Susan London

SAN DIEGO – Fecal microbiota transplantation by colonoscopy is cost-effective when used as the initial treatment for recurrent Clostridium difficile infection, new data show.

A team led by Dr. Gauree Konijeti, a gastroenterology fellow at Massachusetts General Hospital in Boston, constructed decision analytic models of various treatment strategies in a hypothetical cohort of patients with a first, mild to moderate recurrence of C. difficile infection.

Relative to vancomycin, fecal microbiota transplantation (FMT) delivered by colonoscopy had an incremental cost-effectiveness ratio (ICER) of about $38,000 per quality-adjusted life-year gained, placing it well within the conventional willingness-to-pay threshold of $50,000, she reported at the annual meeting of the American College of Gastroenterology.

Additionally, FMT colonoscopy was more effective and less costly than both metronidazole (Flagyl) and fidaxomicin (Dificid).

However, FMT using other modes of delivery – either enema or duodenal infusion through esophagogastroduodenoscopy – was not cost-effective because of its relatively lower cure rates.

"A strategy consisting of first-line treatment with FMT colonoscopy for an initial recurrence of C. difficile appeared cost-effective at conventional willingness-to-pay thresholds," Dr. Konijeti commented.

"Guidelines should consider earlier use of FMT in the treatment of C. difficile infection, and future studies should incorporate FMT for comparative effectiveness," she recommended.

A session attendee asked, "What are your thoughts on the future of noncolonoscopic delivery methods?"

"One is if we can increase the infusion cure rates for enema and duodenal infusion, or even nasogastric infusion, those would be cost-effective. Right now they are on the order of 81%, compared to colonoscopic delivery, which is closer to the 93%-95% range," Dr. Konijeti replied.

"The other thought is that there has been a study of a fecal transplant pill that was recently presented at ID Week, where they used fresh donor feces from related donors and encapsulated a concentrated form of bacteria into these pills, and then gave about 20 pills to patients in a case series. They showed about a 100% efficacy rate, with only one recurrence in the setting of antibiotics," she said. "So I think we are in an era where we have the opportunity to deliver FMT via a variety of strategies, but we need to find more standardized ways of doing it and then optimize the efficacy."

Giving some background to the research, Dr. Konijeti noted that C. difficile infection has become increasingly challenging to manage. Emergence of the 027 strain has led to lower cure rates and higher rates of resistance. Today, up to one-third of patients have a recurrence after an initial infection, and up to two-thirds of that group go on to have yet more recurrences.

"FMT has emerged as a highly effective therapy because of high cure rates and low rates of recurrence," she commented.

The investigators studied four competing treatment strategies – vancomycin, metronidazole, fidaxomicin, and FMT – for treatment of a first, mild to moderate recurrence of C. difficile infection in a hypothetical cohort of patients having a median age of 65 years.

The models used various subsequent treatments in the event of a second and third recurrence, and the time horizon was 6 months. A key assumption was that payers would be willing to pay up to $50,000 per quality-adjusted life-year gained.

Base-case results showed that FMT colonoscopy was the most cost-effective strategy relative to vancomycin, with an ICER of $38,382 per quality-adjusted life-year gained, and was much more effective than both metronidazole and fidaxomicin.

However, in sensitivity analyses, FMT delivered by duodenal infusion or enema was not superior to other strategies.

Additional analyses tinkering with various model components showed that FMT colonoscopy was the most cost-effective strategy as long as its cure rate exceeded 93.8%, its cost was less than $2,324, or the probability of a post-treatment recurrence was less than 10%.

When the investigators explored thresholds for other treatment strategies, they found vancomycin would be the most cost-effective if its post-treatment recurrence rate were less than 33.9% (vs. 35.5% in the base case); fidaxomicin if its cost dropped to less than $1,539 (vs. $2,800 in the base case); and FMT by duodenal infusion or enema if the cure rate with one-time infusion hit 89.4% and 88.8%, respectively (vs. 81.3% and 81.5%).

Finally, when analyses assumed that FMT was not available, vancomycin was the most cost-effective strategy.

Dr. Konijeti disclosed no relevant conflicts of interest.

SAN DIEGO – Fecal microbiota transplantation by colonoscopy is cost-effective when used as the initial treatment for recurrent Clostridium difficile infection, new data show.

A team led by Dr. Gauree Konijeti, a gastroenterology fellow at Massachusetts General Hospital in Boston, constructed decision analytic models of various treatment strategies in a hypothetical cohort of patients with a first, mild to moderate recurrence of C. difficile infection.

Relative to vancomycin, fecal microbiota transplantation (FMT) delivered by colonoscopy had an incremental cost-effectiveness ratio (ICER) of about $38,000 per quality-adjusted life-year gained, placing it well within the conventional willingness-to-pay threshold of $50,000, she reported at the annual meeting of the American College of Gastroenterology.

Additionally, FMT colonoscopy was more effective and less costly than both metronidazole (Flagyl) and fidaxomicin (Dificid).

However, FMT using other modes of delivery – either enema or duodenal infusion through esophagogastroduodenoscopy – was not cost-effective because of its relatively lower cure rates.

"A strategy consisting of first-line treatment with FMT colonoscopy for an initial recurrence of C. difficile appeared cost-effective at conventional willingness-to-pay thresholds," Dr. Konijeti commented.

"Guidelines should consider earlier use of FMT in the treatment of C. difficile infection, and future studies should incorporate FMT for comparative effectiveness," she recommended.

A session attendee asked, "What are your thoughts on the future of noncolonoscopic delivery methods?"

"One is if we can increase the infusion cure rates for enema and duodenal infusion, or even nasogastric infusion, those would be cost-effective. Right now they are on the order of 81%, compared to colonoscopic delivery, which is closer to the 93%-95% range," Dr. Konijeti replied.

"The other thought is that there has been a study of a fecal transplant pill that was recently presented at ID Week, where they used fresh donor feces from related donors and encapsulated a concentrated form of bacteria into these pills, and then gave about 20 pills to patients in a case series. They showed about a 100% efficacy rate, with only one recurrence in the setting of antibiotics," she said. "So I think we are in an era where we have the opportunity to deliver FMT via a variety of strategies, but we need to find more standardized ways of doing it and then optimize the efficacy."

Giving some background to the research, Dr. Konijeti noted that C. difficile infection has become increasingly challenging to manage. Emergence of the 027 strain has led to lower cure rates and higher rates of resistance. Today, up to one-third of patients have a recurrence after an initial infection, and up to two-thirds of that group go on to have yet more recurrences.

"FMT has emerged as a highly effective therapy because of high cure rates and low rates of recurrence," she commented.

The investigators studied four competing treatment strategies – vancomycin, metronidazole, fidaxomicin, and FMT – for treatment of a first, mild to moderate recurrence of C. difficile infection in a hypothetical cohort of patients having a median age of 65 years.

The models used various subsequent treatments in the event of a second and third recurrence, and the time horizon was 6 months. A key assumption was that payers would be willing to pay up to $50,000 per quality-adjusted life-year gained.

Base-case results showed that FMT colonoscopy was the most cost-effective strategy relative to vancomycin, with an ICER of $38,382 per quality-adjusted life-year gained, and was much more effective than both metronidazole and fidaxomicin.

However, in sensitivity analyses, FMT delivered by duodenal infusion or enema was not superior to other strategies.

Additional analyses tinkering with various model components showed that FMT colonoscopy was the most cost-effective strategy as long as its cure rate exceeded 93.8%, its cost was less than $2,324, or the probability of a post-treatment recurrence was less than 10%.

When the investigators explored thresholds for other treatment strategies, they found vancomycin would be the most cost-effective if its post-treatment recurrence rate were less than 33.9% (vs. 35.5% in the base case); fidaxomicin if its cost dropped to less than $1,539 (vs. $2,800 in the base case); and FMT by duodenal infusion or enema if the cure rate with one-time infusion hit 89.4% and 88.8%, respectively (vs. 81.3% and 81.5%).

Finally, when analyses assumed that FMT was not available, vancomycin was the most cost-effective strategy.

Dr. Konijeti disclosed no relevant conflicts of interest.

SAN DIEGO – Fecal microbiota transplantation by colonoscopy is cost-effective when used as the initial treatment for recurrent Clostridium difficile infection, new data show.

A team led by Dr. Gauree Konijeti, a gastroenterology fellow at Massachusetts General Hospital in Boston, constructed decision analytic models of various treatment strategies in a hypothetical cohort of patients with a first, mild to moderate recurrence of C. difficile infection.

Relative to vancomycin, fecal microbiota transplantation (FMT) delivered by colonoscopy had an incremental cost-effectiveness ratio (ICER) of about $38,000 per quality-adjusted life-year gained, placing it well within the conventional willingness-to-pay threshold of $50,000, she reported at the annual meeting of the American College of Gastroenterology.

Additionally, FMT colonoscopy was more effective and less costly than both metronidazole (Flagyl) and fidaxomicin (Dificid).

However, FMT using other modes of delivery – either enema or duodenal infusion through esophagogastroduodenoscopy – was not cost-effective because of its relatively lower cure rates.

"A strategy consisting of first-line treatment with FMT colonoscopy for an initial recurrence of C. difficile appeared cost-effective at conventional willingness-to-pay thresholds," Dr. Konijeti commented.

"Guidelines should consider earlier use of FMT in the treatment of C. difficile infection, and future studies should incorporate FMT for comparative effectiveness," she recommended.

A session attendee asked, "What are your thoughts on the future of noncolonoscopic delivery methods?"

"One is if we can increase the infusion cure rates for enema and duodenal infusion, or even nasogastric infusion, those would be cost-effective. Right now they are on the order of 81%, compared to colonoscopic delivery, which is closer to the 93%-95% range," Dr. Konijeti replied.

"The other thought is that there has been a study of a fecal transplant pill that was recently presented at ID Week, where they used fresh donor feces from related donors and encapsulated a concentrated form of bacteria into these pills, and then gave about 20 pills to patients in a case series. They showed about a 100% efficacy rate, with only one recurrence in the setting of antibiotics," she said. "So I think we are in an era where we have the opportunity to deliver FMT via a variety of strategies, but we need to find more standardized ways of doing it and then optimize the efficacy."

Giving some background to the research, Dr. Konijeti noted that C. difficile infection has become increasingly challenging to manage. Emergence of the 027 strain has led to lower cure rates and higher rates of resistance. Today, up to one-third of patients have a recurrence after an initial infection, and up to two-thirds of that group go on to have yet more recurrences.

"FMT has emerged as a highly effective therapy because of high cure rates and low rates of recurrence," she commented.

The investigators studied four competing treatment strategies – vancomycin, metronidazole, fidaxomicin, and FMT – for treatment of a first, mild to moderate recurrence of C. difficile infection in a hypothetical cohort of patients having a median age of 65 years.

The models used various subsequent treatments in the event of a second and third recurrence, and the time horizon was 6 months. A key assumption was that payers would be willing to pay up to $50,000 per quality-adjusted life-year gained.

Base-case results showed that FMT colonoscopy was the most cost-effective strategy relative to vancomycin, with an ICER of $38,382 per quality-adjusted life-year gained, and was much more effective than both metronidazole and fidaxomicin.

However, in sensitivity analyses, FMT delivered by duodenal infusion or enema was not superior to other strategies.

Additional analyses tinkering with various model components showed that FMT colonoscopy was the most cost-effective strategy as long as its cure rate exceeded 93.8%, its cost was less than $2,324, or the probability of a post-treatment recurrence was less than 10%.

When the investigators explored thresholds for other treatment strategies, they found vancomycin would be the most cost-effective if its post-treatment recurrence rate were less than 33.9% (vs. 35.5% in the base case); fidaxomicin if its cost dropped to less than $1,539 (vs. $2,800 in the base case); and FMT by duodenal infusion or enema if the cure rate with one-time infusion hit 89.4% and 88.8%, respectively (vs. 81.3% and 81.5%).

Finally, when analyses assumed that FMT was not available, vancomycin was the most cost-effective strategy.

Dr. Konijeti disclosed no relevant conflicts of interest.

SAN DIEGO – A negative screening colonoscopy dramatically reduces the subsequent risk of colorectal cancer, according to a systematic review and meta-analysis of 18 studies presented at the annual meeting of the American College of Gastroenterology.

In the analysis, average-risk individuals whose colonoscopy showed neither cancer nor polyps had an incidence rate of colorectal cancer (CRC) of 0.58 per 1,000 person-years, corresponding to an estimated 10-year risk of just 0.58%, reported first author Dr. Larissa L. Fujii, a physician with the Mayo Clinic in Scottsdale, Ariz.

Compared with the expected risk for the general population based on surveillance data, these individuals were 57% less likely to receive a CRC diagnosis.

"Our findings support the effectiveness of colonoscopy as a screening and risk-stratification tool, and can be used to help educate patients who come in asking about their risk of colorectal cancer after having a negative colonoscopy," she commented.

Session comoderator Dr. Michael B. Wallace of the Mayo Clinic, Jacksonville, Fla., noted that a recent study found a higher incidence of CRC after a colonoscopy with polypectomy, at about 1.5 per 1,000 person-years of follow-up (Gut 2013 June 21 [Epub ahead of print]). "Do you think that your study might underestimate [the rate] because of follow-up? Was that a limitation in these patients?"

Adequacy of follow-up was included when assessing the studies’ methodologic quality, Dr. Fujii replied. "The incidence was lower in the higher-methodological-quality studies, so I would say that we are probably not underestimating. In fact, we might still be overestimating the risk based off of the population and the quality subgroup analyses."

