From the AGA Journals

There is no significant difference between infliximab and adalimumab in Crohn’s disease, reported Dr. Mark T. Osterman and his colleagues in the May 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.010).

Indeed, in a study that they called "one of the first to directly compare the effectiveness of these two therapies for CD [Crohn’s disease]," the researchers calculated that rates of hospitalization and surgery while on these therapies were statistically similar, providing "justification for allowing patients’ preferences to be a major factor when choosing between these two medications."

Dr. Osterman of the department of medicine at the University of Pennsylvania, Philadelphia, and his colleagues conducted a retrospective cohort analysis of Medicare data on new users of the either adalimumab or infliximab between 2006 and 2010.

Participants had no history of using any anti–tumor necrosis factor (TNF) medications before the index prescription, as well as a diagnosis of Crohn’s in the 12 months prior.

Exclusion criteria included age greater than 85 years on the index anti-TNF prescription date; a coexisting diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis; or a diagnosis of ulcerative colitis on or immediately preceding the index date.

In total, the authors analyzed data on 1,445 infliximab patients and 865 adalimumab patients, more than 60% of whom were female and more than 90% of whom were white.

First, the authors assessed the persistence of each drug. They found that after 26 weeks of therapy, 49% of infliximab patients were still taking the drug, as were 47% of adalimumab users (adjusted odds ratio, 0.98; 95% confidence interval 0.81-1.19).

Similarly, by 1 year, the rates of persistence were 31% and 28% for infliximab and adalimumab, respectively (adjusted OR, 1.08; 95% CI, 0.86-1.37).

Next, the authors analyzed surgery-related outcomes. They found that although infliximab patients had a numerically lower incidence of surgery (including bowel resection, ostomy creation, or treatment of a perforation or abscess), the difference did not reach statistical significance (5.5 vs. 6.9 surgeries per 100 person-years, respectively; adjusted hazard ratio, 0.79; 95% CI, 0.60-1.05).

The final outcome assessed was the rate of hospitalizations attributed to Crohn’s disease. Here, too, Dr. Osterman found no significant difference between infliximab (11.8/100 patient-years) and adalimumab patients (15.4/100 patient-years) (adjusted HR, 0.88; 95% CI, 0.72-1.07).

The researchers did concede several limitations, including the fact that they did not compare adverse event rates in their analysis, although they stated that, "In general, the safety profiles of infliximab and adalimumab are believed to be similar with a few exceptions."

Dr. Osterman also wrote that the observational nature of the present analysis is by definition less robust than a head-to-head clinical trial; however, given the extreme cost of such studies, such potentially more definitive analyses "are unlikely to ever be undertaken."

Nevertheless, the current retrospective study should "allow patients, physicians, and insurers to develop rational treatment strategies and guidelines" in the treatment of CD.

Dr. Osterman and several of his coauthors disclosed financial relationships with pharmaceutical companies, including the makers of infliximab and adalimumab, Janssen Biotech and AbbVie, respectively. The researchers disclosed grant funding for this study from the Agency for Healthcare Research and Quality and the National Institutes of Health.

There is no significant difference between infliximab and adalimumab in Crohn’s disease, reported Dr. Mark T. Osterman and his colleagues in the May 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.010).

Indeed, in a study that they called "one of the first to directly compare the effectiveness of these two therapies for CD [Crohn’s disease]," the researchers calculated that rates of hospitalization and surgery while on these therapies were statistically similar, providing "justification for allowing patients’ preferences to be a major factor when choosing between these two medications."

Dr. Osterman of the department of medicine at the University of Pennsylvania, Philadelphia, and his colleagues conducted a retrospective cohort analysis of Medicare data on new users of the either adalimumab or infliximab between 2006 and 2010.

Participants had no history of using any anti–tumor necrosis factor (TNF) medications before the index prescription, as well as a diagnosis of Crohn’s in the 12 months prior.

Exclusion criteria included age greater than 85 years on the index anti-TNF prescription date; a coexisting diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis; or a diagnosis of ulcerative colitis on or immediately preceding the index date.

In total, the authors analyzed data on 1,445 infliximab patients and 865 adalimumab patients, more than 60% of whom were female and more than 90% of whom were white.

First, the authors assessed the persistence of each drug. They found that after 26 weeks of therapy, 49% of infliximab patients were still taking the drug, as were 47% of adalimumab users (adjusted odds ratio, 0.98; 95% confidence interval 0.81-1.19).

Similarly, by 1 year, the rates of persistence were 31% and 28% for infliximab and adalimumab, respectively (adjusted OR, 1.08; 95% CI, 0.86-1.37).

Next, the authors analyzed surgery-related outcomes. They found that although infliximab patients had a numerically lower incidence of surgery (including bowel resection, ostomy creation, or treatment of a perforation or abscess), the difference did not reach statistical significance (5.5 vs. 6.9 surgeries per 100 person-years, respectively; adjusted hazard ratio, 0.79; 95% CI, 0.60-1.05).

