, compared with the placebo group. At week 12, mean changes from baseline in patient satisfaction scores were significantly higher for the 100 U, 150 U, and 300 U groups.

Patient reports of side effects on the PSTQ did not differ between the placebo and Botox groups past week 12 of the study. Patients in the 200-U group had the highest incidence of postvoid residual urine of 200 mL or more. The proportion of patients with postvoid retention over 200 mL were 0%, 12.5%, 14.5%, 20.0%, 28.8%, and 27.3% for the placebo and Botox 50-U, 100-U, 150-U, 200-U, and 300-U dose groups, respectively.

A recent study of Botox in 81 patients with idiopathic overactive bladder (J. Urol. 2009;181:1773–8) reported that more than 2 of 5 patients required clean intermittent self-catheterization following treatment. Dr. Ginsberg noted that patients in this study received Botox 200 U, an amount higher than what appears to be the optimal dose of 100 U.

“I tell my patients there is about a 10%–20% risk that they might need [intermittent catheterization] to empty their bladder,” Dr. Ginsberg said.

CHICAGO — Autologous active cellular immunotherapy with sipuleucel-T, the controversial investigative agent with the brand name Provenge, extended survival by a median of 4.1 months in men with metastatic androgen-independent prostate cancer, according to the most recent data from the IMPACT study.

The much-anticipated results of the phase III, multicenter, randomized, double-blind, placebo-controlled trial were presented in a late-breaking science forum at the annual meeting of the American Urological Association.

“The data show that sipuleucel-T is the first active immunotherapy to demonstrate an improvement in overall survival for advanced prostate cancer,” said coinvestigator Dr. David F. Penson of the University of Southern California in Los Angeles.

“Provenge appears to have a highly favorable benefit-to-risk profile [and] a short duration of therapy, and perhaps most importantly, will not only change the way we manage prostate cancer, but also has the potential to create an entirely novel therapeutic paradigm across the field of oncology,” he said.

Median survival reached 25.8 months with treatment and 21.7 months with placebo. The 3-year survival rate was 31.7% with treatment and 23% with placebo, a relative increase of 38% (P = .032). The hazard ratio was 0.775, indicating a 22.5% reduction in the risk of death in the sipuleucel-T treatment arm.

The experimental vaccine from Dendreon Corp. still had not met the primary end point when interim results from the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial were made public in fall 2008. An earlier Food and Drug Administration decision not to approve Provenge, pending more data, had triggered demonstrations by patient advocates of the therapy.

The IMPACT trial included 512 patients with minimally symptomatic or asymptomatic advanced androgen-independent prostatic adenocarcinoma with metastasis to lymph nodes or bone, who had a life expectancy of at least 6 months and a serum prostate-specific antigen (PSA) level greater than 5 ng/mL. They were randomized at a 2:1 ratio to receive the experimental vaccine or a placebo. In all, 90% of patients completed treatment.

The active cellular immunotherapy is designed to stimulate and optimize production of the patient's T cells and to enlist these cells in the destruction of specific tumor cell types.

At the time of disease progression, patients in both arms of the study were able to receive treatment at the physician's discretion. Patients who were randomized to placebo had the option of receiving immunotherapy in which they received a version of sipuleucel-T prepared from their own cryopreserved cells, which had been harvested at the time of placebo generation. Patients randomized to sipuleucel-T had the option of receiving an additional dose of docetaxel (Taxotere).

The investigational therapy produced only minor—in most cases, transitory—side effects, Dr. Penson said.

This favorable safety profile makes the immunotherapy particularly promising as a treatment for patients with terminal prostate cancer because it preserves quality of life while prolonging life, he said.

The survival benefit found with sipuleucel-T in this study has major significance for patients with advanced prostate cancer, he said. “When you consider that these patients have less than a 2-year survival advantage on average, and you're going to give them 4 more months of life, that's a 20% advantage.”

To rule out the possibility of the survival benefit being driven by a particular group of patients, the treatment effect was assessed in multiple population subsets. All subpopulations demonstrated a positive treatment effect, Dr. Penson reported.

The survival benefit of sipuleucel-T shown in this study is consistent with two earlier multicenter, randomized, double-blind, placebo-controlled trials of the agent, Dr. Penson said. An integrated analysis of the three studies, which includes a total of 737 patients, reveals a hazard ratio of 0.735, which represents a 26.5% reduction in the risk of death, with a P value of less than .001, he said.

Dr. Penson said that he had no disclosures related to the study.

CHICAGO — Autologous active cellular immunotherapy with sipuleucel-T, the controversial investigative agent with the brand name Provenge, extended survival by a median of 4.1 months in men with metastatic androgen-independent prostate cancer, according to the most recent data from the IMPACT study.

The much-anticipated results of the phase III, multicenter, randomized, double-blind, placebo-controlled trial were presented in a late-breaking science forum at the annual meeting of the American Urological Association.

“The data show that sipuleucel-T is the first active immunotherapy to demonstrate an improvement in overall survival for advanced prostate cancer,” said coinvestigator Dr. David F. Penson of the University of Southern California in Los Angeles.

“Provenge appears to have a highly favorable benefit-to-risk profile [and] a short duration of therapy, and perhaps most importantly, will not only change the way we manage prostate cancer, but also has the potential to create an entirely novel therapeutic paradigm across the field of oncology,” he said.

Median survival reached 25.8 months with treatment and 21.7 months with placebo. The 3-year survival rate was 31.7% with treatment and 23% with placebo, a relative increase of 38% (P = .032). The hazard ratio was 0.775, indicating a 22.5% reduction in the risk of death in the sipuleucel-T treatment arm.

The experimental vaccine from Dendreon Corp. still had not met the primary end point when interim results from the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial were made public in fall 2008. An earlier Food and Drug Administration decision not to approve Provenge, pending more data, had triggered demonstrations by patient advocates of the therapy.

The IMPACT trial included 512 patients with minimally symptomatic or asymptomatic advanced androgen-independent prostatic adenocarcinoma with metastasis to lymph nodes or bone, who had a life expectancy of at least 6 months and a serum prostate-specific antigen (PSA) level greater than 5 ng/mL. They were randomized at a 2:1 ratio to receive the experimental vaccine or a placebo. In all, 90% of patients completed treatment.

The active cellular immunotherapy is designed to stimulate and optimize production of the patient's T cells and to enlist these cells in the destruction of specific tumor cell types.

At the time of disease progression, patients in both arms of the study were able to receive treatment at the physician's discretion. Patients who were randomized to placebo had the option of receiving immunotherapy in which they received a version of sipuleucel-T prepared from their own cryopreserved cells, which had been harvested at the time of placebo generation. Patients randomized to sipuleucel-T had the option of receiving an additional dose of docetaxel (Taxotere).

The investigational therapy produced only minor—in most cases, transitory—side effects, Dr. Penson said.

This favorable safety profile makes the immunotherapy particularly promising as a treatment for patients with terminal prostate cancer because it preserves quality of life while prolonging life, he said.

The survival benefit found with sipuleucel-T in this study has major significance for patients with advanced prostate cancer, he said. “When you consider that these patients have less than a 2-year survival advantage on average, and you're going to give them 4 more months of life, that's a 20% advantage.”

To rule out the possibility of the survival benefit being driven by a particular group of patients, the treatment effect was assessed in multiple population subsets. All subpopulations demonstrated a positive treatment effect, Dr. Penson reported.

The survival benefit of sipuleucel-T shown in this study is consistent with two earlier multicenter, randomized, double-blind, placebo-controlled trials of the agent, Dr. Penson said. An integrated analysis of the three studies, which includes a total of 737 patients, reveals a hazard ratio of 0.735, which represents a 26.5% reduction in the risk of death, with a P value of less than .001, he said.

Dr. Penson said that he had no disclosures related to the study.

CHICAGO — Autologous active cellular immunotherapy with sipuleucel-T, the controversial investigative agent with the brand name Provenge, extended survival by a median of 4.1 months in men with metastatic androgen-independent prostate cancer, according to the most recent data from the IMPACT study.

The much-anticipated results of the phase III, multicenter, randomized, double-blind, placebo-controlled trial were presented in a late-breaking science forum at the annual meeting of the American Urological Association.