Dr. Wallace also noted that there was a much lower CRC rate after negative colonoscopy for studies conducted in hospital settings as compared with those conducted in population settings. "Which do you think might be more accurate in terms of the rate?" he asked.

"I do think, because the population probably captured more colorectal cancers, that might be more indicative of what the actual incidence rate is," Dr. Fujii said.

Session attendee Dr. Douglas Robertson of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said, "We like to think we are doing better colonoscopy over time. So can you see any differences as you look at newer studies versus older studies?"

The investigators have not yet assessed temporal trends, but identifying any might be difficult because only a single study was conducted before 2000, according to Dr. Fujii.

"I guess the subtext here is, is 10 years the right interval" for repeating colonoscopy after a negative result? Dr. Robertson further asked. "So you have thought a lot about this. What do you think – is a 57% reduction enough to stick with the 10-year interval?"

"I do like to think that this does support the 10-year recommendation – repeat the colonoscopy after 10 years rather than doing what many people might do, which is 5 years for average-risk patients, because the incidence is lower than what we would expect for the general population," Dr. Fujii replied.

In the study, the investigators searched for cohort studies and randomized controlled trials of average-risk patients undergoing screening colonoscopy. Studies were included if they had a mean follow-up duration exceeding 1 year.

All of the 18 studies meeting inclusion criteria were cohort studies, according to Dr. Fujii.

Thirteen studies each were conducted in hospital-based settings and in Western countries. The patients included in the studies had a weighted mean age of 72.5 years, and the weighted mean percentage of males was 41%.

The mean duration of follow-up was 5 years (range, 2-12 years). During follow-up, nearly 7,000 colorectal cancers were diagnosed.

Main results showed that the pooled incidence of CRC after a negative colonoscopy was 0.058% per year.

In subgroup analyses, the rate was significantly lower in studies conducted in hospital- versus population-based settings (0.08 vs. 0.96 per 1,000 person-years) and in studies conducted in Eastern versus Western countries (0.05 vs. 0.66). The rate also differed significantly according to whether studies were of high, moderate, or low quality (0.01, 0.88, and 0.38, respectively).

However, there was no significant difference according to whether the physician performing the colonoscopy was a gastroenterologist or some other specialist.

The estimated 5- and 10-year risks of CRC after a negative colonoscopy were 0.29% and 0.58%, respectively. These values compared with the expected rates of 0.6% and 1.5% for the general population according to Surveillance, Epidemiology, and End Results (SEER) data.

The difference amounted to more than halving of the rate of CRC after a negative colonoscopy relative to the general population (rate ratio, 0.43).

Dr. Fujii disclosed no relevant conflicts of interest.

SAN DIEGO – A negative screening colonoscopy dramatically reduces the subsequent risk of colorectal cancer, according to a systematic review and meta-analysis of 18 studies presented at the annual meeting of the American College of Gastroenterology.

In the analysis, average-risk individuals whose colonoscopy showed neither cancer nor polyps had an incidence rate of colorectal cancer (CRC) of 0.58 per 1,000 person-years, corresponding to an estimated 10-year risk of just 0.58%, reported first author Dr. Larissa L. Fujii, a physician with the Mayo Clinic in Scottsdale, Ariz.

Compared with the expected risk for the general population based on surveillance data, these individuals were 57% less likely to receive a CRC diagnosis.

"Our findings support the effectiveness of colonoscopy as a screening and risk-stratification tool, and can be used to help educate patients who come in asking about their risk of colorectal cancer after having a negative colonoscopy," she commented.

Session comoderator Dr. Michael B. Wallace of the Mayo Clinic, Jacksonville, Fla., noted that a recent study found a higher incidence of CRC after a colonoscopy with polypectomy, at about 1.5 per 1,000 person-years of follow-up (Gut 2013 June 21 [Epub ahead of print]). "Do you think that your study might underestimate [the rate] because of follow-up? Was that a limitation in these patients?"

Adequacy of follow-up was included when assessing the studies’ methodologic quality, Dr. Fujii replied. "The incidence was lower in the higher-methodological-quality studies, so I would say that we are probably not underestimating. In fact, we might still be overestimating the risk based off of the population and the quality subgroup analyses."

Dr. Wallace also noted that there was a much lower CRC rate after negative colonoscopy for studies conducted in hospital settings as compared with those conducted in population settings. "Which do you think might be more accurate in terms of the rate?" he asked.

"I do think, because the population probably captured more colorectal cancers, that might be more indicative of what the actual incidence rate is," Dr. Fujii said.

Session attendee Dr. Douglas Robertson of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said, "We like to think we are doing better colonoscopy over time. So can you see any differences as you look at newer studies versus older studies?"

The investigators have not yet assessed temporal trends, but identifying any might be difficult because only a single study was conducted before 2000, according to Dr. Fujii.

"I guess the subtext here is, is 10 years the right interval" for repeating colonoscopy after a negative result? Dr. Robertson further asked. "So you have thought a lot about this. What do you think – is a 57% reduction enough to stick with the 10-year interval?"

"I do like to think that this does support the 10-year recommendation – repeat the colonoscopy after 10 years rather than doing what many people might do, which is 5 years for average-risk patients, because the incidence is lower than what we would expect for the general population," Dr. Fujii replied.

In the study, the investigators searched for cohort studies and randomized controlled trials of average-risk patients undergoing screening colonoscopy. Studies were included if they had a mean follow-up duration exceeding 1 year.

All of the 18 studies meeting inclusion criteria were cohort studies, according to Dr. Fujii.

Thirteen studies each were conducted in hospital-based settings and in Western countries. The patients included in the studies had a weighted mean age of 72.5 years, and the weighted mean percentage of males was 41%.

The mean duration of follow-up was 5 years (range, 2-12 years). During follow-up, nearly 7,000 colorectal cancers were diagnosed.

Main results showed that the pooled incidence of CRC after a negative colonoscopy was 0.058% per year.

In subgroup analyses, the rate was significantly lower in studies conducted in hospital- versus population-based settings (0.08 vs. 0.96 per 1,000 person-years) and in studies conducted in Eastern versus Western countries (0.05 vs. 0.66). The rate also differed significantly according to whether studies were of high, moderate, or low quality (0.01, 0.88, and 0.38, respectively).

However, there was no significant difference according to whether the physician performing the colonoscopy was a gastroenterologist or some other specialist.

The estimated 5- and 10-year risks of CRC after a negative colonoscopy were 0.29% and 0.58%, respectively. These values compared with the expected rates of 0.6% and 1.5% for the general population according to Surveillance, Epidemiology, and End Results (SEER) data.

The difference amounted to more than halving of the rate of CRC after a negative colonoscopy relative to the general population (rate ratio, 0.43).

Dr. Fujii disclosed no relevant conflicts of interest.

SAN DIEGO – A negative screening colonoscopy dramatically reduces the subsequent risk of colorectal cancer, according to a systematic review and meta-analysis of 18 studies presented at the annual meeting of the American College of Gastroenterology.

In the analysis, average-risk individuals whose colonoscopy showed neither cancer nor polyps had an incidence rate of colorectal cancer (CRC) of 0.58 per 1,000 person-years, corresponding to an estimated 10-year risk of just 0.58%, reported first author Dr. Larissa L. Fujii, a physician with the Mayo Clinic in Scottsdale, Ariz.

Compared with the expected risk for the general population based on surveillance data, these individuals were 57% less likely to receive a CRC diagnosis.

"Our findings support the effectiveness of colonoscopy as a screening and risk-stratification tool, and can be used to help educate patients who come in asking about their risk of colorectal cancer after having a negative colonoscopy," she commented.

Session comoderator Dr. Michael B. Wallace of the Mayo Clinic, Jacksonville, Fla., noted that a recent study found a higher incidence of CRC after a colonoscopy with polypectomy, at about 1.5 per 1,000 person-years of follow-up (Gut 2013 June 21 [Epub ahead of print]). "Do you think that your study might underestimate [the rate] because of follow-up? Was that a limitation in these patients?"

Adequacy of follow-up was included when assessing the studies’ methodologic quality, Dr. Fujii replied. "The incidence was lower in the higher-methodological-quality studies, so I would say that we are probably not underestimating. In fact, we might still be overestimating the risk based off of the population and the quality subgroup analyses."

Dr. Wallace also noted that there was a much lower CRC rate after negative colonoscopy for studies conducted in hospital settings as compared with those conducted in population settings. "Which do you think might be more accurate in terms of the rate?" he asked.

"I do think, because the population probably captured more colorectal cancers, that might be more indicative of what the actual incidence rate is," Dr. Fujii said.

Session attendee Dr. Douglas Robertson of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said, "We like to think we are doing better colonoscopy over time. So can you see any differences as you look at newer studies versus older studies?"

The investigators have not yet assessed temporal trends, but identifying any might be difficult because only a single study was conducted before 2000, according to Dr. Fujii.

"I guess the subtext here is, is 10 years the right interval" for repeating colonoscopy after a negative result? Dr. Robertson further asked. "So you have thought a lot about this. What do you think – is a 57% reduction enough to stick with the 10-year interval?"

"I do like to think that this does support the 10-year recommendation – repeat the colonoscopy after 10 years rather than doing what many people might do, which is 5 years for average-risk patients, because the incidence is lower than what we would expect for the general population," Dr. Fujii replied.

In the study, the investigators searched for cohort studies and randomized controlled trials of average-risk patients undergoing screening colonoscopy. Studies were included if they had a mean follow-up duration exceeding 1 year.

All of the 18 studies meeting inclusion criteria were cohort studies, according to Dr. Fujii.

Thirteen studies each were conducted in hospital-based settings and in Western countries. The patients included in the studies had a weighted mean age of 72.5 years, and the weighted mean percentage of males was 41%.

The mean duration of follow-up was 5 years (range, 2-12 years). During follow-up, nearly 7,000 colorectal cancers were diagnosed.

Main results showed that the pooled incidence of CRC after a negative colonoscopy was 0.058% per year.

In subgroup analyses, the rate was significantly lower in studies conducted in hospital- versus population-based settings (0.08 vs. 0.96 per 1,000 person-years) and in studies conducted in Eastern versus Western countries (0.05 vs. 0.66). The rate also differed significantly according to whether studies were of high, moderate, or low quality (0.01, 0.88, and 0.38, respectively).

However, there was no significant difference according to whether the physician performing the colonoscopy was a gastroenterologist or some other specialist.

The estimated 5- and 10-year risks of CRC after a negative colonoscopy were 0.29% and 0.58%, respectively. These values compared with the expected rates of 0.6% and 1.5% for the general population according to Surveillance, Epidemiology, and End Results (SEER) data.

The difference amounted to more than halving of the rate of CRC after a negative colonoscopy relative to the general population (rate ratio, 0.43).

Dr. Fujii disclosed no relevant conflicts of interest.

SAN DIEGO – A blood test for antibodies to vinculin, a protein involved in nerve cell migration, may allow objective diagnosis of irritable bowel syndrome, a condition historically diagnosed clinically, after a thorough workup excludes other possibilities.

Investigators led by Dr. Mark Pimentel, director of the GI Motility Program at the Cedars-Sinai Medical Center in Los Angeles, performed a multicenter validation study of the test among patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), and healthy individuals.

Study results, reported at the annual meeting of the American College of Gastroenterology, showed that the anti-vinculin antibody test had a positive predictive value of at least 90% for distinguishing IBS from IBD.

And when analyses also took into account antibodies to cytolethal distending toxin B (CdtB) – a toxin produced by bacteria commonly associated with food poisoning – the positive predictive value was at least 94%.

"Elevated anti-vinculin antibodies are specific for IBS compared to IBD, and an increase in anti-vinculin antibodies with respect to anti-CdtB increases that specificity," Dr. Pimentel said, summing up the findings. "This may be the first serum diagnostic biomarker that can discriminate IBS from IBD, and it would help avoid unnecessary tests."

Additionally, the findings lend support to a pathogenic mechanism for postinfectious IBS suggested by a rodent model, whereby bacterial gastroenteritis gives rise to autoimmunity against vinculin in the digestive tract.

The assay may be useful in IBD research too, he noted. "One of the problems with IBD studies is those patients who don’t respond to therapies, and maybe they have IBS and they don’t have IBD. Maybe this test could be used to screen those patients out before the study begins."

A session attendee expressed reservations about the study, noting that some analyses compared IBS patients with healthy individuals, and that positive predictive values may not be the best statistic given the composition of the study population.

"We don’t need a test to tell us someone that has no symptoms versus someone that does. So this is the start of your validation, not the end of it," he said. "If you apply this to the population right now, I’ve done some calculations, your positive predictive value would be about 20%. So it’s not that great in clinical practice. ... I’m sure you will develop this more and it will get better, but right now, I don’t think this is ready for prime time."

"First, you can use a likelihood ratio, which accounts for the volumes of patients. ... Our likelihood ratio is between 3 and 4, which I hope gives you more confidence in it," Dr. Pimentel replied. "The second thing is that the patients who arrive in a doctor’s office are not healthy: They are going to have IBD or IBS or something else if they have diarrhea in the clinic."

In a related press briefing, Dr. Brian E. Lacy, of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., commented, "This is an incredibly important topic, when we are talking about prevalence rates of IBS – a conservative rate is 12% to 15% – and when you are talking about spending $20 billion to $30 billion a year diagnosing and treating IBS."

"For many patients, IBS is a diagnosis of exclusion; they undergo a battery of unnecessary tests which are usually fruitless because this is a functional bowel disorder," he added. "To possibly have a diagnostic test – a blood test – that could confidently make the diagnosis of IBS to me would be incredibly important. And I think for the community primary care providers, family practice doctors, who are not confident at diagnosing IBS, to have somebody say, ‘This is a great test, and we can not only make the diagnosis, but exclude or maybe improve our ability to exclude the patients with IBD,’ that would be incredibly important."