The final outcome assessed was the rate of hospitalizations attributed to Crohn’s disease. Here, too, Dr. Osterman found no significant difference between infliximab (11.8/100 patient-years) and adalimumab patients (15.4/100 patient-years) (adjusted HR, 0.88; 95% CI, 0.72-1.07).

The researchers did concede several limitations, including the fact that they did not compare adverse event rates in their analysis, although they stated that, "In general, the safety profiles of infliximab and adalimumab are believed to be similar with a few exceptions."

Dr. Osterman also wrote that the observational nature of the present analysis is by definition less robust than a head-to-head clinical trial; however, given the extreme cost of such studies, such potentially more definitive analyses "are unlikely to ever be undertaken."

Nevertheless, the current retrospective study should "allow patients, physicians, and insurers to develop rational treatment strategies and guidelines" in the treatment of CD.

Dr. Osterman and several of his coauthors disclosed financial relationships with pharmaceutical companies, including the makers of infliximab and adalimumab, Janssen Biotech and AbbVie, respectively. The researchers disclosed grant funding for this study from the Agency for Healthcare Research and Quality and the National Institutes of Health.

There is no significant difference between infliximab and adalimumab in Crohn’s disease, reported Dr. Mark T. Osterman and his colleagues in the May 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.010).

Indeed, in a study that they called "one of the first to directly compare the effectiveness of these two therapies for CD [Crohn’s disease]," the researchers calculated that rates of hospitalization and surgery while on these therapies were statistically similar, providing "justification for allowing patients’ preferences to be a major factor when choosing between these two medications."

Dr. Osterman of the department of medicine at the University of Pennsylvania, Philadelphia, and his colleagues conducted a retrospective cohort analysis of Medicare data on new users of the either adalimumab or infliximab between 2006 and 2010.

Participants had no history of using any anti–tumor necrosis factor (TNF) medications before the index prescription, as well as a diagnosis of Crohn’s in the 12 months prior.

Exclusion criteria included age greater than 85 years on the index anti-TNF prescription date; a coexisting diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis; or a diagnosis of ulcerative colitis on or immediately preceding the index date.

In total, the authors analyzed data on 1,445 infliximab patients and 865 adalimumab patients, more than 60% of whom were female and more than 90% of whom were white.

First, the authors assessed the persistence of each drug. They found that after 26 weeks of therapy, 49% of infliximab patients were still taking the drug, as were 47% of adalimumab users (adjusted odds ratio, 0.98; 95% confidence interval 0.81-1.19).

Similarly, by 1 year, the rates of persistence were 31% and 28% for infliximab and adalimumab, respectively (adjusted OR, 1.08; 95% CI, 0.86-1.37).

Next, the authors analyzed surgery-related outcomes. They found that although infliximab patients had a numerically lower incidence of surgery (including bowel resection, ostomy creation, or treatment of a perforation or abscess), the difference did not reach statistical significance (5.5 vs. 6.9 surgeries per 100 person-years, respectively; adjusted hazard ratio, 0.79; 95% CI, 0.60-1.05).

The final outcome assessed was the rate of hospitalizations attributed to Crohn’s disease. Here, too, Dr. Osterman found no significant difference between infliximab (11.8/100 patient-years) and adalimumab patients (15.4/100 patient-years) (adjusted HR, 0.88; 95% CI, 0.72-1.07).

The researchers did concede several limitations, including the fact that they did not compare adverse event rates in their analysis, although they stated that, "In general, the safety profiles of infliximab and adalimumab are believed to be similar with a few exceptions."

Dr. Osterman also wrote that the observational nature of the present analysis is by definition less robust than a head-to-head clinical trial; however, given the extreme cost of such studies, such potentially more definitive analyses "are unlikely to ever be undertaken."

Nevertheless, the current retrospective study should "allow patients, physicians, and insurers to develop rational treatment strategies and guidelines" in the treatment of CD.

Dr. Osterman and several of his coauthors disclosed financial relationships with pharmaceutical companies, including the makers of infliximab and adalimumab, Janssen Biotech and AbbVie, respectively. The researchers disclosed grant funding for this study from the Agency for Healthcare Research and Quality and the National Institutes of Health.

Clonidine was not better than placebo for fecal incontinence despite previous reports to the contrary.

The finding, reported in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.035), gives further weight to a 2010 Cochrane review, which concluded that there was "limited evidence to guide clinicians in the selection of drug therapies for fecal incontinence," wrote Dr. Adil E. Bharucha and his colleagues. Clonidine, a centrally acting adrenergic agent, is approved to treat high blood pressure and is sometimes used to treat attention-deficit/hyperactivity disorder, dysmenorrhea, and Tourette’s syndrome.