“The data show that sipuleucel-T is the first active immunotherapy to demonstrate an improvement in overall survival for advanced prostate cancer,” said coinvestigator Dr. David F. Penson of the University of Southern California in Los Angeles.

“Provenge appears to have a highly favorable benefit-to-risk profile [and] a short duration of therapy, and perhaps most importantly, will not only change the way we manage prostate cancer, but also has the potential to create an entirely novel therapeutic paradigm across the field of oncology,” he said.

Median survival reached 25.8 months with treatment and 21.7 months with placebo. The 3-year survival rate was 31.7% with treatment and 23% with placebo, a relative increase of 38% (P = .032). The hazard ratio was 0.775, indicating a 22.5% reduction in the risk of death in the sipuleucel-T treatment arm.

The experimental vaccine from Dendreon Corp. still had not met the primary end point when interim results from the IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment) trial were made public in fall 2008. An earlier Food and Drug Administration decision not to approve Provenge, pending more data, had triggered demonstrations by patient advocates of the therapy.

The IMPACT trial included 512 patients with minimally symptomatic or asymptomatic advanced androgen-independent prostatic adenocarcinoma with metastasis to lymph nodes or bone, who had a life expectancy of at least 6 months and a serum prostate-specific antigen (PSA) level greater than 5 ng/mL. They were randomized at a 2:1 ratio to receive the experimental vaccine or a placebo. In all, 90% of patients completed treatment.

The active cellular immunotherapy is designed to stimulate and optimize production of the patient's T cells and to enlist these cells in the destruction of specific tumor cell types.

At the time of disease progression, patients in both arms of the study were able to receive treatment at the physician's discretion. Patients who were randomized to placebo had the option of receiving immunotherapy in which they received a version of sipuleucel-T prepared from their own cryopreserved cells, which had been harvested at the time of placebo generation. Patients randomized to sipuleucel-T had the option of receiving an additional dose of docetaxel (Taxotere).

The investigational therapy produced only minor—in most cases, transitory—side effects, Dr. Penson said.

This favorable safety profile makes the immunotherapy particularly promising as a treatment for patients with terminal prostate cancer because it preserves quality of life while prolonging life, he said.

The survival benefit found with sipuleucel-T in this study has major significance for patients with advanced prostate cancer, he said. “When you consider that these patients have less than a 2-year survival advantage on average, and you're going to give them 4 more months of life, that's a 20% advantage.”

To rule out the possibility of the survival benefit being driven by a particular group of patients, the treatment effect was assessed in multiple population subsets. All subpopulations demonstrated a positive treatment effect, Dr. Penson reported.

The survival benefit of sipuleucel-T shown in this study is consistent with two earlier multicenter, randomized, double-blind, placebo-controlled trials of the agent, Dr. Penson said. An integrated analysis of the three studies, which includes a total of 737 patients, reveals a hazard ratio of 0.735, which represents a 26.5% reduction in the risk of death, with a P value of less than .001, he said.

Dr. Penson said that he had no disclosures related to the study.

CHICAGO — The instillation of 25–50 cc of ultrasound gel into the vaginal vault before endovaginal or transperineal sonography can aid in the diagnosis of a wide range of abnormalities, according to a diagnostic radiologist.

These abnormalities would be invisible or too difficult to delineate with standard sonographic methods or would be missed on pelvic examination, said Dr. Samuel C. Johnson of the Hutzel Women's Hospital in Detroit.

The instillation technique, referred to as sonovaginography, provides a contrast medium and vaginal distention analogous to the inflation of the abdomen with gas in laparoscopy, greatly facilitating definition of the vaginal wall, he said.

Dr. Johnson said he has been using this technique in his practice for approximately 11/2; years as an adjunct to routine sonography to better delineate or confirm the presence of a suspected abnormality in the cervix or vagina, or to investigate cases of unexplained vaginal bleeding.

In isolated cases, a referring ob.gyn. will order sonovaginography without transvaginal ultrasound to assess an abnormality found on physical examination, he said in a poster presentation at the annual meeting of the Radiological Society of North America.

“This is a very difficult area [to image clearly] just on routine vaginal ultrasound,” Dr. Johnson said in an interview. “You tend to get artifact just from the curvature between the cervix and the vagina. Also, on ultrasound, the cervix and the vagina are very similar in echotexture. You can't discriminate them just based on their echogenicity. That's why I think [sonovaginography] is tremendously helpful.”

Safe, inexpensive, and “a very simple maneuver,” according to Dr. Johnson, the technique can identify cervical polyps, fistulas, congenital vaginal septa, vaginal cysts, vaginal ulcers, and other conditions that otherwise could go undetected.

In cases of unexplained bleeding, for example, sonovaginography is “a useful addendum to routine vaginal ultrasound for identifying any potential lesions that could be causing the symptoms,” he said.

The technique has enabled him to diagnose several cases of an abnormality that often manifests in unexplained bleeding—vaginal prolapse of the fallopian tube after laparoscopic hysterectomy. Women who have undergone this relatively conservative surgery and who return to work and regular activities relatively quickly are at increased risk of developing a dehiscence in which the fallopian tube herniates through the separation, extends into the vagina, becomes irritated, and bleeds. He said that this abnormality has never been reported on routine ultrasound.

Other types of abnormalities, such as polyps in the distal cervix—especially those protruding through the external os, will likely be seen only with sonovaginography, Dr. Johnson said.

“I have plenty of cases where routine ultrasound looks completely normal, and on sonovaginography, we can see the polyp at the external os. You're not going to see it in a nondistended vagina. Sonovaginography can better delineate the extent of the mass and the associated vascularity, and aid in the removal of that lesion.”

The technique also can assist in differentiating a vaginal leiomyoma from a malignancy by determining whether a palpable abnormality on the vaginal wall originates in the vaginal mucosa or the vaginal muscularis, he said.

He described a case of vaginal cancer referred for sonovaginography by a radiation oncologist who was planning brachytherapy and needed to pinpoint a lesion's depth from the vaginal lumen. The information was not obtainable on MRI; however, sonovaginography provided precise dimensions.

A study by researchers at the University of Sassari (Italy) found distension of the vagina with saline to be a reliable method for the assessment of rectovaginal endometriosis (Fertil. Steril. 2003;79:1023–7).

However, according to Dr. Johnson, saline tends not to provide sufficient distention because it leaks quickly from the vagina.

Dr. Johnson said that he began using the technique after noticing the clear delineation of the cervix and proximal vagina during distension of the vaginal fornices at the end of saline infusion sonohysterography. After attempting, with poor results, to distend the vagina of several subsequent patients with saline, “I recalled how a large dollop of [ultrasound] gel was useful in scanning structures closely related to the skin or in scanning through the umbilicus,” he said.

Dr. Johnson and his colleagues are conducting a prospective study of sonovaginography for the diagnosis of unexplained bleeding.

He disclosed that he has no financial conflicts of interest related to his poster presentation.

Initial transvaginal sonogram shows a normal cervical canal (arrow) without a mass.

Sonovaginography delineates a polyp (arrows) protruding through the external os (arrowhead). PHOTOS COURTESY DR. SAMUEL C. JOHNSON

A thin-walled cyst (C) is in the anterior vaginal wall on sonovaginography, separate from the vaginal canal (v).

CHICAGO — The instillation of 25–50 cc of ultrasound gel into the vaginal vault before endovaginal or transperineal sonography can aid in the diagnosis of a wide range of abnormalities, according to a diagnostic radiologist.

These abnormalities would be invisible or too difficult to delineate with standard sonographic methods or would be missed on pelvic examination, said Dr. Samuel C. Johnson of the Hutzel Women's Hospital in Detroit.

The instillation technique, referred to as sonovaginography, provides a contrast medium and vaginal distention analogous to the inflation of the abdomen with gas in laparoscopy, greatly facilitating definition of the vaginal wall, he said.

Dr. Johnson said he has been using this technique in his practice for approximately 11/2; years as an adjunct to routine sonography to better delineate or confirm the presence of a suspected abnormality in the cervix or vagina, or to investigate cases of unexplained vaginal bleeding.