The test may also have implications for treatment, according to Dr. Pimentel. "Another question is, could this antibody test predict who will respond to antibiotics, or does it predict bacterial overgrowth or other treatable aspects of IBS?" he explained.

Finally, such a test would help validate IBS as a legitimate medical condition. "IBS is a very, very difficult illness because nobody understands it, and it kind of gets the short end of the stick because it is viewed as a lifestyle disorder instead of a legitimate disease," he commented. "So what I’d like to do in my career is to make IBS a real disease, not just a syndrome as it’s been for at least the last 2 decades."

Press briefing moderator Dr. Michael E. Cox of the Mercy Medical Center in Baltimore, said, "The $64,000 question is, when would this possibly be ready for prime time?"

"We are validating this antibody every day," Dr. Pimentel replied, although as yet, no companies are collaborating in developing the assay. "When it will be ready for prime time, I’m not sure."

In the study, the investigators assayed serum samples from 162 prospectively identified patients who met Rome III criteria for IBS, 30 patients with active IBD who were not receiving biologic agents, and 26 consecutive healthy individuals.

Across groups, about 70% of patients were female, with no significant differences in the sex and age distributions.

Results showed that the anti-vinculin antibody optical density (OD) reading was higher in patients with IBS than in patients with IBD (P less than .01) and healthy individuals (P less than .01), reported Dr. Pimentel.

Meanwhile, the anti-CdtB antibody OD reading was higher in the patients with IBD than in the patients with IBS (P = .02).

For distinguishing IBS from IBD, an anti-vinculin antibody OD reading exceeding 0.8 had a sensitivity of 43%, a specificity of 73%, and a positive predictive value of 90%.

There is a good rationale for simultaneously looking at anti-CdtB and anti-vinculin, according to Dr. Pimentel: In the model of postinfectious IBS, anti-vinculin antibodies persist over time, whereas anti-CdtB antibodies decline.

And indeed, in the study, the difference between the two OD readings (anti-vinculin minus anti-CdtB) was higher in the patients with IBS than in both the patients with IBD (P less than .0001) and the healthy individuals (P less than .001).

For distinguishing IBS from IBD, a difference exceeding 0.2 had a sensitivity of 41%, a specificity of 88%, and a positive predictive value of 94%.

A confounding issue is that about 10% of patients with IBD also have IBS, Dr. Pimentel noted. But a model taking this into account showed high positive predictive values for an anti-vinculin antibody OD reading exceeding 0.8 (92%) and for a difference between the OD readings of anti-vinculin and anti-CdtB exceeding 0.2 (97%).

Dr. Pimentel disclosed no relevant conflicts of interest.

SAN DIEGO – A blood test for antibodies to vinculin, a protein involved in nerve cell migration, may allow objective diagnosis of irritable bowel syndrome, a condition historically diagnosed clinically, after a thorough workup excludes other possibilities.

Investigators led by Dr. Mark Pimentel, director of the GI Motility Program at the Cedars-Sinai Medical Center in Los Angeles, performed a multicenter validation study of the test among patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), and healthy individuals.

Study results, reported at the annual meeting of the American College of Gastroenterology, showed that the anti-vinculin antibody test had a positive predictive value of at least 90% for distinguishing IBS from IBD.

And when analyses also took into account antibodies to cytolethal distending toxin B (CdtB) – a toxin produced by bacteria commonly associated with food poisoning – the positive predictive value was at least 94%.

"Elevated anti-vinculin antibodies are specific for IBS compared to IBD, and an increase in anti-vinculin antibodies with respect to anti-CdtB increases that specificity," Dr. Pimentel said, summing up the findings. "This may be the first serum diagnostic biomarker that can discriminate IBS from IBD, and it would help avoid unnecessary tests."

Additionally, the findings lend support to a pathogenic mechanism for postinfectious IBS suggested by a rodent model, whereby bacterial gastroenteritis gives rise to autoimmunity against vinculin in the digestive tract.

The assay may be useful in IBD research too, he noted. "One of the problems with IBD studies is those patients who don’t respond to therapies, and maybe they have IBS and they don’t have IBD. Maybe this test could be used to screen those patients out before the study begins."

A session attendee expressed reservations about the study, noting that some analyses compared IBS patients with healthy individuals, and that positive predictive values may not be the best statistic given the composition of the study population.

"We don’t need a test to tell us someone that has no symptoms versus someone that does. So this is the start of your validation, not the end of it," he said. "If you apply this to the population right now, I’ve done some calculations, your positive predictive value would be about 20%. So it’s not that great in clinical practice. ... I’m sure you will develop this more and it will get better, but right now, I don’t think this is ready for prime time."

"First, you can use a likelihood ratio, which accounts for the volumes of patients. ... Our likelihood ratio is between 3 and 4, which I hope gives you more confidence in it," Dr. Pimentel replied. "The second thing is that the patients who arrive in a doctor’s office are not healthy: They are going to have IBD or IBS or something else if they have diarrhea in the clinic."

In a related press briefing, Dr. Brian E. Lacy, of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., commented, "This is an incredibly important topic, when we are talking about prevalence rates of IBS – a conservative rate is 12% to 15% – and when you are talking about spending $20 billion to $30 billion a year diagnosing and treating IBS."

"For many patients, IBS is a diagnosis of exclusion; they undergo a battery of unnecessary tests which are usually fruitless because this is a functional bowel disorder," he added. "To possibly have a diagnostic test – a blood test – that could confidently make the diagnosis of IBS to me would be incredibly important. And I think for the community primary care providers, family practice doctors, who are not confident at diagnosing IBS, to have somebody say, ‘This is a great test, and we can not only make the diagnosis, but exclude or maybe improve our ability to exclude the patients with IBD,’ that would be incredibly important."

The test may also have implications for treatment, according to Dr. Pimentel. "Another question is, could this antibody test predict who will respond to antibiotics, or does it predict bacterial overgrowth or other treatable aspects of IBS?" he explained.

Finally, such a test would help validate IBS as a legitimate medical condition. "IBS is a very, very difficult illness because nobody understands it, and it kind of gets the short end of the stick because it is viewed as a lifestyle disorder instead of a legitimate disease," he commented. "So what I’d like to do in my career is to make IBS a real disease, not just a syndrome as it’s been for at least the last 2 decades."

Press briefing moderator Dr. Michael E. Cox of the Mercy Medical Center in Baltimore, said, "The $64,000 question is, when would this possibly be ready for prime time?"

"We are validating this antibody every day," Dr. Pimentel replied, although as yet, no companies are collaborating in developing the assay. "When it will be ready for prime time, I’m not sure."

In the study, the investigators assayed serum samples from 162 prospectively identified patients who met Rome III criteria for IBS, 30 patients with active IBD who were not receiving biologic agents, and 26 consecutive healthy individuals.

Across groups, about 70% of patients were female, with no significant differences in the sex and age distributions.

Results showed that the anti-vinculin antibody optical density (OD) reading was higher in patients with IBS than in patients with IBD (P less than .01) and healthy individuals (P less than .01), reported Dr. Pimentel.

Meanwhile, the anti-CdtB antibody OD reading was higher in the patients with IBD than in the patients with IBS (P = .02).

For distinguishing IBS from IBD, an anti-vinculin antibody OD reading exceeding 0.8 had a sensitivity of 43%, a specificity of 73%, and a positive predictive value of 90%.

There is a good rationale for simultaneously looking at anti-CdtB and anti-vinculin, according to Dr. Pimentel: In the model of postinfectious IBS, anti-vinculin antibodies persist over time, whereas anti-CdtB antibodies decline.

And indeed, in the study, the difference between the two OD readings (anti-vinculin minus anti-CdtB) was higher in the patients with IBS than in both the patients with IBD (P less than .0001) and the healthy individuals (P less than .001).

For distinguishing IBS from IBD, a difference exceeding 0.2 had a sensitivity of 41%, a specificity of 88%, and a positive predictive value of 94%.

A confounding issue is that about 10% of patients with IBD also have IBS, Dr. Pimentel noted. But a model taking this into account showed high positive predictive values for an anti-vinculin antibody OD reading exceeding 0.8 (92%) and for a difference between the OD readings of anti-vinculin and anti-CdtB exceeding 0.2 (97%).

Dr. Pimentel disclosed no relevant conflicts of interest.

SAN DIEGO – A blood test for antibodies to vinculin, a protein involved in nerve cell migration, may allow objective diagnosis of irritable bowel syndrome, a condition historically diagnosed clinically, after a thorough workup excludes other possibilities.

Investigators led by Dr. Mark Pimentel, director of the GI Motility Program at the Cedars-Sinai Medical Center in Los Angeles, performed a multicenter validation study of the test among patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), and healthy individuals.

Study results, reported at the annual meeting of the American College of Gastroenterology, showed that the anti-vinculin antibody test had a positive predictive value of at least 90% for distinguishing IBS from IBD.

And when analyses also took into account antibodies to cytolethal distending toxin B (CdtB) – a toxin produced by bacteria commonly associated with food poisoning – the positive predictive value was at least 94%.

"Elevated anti-vinculin antibodies are specific for IBS compared to IBD, and an increase in anti-vinculin antibodies with respect to anti-CdtB increases that specificity," Dr. Pimentel said, summing up the findings. "This may be the first serum diagnostic biomarker that can discriminate IBS from IBD, and it would help avoid unnecessary tests."

Additionally, the findings lend support to a pathogenic mechanism for postinfectious IBS suggested by a rodent model, whereby bacterial gastroenteritis gives rise to autoimmunity against vinculin in the digestive tract.

The assay may be useful in IBD research too, he noted. "One of the problems with IBD studies is those patients who don’t respond to therapies, and maybe they have IBS and they don’t have IBD. Maybe this test could be used to screen those patients out before the study begins."

A session attendee expressed reservations about the study, noting that some analyses compared IBS patients with healthy individuals, and that positive predictive values may not be the best statistic given the composition of the study population.

"We don’t need a test to tell us someone that has no symptoms versus someone that does. So this is the start of your validation, not the end of it," he said. "If you apply this to the population right now, I’ve done some calculations, your positive predictive value would be about 20%. So it’s not that great in clinical practice. ... I’m sure you will develop this more and it will get better, but right now, I don’t think this is ready for prime time."

"First, you can use a likelihood ratio, which accounts for the volumes of patients. ... Our likelihood ratio is between 3 and 4, which I hope gives you more confidence in it," Dr. Pimentel replied. "The second thing is that the patients who arrive in a doctor’s office are not healthy: They are going to have IBD or IBS or something else if they have diarrhea in the clinic."

In a related press briefing, Dr. Brian E. Lacy, of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., commented, "This is an incredibly important topic, when we are talking about prevalence rates of IBS – a conservative rate is 12% to 15% – and when you are talking about spending $20 billion to $30 billion a year diagnosing and treating IBS."

"For many patients, IBS is a diagnosis of exclusion; they undergo a battery of unnecessary tests which are usually fruitless because this is a functional bowel disorder," he added. "To possibly have a diagnostic test – a blood test – that could confidently make the diagnosis of IBS to me would be incredibly important. And I think for the community primary care providers, family practice doctors, who are not confident at diagnosing IBS, to have somebody say, ‘This is a great test, and we can not only make the diagnosis, but exclude or maybe improve our ability to exclude the patients with IBD,’ that would be incredibly important."

The test may also have implications for treatment, according to Dr. Pimentel. "Another question is, could this antibody test predict who will respond to antibiotics, or does it predict bacterial overgrowth or other treatable aspects of IBS?" he explained.

Finally, such a test would help validate IBS as a legitimate medical condition. "IBS is a very, very difficult illness because nobody understands it, and it kind of gets the short end of the stick because it is viewed as a lifestyle disorder instead of a legitimate disease," he commented. "So what I’d like to do in my career is to make IBS a real disease, not just a syndrome as it’s been for at least the last 2 decades."

Press briefing moderator Dr. Michael E. Cox of the Mercy Medical Center in Baltimore, said, "The $64,000 question is, when would this possibly be ready for prime time?"

"We are validating this antibody every day," Dr. Pimentel replied, although as yet, no companies are collaborating in developing the assay. "When it will be ready for prime time, I’m not sure."

In the study, the investigators assayed serum samples from 162 prospectively identified patients who met Rome III criteria for IBS, 30 patients with active IBD who were not receiving biologic agents, and 26 consecutive healthy individuals.

Across groups, about 70% of patients were female, with no significant differences in the sex and age distributions.

Results showed that the anti-vinculin antibody optical density (OD) reading was higher in patients with IBS than in patients with IBD (P less than .01) and healthy individuals (P less than .01), reported Dr. Pimentel.

Meanwhile, the anti-CdtB antibody OD reading was higher in the patients with IBD than in the patients with IBS (P = .02).

For distinguishing IBS from IBD, an anti-vinculin antibody OD reading exceeding 0.8 had a sensitivity of 43%, a specificity of 73%, and a positive predictive value of 90%.

There is a good rationale for simultaneously looking at anti-CdtB and anti-vinculin, according to Dr. Pimentel: In the model of postinfectious IBS, anti-vinculin antibodies persist over time, whereas anti-CdtB antibodies decline.

And indeed, in the study, the difference between the two OD readings (anti-vinculin minus anti-CdtB) was higher in the patients with IBS than in both the patients with IBD (P less than .0001) and the healthy individuals (P less than .001).

For distinguishing IBS from IBD, a difference exceeding 0.2 had a sensitivity of 41%, a specificity of 88%, and a positive predictive value of 94%.

A confounding issue is that about 10% of patients with IBD also have IBS, Dr. Pimentel noted. But a model taking this into account showed high positive predictive values for an anti-vinculin antibody OD reading exceeding 0.8 (92%) and for a difference between the OD readings of anti-vinculin and anti-CdtB exceeding 0.2 (97%).

Dr. Pimentel disclosed no relevant conflicts of interest.

PHOENIX – A new model based on clinical, hospital, and operative factors predicted the risk of ureteral injury among patients undergoing colorectal surgery.

Using data from the Nationwide Inpatient Sample, which includes more than 2 million patients in the United States, researchers retrospectively studied patients undergoing surgery in the United States between 2001 and 2010 for colorectal cancer, polyps, diverticular disease, or inflammatory bowel disease.

Less than 1% of patients sustained a ureteral injury, but the incidence rose significantly during the study period and injured patients had sharply higher rates of complications, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Eight factors were independently associated with the risk of ureteral injury. A predictive model incorporating these factors had an area under the receiver operating characteristic curve of 0.73. The model-predicted probability of injury ranged from 0.1% to 1.65%, depending on hospital factors, disease type, and procedure type, said Dr. Wissam J. Halabi, a research fellow at the University of California-Irvine, Orange.

Patients had higher adjusted odds of ureteral injury if they had rectal cancer (odds ratio, 1.85), adhesions (OR, 1.83), and metastatic cancer (OR, 1.76); if they had lost weight (OR, 1.08); and if they underwent surgery at a teaching hospital (OR, 1.05). On the other hand, patients had lower odds of injury if they had a laparoscopic procedure (OR, 0.91), a transverse colectomy (OR, 0.90), or a right hemicolectomy (OR, 0.43).

With the new predictive model incorporating these factors, the probability of injury ranged from 0.1% for patients undergoing laparoscopic right hemicolectomy to 1.65% for patients having all five adverse risk factors.

"Diverticulitis did not appear as a predictor in our model," Dr. Halabi said. "As for radiation, one of our predictors was metastatic cancer. So this goes for any cancer at advanced stage that has spread to lymph nodes or distant organ metastasis. In the case of rectal cancer, those are most likely to have received radiation therapy. So part of this effect of radiation therapy was apparent in the metastatic cancer group predictor."

Analyses were based on 2,165,848 colorectal surgery procedures. The overall rate of ureteral injury was 0.28%, he reported.

There was a significant 24% increase in the rate during the study period, from 2.5 per 1,000 cases in 2001-2005 to 3.1 per 1,000 cases in 2006-2010.

On average, the patients sustaining injury were younger and were more likely to be female and to have metastatic cancer, to be immunosuppressed, and to have had weight loss. They were less likely to have certain major comorbidities, such as diabetes and hypertension.

"Interestingly, obesity was similar in the two groups," Dr. Halabi commented.

Patients who sustained ureteral injuries had longer hospital stays and higher rates of a variety of postoperative complications, such as anastomotic leak and acute renal failure, but in-hospital mortality was statistically indistinguishable.

In adjusted analysis, patients with ureteral injury were significantly more likely to die (OR, 1.45) and to experience complications (OR, 1.66), and they had a longer hospital stay (+3.65 days) and total hospital charges (+$31,497).

Ureteral injuries "affect a relatively younger and healthier population. However, they have a significant and dramatic impact on outcomes," he added. "This predictive model can be used for risk stratification and counseling."

Dr. Halabi disclosed no relevant conflicts of interest.

PHOENIX – A new model based on clinical, hospital, and operative factors predicted the risk of ureteral injury among patients undergoing colorectal surgery.

Using data from the Nationwide Inpatient Sample, which includes more than 2 million patients in the United States, researchers retrospectively studied patients undergoing surgery in the United States between 2001 and 2010 for colorectal cancer, polyps, diverticular disease, or inflammatory bowel disease.

Less than 1% of patients sustained a ureteral injury, but the incidence rose significantly during the study period and injured patients had sharply higher rates of complications, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Eight factors were independently associated with the risk of ureteral injury. A predictive model incorporating these factors had an area under the receiver operating characteristic curve of 0.73. The model-predicted probability of injury ranged from 0.1% to 1.65%, depending on hospital factors, disease type, and procedure type, said Dr. Wissam J. Halabi, a research fellow at the University of California-Irvine, Orange.

Patients had higher adjusted odds of ureteral injury if they had rectal cancer (odds ratio, 1.85), adhesions (OR, 1.83), and metastatic cancer (OR, 1.76); if they had lost weight (OR, 1.08); and if they underwent surgery at a teaching hospital (OR, 1.05). On the other hand, patients had lower odds of injury if they had a laparoscopic procedure (OR, 0.91), a transverse colectomy (OR, 0.90), or a right hemicolectomy (OR, 0.43).

With the new predictive model incorporating these factors, the probability of injury ranged from 0.1% for patients undergoing laparoscopic right hemicolectomy to 1.65% for patients having all five adverse risk factors.

"Diverticulitis did not appear as a predictor in our model," Dr. Halabi said. "As for radiation, one of our predictors was metastatic cancer. So this goes for any cancer at advanced stage that has spread to lymph nodes or distant organ metastasis. In the case of rectal cancer, those are most likely to have received radiation therapy. So part of this effect of radiation therapy was apparent in the metastatic cancer group predictor."

Analyses were based on 2,165,848 colorectal surgery procedures. The overall rate of ureteral injury was 0.28%, he reported.

There was a significant 24% increase in the rate during the study period, from 2.5 per 1,000 cases in 2001-2005 to 3.1 per 1,000 cases in 2006-2010.

On average, the patients sustaining injury were younger and were more likely to be female and to have metastatic cancer, to be immunosuppressed, and to have had weight loss. They were less likely to have certain major comorbidities, such as diabetes and hypertension.

"Interestingly, obesity was similar in the two groups," Dr. Halabi commented.

Patients who sustained ureteral injuries had longer hospital stays and higher rates of a variety of postoperative complications, such as anastomotic leak and acute renal failure, but in-hospital mortality was statistically indistinguishable.

In adjusted analysis, patients with ureteral injury were significantly more likely to die (OR, 1.45) and to experience complications (OR, 1.66), and they had a longer hospital stay (+3.65 days) and total hospital charges (+$31,497).

Ureteral injuries "affect a relatively younger and healthier population. However, they have a significant and dramatic impact on outcomes," he added. "This predictive model can be used for risk stratification and counseling."

Dr. Halabi disclosed no relevant conflicts of interest.

PHOENIX – A new model based on clinical, hospital, and operative factors predicted the risk of ureteral injury among patients undergoing colorectal surgery.

Using data from the Nationwide Inpatient Sample, which includes more than 2 million patients in the United States, researchers retrospectively studied patients undergoing surgery in the United States between 2001 and 2010 for colorectal cancer, polyps, diverticular disease, or inflammatory bowel disease.

Less than 1% of patients sustained a ureteral injury, but the incidence rose significantly during the study period and injured patients had sharply higher rates of complications, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

Eight factors were independently associated with the risk of ureteral injury. A predictive model incorporating these factors had an area under the receiver operating characteristic curve of 0.73. The model-predicted probability of injury ranged from 0.1% to 1.65%, depending on hospital factors, disease type, and procedure type, said Dr. Wissam J. Halabi, a research fellow at the University of California-Irvine, Orange.

Patients had higher adjusted odds of ureteral injury if they had rectal cancer (odds ratio, 1.85), adhesions (OR, 1.83), and metastatic cancer (OR, 1.76); if they had lost weight (OR, 1.08); and if they underwent surgery at a teaching hospital (OR, 1.05). On the other hand, patients had lower odds of injury if they had a laparoscopic procedure (OR, 0.91), a transverse colectomy (OR, 0.90), or a right hemicolectomy (OR, 0.43).

With the new predictive model incorporating these factors, the probability of injury ranged from 0.1% for patients undergoing laparoscopic right hemicolectomy to 1.65% for patients having all five adverse risk factors.

"Diverticulitis did not appear as a predictor in our model," Dr. Halabi said. "As for radiation, one of our predictors was metastatic cancer. So this goes for any cancer at advanced stage that has spread to lymph nodes or distant organ metastasis. In the case of rectal cancer, those are most likely to have received radiation therapy. So part of this effect of radiation therapy was apparent in the metastatic cancer group predictor."

Analyses were based on 2,165,848 colorectal surgery procedures. The overall rate of ureteral injury was 0.28%, he reported.

There was a significant 24% increase in the rate during the study period, from 2.5 per 1,000 cases in 2001-2005 to 3.1 per 1,000 cases in 2006-2010.

On average, the patients sustaining injury were younger and were more likely to be female and to have metastatic cancer, to be immunosuppressed, and to have had weight loss. They were less likely to have certain major comorbidities, such as diabetes and hypertension.

"Interestingly, obesity was similar in the two groups," Dr. Halabi commented.

Patients who sustained ureteral injuries had longer hospital stays and higher rates of a variety of postoperative complications, such as anastomotic leak and acute renal failure, but in-hospital mortality was statistically indistinguishable.

In adjusted analysis, patients with ureteral injury were significantly more likely to die (OR, 1.45) and to experience complications (OR, 1.66), and they had a longer hospital stay (+3.65 days) and total hospital charges (+$31,497).

Ureteral injuries "affect a relatively younger and healthier population. However, they have a significant and dramatic impact on outcomes," he added. "This predictive model can be used for risk stratification and counseling."

Dr. Halabi disclosed no relevant conflicts of interest.

SAN DIEGO – The mortality-reducing benefit of colorectal cancer screening persists long term, according to an updated analysis of the randomized Minnesota Fecal Occult Blood Trial.

Investigators led by Dr. Aasma Shaukat, a gastroenterologist with the University of Minnesota, Minneapolis, analyzed data for more than 46,000 participants aged 50-80 years who were assigned to screening with the fecal occult blood test (FOBT) or no screening.

After the first 18 years, the cumulative colorectal cancer mortality rate was reduced by one-third with annual screening and by one-fifth with biennial screening as compared with no screening, according to initially reported results (J. Natl. Cancer Inst. 1999;91:434-7).

The updated results, now after 30 years of follow-up – the longest of any such trial to date – showed that the reductions in risk with screening were essentially unchanged, Dr. Shaukat reported at the annual meeting of the American College of Gastroenterology.

"Screening for colon cancer using fecal occult blood testing consistently reduces colorectal cancer mortality..., and this effect is sustained through 30 years of follow-up," she commented. "This suggests the effect of polypectomy, because [if] fecal occult blood testing [detected only] early cancers, most of the benefit would be seen in the first 8-10 years. The sustained benefit suggests that these individuals underwent removal of polyps that would have turned into cancer and resulted in a death at 30 years."

In additional trial findings, the benefit of screening appeared to be greater for men than women and greater for those who began screening after the age of 60 years.

Session attendee Dr. Samir Gupta, of the University of California, San Diego, asked, "After the initial 10 or 15 years of protocolized screening, is it possible that screening was going on in the control group" and that might explain the lesser benefit in younger individuals, as they would have had more time to be screened.

"During the trial, through 1998, the screening in the control group was less than 5%, so there wasn’t much screening going on in the control group," Dr. Shaukat replied. However, "after the trial ended, we don’t have information on people’s screening behavior. And screening became popular, particularly in the last two decades. So there is a possibility that a large number of people that were in the control group underwent screening, and that’s diluting the effects that we would have otherwise seen."

She offered a few possible additional reasons for the smaller benefit in the younger group. "One is that group doesn’t have a higher risk of colon cancer and of dying from colon cancer, and hence, we are just not seeing the effect of screening," she said. "The second is that perhaps fecal occult blood testing is fairly insensitive in that age group; that’s something that needs to be explored further."

Session comoderator Dr. Jonathan A. Leighton of the Mayo Clinic in Scottsdale, Ariz., asked, "Why do you think there was that benefit in men over women?"

"That’s something that’s actually been shown in several natural history and modeling studies," Dr. Shaukat replied. "Men have a higher incidence of colon cancer and they have a higher risk of dying from colon cancer compared to women. So it bears to reason that we would see a larger effect of screening among men compared to women." That said, subgroup analyses should be considered hypothesis generating and require confirmation, she acknowledged.

Dr. Carol Burke of the Cleveland Clinic, who also attended the session, asked whether the screening benefit would have been even greater in analyses restricted to adherent patients.

"Compliance-adjusted estimates ... are a lot larger, to the magnitude of about a 40% reduction in colorectal cancer mortality," Dr. Shaukat replied.

"What effect do you think FIT [fecal immunochemical test] would have on the magnitude [of benefit] – similar for FIT or better because of adherence?" Dr. Burke further queried.

"These fecal occult blood tests were rehydrated, so their sensitivity is comparable to modern-day FIT. So we expect FIT to do the same if not better," Dr. Shaukat replied.

In the trial, 46,551 participants in the Minnesota Colon Cancer Control Study were assigned to annual or biennial screening or no screening between 1976 and 1992. Those with positive FOBT results underwent colonoscopy with polypectomy if needed. All groups had annual follow-up thereafter through 1998.

Adherence to screening was high in the trial, with 90% of participants in the screening groups completing at least one FOBT, and no difference between men and women, according to Dr. Shaukat.

At each screening, 10% of participants had positive results, and 83% of this subset overall underwent colonoscopy. The complication rate from colonoscopy was low, at less than 0.1%.

In the updated analysis, 71% of trial participants had died as ascertained from the National Death Index.

In intention-to-treat analyses, the risk of colorectal cancer mortality was a significant 32% lower in the group screened annually (relative risk, 0.68) and 22% lower in the group screened biennially (RR, 0.78) as compared with the nonscreened group, according to data reported at the meeting and recently published (N. Engl. J. Med. 2013;369:1106-14).