In isolated cases, a referring ob.gyn. will order sonovaginography without transvaginal ultrasound to assess an abnormality found on physical examination, he said in a poster presentation at the annual meeting of the Radiological Society of North America.

“This is a very difficult area [to image clearly] just on routine vaginal ultrasound,” Dr. Johnson said in an interview. “You tend to get artifact just from the curvature between the cervix and the vagina. Also, on ultrasound, the cervix and the vagina are very similar in echotexture. You can't discriminate them just based on their echogenicity. That's why I think [sonovaginography] is tremendously helpful.”

Safe, inexpensive, and “a very simple maneuver,” according to Dr. Johnson, the technique can identify cervical polyps, fistulas, congenital vaginal septa, vaginal cysts, vaginal ulcers, and other conditions that otherwise could go undetected.

In cases of unexplained bleeding, for example, sonovaginography is “a useful addendum to routine vaginal ultrasound for identifying any potential lesions that could be causing the symptoms,” he said.

The technique has enabled him to diagnose several cases of an abnormality that often manifests in unexplained bleeding—vaginal prolapse of the fallopian tube after laparoscopic hysterectomy. Women who have undergone this relatively conservative surgery and who return to work and regular activities relatively quickly are at increased risk of developing a dehiscence in which the fallopian tube herniates through the separation, extends into the vagina, becomes irritated, and bleeds. He said that this abnormality has never been reported on routine ultrasound.

Other types of abnormalities, such as polyps in the distal cervix—especially those protruding through the external os, will likely be seen only with sonovaginography, Dr. Johnson said.

“I have plenty of cases where routine ultrasound looks completely normal, and on sonovaginography, we can see the polyp at the external os. You're not going to see it in a nondistended vagina. Sonovaginography can better delineate the extent of the mass and the associated vascularity, and aid in the removal of that lesion.”

The technique also can assist in differentiating a vaginal leiomyoma from a malignancy by determining whether a palpable abnormality on the vaginal wall originates in the vaginal mucosa or the vaginal muscularis, he said.

He described a case of vaginal cancer referred for sonovaginography by a radiation oncologist who was planning brachytherapy and needed to pinpoint a lesion's depth from the vaginal lumen. The information was not obtainable on MRI; however, sonovaginography provided precise dimensions.

A study by researchers at the University of Sassari (Italy) found distension of the vagina with saline to be a reliable method for the assessment of rectovaginal endometriosis (Fertil. Steril. 2003;79:1023–7).

However, according to Dr. Johnson, saline tends not to provide sufficient distention because it leaks quickly from the vagina.

Dr. Johnson said that he began using the technique after noticing the clear delineation of the cervix and proximal vagina during distension of the vaginal fornices at the end of saline infusion sonohysterography. After attempting, with poor results, to distend the vagina of several subsequent patients with saline, “I recalled how a large dollop of [ultrasound] gel was useful in scanning structures closely related to the skin or in scanning through the umbilicus,” he said.

Dr. Johnson and his colleagues are conducting a prospective study of sonovaginography for the diagnosis of unexplained bleeding.

He disclosed that he has no financial conflicts of interest related to his poster presentation.

Initial transvaginal sonogram shows a normal cervical canal (arrow) without a mass.

Sonovaginography delineates a polyp (arrows) protruding through the external os (arrowhead). PHOTOS COURTESY DR. SAMUEL C. JOHNSON

A thin-walled cyst (C) is in the anterior vaginal wall on sonovaginography, separate from the vaginal canal (v).

CHICAGO — The instillation of 25–50 cc of ultrasound gel into the vaginal vault before endovaginal or transperineal sonography can aid in the diagnosis of a wide range of abnormalities, according to a diagnostic radiologist.

These abnormalities would be invisible or too difficult to delineate with standard sonographic methods or would be missed on pelvic examination, said Dr. Samuel C. Johnson of the Hutzel Women's Hospital in Detroit.

The instillation technique, referred to as sonovaginography, provides a contrast medium and vaginal distention analogous to the inflation of the abdomen with gas in laparoscopy, greatly facilitating definition of the vaginal wall, he said.

Dr. Johnson said he has been using this technique in his practice for approximately 11/2; years as an adjunct to routine sonography to better delineate or confirm the presence of a suspected abnormality in the cervix or vagina, or to investigate cases of unexplained vaginal bleeding.

In isolated cases, a referring ob.gyn. will order sonovaginography without transvaginal ultrasound to assess an abnormality found on physical examination, he said in a poster presentation at the annual meeting of the Radiological Society of North America.

“This is a very difficult area [to image clearly] just on routine vaginal ultrasound,” Dr. Johnson said in an interview. “You tend to get artifact just from the curvature between the cervix and the vagina. Also, on ultrasound, the cervix and the vagina are very similar in echotexture. You can't discriminate them just based on their echogenicity. That's why I think [sonovaginography] is tremendously helpful.”

Safe, inexpensive, and “a very simple maneuver,” according to Dr. Johnson, the technique can identify cervical polyps, fistulas, congenital vaginal septa, vaginal cysts, vaginal ulcers, and other conditions that otherwise could go undetected.

In cases of unexplained bleeding, for example, sonovaginography is “a useful addendum to routine vaginal ultrasound for identifying any potential lesions that could be causing the symptoms,” he said.

The technique has enabled him to diagnose several cases of an abnormality that often manifests in unexplained bleeding—vaginal prolapse of the fallopian tube after laparoscopic hysterectomy. Women who have undergone this relatively conservative surgery and who return to work and regular activities relatively quickly are at increased risk of developing a dehiscence in which the fallopian tube herniates through the separation, extends into the vagina, becomes irritated, and bleeds. He said that this abnormality has never been reported on routine ultrasound.

Other types of abnormalities, such as polyps in the distal cervix—especially those protruding through the external os, will likely be seen only with sonovaginography, Dr. Johnson said.

“I have plenty of cases where routine ultrasound looks completely normal, and on sonovaginography, we can see the polyp at the external os. You're not going to see it in a nondistended vagina. Sonovaginography can better delineate the extent of the mass and the associated vascularity, and aid in the removal of that lesion.”

The technique also can assist in differentiating a vaginal leiomyoma from a malignancy by determining whether a palpable abnormality on the vaginal wall originates in the vaginal mucosa or the vaginal muscularis, he said.

He described a case of vaginal cancer referred for sonovaginography by a radiation oncologist who was planning brachytherapy and needed to pinpoint a lesion's depth from the vaginal lumen. The information was not obtainable on MRI; however, sonovaginography provided precise dimensions.

A study by researchers at the University of Sassari (Italy) found distension of the vagina with saline to be a reliable method for the assessment of rectovaginal endometriosis (Fertil. Steril. 2003;79:1023–7).

However, according to Dr. Johnson, saline tends not to provide sufficient distention because it leaks quickly from the vagina.

Dr. Johnson said that he began using the technique after noticing the clear delineation of the cervix and proximal vagina during distension of the vaginal fornices at the end of saline infusion sonohysterography. After attempting, with poor results, to distend the vagina of several subsequent patients with saline, “I recalled how a large dollop of [ultrasound] gel was useful in scanning structures closely related to the skin or in scanning through the umbilicus,” he said.

Dr. Johnson and his colleagues are conducting a prospective study of sonovaginography for the diagnosis of unexplained bleeding.

He disclosed that he has no financial conflicts of interest related to his poster presentation.

Initial transvaginal sonogram shows a normal cervical canal (arrow) without a mass.

Sonovaginography delineates a polyp (arrows) protruding through the external os (arrowhead). PHOTOS COURTESY DR. SAMUEL C. JOHNSON

A thin-walled cyst (C) is in the anterior vaginal wall on sonovaginography, separate from the vaginal canal (v).

CHICAGO — Volumetric reduction of the hippocampus has emerged as a promising noninvasive imaging biomarker for prodromal and early stages of Alzheimer's disease, according to a study of 373 patients.

The hippocampus was the site of the most dramatic changes in patients with single-domain mild cognitive impairment (memory loss), compared with normal controls. This part of the brain is therefore one of the most significant regions of interest for the early diagnosis of Alzheimer's disease (AD), reported Dr. David S. Karow of the University of California, San Diego (UCSD), Medical Center.