"We don’t know what happened after 1998," Dr. Shaukat reminded attendees. "At best, the effects that we are seeing might be dilute, and if truly the control group had remained unscreened, we would have seen perhaps larger differences."

The absolute cumulative colorectal cancer mortality rates were 0.02 with annual screening, 0.02 with biennial screening, and 0.03 with no screening. "This separation [in curves] started at about 13 years of follow-up and persisted through 30 years of follow-up," she pointed out.

All-cause mortality was statistically indistinguishable between groups, although the trial was underpowered to assess this outcome.

In subgroup analyses, there was a near-significant interaction of screening with sex (P = .06), whereby the benefit was greater among men (RR, 0.62) than among women (RR, 0.83).

Additionally, among men, there was a significant interaction with age (P = .04), whereby screening was most beneficial among those 60-69 years old at baseline (RR, 0.46). The benefit among women appeared to be restricted to those who started screening at age 60 or later.

"We don’t have information on the incidence of colon cancer, and hence we can’t comment on right- versus left-sided colon cancer mortality," Dr. Shaukat noted.

Dr. Shaukat disclosed no conflicts of interest.

SAN DIEGO – The mortality-reducing benefit of colorectal cancer screening persists long term, according to an updated analysis of the randomized Minnesota Fecal Occult Blood Trial.

Investigators led by Dr. Aasma Shaukat, a gastroenterologist with the University of Minnesota, Minneapolis, analyzed data for more than 46,000 participants aged 50-80 years who were assigned to screening with the fecal occult blood test (FOBT) or no screening.

After the first 18 years, the cumulative colorectal cancer mortality rate was reduced by one-third with annual screening and by one-fifth with biennial screening as compared with no screening, according to initially reported results (J. Natl. Cancer Inst. 1999;91:434-7).

The updated results, now after 30 years of follow-up – the longest of any such trial to date – showed that the reductions in risk with screening were essentially unchanged, Dr. Shaukat reported at the annual meeting of the American College of Gastroenterology.

"Screening for colon cancer using fecal occult blood testing consistently reduces colorectal cancer mortality..., and this effect is sustained through 30 years of follow-up," she commented. "This suggests the effect of polypectomy, because [if] fecal occult blood testing [detected only] early cancers, most of the benefit would be seen in the first 8-10 years. The sustained benefit suggests that these individuals underwent removal of polyps that would have turned into cancer and resulted in a death at 30 years."

In additional trial findings, the benefit of screening appeared to be greater for men than women and greater for those who began screening after the age of 60 years.

Session attendee Dr. Samir Gupta, of the University of California, San Diego, asked, "After the initial 10 or 15 years of protocolized screening, is it possible that screening was going on in the control group" and that might explain the lesser benefit in younger individuals, as they would have had more time to be screened.

"During the trial, through 1998, the screening in the control group was less than 5%, so there wasn’t much screening going on in the control group," Dr. Shaukat replied. However, "after the trial ended, we don’t have information on people’s screening behavior. And screening became popular, particularly in the last two decades. So there is a possibility that a large number of people that were in the control group underwent screening, and that’s diluting the effects that we would have otherwise seen."

She offered a few possible additional reasons for the smaller benefit in the younger group. "One is that group doesn’t have a higher risk of colon cancer and of dying from colon cancer, and hence, we are just not seeing the effect of screening," she said. "The second is that perhaps fecal occult blood testing is fairly insensitive in that age group; that’s something that needs to be explored further."

Session comoderator Dr. Jonathan A. Leighton of the Mayo Clinic in Scottsdale, Ariz., asked, "Why do you think there was that benefit in men over women?"

"That’s something that’s actually been shown in several natural history and modeling studies," Dr. Shaukat replied. "Men have a higher incidence of colon cancer and they have a higher risk of dying from colon cancer compared to women. So it bears to reason that we would see a larger effect of screening among men compared to women." That said, subgroup analyses should be considered hypothesis generating and require confirmation, she acknowledged.

Dr. Carol Burke of the Cleveland Clinic, who also attended the session, asked whether the screening benefit would have been even greater in analyses restricted to adherent patients.

"Compliance-adjusted estimates ... are a lot larger, to the magnitude of about a 40% reduction in colorectal cancer mortality," Dr. Shaukat replied.

"What effect do you think FIT [fecal immunochemical test] would have on the magnitude [of benefit] – similar for FIT or better because of adherence?" Dr. Burke further queried.

"These fecal occult blood tests were rehydrated, so their sensitivity is comparable to modern-day FIT. So we expect FIT to do the same if not better," Dr. Shaukat replied.

In the trial, 46,551 participants in the Minnesota Colon Cancer Control Study were assigned to annual or biennial screening or no screening between 1976 and 1992. Those with positive FOBT results underwent colonoscopy with polypectomy if needed. All groups had annual follow-up thereafter through 1998.

Adherence to screening was high in the trial, with 90% of participants in the screening groups completing at least one FOBT, and no difference between men and women, according to Dr. Shaukat.

At each screening, 10% of participants had positive results, and 83% of this subset overall underwent colonoscopy. The complication rate from colonoscopy was low, at less than 0.1%.

In the updated analysis, 71% of trial participants had died as ascertained from the National Death Index.

In intention-to-treat analyses, the risk of colorectal cancer mortality was a significant 32% lower in the group screened annually (relative risk, 0.68) and 22% lower in the group screened biennially (RR, 0.78) as compared with the nonscreened group, according to data reported at the meeting and recently published (N. Engl. J. Med. 2013;369:1106-14).

"We don’t know what happened after 1998," Dr. Shaukat reminded attendees. "At best, the effects that we are seeing might be dilute, and if truly the control group had remained unscreened, we would have seen perhaps larger differences."

The absolute cumulative colorectal cancer mortality rates were 0.02 with annual screening, 0.02 with biennial screening, and 0.03 with no screening. "This separation [in curves] started at about 13 years of follow-up and persisted through 30 years of follow-up," she pointed out.

All-cause mortality was statistically indistinguishable between groups, although the trial was underpowered to assess this outcome.

In subgroup analyses, there was a near-significant interaction of screening with sex (P = .06), whereby the benefit was greater among men (RR, 0.62) than among women (RR, 0.83).

Additionally, among men, there was a significant interaction with age (P = .04), whereby screening was most beneficial among those 60-69 years old at baseline (RR, 0.46). The benefit among women appeared to be restricted to those who started screening at age 60 or later.

"We don’t have information on the incidence of colon cancer, and hence we can’t comment on right- versus left-sided colon cancer mortality," Dr. Shaukat noted.

Dr. Shaukat disclosed no conflicts of interest.

SAN DIEGO – The mortality-reducing benefit of colorectal cancer screening persists long term, according to an updated analysis of the randomized Minnesota Fecal Occult Blood Trial.

Investigators led by Dr. Aasma Shaukat, a gastroenterologist with the University of Minnesota, Minneapolis, analyzed data for more than 46,000 participants aged 50-80 years who were assigned to screening with the fecal occult blood test (FOBT) or no screening.

After the first 18 years, the cumulative colorectal cancer mortality rate was reduced by one-third with annual screening and by one-fifth with biennial screening as compared with no screening, according to initially reported results (J. Natl. Cancer Inst. 1999;91:434-7).

The updated results, now after 30 years of follow-up – the longest of any such trial to date – showed that the reductions in risk with screening were essentially unchanged, Dr. Shaukat reported at the annual meeting of the American College of Gastroenterology.

"Screening for colon cancer using fecal occult blood testing consistently reduces colorectal cancer mortality..., and this effect is sustained through 30 years of follow-up," she commented. "This suggests the effect of polypectomy, because [if] fecal occult blood testing [detected only] early cancers, most of the benefit would be seen in the first 8-10 years. The sustained benefit suggests that these individuals underwent removal of polyps that would have turned into cancer and resulted in a death at 30 years."

In additional trial findings, the benefit of screening appeared to be greater for men than women and greater for those who began screening after the age of 60 years.

Session attendee Dr. Samir Gupta, of the University of California, San Diego, asked, "After the initial 10 or 15 years of protocolized screening, is it possible that screening was going on in the control group" and that might explain the lesser benefit in younger individuals, as they would have had more time to be screened.

"During the trial, through 1998, the screening in the control group was less than 5%, so there wasn’t much screening going on in the control group," Dr. Shaukat replied. However, "after the trial ended, we don’t have information on people’s screening behavior. And screening became popular, particularly in the last two decades. So there is a possibility that a large number of people that were in the control group underwent screening, and that’s diluting the effects that we would have otherwise seen."

She offered a few possible additional reasons for the smaller benefit in the younger group. "One is that group doesn’t have a higher risk of colon cancer and of dying from colon cancer, and hence, we are just not seeing the effect of screening," she said. "The second is that perhaps fecal occult blood testing is fairly insensitive in that age group; that’s something that needs to be explored further."

Session comoderator Dr. Jonathan A. Leighton of the Mayo Clinic in Scottsdale, Ariz., asked, "Why do you think there was that benefit in men over women?"

"That’s something that’s actually been shown in several natural history and modeling studies," Dr. Shaukat replied. "Men have a higher incidence of colon cancer and they have a higher risk of dying from colon cancer compared to women. So it bears to reason that we would see a larger effect of screening among men compared to women." That said, subgroup analyses should be considered hypothesis generating and require confirmation, she acknowledged.

Dr. Carol Burke of the Cleveland Clinic, who also attended the session, asked whether the screening benefit would have been even greater in analyses restricted to adherent patients.

"Compliance-adjusted estimates ... are a lot larger, to the magnitude of about a 40% reduction in colorectal cancer mortality," Dr. Shaukat replied.

"What effect do you think FIT [fecal immunochemical test] would have on the magnitude [of benefit] – similar for FIT or better because of adherence?" Dr. Burke further queried.

"These fecal occult blood tests were rehydrated, so their sensitivity is comparable to modern-day FIT. So we expect FIT to do the same if not better," Dr. Shaukat replied.

In the trial, 46,551 participants in the Minnesota Colon Cancer Control Study were assigned to annual or biennial screening or no screening between 1976 and 1992. Those with positive FOBT results underwent colonoscopy with polypectomy if needed. All groups had annual follow-up thereafter through 1998.

Adherence to screening was high in the trial, with 90% of participants in the screening groups completing at least one FOBT, and no difference between men and women, according to Dr. Shaukat.

At each screening, 10% of participants had positive results, and 83% of this subset overall underwent colonoscopy. The complication rate from colonoscopy was low, at less than 0.1%.

In the updated analysis, 71% of trial participants had died as ascertained from the National Death Index.

In intention-to-treat analyses, the risk of colorectal cancer mortality was a significant 32% lower in the group screened annually (relative risk, 0.68) and 22% lower in the group screened biennially (RR, 0.78) as compared with the nonscreened group, according to data reported at the meeting and recently published (N. Engl. J. Med. 2013;369:1106-14).

"We don’t know what happened after 1998," Dr. Shaukat reminded attendees. "At best, the effects that we are seeing might be dilute, and if truly the control group had remained unscreened, we would have seen perhaps larger differences."

The absolute cumulative colorectal cancer mortality rates were 0.02 with annual screening, 0.02 with biennial screening, and 0.03 with no screening. "This separation [in curves] started at about 13 years of follow-up and persisted through 30 years of follow-up," she pointed out.

All-cause mortality was statistically indistinguishable between groups, although the trial was underpowered to assess this outcome.

In subgroup analyses, there was a near-significant interaction of screening with sex (P = .06), whereby the benefit was greater among men (RR, 0.62) than among women (RR, 0.83).

Additionally, among men, there was a significant interaction with age (P = .04), whereby screening was most beneficial among those 60-69 years old at baseline (RR, 0.46). The benefit among women appeared to be restricted to those who started screening at age 60 or later.

"We don’t have information on the incidence of colon cancer, and hence we can’t comment on right- versus left-sided colon cancer mortality," Dr. Shaukat noted.

Dr. Shaukat disclosed no conflicts of interest.

WOODINVILLE, WASH. – Make decisions about whether to surgically or medically manage keloids according to features of the lesion and patient-related factors, especially likely treatment compliance, Dr. Hilary E. Baldwin advised.

"Step one when we are dealing with our patients with keloids is trying to decide what the patients actually hope for," Dr. Baldwin said at the annual Coastal Dermatology Symposium. That might be eradication of the keloid; palliation of symptoms such as itching or pain; flattening, lightening, or softening of the keloid; ability to wear clip-on earrings; or restoration of mobility.

"Most patients, in my opinion, are actually not surgical candidates, and most need to be convinced to pursue other options," said Dr. Baldwin of the dermatology department at the State University of New York, Brooklyn.

Surgical management

Size and shape should factor into decisions about surgical removal of keloids, said Dr. Baldwin. Larger keloids are not much more difficult to remove than smaller ones, and pedunculated keloids are generally the most amenable to surgery, she noted.

Keloid age also comes into play, as the older, mature, brown lesions are less likely to recur after surgery than the younger, pink, symptomatic ones. Location affects outcome as well, Dr. Baldwin said. Keloids on the jaw, the deltoid, mid-back, mid-chest, and upper back are most likely to recur if treated surgically, and those in low-tension areas are less likely to do so.

Surgery also may be considered for keloids that are truly unresponsive to intralesional corticosteroids, but those are uncommon as previous lack of response is usually because of an inadequate dose, Dr. Baldwin explained.