Dr. Karow, a radiology resident, and his colleagues analyzed baseline MRI and fluorodeoxyglucose positron-emission tomography (FDG-PET) images of the cohort of patients. All the patients were participants in the multicenter Alzheimer's Disease Neuroimaging Initiative, which is funded by the National Institutes of Health and by industry.

The finding of hippocampal volume reductions could help pave the way for the development of an objective, noninvasive test for early AD that would enable physicians to prescribe medications sooner in order to slow the progression of the disease, Dr. Karow said in an interview.

“The data we have gives us confidence that hippocampal volume is very promising for the diagnosis of early AD,” he said. “If you were going to pick one region as a noninvasive biomarker, whether it's for mild AD, mild cognitive impairment, or single-domain cognitive impairment, it's likely that the hippocampus is the region to monitor.”

The study revealed significant metabolic as well as structural reductions in the hippocampus, but volumetric reductions were more pronounced, he said.

The findings support a model of AD characterized by a process of downstream deinnervation, in which volume loss in regions of the mesial temporal lobe—the hippocampus in particular—leads to loss of activity in other regions, Dr. Karow said.

In this study, the posterior cingulate cortex surfaced as the region of greatest early metabolic change without structural change. “This region is not the initial site of pathology, but because it's linked neurochemically to the mesial temporal lobe, you'll see metabolic changes there first,” he said. According to the model of AD, once these regions have been deprived of chemical and electrical input, atrophy will ultimately follow, he said.

Dr. Karow noted that, to his knowledge, the study is the first in AD research to combine data from both PET and MRI images, and to look at the relationship between metabolic and structural changes using a region of interest (ROI)-based approach across the whole brain. He presented the findings at the annual meeting of the Radiological Society of North America, and won the Trainee Research Prize for this work.

Dr. Karow and his colleagues analyzed data from PET and MRI images for 80 normal controls, 156 patients with mild cognitive impairment (MCI), 69 patients with single-domain mild cognitive impairment (SMCI), and 68 patients with AD. Forty-five regions of interest were identified using FreeSurfer, 3D reconstruction and segmentation software that assessed average differences in the volume/thickness and metabolic activity of these regions. Effect sizes for each group of patients were then calculated for each region.

Hippocampal volume reductions in SMCI patients averaged 9.5%, compared with controls. This group of patients also exhibited mean morphometric reductions of 6.2% in the entorhinal cortex, 5.5% in the amygdala, and 4.1% in the parahippocampal cortex. Compared with controls, volumetric losses in these structures were greatest for patients with mild AD, followed by MCI and then SMCI patients.

The largest metabolic differences among SMCI patients were declines of 4.2% in the entorhinal cortex, 3.3% in the posterior cingulate cortex, and 3.1% in the hippocampus, compared with controls.

Although the study revealed regions of the brain with greater metabolic reductions than atrophy in the SMCI, MCI, and AD groups, the magnitude of these changes was not as dramatic as the structural changes taking place in the hippocampus, Dr. Karow said. In terms of effect size, ROIs in the mesial temporal lobe, including the entorhinal cortex and, in particular, the hippocampus, stood out as the most important in all three groups of patients, compared with controls.

Dr. Karow reported that neuroradiologists at UCSD have used the findings to create an imaging protocol that employs a commercial version of the brain imaging software used in this study. The protocol generates an automated segmentation of the patient's brain and compares the volume size of the hippocampus and the temporal horn of the lateral ventricle against normal volumes.

Hippocampal volume in patients with AD is typically at least two standard deviations below normal, and volume of the temporal horn of the lateral ventricle is typically two standard deviations above normal, Dr. Karow noted.

He disclosed that he has no financial conflicts of interest related to this study. Dr. Karow's coinvestigators included his mentors Anders Dale, Ph.D., and Dr. Carl K. Hoh. Dr. Dale is a founder of CorTechs Labs Inc., which developed the commercial version of the FreeSurfer software, called NeuroQuant; he holds equity interest in the company and serves on its scientific advisory board. Dr. Karow said the terms of this arrangement were reviewed and approved by UCSD in accordance with its conflict of interest policies.

According to Dr. Karow, the FreeSurfer-based methods used in the study also hold potential for the diagnosis of different types of dementia and behavioral disorders, as well as for clinical evaluations of medications, including those designed to slow the progression of AD.

Brain thickness and activity differed in patients with AD (left) compared with controls (right). Courtesy Dr. David S. Karow

CHICAGO — Volumetric reduction of the hippocampus has emerged as a promising noninvasive imaging biomarker for prodromal and early stages of Alzheimer's disease, according to a study of 373 patients.

The hippocampus was the site of the most dramatic changes in patients with single-domain mild cognitive impairment (memory loss), compared with normal controls. This part of the brain is therefore one of the most significant regions of interest for the early diagnosis of Alzheimer's disease (AD), reported Dr. David S. Karow of the University of California, San Diego (UCSD), Medical Center.

Dr. Karow, a radiology resident, and his colleagues analyzed baseline MRI and fluorodeoxyglucose positron-emission tomography (FDG-PET) images of the cohort of patients. All the patients were participants in the multicenter Alzheimer's Disease Neuroimaging Initiative, which is funded by the National Institutes of Health and by industry.

The finding of hippocampal volume reductions could help pave the way for the development of an objective, noninvasive test for early AD that would enable physicians to prescribe medications sooner in order to slow the progression of the disease, Dr. Karow said in an interview.

“The data we have gives us confidence that hippocampal volume is very promising for the diagnosis of early AD,” he said. “If you were going to pick one region as a noninvasive biomarker, whether it's for mild AD, mild cognitive impairment, or single-domain cognitive impairment, it's likely that the hippocampus is the region to monitor.”

The study revealed significant metabolic as well as structural reductions in the hippocampus, but volumetric reductions were more pronounced, he said.

The findings support a model of AD characterized by a process of downstream deinnervation, in which volume loss in regions of the mesial temporal lobe—the hippocampus in particular—leads to loss of activity in other regions, Dr. Karow said.

In this study, the posterior cingulate cortex surfaced as the region of greatest early metabolic change without structural change. “This region is not the initial site of pathology, but because it's linked neurochemically to the mesial temporal lobe, you'll see metabolic changes there first,” he said. According to the model of AD, once these regions have been deprived of chemical and electrical input, atrophy will ultimately follow, he said.

Dr. Karow noted that, to his knowledge, the study is the first in AD research to combine data from both PET and MRI images, and to look at the relationship between metabolic and structural changes using a region of interest (ROI)-based approach across the whole brain. He presented the findings at the annual meeting of the Radiological Society of North America, and won the Trainee Research Prize for this work.

Dr. Karow and his colleagues analyzed data from PET and MRI images for 80 normal controls, 156 patients with mild cognitive impairment (MCI), 69 patients with single-domain mild cognitive impairment (SMCI), and 68 patients with AD. Forty-five regions of interest were identified using FreeSurfer, 3D reconstruction and segmentation software that assessed average differences in the volume/thickness and metabolic activity of these regions. Effect sizes for each group of patients were then calculated for each region.

Hippocampal volume reductions in SMCI patients averaged 9.5%, compared with controls. This group of patients also exhibited mean morphometric reductions of 6.2% in the entorhinal cortex, 5.5% in the amygdala, and 4.1% in the parahippocampal cortex. Compared with controls, volumetric losses in these structures were greatest for patients with mild AD, followed by MCI and then SMCI patients.

The largest metabolic differences among SMCI patients were declines of 4.2% in the entorhinal cortex, 3.3% in the posterior cingulate cortex, and 3.1% in the hippocampus, compared with controls.

Although the study revealed regions of the brain with greater metabolic reductions than atrophy in the SMCI, MCI, and AD groups, the magnitude of these changes was not as dramatic as the structural changes taking place in the hippocampus, Dr. Karow said. In terms of effect size, ROIs in the mesial temporal lobe, including the entorhinal cortex and, in particular, the hippocampus, stood out as the most important in all three groups of patients, compared with controls.