"Most important is patient commitment. They often believe that cutting is a quick fix and they are not going to have to do anything afterward, and they are poor flight risks because of that," she said. Statistics suggest that the nearly 100% of keloids recur with surgery alone, but the value falls to 50% with adjunctive corticosteroids, and 20% with adjunctive radiation therapy, she added.

Adjunctive therapies

When adjunctive corticosteroids are used after surgery, the steroid is injected into the base and walls of the excision site, according to Dr. Baldwin; her preference is to use 40 mg/cc triamcinolone, with injections given for at least 6 months.

"Radiation therapy ... works really well postop; in fact, it’s our best adjunctive therapy, if you’re not afraid of it and the patient’s not afraid of it," she said. At her institution, this therapy is completed within a week after surgery, "so even if patients are a flight risk, they always return for that first visit, and then they are done with at least one adjunctive therapy."

The main barrier to use has been a fear of secondary malignancy. But reports of cancer after radiation therapy are rare and questionably associated with the treatment, Dr. Baldwin said.

Pressure dressings also are effective, and these are most practical in the form of compression earrings worn after excision of earlobe keloids, usually for at least 6 months. The earrings also come in a form called "sleepers" that may be more acceptable to patients.

Interferon injections also can help prevent recurrence. "I treat the very first day ... into the wall and into the base, just as I would with steroids, and then repeat 1 week later," Dr. Baldwin explained. "So if you use this and radiation therapy, 1 week later, you have finished two adjunctive therapies."

Especially challenging are keloids nearly obliterating normal tissue, such as extensive earlobe keloids. "I call them last-chance keloids," Dr. Baldwin commented. "If I don’t do a good job and don’t have good adjunctive therapy, it’s going to regrow and that’s the last time I am going to be able to cut. The earlobe will be eaten away with keloid, and we are never going to be able to give [the patient] an earlobe on which to hang an earring."

After excision of last-chance keloids, "I recommend that you do everything ... Use everything that is available to you," Dr. Baldwin advised. In addition to excision, that includes "intralesional steroids, intralesional interferon, radiation therapy, and earrings. Why pick one? Use them all if appropriate, and you are much less likely to have a recurrence," she said.

Medical management

Medical therapy is indicated for large, sessile keloids and for those located in areas where surgery could lead to complications, according to Dr. Baldwin.

In these cases, intralesional corticosteroids are the mainstay, and her preference is to use a high dose of triamcinolone. "I only use 40 [mg/cc]—that’s it. I never use anything less," she said. "I don’t care where the keloid is: A keloid on the face is the same as a keloid on the back. Most of the failures that I see are due to inadequate concentration. It’s almost always on the face where people are a little bit shy about using the extraordinarily high doses," she added.

Dr. Baldwin dismissed the dogma of not exceeding 40 mg per month, given that this translates to a dose of just 50 mg of prednisone. "I will sometimes use 80 [mg] in one sitting. I don’t really have that kind of a restriction because it doesn’t make a ton of sense," she said.

For pre-injection anesthesia, Dr. Baldwin recommended applying topical anesthetic followed by a lidocaine ring block. When treating hard keloids, to prevent backwash of the corticosteroid along the needle track, she said she preapplies Krazy Glue and, immediately after removing the needle, applies a strip of precut tape.

Patients should be advised of the possible complications of hypopigmentation, telangiectasia, and atrophy. "You also have to warn your patients about what I call the Play-Doh effect," whereby the keloid spreads as it softens, Dr. Baldwin said. "So the footprint is ultimately much bigger than it was originally, although it’s now flatter."

Intralesional injection of 5-fluorouracil can be used alone or with admixed steroids. However, Dr. Baldwin said that in her hands, the combination has been disappointing, perhaps because the triamcinolone is diluted in the process. "So I’ve reconsidered recently the possibility of doing the steroids the way I like it and following [with 5-fluoruracil] in addition to it, rather than diluting my triamcinolone," she said.

The newest nonsurgical therapy is intralesional cryotherapy, whereby the keloid is frozen from the inside out with a probe attached to a cryotherapy device, so it eventually undergoes necrosis while the skin is preserved. The reduction in volume achieved has ranged from 51% to 93% across studies, with minimal to no hypopigmentation.

"The probe itself unfortunately costs $450 and is not reusable, which is a problem. At the present time this is not covered by insurance," said Dr. Baldwin, who disclosed no relevant conflicts of interest. "But for keloids that really can’t be treated any other way, it has been quite helpful."

The meeting was presented by the Caribbean Dermatology Symposium.

sknews@frontlinemedcom.com

WOODINVILLE, WASH. – Make decisions about whether to surgically or medically manage keloids according to features of the lesion and patient-related factors, especially likely treatment compliance, Dr. Hilary E. Baldwin advised.

"Step one when we are dealing with our patients with keloids is trying to decide what the patients actually hope for," Dr. Baldwin said at the annual Coastal Dermatology Symposium. That might be eradication of the keloid; palliation of symptoms such as itching or pain; flattening, lightening, or softening of the keloid; ability to wear clip-on earrings; or restoration of mobility.

"Most patients, in my opinion, are actually not surgical candidates, and most need to be convinced to pursue other options," said Dr. Baldwin of the dermatology department at the State University of New York, Brooklyn.

Surgical management

Size and shape should factor into decisions about surgical removal of keloids, said Dr. Baldwin. Larger keloids are not much more difficult to remove than smaller ones, and pedunculated keloids are generally the most amenable to surgery, she noted.

Keloid age also comes into play, as the older, mature, brown lesions are less likely to recur after surgery than the younger, pink, symptomatic ones. Location affects outcome as well, Dr. Baldwin said. Keloids on the jaw, the deltoid, mid-back, mid-chest, and upper back are most likely to recur if treated surgically, and those in low-tension areas are less likely to do so.

Surgery also may be considered for keloids that are truly unresponsive to intralesional corticosteroids, but those are uncommon as previous lack of response is usually because of an inadequate dose, Dr. Baldwin explained.

"Most important is patient commitment. They often believe that cutting is a quick fix and they are not going to have to do anything afterward, and they are poor flight risks because of that," she said. Statistics suggest that the nearly 100% of keloids recur with surgery alone, but the value falls to 50% with adjunctive corticosteroids, and 20% with adjunctive radiation therapy, she added.

Adjunctive therapies

When adjunctive corticosteroids are used after surgery, the steroid is injected into the base and walls of the excision site, according to Dr. Baldwin; her preference is to use 40 mg/cc triamcinolone, with injections given for at least 6 months.

"Radiation therapy ... works really well postop; in fact, it’s our best adjunctive therapy, if you’re not afraid of it and the patient’s not afraid of it," she said. At her institution, this therapy is completed within a week after surgery, "so even if patients are a flight risk, they always return for that first visit, and then they are done with at least one adjunctive therapy."

The main barrier to use has been a fear of secondary malignancy. But reports of cancer after radiation therapy are rare and questionably associated with the treatment, Dr. Baldwin said.

Pressure dressings also are effective, and these are most practical in the form of compression earrings worn after excision of earlobe keloids, usually for at least 6 months. The earrings also come in a form called "sleepers" that may be more acceptable to patients.

Interferon injections also can help prevent recurrence. "I treat the very first day ... into the wall and into the base, just as I would with steroids, and then repeat 1 week later," Dr. Baldwin explained. "So if you use this and radiation therapy, 1 week later, you have finished two adjunctive therapies."

Especially challenging are keloids nearly obliterating normal tissue, such as extensive earlobe keloids. "I call them last-chance keloids," Dr. Baldwin commented. "If I don’t do a good job and don’t have good adjunctive therapy, it’s going to regrow and that’s the last time I am going to be able to cut. The earlobe will be eaten away with keloid, and we are never going to be able to give [the patient] an earlobe on which to hang an earring."

After excision of last-chance keloids, "I recommend that you do everything ... Use everything that is available to you," Dr. Baldwin advised. In addition to excision, that includes "intralesional steroids, intralesional interferon, radiation therapy, and earrings. Why pick one? Use them all if appropriate, and you are much less likely to have a recurrence," she said.

Medical management

Medical therapy is indicated for large, sessile keloids and for those located in areas where surgery could lead to complications, according to Dr. Baldwin.

In these cases, intralesional corticosteroids are the mainstay, and her preference is to use a high dose of triamcinolone. "I only use 40 [mg/cc]—that’s it. I never use anything less," she said. "I don’t care where the keloid is: A keloid on the face is the same as a keloid on the back. Most of the failures that I see are due to inadequate concentration. It’s almost always on the face where people are a little bit shy about using the extraordinarily high doses," she added.

Dr. Baldwin dismissed the dogma of not exceeding 40 mg per month, given that this translates to a dose of just 50 mg of prednisone. "I will sometimes use 80 [mg] in one sitting. I don’t really have that kind of a restriction because it doesn’t make a ton of sense," she said.

For pre-injection anesthesia, Dr. Baldwin recommended applying topical anesthetic followed by a lidocaine ring block. When treating hard keloids, to prevent backwash of the corticosteroid along the needle track, she said she preapplies Krazy Glue and, immediately after removing the needle, applies a strip of precut tape.

Patients should be advised of the possible complications of hypopigmentation, telangiectasia, and atrophy. "You also have to warn your patients about what I call the Play-Doh effect," whereby the keloid spreads as it softens, Dr. Baldwin said. "So the footprint is ultimately much bigger than it was originally, although it’s now flatter."

Intralesional injection of 5-fluorouracil can be used alone or with admixed steroids. However, Dr. Baldwin said that in her hands, the combination has been disappointing, perhaps because the triamcinolone is diluted in the process. "So I’ve reconsidered recently the possibility of doing the steroids the way I like it and following [with 5-fluoruracil] in addition to it, rather than diluting my triamcinolone," she said.

The newest nonsurgical therapy is intralesional cryotherapy, whereby the keloid is frozen from the inside out with a probe attached to a cryotherapy device, so it eventually undergoes necrosis while the skin is preserved. The reduction in volume achieved has ranged from 51% to 93% across studies, with minimal to no hypopigmentation.

"The probe itself unfortunately costs $450 and is not reusable, which is a problem. At the present time this is not covered by insurance," said Dr. Baldwin, who disclosed no relevant conflicts of interest. "But for keloids that really can’t be treated any other way, it has been quite helpful."

The meeting was presented by the Caribbean Dermatology Symposium.

sknews@frontlinemedcom.com

WOODINVILLE, WASH. – Make decisions about whether to surgically or medically manage keloids according to features of the lesion and patient-related factors, especially likely treatment compliance, Dr. Hilary E. Baldwin advised.

"Step one when we are dealing with our patients with keloids is trying to decide what the patients actually hope for," Dr. Baldwin said at the annual Coastal Dermatology Symposium. That might be eradication of the keloid; palliation of symptoms such as itching or pain; flattening, lightening, or softening of the keloid; ability to wear clip-on earrings; or restoration of mobility.

"Most patients, in my opinion, are actually not surgical candidates, and most need to be convinced to pursue other options," said Dr. Baldwin of the dermatology department at the State University of New York, Brooklyn.

Surgical management

Size and shape should factor into decisions about surgical removal of keloids, said Dr. Baldwin. Larger keloids are not much more difficult to remove than smaller ones, and pedunculated keloids are generally the most amenable to surgery, she noted.

Keloid age also comes into play, as the older, mature, brown lesions are less likely to recur after surgery than the younger, pink, symptomatic ones. Location affects outcome as well, Dr. Baldwin said. Keloids on the jaw, the deltoid, mid-back, mid-chest, and upper back are most likely to recur if treated surgically, and those in low-tension areas are less likely to do so.

Surgery also may be considered for keloids that are truly unresponsive to intralesional corticosteroids, but those are uncommon as previous lack of response is usually because of an inadequate dose, Dr. Baldwin explained.

"Most important is patient commitment. They often believe that cutting is a quick fix and they are not going to have to do anything afterward, and they are poor flight risks because of that," she said. Statistics suggest that the nearly 100% of keloids recur with surgery alone, but the value falls to 50% with adjunctive corticosteroids, and 20% with adjunctive radiation therapy, she added.

Adjunctive therapies

When adjunctive corticosteroids are used after surgery, the steroid is injected into the base and walls of the excision site, according to Dr. Baldwin; her preference is to use 40 mg/cc triamcinolone, with injections given for at least 6 months.

"Radiation therapy ... works really well postop; in fact, it’s our best adjunctive therapy, if you’re not afraid of it and the patient’s not afraid of it," she said. At her institution, this therapy is completed within a week after surgery, "so even if patients are a flight risk, they always return for that first visit, and then they are done with at least one adjunctive therapy."

The main barrier to use has been a fear of secondary malignancy. But reports of cancer after radiation therapy are rare and questionably associated with the treatment, Dr. Baldwin said.

Pressure dressings also are effective, and these are most practical in the form of compression earrings worn after excision of earlobe keloids, usually for at least 6 months. The earrings also come in a form called "sleepers" that may be more acceptable to patients.

Interferon injections also can help prevent recurrence. "I treat the very first day ... into the wall and into the base, just as I would with steroids, and then repeat 1 week later," Dr. Baldwin explained. "So if you use this and radiation therapy, 1 week later, you have finished two adjunctive therapies."

Especially challenging are keloids nearly obliterating normal tissue, such as extensive earlobe keloids. "I call them last-chance keloids," Dr. Baldwin commented. "If I don’t do a good job and don’t have good adjunctive therapy, it’s going to regrow and that’s the last time I am going to be able to cut. The earlobe will be eaten away with keloid, and we are never going to be able to give [the patient] an earlobe on which to hang an earring."

After excision of last-chance keloids, "I recommend that you do everything ... Use everything that is available to you," Dr. Baldwin advised. In addition to excision, that includes "intralesional steroids, intralesional interferon, radiation therapy, and earrings. Why pick one? Use them all if appropriate, and you are much less likely to have a recurrence," she said.