Dr. Karow reported that neuroradiologists at UCSD have used the findings to create an imaging protocol that employs a commercial version of the brain imaging software used in this study. The protocol generates an automated segmentation of the patient's brain and compares the volume size of the hippocampus and the temporal horn of the lateral ventricle against normal volumes.

Hippocampal volume in patients with AD is typically at least two standard deviations below normal, and volume of the temporal horn of the lateral ventricle is typically two standard deviations above normal, Dr. Karow noted.

He disclosed that he has no financial conflicts of interest related to this study. Dr. Karow's coinvestigators included his mentors Anders Dale, Ph.D., and Dr. Carl K. Hoh. Dr. Dale is a founder of CorTechs Labs Inc., which developed the commercial version of the FreeSurfer software, called NeuroQuant; he holds equity interest in the company and serves on its scientific advisory board. Dr. Karow said the terms of this arrangement were reviewed and approved by UCSD in accordance with its conflict of interest policies.

According to Dr. Karow, the FreeSurfer-based methods used in the study also hold potential for the diagnosis of different types of dementia and behavioral disorders, as well as for clinical evaluations of medications, including those designed to slow the progression of AD.

Brain thickness and activity differed in patients with AD (left) compared with controls (right). Courtesy Dr. David S. Karow

CHICAGO — Volumetric reduction of the hippocampus has emerged as a promising noninvasive imaging biomarker for prodromal and early stages of Alzheimer's disease, according to a study of 373 patients.

The hippocampus was the site of the most dramatic changes in patients with single-domain mild cognitive impairment (memory loss), compared with normal controls. This part of the brain is therefore one of the most significant regions of interest for the early diagnosis of Alzheimer's disease (AD), reported Dr. David S. Karow of the University of California, San Diego (UCSD), Medical Center.

Dr. Karow, a radiology resident, and his colleagues analyzed baseline MRI and fluorodeoxyglucose positron-emission tomography (FDG-PET) images of the cohort of patients. All the patients were participants in the multicenter Alzheimer's Disease Neuroimaging Initiative, which is funded by the National Institutes of Health and by industry.

The finding of hippocampal volume reductions could help pave the way for the development of an objective, noninvasive test for early AD that would enable physicians to prescribe medications sooner in order to slow the progression of the disease, Dr. Karow said in an interview.

“The data we have gives us confidence that hippocampal volume is very promising for the diagnosis of early AD,” he said. “If you were going to pick one region as a noninvasive biomarker, whether it's for mild AD, mild cognitive impairment, or single-domain cognitive impairment, it's likely that the hippocampus is the region to monitor.”

The study revealed significant metabolic as well as structural reductions in the hippocampus, but volumetric reductions were more pronounced, he said.

The findings support a model of AD characterized by a process of downstream deinnervation, in which volume loss in regions of the mesial temporal lobe—the hippocampus in particular—leads to loss of activity in other regions, Dr. Karow said.

In this study, the posterior cingulate cortex surfaced as the region of greatest early metabolic change without structural change. “This region is not the initial site of pathology, but because it's linked neurochemically to the mesial temporal lobe, you'll see metabolic changes there first,” he said. According to the model of AD, once these regions have been deprived of chemical and electrical input, atrophy will ultimately follow, he said.

Dr. Karow noted that, to his knowledge, the study is the first in AD research to combine data from both PET and MRI images, and to look at the relationship between metabolic and structural changes using a region of interest (ROI)-based approach across the whole brain. He presented the findings at the annual meeting of the Radiological Society of North America, and won the Trainee Research Prize for this work.

Dr. Karow and his colleagues analyzed data from PET and MRI images for 80 normal controls, 156 patients with mild cognitive impairment (MCI), 69 patients with single-domain mild cognitive impairment (SMCI), and 68 patients with AD. Forty-five regions of interest were identified using FreeSurfer, 3D reconstruction and segmentation software that assessed average differences in the volume/thickness and metabolic activity of these regions. Effect sizes for each group of patients were then calculated for each region.

Hippocampal volume reductions in SMCI patients averaged 9.5%, compared with controls. This group of patients also exhibited mean morphometric reductions of 6.2% in the entorhinal cortex, 5.5% in the amygdala, and 4.1% in the parahippocampal cortex. Compared with controls, volumetric losses in these structures were greatest for patients with mild AD, followed by MCI and then SMCI patients.

The largest metabolic differences among SMCI patients were declines of 4.2% in the entorhinal cortex, 3.3% in the posterior cingulate cortex, and 3.1% in the hippocampus, compared with controls.

Although the study revealed regions of the brain with greater metabolic reductions than atrophy in the SMCI, MCI, and AD groups, the magnitude of these changes was not as dramatic as the structural changes taking place in the hippocampus, Dr. Karow said. In terms of effect size, ROIs in the mesial temporal lobe, including the entorhinal cortex and, in particular, the hippocampus, stood out as the most important in all three groups of patients, compared with controls.

Dr. Karow reported that neuroradiologists at UCSD have used the findings to create an imaging protocol that employs a commercial version of the brain imaging software used in this study. The protocol generates an automated segmentation of the patient's brain and compares the volume size of the hippocampus and the temporal horn of the lateral ventricle against normal volumes.

Hippocampal volume in patients with AD is typically at least two standard deviations below normal, and volume of the temporal horn of the lateral ventricle is typically two standard deviations above normal, Dr. Karow noted.

He disclosed that he has no financial conflicts of interest related to this study. Dr. Karow's coinvestigators included his mentors Anders Dale, Ph.D., and Dr. Carl K. Hoh. Dr. Dale is a founder of CorTechs Labs Inc., which developed the commercial version of the FreeSurfer software, called NeuroQuant; he holds equity interest in the company and serves on its scientific advisory board. Dr. Karow said the terms of this arrangement were reviewed and approved by UCSD in accordance with its conflict of interest policies.

According to Dr. Karow, the FreeSurfer-based methods used in the study also hold potential for the diagnosis of different types of dementia and behavioral disorders, as well as for clinical evaluations of medications, including those designed to slow the progression of AD.

Brain thickness and activity differed in patients with AD (left) compared with controls (right). Courtesy Dr. David S. Karow

CHICAGO — Volumetric reduction of the hippocampus is a promising noninvasive imaging biomarker for prodromal and early stages of Alzheimer's disease, according to a study of 373 patients.

The hippocampus was the site of the most dramatic changes in patients with single-domain mild cognitive impairment (memory loss), compared with normal controls. This part of the brain is therefore one of the most significant regions of interest for the early diagnosis of Alzheimer's disease (AD), reported Dr. David S. Karow of the University of California, San Diego (UCSD), Medical Center.

Dr. Karow, a radiology resident, and his colleagues analyzed baseline MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) images. All patients were participants in the multicenter Alzheimer's Disease Neuroimaging Initiative, funded by the National Institutes of Health and by industry.

The finding of hippocampal volume reductions could help pave the way for the development of an objective, noninvasive test for early AD that would enable physicians to prescribe medications sooner in order to slow the disease's progression, Dr. Karow said in an interview. “The data we have gives us confidence that hippocampal volume is very promising for the diagnosis of early AD…. If you were going to pick one region as a noninvasive biomarker, whether it's for mild AD, mild cognitive impairment, or single-domain cognitive impairment, it's likely that the hippocampus is the region to monitor,” he said.

The study revealed significant metabolic as well as structural reductions in the hippocampus, but volumetric reductions were more pronounced, he said.

The findings support a model of AD characterized by a process of downstream deinnervation, in which volume loss in regions of the mesial temporal lobe—the hippocampus in particular—leads to loss of activity in other regions, Dr. Karow said.

In this study, the posterior cingulate cortex surfaced as the region of greatest early metabolic change without structural change. “This region is not the initial site of pathology, but because it's linked neurochemically to the mesial temporal lobe, you'll see metabolic changes there first,” he said. According to the model of AD, once these regions have been deprived of chemical and electrical input, atrophy will ultimately follow, he said.

Dr. Karow noted that, to his knowledge, the study is the first in AD research to combine data from both PET and MRI images, and to look at the relationship between metabolic and structural changes using a region of interest (ROI)-based approach across the whole brain. He presented the findings at the annual meeting of the Radiological Society of North America, and won the Trainee Research Prize for this work.