Medical management

Medical therapy is indicated for large, sessile keloids and for those located in areas where surgery could lead to complications, according to Dr. Baldwin.

In these cases, intralesional corticosteroids are the mainstay, and her preference is to use a high dose of triamcinolone. "I only use 40 [mg/cc]—that’s it. I never use anything less," she said. "I don’t care where the keloid is: A keloid on the face is the same as a keloid on the back. Most of the failures that I see are due to inadequate concentration. It’s almost always on the face where people are a little bit shy about using the extraordinarily high doses," she added.

Dr. Baldwin dismissed the dogma of not exceeding 40 mg per month, given that this translates to a dose of just 50 mg of prednisone. "I will sometimes use 80 [mg] in one sitting. I don’t really have that kind of a restriction because it doesn’t make a ton of sense," she said.

For pre-injection anesthesia, Dr. Baldwin recommended applying topical anesthetic followed by a lidocaine ring block. When treating hard keloids, to prevent backwash of the corticosteroid along the needle track, she said she preapplies Krazy Glue and, immediately after removing the needle, applies a strip of precut tape.

Patients should be advised of the possible complications of hypopigmentation, telangiectasia, and atrophy. "You also have to warn your patients about what I call the Play-Doh effect," whereby the keloid spreads as it softens, Dr. Baldwin said. "So the footprint is ultimately much bigger than it was originally, although it’s now flatter."

Intralesional injection of 5-fluorouracil can be used alone or with admixed steroids. However, Dr. Baldwin said that in her hands, the combination has been disappointing, perhaps because the triamcinolone is diluted in the process. "So I’ve reconsidered recently the possibility of doing the steroids the way I like it and following [with 5-fluoruracil] in addition to it, rather than diluting my triamcinolone," she said.

The newest nonsurgical therapy is intralesional cryotherapy, whereby the keloid is frozen from the inside out with a probe attached to a cryotherapy device, so it eventually undergoes necrosis while the skin is preserved. The reduction in volume achieved has ranged from 51% to 93% across studies, with minimal to no hypopigmentation.

"The probe itself unfortunately costs $450 and is not reusable, which is a problem. At the present time this is not covered by insurance," said Dr. Baldwin, who disclosed no relevant conflicts of interest. "But for keloids that really can’t be treated any other way, it has been quite helpful."

The meeting was presented by the Caribbean Dermatology Symposium.

sknews@frontlinemedcom.com

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – Commonly used pain medications increase the risk of exacerbations of Crohn’s disease, judging from the findings of a prospective cohort study of nearly 800 patients with inflammatory bowel disease initially in remission.

Patients with Crohn’s disease who used nonsteroidal anti-inflammatory drugs (NSAIDs) at least five times monthly were 65% more likely to have active disease 6 months later, investigators reported at the annual meeting of the American College of Gastroenterology. Unexpectedly, any use of acetaminophen was also an independent risk factor in this group.

"A lot of our patients in remission are taking these medications. We need to ask detailed histories about this," she added. It is noteworthy that no such effect was seen in ulcerative colitis patients. "There might be a dose/response issue here. We have a lot of young women obviously with inflammatory bowel disease who take ibuprofen for menstrual cramping." When taken fewer than five times monthly, these drugs do not seem to have an effect, she noted.

"Implications may be that the requirement for any pain medication while in remission may actually be a marker of occult ongoing disease. Occult disease itself may be the risk factor for disease activity," commented lead investigator Dr. Millie Long, an assistant professor at the University of North Carolina, Chapel Hill.

"It’s also theoretically possible that a mechanism common to both drugs may be associated with increased disease activity," she added. For example, both NSAIDs and acetaminophen inhibit cyclooxygenase-3.

"Further prospective studies are needed with objective inflammatory outcomes to better assess the risks of these pain medications and better counsel patients," Dr. Long maintained.

One audience member noted that the study could not tease apart whether analgesic use was the cause or the result of an exacerbation.

"I would argue that we specifically limited this to a population of patients in remission by validated disease activity indices at baseline. ... We also had data on the quality of life of these individuals, the Shortened Inflammatory Bowel Disease questionnaire. These were individuals who felt well," Dr. Long replied. "That said, they could have been taking their pain medication for gut pain, I agree. They could have been taking it for arthritis, they could have been taking it for a headache."

Session comoderator Dr. Miguel D. Regueiro, a gastroenterologist at the University of Pittsburgh, asked, "In your practice, will you allow Crohn’s patients to take an NSAID three or four times a month?"

"I do, particularly for my young women who really need it for menstrual cramping. I don’t think that one time a week – and obviously these data support that – is going to cause a problem," Dr. Long replied. "I do feel these data as well as the Bonner prospective cohort data [Inflamm. Bowel Dis. 2004;10:751-57] show that high-dose NSAIDs may be bad news in patients with Crohn’s disease."

The investigators conducted the study among Crohn’s and Colitis Foundation of America (CCFA) Partners, an Internet-based cohort of patients with inflammatory bowel disease. The patients completed online surveys at baseline and 6 months, answering questions about disease activity and average number of times per month they used various pain medications.

Analyses were based on 791 patients who were in remission at baseline. About 75% had Crohn’s disease, reported Dr. Long. The mean duration of inflammatory bowel disease was approximately 14 years.

Overall, 43% of patients reported using any NSAIDs, and 19% reported using them at least five times monthly. Additionally, 65% reported any use of acetaminophen.

At follow-up, about a fifth of patients overall had experienced an exacerbation and now had active disease, defined as a simplified Crohn’s Disease Activity Index (sCDAI) score of at least 150 or a Simple Clinical Colitis Activity Index (SCCAI) score of greater than 2.

In the cohort as a whole, the proportion of patients with an exacerbation did not vary significantly according NSAID use, but it was higher among acetaminophen users versus nonusers (20% vs. 14%; P = .03).

Analyses stratified by type of disease showed that patients with Crohn’s disease were more likely to have an exacerbation if they used NSAIDs at least five times monthly versus less often, and if they used acetaminophen at all. In contrast, patients with ulcerative colitis were not affected.

In multivariate analyses that controlled for potential confounders, including use of other medications, NSAID use five or more times monthly was an independent risk factor for exacerbation in the entire cohort (relative risk, 1.46) and in the subset with Crohn’s disease (RR, 1.65).

Any use of acetaminophen was also an independent risk factor, both in the entire cohort (RR, 1.41) and in the subset with Crohn’s disease (RR, 1.72).

Dr. Long disclosed no relevant conflicts of interest.

SAN DIEGO – Commonly used pain medications increase the risk of exacerbations of Crohn’s disease, judging from the findings of a prospective cohort study of nearly 800 patients with inflammatory bowel disease initially in remission.

Patients with Crohn’s disease who used nonsteroidal anti-inflammatory drugs (NSAIDs) at least five times monthly were 65% more likely to have active disease 6 months later, investigators reported at the annual meeting of the American College of Gastroenterology. Unexpectedly, any use of acetaminophen was also an independent risk factor in this group.

"A lot of our patients in remission are taking these medications. We need to ask detailed histories about this," she added. It is noteworthy that no such effect was seen in ulcerative colitis patients. "There might be a dose/response issue here. We have a lot of young women obviously with inflammatory bowel disease who take ibuprofen for menstrual cramping." When taken fewer than five times monthly, these drugs do not seem to have an effect, she noted.

"Implications may be that the requirement for any pain medication while in remission may actually be a marker of occult ongoing disease. Occult disease itself may be the risk factor for disease activity," commented lead investigator Dr. Millie Long, an assistant professor at the University of North Carolina, Chapel Hill.

"It’s also theoretically possible that a mechanism common to both drugs may be associated with increased disease activity," she added. For example, both NSAIDs and acetaminophen inhibit cyclooxygenase-3.

"Further prospective studies are needed with objective inflammatory outcomes to better assess the risks of these pain medications and better counsel patients," Dr. Long maintained.

One audience member noted that the study could not tease apart whether analgesic use was the cause or the result of an exacerbation.

"I would argue that we specifically limited this to a population of patients in remission by validated disease activity indices at baseline. ... We also had data on the quality of life of these individuals, the Shortened Inflammatory Bowel Disease questionnaire. These were individuals who felt well," Dr. Long replied. "That said, they could have been taking their pain medication for gut pain, I agree. They could have been taking it for arthritis, they could have been taking it for a headache."

Session comoderator Dr. Miguel D. Regueiro, a gastroenterologist at the University of Pittsburgh, asked, "In your practice, will you allow Crohn’s patients to take an NSAID three or four times a month?"

"I do, particularly for my young women who really need it for menstrual cramping. I don’t think that one time a week – and obviously these data support that – is going to cause a problem," Dr. Long replied. "I do feel these data as well as the Bonner prospective cohort data [Inflamm. Bowel Dis. 2004;10:751-57] show that high-dose NSAIDs may be bad news in patients with Crohn’s disease."

The investigators conducted the study among Crohn’s and Colitis Foundation of America (CCFA) Partners, an Internet-based cohort of patients with inflammatory bowel disease. The patients completed online surveys at baseline and 6 months, answering questions about disease activity and average number of times per month they used various pain medications.

Analyses were based on 791 patients who were in remission at baseline. About 75% had Crohn’s disease, reported Dr. Long. The mean duration of inflammatory bowel disease was approximately 14 years.

Overall, 43% of patients reported using any NSAIDs, and 19% reported using them at least five times monthly. Additionally, 65% reported any use of acetaminophen.

At follow-up, about a fifth of patients overall had experienced an exacerbation and now had active disease, defined as a simplified Crohn’s Disease Activity Index (sCDAI) score of at least 150 or a Simple Clinical Colitis Activity Index (SCCAI) score of greater than 2.

In the cohort as a whole, the proportion of patients with an exacerbation did not vary significantly according NSAID use, but it was higher among acetaminophen users versus nonusers (20% vs. 14%; P = .03).

Analyses stratified by type of disease showed that patients with Crohn’s disease were more likely to have an exacerbation if they used NSAIDs at least five times monthly versus less often, and if they used acetaminophen at all. In contrast, patients with ulcerative colitis were not affected.

In multivariate analyses that controlled for potential confounders, including use of other medications, NSAID use five or more times monthly was an independent risk factor for exacerbation in the entire cohort (relative risk, 1.46) and in the subset with Crohn’s disease (RR, 1.65).

Any use of acetaminophen was also an independent risk factor, both in the entire cohort (RR, 1.41) and in the subset with Crohn’s disease (RR, 1.72).

Dr. Long disclosed no relevant conflicts of interest.

SAN DIEGO – Commonly used pain medications increase the risk of exacerbations of Crohn’s disease, judging from the findings of a prospective cohort study of nearly 800 patients with inflammatory bowel disease initially in remission.

Patients with Crohn’s disease who used nonsteroidal anti-inflammatory drugs (NSAIDs) at least five times monthly were 65% more likely to have active disease 6 months later, investigators reported at the annual meeting of the American College of Gastroenterology. Unexpectedly, any use of acetaminophen was also an independent risk factor in this group.

"A lot of our patients in remission are taking these medications. We need to ask detailed histories about this," she added. It is noteworthy that no such effect was seen in ulcerative colitis patients. "There might be a dose/response issue here. We have a lot of young women obviously with inflammatory bowel disease who take ibuprofen for menstrual cramping." When taken fewer than five times monthly, these drugs do not seem to have an effect, she noted.

"Implications may be that the requirement for any pain medication while in remission may actually be a marker of occult ongoing disease. Occult disease itself may be the risk factor for disease activity," commented lead investigator Dr. Millie Long, an assistant professor at the University of North Carolina, Chapel Hill.

"It’s also theoretically possible that a mechanism common to both drugs may be associated with increased disease activity," she added. For example, both NSAIDs and acetaminophen inhibit cyclooxygenase-3.

"Further prospective studies are needed with objective inflammatory outcomes to better assess the risks of these pain medications and better counsel patients," Dr. Long maintained.

One audience member noted that the study could not tease apart whether analgesic use was the cause or the result of an exacerbation.

"I would argue that we specifically limited this to a population of patients in remission by validated disease activity indices at baseline. ... We also had data on the quality of life of these individuals, the Shortened Inflammatory Bowel Disease questionnaire. These were individuals who felt well," Dr. Long replied. "That said, they could have been taking their pain medication for gut pain, I agree. They could have been taking it for arthritis, they could have been taking it for a headache."

Session comoderator Dr. Miguel D. Regueiro, a gastroenterologist at the University of Pittsburgh, asked, "In your practice, will you allow Crohn’s patients to take an NSAID three or four times a month?"

"I do, particularly for my young women who really need it for menstrual cramping. I don’t think that one time a week – and obviously these data support that – is going to cause a problem," Dr. Long replied. "I do feel these data as well as the Bonner prospective cohort data [Inflamm. Bowel Dis. 2004;10:751-57] show that high-dose NSAIDs may be bad news in patients with Crohn’s disease."

The investigators conducted the study among Crohn’s and Colitis Foundation of America (CCFA) Partners, an Internet-based cohort of patients with inflammatory bowel disease. The patients completed online surveys at baseline and 6 months, answering questions about disease activity and average number of times per month they used various pain medications.

Analyses were based on 791 patients who were in remission at baseline. About 75% had Crohn’s disease, reported Dr. Long. The mean duration of inflammatory bowel disease was approximately 14 years.

Overall, 43% of patients reported using any NSAIDs, and 19% reported using them at least five times monthly. Additionally, 65% reported any use of acetaminophen.