Dr. Karow and his colleagues analyzed data from PET and MRI images for 80 normal controls, 156 patients with mild cognitive impairment (MCI), 69 patients with single-domain mild cognitive impairment (SMCI), and 68 patients with AD. Forty-five regions of interest were identified using FreeSurfer, 3D reconstruction and segmentation software that assessed average differences in the volume/thickness and metabolic activity of these regions. Effect sizes for each group were then calculated for each region.

Hippocampal volume reductions in SMCI patients averaged 9.5%, compared with controls. This group of patients also exhibited mean morphometric reductions of 6.2% in the entorhinal cortex, 5.5% in the amygdala, and 4.1% in the parahippocampal cortex. Compared with controls, volumetric losses in these structures were greatest for patients with mild AD, followed by MCI and then SMCI patients.

The largest metabolic differences among SMCI patients were declines of 4.2% in the entorhinal cortex, 3.3% in the posterior cingulate cortex, and 3.1% in the hippocampus, compared with controls.

Although the study revealed regions of the brain with greater metabolic reductions than atrophy in the SMCI, MCI, and AD groups, the magnitude of these changes was not as dramatic as the structural changes taking place in the hippocampus, Dr. Karow said.

Dr. Karow reported that neuroradiologists at UCSD have used the findings to create an imaging protocol that employs a commercial version of the brain imaging software used in this study. The protocol generates an automated segmentation of the patient's brain and compares the volume size of the hippocampus and the temporal horn of the lateral ventricle against normal volumes.

Hippocampal volume in AD is typically at least two standard deviations below normal, and volume of the temporal horn of the lateral ventricle is typically two standard deviations above normal.

Dr. Karow disclosed that he has no financial conflicts of interest related to this study. Dr. Karow's coinvestigators included his mentors Anders Dale, Ph.D., and Dr. Carl K. Hoh. Dr. Dale is a founder of CorTechs Labs Inc., which developed the commercial version of the FreeSurfer software, called NeuroQuant; he holds equity interest in the company and serves on its scientific advisory board. Dr. Karow said the terms of this arrangement were reviewed and approved by UCSD.

Maps show average differences in activity/thickness between diagnostic groups. Courtesy Dr. David S. Karow

CHICAGO — Volumetric reduction of the hippocampus is a promising noninvasive imaging biomarker for prodromal and early stages of Alzheimer's disease, according to a study of 373 patients.

The hippocampus was the site of the most dramatic changes in patients with single-domain mild cognitive impairment (memory loss), compared with normal controls. This part of the brain is therefore one of the most significant regions of interest for the early diagnosis of Alzheimer's disease (AD), reported Dr. David S. Karow of the University of California, San Diego (UCSD), Medical Center.

Dr. Karow, a radiology resident, and his colleagues analyzed baseline MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) images. All patients were participants in the multicenter Alzheimer's Disease Neuroimaging Initiative, funded by the National Institutes of Health and by industry.

The finding of hippocampal volume reductions could help pave the way for the development of an objective, noninvasive test for early AD that would enable physicians to prescribe medications sooner in order to slow the disease's progression, Dr. Karow said in an interview. “The data we have gives us confidence that hippocampal volume is very promising for the diagnosis of early AD…. If you were going to pick one region as a noninvasive biomarker, whether it's for mild AD, mild cognitive impairment, or single-domain cognitive impairment, it's likely that the hippocampus is the region to monitor,” he said.

The study revealed significant metabolic as well as structural reductions in the hippocampus, but volumetric reductions were more pronounced, he said.

The findings support a model of AD characterized by a process of downstream deinnervation, in which volume loss in regions of the mesial temporal lobe—the hippocampus in particular—leads to loss of activity in other regions, Dr. Karow said.

In this study, the posterior cingulate cortex surfaced as the region of greatest early metabolic change without structural change. “This region is not the initial site of pathology, but because it's linked neurochemically to the mesial temporal lobe, you'll see metabolic changes there first,” he said. According to the model of AD, once these regions have been deprived of chemical and electrical input, atrophy will ultimately follow, he said.

Dr. Karow noted that, to his knowledge, the study is the first in AD research to combine data from both PET and MRI images, and to look at the relationship between metabolic and structural changes using a region of interest (ROI)-based approach across the whole brain. He presented the findings at the annual meeting of the Radiological Society of North America, and won the Trainee Research Prize for this work.

Dr. Karow and his colleagues analyzed data from PET and MRI images for 80 normal controls, 156 patients with mild cognitive impairment (MCI), 69 patients with single-domain mild cognitive impairment (SMCI), and 68 patients with AD. Forty-five regions of interest were identified using FreeSurfer, 3D reconstruction and segmentation software that assessed average differences in the volume/thickness and metabolic activity of these regions. Effect sizes for each group were then calculated for each region.

Hippocampal volume reductions in SMCI patients averaged 9.5%, compared with controls. This group of patients also exhibited mean morphometric reductions of 6.2% in the entorhinal cortex, 5.5% in the amygdala, and 4.1% in the parahippocampal cortex. Compared with controls, volumetric losses in these structures were greatest for patients with mild AD, followed by MCI and then SMCI patients.

The largest metabolic differences among SMCI patients were declines of 4.2% in the entorhinal cortex, 3.3% in the posterior cingulate cortex, and 3.1% in the hippocampus, compared with controls.

Although the study revealed regions of the brain with greater metabolic reductions than atrophy in the SMCI, MCI, and AD groups, the magnitude of these changes was not as dramatic as the structural changes taking place in the hippocampus, Dr. Karow said.

Dr. Karow reported that neuroradiologists at UCSD have used the findings to create an imaging protocol that employs a commercial version of the brain imaging software used in this study. The protocol generates an automated segmentation of the patient's brain and compares the volume size of the hippocampus and the temporal horn of the lateral ventricle against normal volumes.

Hippocampal volume in AD is typically at least two standard deviations below normal, and volume of the temporal horn of the lateral ventricle is typically two standard deviations above normal.

Dr. Karow disclosed that he has no financial conflicts of interest related to this study. Dr. Karow's coinvestigators included his mentors Anders Dale, Ph.D., and Dr. Carl K. Hoh. Dr. Dale is a founder of CorTechs Labs Inc., which developed the commercial version of the FreeSurfer software, called NeuroQuant; he holds equity interest in the company and serves on its scientific advisory board. Dr. Karow said the terms of this arrangement were reviewed and approved by UCSD.

Maps show average differences in activity/thickness between diagnostic groups. Courtesy Dr. David S. Karow

CHICAGO — Volumetric reduction of the hippocampus is a promising noninvasive imaging biomarker for prodromal and early stages of Alzheimer's disease, according to a study of 373 patients.

The hippocampus was the site of the most dramatic changes in patients with single-domain mild cognitive impairment (memory loss), compared with normal controls. This part of the brain is therefore one of the most significant regions of interest for the early diagnosis of Alzheimer's disease (AD), reported Dr. David S. Karow of the University of California, San Diego (UCSD), Medical Center.

Dr. Karow, a radiology resident, and his colleagues analyzed baseline MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) images. All patients were participants in the multicenter Alzheimer's Disease Neuroimaging Initiative, funded by the National Institutes of Health and by industry.

The finding of hippocampal volume reductions could help pave the way for the development of an objective, noninvasive test for early AD that would enable physicians to prescribe medications sooner in order to slow the disease's progression, Dr. Karow said in an interview. “The data we have gives us confidence that hippocampal volume is very promising for the diagnosis of early AD…. If you were going to pick one region as a noninvasive biomarker, whether it's for mild AD, mild cognitive impairment, or single-domain cognitive impairment, it's likely that the hippocampus is the region to monitor,” he said.

The study revealed significant metabolic as well as structural reductions in the hippocampus, but volumetric reductions were more pronounced, he said.

The findings support a model of AD characterized by a process of downstream deinnervation, in which volume loss in regions of the mesial temporal lobe—the hippocampus in particular—leads to loss of activity in other regions, Dr. Karow said.

In this study, the posterior cingulate cortex surfaced as the region of greatest early metabolic change without structural change. “This region is not the initial site of pathology, but because it's linked neurochemically to the mesial temporal lobe, you'll see metabolic changes there first,” he said. According to the model of AD, once these regions have been deprived of chemical and electrical input, atrophy will ultimately follow, he said.

Dr. Karow noted that, to his knowledge, the study is the first in AD research to combine data from both PET and MRI images, and to look at the relationship between metabolic and structural changes using a region of interest (ROI)-based approach across the whole brain. He presented the findings at the annual meeting of the Radiological Society of North America, and won the Trainee Research Prize for this work.

Dr. Karow and his colleagues analyzed data from PET and MRI images for 80 normal controls, 156 patients with mild cognitive impairment (MCI), 69 patients with single-domain mild cognitive impairment (SMCI), and 68 patients with AD. Forty-five regions of interest were identified using FreeSurfer, 3D reconstruction and segmentation software that assessed average differences in the volume/thickness and metabolic activity of these regions. Effect sizes for each group were then calculated for each region.

Hippocampal volume reductions in SMCI patients averaged 9.5%, compared with controls. This group of patients also exhibited mean morphometric reductions of 6.2% in the entorhinal cortex, 5.5% in the amygdala, and 4.1% in the parahippocampal cortex. Compared with controls, volumetric losses in these structures were greatest for patients with mild AD, followed by MCI and then SMCI patients.

The largest metabolic differences among SMCI patients were declines of 4.2% in the entorhinal cortex, 3.3% in the posterior cingulate cortex, and 3.1% in the hippocampus, compared with controls.

Although the study revealed regions of the brain with greater metabolic reductions than atrophy in the SMCI, MCI, and AD groups, the magnitude of these changes was not as dramatic as the structural changes taking place in the hippocampus, Dr. Karow said.

Dr. Karow reported that neuroradiologists at UCSD have used the findings to create an imaging protocol that employs a commercial version of the brain imaging software used in this study. The protocol generates an automated segmentation of the patient's brain and compares the volume size of the hippocampus and the temporal horn of the lateral ventricle against normal volumes.

Hippocampal volume in AD is typically at least two standard deviations below normal, and volume of the temporal horn of the lateral ventricle is typically two standard deviations above normal.

Dr. Karow disclosed that he has no financial conflicts of interest related to this study. Dr. Karow's coinvestigators included his mentors Anders Dale, Ph.D., and Dr. Carl K. Hoh. Dr. Dale is a founder of CorTechs Labs Inc., which developed the commercial version of the FreeSurfer software, called NeuroQuant; he holds equity interest in the company and serves on its scientific advisory board. Dr. Karow said the terms of this arrangement were reviewed and approved by UCSD.

Maps show average differences in activity/thickness between diagnostic groups. Courtesy Dr. David S. Karow

CHICAGO — Radiologists have reported cases of self-mutilation by adolescents involving the deliberate embedding of foreign objects such as paper clips, staples, and pieces of glass into soft tissues of the arms, hands, feet, and ankles.

The behavior, which exceeds in severity the more well-documented patterns of adolescent self-injury such as cutting, burning, and bruising, may represent “a new, discrete entity,” said Dr. William Shiels II, chief of radiology at Nationwide Children's Hospital, Columbus, Ohio.

Dr. Shiels presented the results of a study of 10 patients at the annual meeting of the Radiological Society of North America. He said the behavior has not been reported as a problem in adolescents in any of the world literature to date.

Researchers noticed the pattern of self-injury during the course of an ongoing longitudinal study of a novel percutaneous, image-guided, minimally invasive technique to remove soft tissue foreign bodies (STFBs) in pediatric patients.

Data on 505 patients have shown the technique's safety and effectiveness in removing STFBs with minimal scarring. In most patients treated with the procedure, the injuries were accidental (stepping on a piece of glass, for example); however, in 10 patients, the injuries clearly were self-inflicted. One patient had inserted unfolded paper clips measuring 16 cm in length bilaterally into her biceps muscles.

Of these patients, 90% demonstrated suicidal ideation or behavior, and all had multiple psychiatric comorbidities, such as bipolar disorder, borderline personality disorder, depression, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and obsessive compulsive disorder.

All of the teens had histories of psychological, physical, and/or sexual abuse and were living in foster homes or group homes. They crossed all socioeconomic strata and racial groups; 90% of the patients were girls. Most (70%) embedded objects more than once, and of these, 71% had an escalating pattern of self-injury with increasingly large, painful objects.

Dr. John Campo, chief of child and adolescent psychiatry at Nationwide Children's Hospital and Ohio State University, also in Columbus, said in an interview that the self-embedding behaviors “might represent one extreme of nonsuicidal self-injury or perhaps even a distinct problem.” However, he added, “this is a clinical case series—no more and no less—so we do need to be careful about making excessive generalizations.”

In response to these findings, Dr. Shiels and his colleagues are working with the hospital's institutional review board and information systems department to develop a secure national registry for long-term research and sharing of case histories and radiologic images by clinicians.

The percutaneous treatment technique, which involves the insertion of small surgical instruments through a 2- to 8-mm incision and hydrodissection with lidocaine to separate the foreign object from surrounding soft tissue, results in minimal scarring, compared with traditional surgical procedures, Dr. Shiels said.

A 23-gauge lidocaine needle provides tactile feedback in confirming the object's margins. Some objects require blunt dissection with a forceps. Others are surrounded by dense scar tissue and require sharp dissection with a scalpel blade.

The procedure, which leaves scarring no larger than the size of a freckle, offers an excellent treatment option for this group of patients because it “does not complicate the psychological challenges—including body image and self-esteem issues—that these patients will encounter in their lives,” Dr. Shiels said.

Radiologists removed a total of 53 foreign bodies from the soft tissues of nine adolescents ranging in age from 15 to 18 years in 15 episodes. Objects were removed from the arms (50), the foot (2), and the hand (1) with ultrasound guidance alone (28 objects), fluoroscopic guidance alone (13 objects), and combined ultrasound/fluoroscopy (12 objects).

Ultrasound enabled the identification of nonradiopaque objects not detectable on x-ray. STFBs were metal (29), graphite (9), plastic (9), wood (3), stone (1), glass (1), and crayon (1), and ranged from 2–160 mm by 0.5–3 mm in size.

All 53 objects were successfully removed with a zero incidence of infection; no injury to nerves, tendons, or vascular structures; and no other complications.

Dr. Shiels said Nationwide Children's Hospital has established an interdisciplinary initiative for “self-embedders” led by professionals from the hospital's behavioral health service that focuses on early recognition and intervention.

“The radiologist is often in the unique position to make the diagnosis,” he said. “Parents are often unaware of what's going on, and health providers, pediatricians, ER physicians don't know what's going on. The radiologist can take one look at the x-ray and immediately mobilize an interdisciplinary health care team to intervene in this patient's life and hopefully stop the cycle of self-harm.”

He emphasized the need for education about early detection because “we are in a new era of communication where kids can communicate instantly across the country through Facebook and other media, so they can talk to each other—not only about how they are being cared for but also, possibly, how to do it.”

Requests for access to the registry should be sent to Dr. Shiels at William.Shiels@nationwidechildrens.org

This x-ray shows eight metal pieces a teenage girl embedded in her arm. Radiological Society of North America

CHICAGO — Radiologists have reported cases of self-mutilation by adolescents involving the deliberate embedding of foreign objects such as paper clips, staples, and pieces of glass into soft tissues of the arms, hands, feet, and ankles.

The behavior, which exceeds in severity the more well-documented patterns of adolescent self-injury such as cutting, burning, and bruising, may represent “a new, discrete entity,” said Dr. William Shiels II, chief of radiology at Nationwide Children's Hospital, Columbus, Ohio.

Dr. Shiels presented the results of a study of 10 patients at the annual meeting of the Radiological Society of North America. He said the behavior has not been reported as a problem in adolescents in any of the world literature to date.

Researchers noticed the pattern of self-injury during the course of an ongoing longitudinal study of a novel percutaneous, image-guided, minimally invasive technique to remove soft tissue foreign bodies (STFBs) in pediatric patients.