At follow-up, about a fifth of patients overall had experienced an exacerbation and now had active disease, defined as a simplified Crohn’s Disease Activity Index (sCDAI) score of at least 150 or a Simple Clinical Colitis Activity Index (SCCAI) score of greater than 2.

In the cohort as a whole, the proportion of patients with an exacerbation did not vary significantly according NSAID use, but it was higher among acetaminophen users versus nonusers (20% vs. 14%; P = .03).

Analyses stratified by type of disease showed that patients with Crohn’s disease were more likely to have an exacerbation if they used NSAIDs at least five times monthly versus less often, and if they used acetaminophen at all. In contrast, patients with ulcerative colitis were not affected.

In multivariate analyses that controlled for potential confounders, including use of other medications, NSAID use five or more times monthly was an independent risk factor for exacerbation in the entire cohort (relative risk, 1.46) and in the subset with Crohn’s disease (RR, 1.65).

Any use of acetaminophen was also an independent risk factor, both in the entire cohort (RR, 1.41) and in the subset with Crohn’s disease (RR, 1.72).

Dr. Long disclosed no relevant conflicts of interest.

Routine use of magnetic resonance imaging does not improve outcomes in women undergoing lumpectomy for ductal carcinoma in situ, according to the results of a retrospective cohort study conducted at the Memorial Sloan-Kettering Cancer Center in New York.

A team led by Dr. Melissa L. Pilewskie studied 2,321 patients who underwent lumpectomy for ductal carcinoma in situ (DCIS) between 1997 and 2010. A quarter had breast MRI before or immediately after their surgery, in addition to conventional imaging with mammography and/or ultrasound.

Study results, being reported in full later this week at the breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that the 5-year rate of locoregional recurrence was about 8%, with no significant difference between the groups who did and did not have MRI.

The findings were the same after adjustment for potential confounders and also when analyses were restricted to the subset of patients who did not receive radiation therapy, according to Dr. Pilewskie, a breast surgeon at Sloan-Kettering.

In addition, perioperative MRI did not reduce the rate of contralateral breast cancer, which stood at about 4% in each group.

"In the absence of evidence that MRI is improving our surgical management or – as we showed here – long-term outcomes, the routine use of this test for DCIS should be questioned," Dr. Pilewskie commented in a related press briefing.

She outlined circumstances that may justify this additional testing. "I think that MRI can be a useful adjunct if there are discrepancies or still clinical questions when someone comes in, between the imaging that they have on their mammogram or ultrasound and their physical exam or their presentation," she said. "The majority of women who present with DCIS have a normal exam and calcifications or changes on a mammogram. So when there are differences, and someone has a palpable mass or nipple discharge or a different presentation that wasn’t answered by their imaging, I think MRI can help give additional information. But that again is not the routine woman who presents with DCIS."

With a median 59-month follow-up, the groups who did and did not receive MRI were statistically indistinguishable in terms of the actuarial rate of locoregional recurrence at 5 years (8.5% vs. 7.2%) and at 8 years (14.6% vs. 10.2%).

"When comparing the MRI and no-MRI groups, there were some differences between them in that the women who had an MRI had more high-risk features," Dr. Pilewskie noted, and those features might have influenced the decision to obtain this additional imaging and outcomes.

However, MRI was not a significant predictor of locoregional recurrence in a multivariate analysis that adjusted for these and other potential confounders: age, family history, mode of presentation, tamoxifen or other hormonal therapy, margin status, number of excisions, and year of surgery.

On the other hand, receipt of radiation therapy, receipt of endocrine therapy, and negative margins were all significantly associated with a lower risk of locoregional recurrence.

In a subset analysis, MRI also failed to reduce the risk of locoregional recurrence in the roughly one-third of patients who did not receive radiation therapy.

Similarly, patients who did and did not receive MRI were statistically indistinguishable in terms of the actuarial rate of contralateral breast cancer at 5 years (3.5% vs. 3.5%) and at 8 years (3.5% vs. 5.1%). Again, results were essentially the same in the subset who did not receive radiation therapy.

Dr. Steven O’Day, director of clinical research at the Beverly Hills Cancer Institute in California and moderator of the press briefing, commented, "There has been a tremendous increase in the use of MRI perioperatively and postoperatively in invasive as well as noninvasive breast cancer. And this [study] I think just grounds us to continue to – as new technologies, new imaging is used – be sure that we are actually" improving outcomes.

He concurred that the added sensitivity of MRI may be helpful in challenging cases. "But its routine use certainly in DCIS from this large retrospective study has not been shown as an independent predictor to improve locoregional or contralateral breast outcomes," he said. "So I think this is an important study" and leads us to want "to study MRI further prospectively both in DCIS and invasive cancer."

Giving some background to the research, Dr. Pilewskie noted that current guidelines do not address when MRI should be used in the work-up of patients with DCIS.

"However, about 30% of physicians currently obtain a perioperative MRI to look for areas of additional disease in patients with DCIS, and theoretically, treating this additional disease found by MRI could result in a lower risk of local recurrence or contralateral breast cancer down the road," she said. "And, again theoretically, this effect could be most pronounced in women treated with excision alone, meaning just having lumpectomy and no radiation therapy."

Overall, 26% of the patients studied had breast MRI near the time of surgery, most commonly preoperatively, to assess disease extent.

Dr. Pilewskie and Dr. O’Day disclosed no relevant conflicts of interest.

Routine use of magnetic resonance imaging does not improve outcomes in women undergoing lumpectomy for ductal carcinoma in situ, according to the results of a retrospective cohort study conducted at the Memorial Sloan-Kettering Cancer Center in New York.

A team led by Dr. Melissa L. Pilewskie studied 2,321 patients who underwent lumpectomy for ductal carcinoma in situ (DCIS) between 1997 and 2010. A quarter had breast MRI before or immediately after their surgery, in addition to conventional imaging with mammography and/or ultrasound.

Study results, being reported in full later this week at the breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that the 5-year rate of locoregional recurrence was about 8%, with no significant difference between the groups who did and did not have MRI.

The findings were the same after adjustment for potential confounders and also when analyses were restricted to the subset of patients who did not receive radiation therapy, according to Dr. Pilewskie, a breast surgeon at Sloan-Kettering.

In addition, perioperative MRI did not reduce the rate of contralateral breast cancer, which stood at about 4% in each group.

"In the absence of evidence that MRI is improving our surgical management or – as we showed here – long-term outcomes, the routine use of this test for DCIS should be questioned," Dr. Pilewskie commented in a related press briefing.

She outlined circumstances that may justify this additional testing. "I think that MRI can be a useful adjunct if there are discrepancies or still clinical questions when someone comes in, between the imaging that they have on their mammogram or ultrasound and their physical exam or their presentation," she said. "The majority of women who present with DCIS have a normal exam and calcifications or changes on a mammogram. So when there are differences, and someone has a palpable mass or nipple discharge or a different presentation that wasn’t answered by their imaging, I think MRI can help give additional information. But that again is not the routine woman who presents with DCIS."

With a median 59-month follow-up, the groups who did and did not receive MRI were statistically indistinguishable in terms of the actuarial rate of locoregional recurrence at 5 years (8.5% vs. 7.2%) and at 8 years (14.6% vs. 10.2%).

"When comparing the MRI and no-MRI groups, there were some differences between them in that the women who had an MRI had more high-risk features," Dr. Pilewskie noted, and those features might have influenced the decision to obtain this additional imaging and outcomes.

However, MRI was not a significant predictor of locoregional recurrence in a multivariate analysis that adjusted for these and other potential confounders: age, family history, mode of presentation, tamoxifen or other hormonal therapy, margin status, number of excisions, and year of surgery.

On the other hand, receipt of radiation therapy, receipt of endocrine therapy, and negative margins were all significantly associated with a lower risk of locoregional recurrence.

In a subset analysis, MRI also failed to reduce the risk of locoregional recurrence in the roughly one-third of patients who did not receive radiation therapy.

Similarly, patients who did and did not receive MRI were statistically indistinguishable in terms of the actuarial rate of contralateral breast cancer at 5 years (3.5% vs. 3.5%) and at 8 years (3.5% vs. 5.1%). Again, results were essentially the same in the subset who did not receive radiation therapy.

Dr. Steven O’Day, director of clinical research at the Beverly Hills Cancer Institute in California and moderator of the press briefing, commented, "There has been a tremendous increase in the use of MRI perioperatively and postoperatively in invasive as well as noninvasive breast cancer. And this [study] I think just grounds us to continue to – as new technologies, new imaging is used – be sure that we are actually" improving outcomes.

He concurred that the added sensitivity of MRI may be helpful in challenging cases. "But its routine use certainly in DCIS from this large retrospective study has not been shown as an independent predictor to improve locoregional or contralateral breast outcomes," he said. "So I think this is an important study" and leads us to want "to study MRI further prospectively both in DCIS and invasive cancer."

Giving some background to the research, Dr. Pilewskie noted that current guidelines do not address when MRI should be used in the work-up of patients with DCIS.

"However, about 30% of physicians currently obtain a perioperative MRI to look for areas of additional disease in patients with DCIS, and theoretically, treating this additional disease found by MRI could result in a lower risk of local recurrence or contralateral breast cancer down the road," she said. "And, again theoretically, this effect could be most pronounced in women treated with excision alone, meaning just having lumpectomy and no radiation therapy."

Overall, 26% of the patients studied had breast MRI near the time of surgery, most commonly preoperatively, to assess disease extent.

Dr. Pilewskie and Dr. O’Day disclosed no relevant conflicts of interest.

Routine use of magnetic resonance imaging does not improve outcomes in women undergoing lumpectomy for ductal carcinoma in situ, according to the results of a retrospective cohort study conducted at the Memorial Sloan-Kettering Cancer Center in New York.

A team led by Dr. Melissa L. Pilewskie studied 2,321 patients who underwent lumpectomy for ductal carcinoma in situ (DCIS) between 1997 and 2010. A quarter had breast MRI before or immediately after their surgery, in addition to conventional imaging with mammography and/or ultrasound.

Study results, being reported in full later this week at the breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that the 5-year rate of locoregional recurrence was about 8%, with no significant difference between the groups who did and did not have MRI.

The findings were the same after adjustment for potential confounders and also when analyses were restricted to the subset of patients who did not receive radiation therapy, according to Dr. Pilewskie, a breast surgeon at Sloan-Kettering.

In addition, perioperative MRI did not reduce the rate of contralateral breast cancer, which stood at about 4% in each group.

"In the absence of evidence that MRI is improving our surgical management or – as we showed here – long-term outcomes, the routine use of this test for DCIS should be questioned," Dr. Pilewskie commented in a related press briefing.

She outlined circumstances that may justify this additional testing. "I think that MRI can be a useful adjunct if there are discrepancies or still clinical questions when someone comes in, between the imaging that they have on their mammogram or ultrasound and their physical exam or their presentation," she said. "The majority of women who present with DCIS have a normal exam and calcifications or changes on a mammogram. So when there are differences, and someone has a palpable mass or nipple discharge or a different presentation that wasn’t answered by their imaging, I think MRI can help give additional information. But that again is not the routine woman who presents with DCIS."

With a median 59-month follow-up, the groups who did and did not receive MRI were statistically indistinguishable in terms of the actuarial rate of locoregional recurrence at 5 years (8.5% vs. 7.2%) and at 8 years (14.6% vs. 10.2%).

"When comparing the MRI and no-MRI groups, there were some differences between them in that the women who had an MRI had more high-risk features," Dr. Pilewskie noted, and those features might have influenced the decision to obtain this additional imaging and outcomes.

However, MRI was not a significant predictor of locoregional recurrence in a multivariate analysis that adjusted for these and other potential confounders: age, family history, mode of presentation, tamoxifen or other hormonal therapy, margin status, number of excisions, and year of surgery.

On the other hand, receipt of radiation therapy, receipt of endocrine therapy, and negative margins were all significantly associated with a lower risk of locoregional recurrence.

In a subset analysis, MRI also failed to reduce the risk of locoregional recurrence in the roughly one-third of patients who did not receive radiation therapy.

Similarly, patients who did and did not receive MRI were statistically indistinguishable in terms of the actuarial rate of contralateral breast cancer at 5 years (3.5% vs. 3.5%) and at 8 years (3.5% vs. 5.1%). Again, results were essentially the same in the subset who did not receive radiation therapy.

Dr. Steven O’Day, director of clinical research at the Beverly Hills Cancer Institute in California and moderator of the press briefing, commented, "There has been a tremendous increase in the use of MRI perioperatively and postoperatively in invasive as well as noninvasive breast cancer. And this [study] I think just grounds us to continue to – as new technologies, new imaging is used – be sure that we are actually" improving outcomes.

He concurred that the added sensitivity of MRI may be helpful in challenging cases. "But its routine use certainly in DCIS from this large retrospective study has not been shown as an independent predictor to improve locoregional or contralateral breast outcomes," he said. "So I think this is an important study" and leads us to want "to study MRI further prospectively both in DCIS and invasive cancer."

Giving some background to the research, Dr. Pilewskie noted that current guidelines do not address when MRI should be used in the work-up of patients with DCIS.

"However, about 30% of physicians currently obtain a perioperative MRI to look for areas of additional disease in patients with DCIS, and theoretically, treating this additional disease found by MRI could result in a lower risk of local recurrence or contralateral breast cancer down the road," she said. "And, again theoretically, this effect could be most pronounced in women treated with excision alone, meaning just having lumpectomy and no radiation therapy."

Overall, 26% of the patients studied had breast MRI near the time of surgery, most commonly preoperatively, to assess disease extent.

Dr. Pilewskie and Dr. O’Day disclosed no relevant conflicts of interest.