Data on 505 patients have shown the technique's safety and effectiveness in removing STFBs with minimal scarring. In most patients treated with the procedure, the injuries were accidental (stepping on a piece of glass, for example); however, in 10 patients, the injuries clearly were self-inflicted. One patient had inserted unfolded paper clips measuring 16 cm in length bilaterally into her biceps muscles.

Of these patients, 90% demonstrated suicidal ideation or behavior, and all had multiple psychiatric comorbidities, such as bipolar disorder, borderline personality disorder, depression, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and obsessive compulsive disorder.

All of the teens had histories of psychological, physical, and/or sexual abuse and were living in foster homes or group homes. They crossed all socioeconomic strata and racial groups; 90% of the patients were girls. Most (70%) embedded objects more than once, and of these, 71% had an escalating pattern of self-injury with increasingly large, painful objects.

Dr. John Campo, chief of child and adolescent psychiatry at Nationwide Children's Hospital and Ohio State University, also in Columbus, said in an interview that the self-embedding behaviors “might represent one extreme of nonsuicidal self-injury or perhaps even a distinct problem.” However, he added, “this is a clinical case series—no more and no less—so we do need to be careful about making excessive generalizations.”

In response to these findings, Dr. Shiels and his colleagues are working with the hospital's institutional review board and information systems department to develop a secure national registry for long-term research and sharing of case histories and radiologic images by clinicians.

The percutaneous treatment technique, which involves the insertion of small surgical instruments through a 2- to 8-mm incision and hydrodissection with lidocaine to separate the foreign object from surrounding soft tissue, results in minimal scarring, compared with traditional surgical procedures, Dr. Shiels said.

A 23-gauge lidocaine needle provides tactile feedback in confirming the object's margins. Some objects require blunt dissection with a forceps. Others are surrounded by dense scar tissue and require sharp dissection with a scalpel blade.

The procedure, which leaves scarring no larger than the size of a freckle, offers an excellent treatment option for this group of patients because it “does not complicate the psychological challenges—including body image and self-esteem issues—that these patients will encounter in their lives,” Dr. Shiels said.

Radiologists removed a total of 53 foreign bodies from the soft tissues of nine adolescents ranging in age from 15 to 18 years in 15 episodes. Objects were removed from the arms (50), the foot (2), and the hand (1) with ultrasound guidance alone (28 objects), fluoroscopic guidance alone (13 objects), and combined ultrasound/fluoroscopy (12 objects).

Ultrasound enabled the identification of nonradiopaque objects not detectable on x-ray. STFBs were metal (29), graphite (9), plastic (9), wood (3), stone (1), glass (1), and crayon (1), and ranged from 2–160 mm by 0.5–3 mm in size.

All 53 objects were successfully removed with a zero incidence of infection; no injury to nerves, tendons, or vascular structures; and no other complications.

Dr. Shiels said Nationwide Children's Hospital has established an interdisciplinary initiative for “self-embedders” led by professionals from the hospital's behavioral health service that focuses on early recognition and intervention.

“The radiologist is often in the unique position to make the diagnosis,” he said. “Parents are often unaware of what's going on, and health providers, pediatricians, ER physicians don't know what's going on. The radiologist can take one look at the x-ray and immediately mobilize an interdisciplinary health care team to intervene in this patient's life and hopefully stop the cycle of self-harm.”

He emphasized the need for education about early detection because “we are in a new era of communication where kids can communicate instantly across the country through Facebook and other media, so they can talk to each other—not only about how they are being cared for but also, possibly, how to do it.”

Requests for access to the registry should be sent to Dr. Shiels at William.Shiels@nationwidechildrens.org

This x-ray shows eight metal pieces a teenage girl embedded in her arm. Radiological Society of North America

CHICAGO — Radiologists have reported cases of self-mutilation by adolescents involving the deliberate embedding of foreign objects such as paper clips, staples, and pieces of glass into soft tissues of the arms, hands, feet, and ankles.

The behavior, which exceeds in severity the more well-documented patterns of adolescent self-injury such as cutting, burning, and bruising, may represent “a new, discrete entity,” said Dr. William Shiels II, chief of radiology at Nationwide Children's Hospital, Columbus, Ohio.

Dr. Shiels presented the results of a study of 10 patients at the annual meeting of the Radiological Society of North America. He said the behavior has not been reported as a problem in adolescents in any of the world literature to date.

Researchers noticed the pattern of self-injury during the course of an ongoing longitudinal study of a novel percutaneous, image-guided, minimally invasive technique to remove soft tissue foreign bodies (STFBs) in pediatric patients.

Data on 505 patients have shown the technique's safety and effectiveness in removing STFBs with minimal scarring. In most patients treated with the procedure, the injuries were accidental (stepping on a piece of glass, for example); however, in 10 patients, the injuries clearly were self-inflicted. One patient had inserted unfolded paper clips measuring 16 cm in length bilaterally into her biceps muscles.

Of these patients, 90% demonstrated suicidal ideation or behavior, and all had multiple psychiatric comorbidities, such as bipolar disorder, borderline personality disorder, depression, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and obsessive compulsive disorder.

All of the teens had histories of psychological, physical, and/or sexual abuse and were living in foster homes or group homes. They crossed all socioeconomic strata and racial groups; 90% of the patients were girls. Most (70%) embedded objects more than once, and of these, 71% had an escalating pattern of self-injury with increasingly large, painful objects.

Dr. John Campo, chief of child and adolescent psychiatry at Nationwide Children's Hospital and Ohio State University, also in Columbus, said in an interview that the self-embedding behaviors “might represent one extreme of nonsuicidal self-injury or perhaps even a distinct problem.” However, he added, “this is a clinical case series—no more and no less—so we do need to be careful about making excessive generalizations.”

In response to these findings, Dr. Shiels and his colleagues are working with the hospital's institutional review board and information systems department to develop a secure national registry for long-term research and sharing of case histories and radiologic images by clinicians.

The percutaneous treatment technique, which involves the insertion of small surgical instruments through a 2- to 8-mm incision and hydrodissection with lidocaine to separate the foreign object from surrounding soft tissue, results in minimal scarring, compared with traditional surgical procedures, Dr. Shiels said.

A 23-gauge lidocaine needle provides tactile feedback in confirming the object's margins. Some objects require blunt dissection with a forceps. Others are surrounded by dense scar tissue and require sharp dissection with a scalpel blade.

The procedure, which leaves scarring no larger than the size of a freckle, offers an excellent treatment option for this group of patients because it “does not complicate the psychological challenges—including body image and self-esteem issues—that these patients will encounter in their lives,” Dr. Shiels said.

Radiologists removed a total of 53 foreign bodies from the soft tissues of nine adolescents ranging in age from 15 to 18 years in 15 episodes. Objects were removed from the arms (50), the foot (2), and the hand (1) with ultrasound guidance alone (28 objects), fluoroscopic guidance alone (13 objects), and combined ultrasound/fluoroscopy (12 objects).

Ultrasound enabled the identification of nonradiopaque objects not detectable on x-ray. STFBs were metal (29), graphite (9), plastic (9), wood (3), stone (1), glass (1), and crayon (1), and ranged from 2–160 mm by 0.5–3 mm in size.

All 53 objects were successfully removed with a zero incidence of infection; no injury to nerves, tendons, or vascular structures; and no other complications.

Dr. Shiels said Nationwide Children's Hospital has established an interdisciplinary initiative for “self-embedders” led by professionals from the hospital's behavioral health service that focuses on early recognition and intervention.

“The radiologist is often in the unique position to make the diagnosis,” he said. “Parents are often unaware of what's going on, and health providers, pediatricians, ER physicians don't know what's going on. The radiologist can take one look at the x-ray and immediately mobilize an interdisciplinary health care team to intervene in this patient's life and hopefully stop the cycle of self-harm.”

He emphasized the need for education about early detection because “we are in a new era of communication where kids can communicate instantly across the country through Facebook and other media, so they can talk to each other—not only about how they are being cared for but also, possibly, how to do it.”

Requests for access to the registry should be sent to Dr. Shiels at William.Shiels@nationwidechildrens.org

This x-ray shows eight metal pieces a teenage girl embedded in her arm. Radiological Society of North America