In a placebo-controlled, double-blind study of 44 women with fecal incontinence, Dr. Bharucha of the Mayo Clinic, in Rochester, Minn., randomized 22 subjects to 0.1 mg oral clonidine twice daily or placebo.

For inclusion in the study, all subjects had to have taken the Fecal Incontinence and Continence Assessment (FICA) and reported that they were "often" or "usually" incontinent because they had "great urgency and could not reach the toilet on time."

Patients with current or prior organic colonic or anorectal diseases, including rectal cancer, were excluded, as were patients with neurologic disorders including spinal cord injury and Parkinson’s disease.

Initially, all participants underwent 4 weeks without treatment, recording their bowel habits, to establish a baseline.

That was then followed by 4 weeks of treatment with either placebo or clonidine 0.1 mg twice daily.

Patients also underwent anorectal sensorimotor function assessment at the conclusion of both the baseline period and the 4-week study period.

Dr. Bharucha found that both placebo and clonidine patients experienced an overall reduction in the number of days with at least one episode of fecal incontinence during the treatment period.

Indeed, placebo patients reported a decrease from 16 days with at least one incontinence episode during the baseline recording phase to 11 days during treatment, while clonidine patients reported a drop from 13 days during baseline to 8 days while on the drug, a difference that was not significant.

Both groups also reported a similar drop in the mean weekly FICA symptom severity score, from 9.1 to 7.6 for placebo patients and from 8.1 to 6.5 in the treatment group.

Finally, a total of eight placebo patients and seven clonidine patients reported a 50% or greater reduction in the number of days with fecal incontinence.

Looking at anorectal function, Dr. Bharucha found that the drug did not significantly affect anal resting or squeeze pressures, rectal capacity, compliance, or sensation assessed by sensory thresholds, or visual analog scale scores during rectal distention, compared with baseline measurements.

Further, "Correlations of changes during treatment in symptoms (that is, number of days and episodes of fecal incontinence, rectal urgency, and stool consistency) separately with rectal compliance and capacity and sensory thresholds were not significant," they added.

Meanwhile, looking at adverse effects, the overall incidence was significantly higher among clonidine patients, who especially reported dry mouth.

"In our prior uncontrolled study (Aliment. Pharmacol. Ther. 2010;32:681-8) with a similar dose (0.2 mg/d) of transdermal clonidine, overall effects on anorectal functions were not significant," the authors wrote.

However, that study did find that symptom relief was correlated with effects on rectal compliance and sensation in a dose-dependent manner, leading the authors to speculate that the failure of the current study might be due to inadequate dosing.

The authors stated that they had no conflicts of interest to disclose. They added that the study was supported by the National Institutes of Health.

Clonidine was not better than placebo for fecal incontinence despite previous reports to the contrary.

The finding, reported in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.035), gives further weight to a 2010 Cochrane review, which concluded that there was "limited evidence to guide clinicians in the selection of drug therapies for fecal incontinence," wrote Dr. Adil E. Bharucha and his colleagues. Clonidine, a centrally acting adrenergic agent, is approved to treat high blood pressure and is sometimes used to treat attention-deficit/hyperactivity disorder, dysmenorrhea, and Tourette’s syndrome.

In a placebo-controlled, double-blind study of 44 women with fecal incontinence, Dr. Bharucha of the Mayo Clinic, in Rochester, Minn., randomized 22 subjects to 0.1 mg oral clonidine twice daily or placebo.

For inclusion in the study, all subjects had to have taken the Fecal Incontinence and Continence Assessment (FICA) and reported that they were "often" or "usually" incontinent because they had "great urgency and could not reach the toilet on time."

Patients with current or prior organic colonic or anorectal diseases, including rectal cancer, were excluded, as were patients with neurologic disorders including spinal cord injury and Parkinson’s disease.

Initially, all participants underwent 4 weeks without treatment, recording their bowel habits, to establish a baseline.

That was then followed by 4 weeks of treatment with either placebo or clonidine 0.1 mg twice daily.

Patients also underwent anorectal sensorimotor function assessment at the conclusion of both the baseline period and the 4-week study period.

Dr. Bharucha found that both placebo and clonidine patients experienced an overall reduction in the number of days with at least one episode of fecal incontinence during the treatment period.

Indeed, placebo patients reported a decrease from 16 days with at least one incontinence episode during the baseline recording phase to 11 days during treatment, while clonidine patients reported a drop from 13 days during baseline to 8 days while on the drug, a difference that was not significant.

Both groups also reported a similar drop in the mean weekly FICA symptom severity score, from 9.1 to 7.6 for placebo patients and from 8.1 to 6.5 in the treatment group.

Finally, a total of eight placebo patients and seven clonidine patients reported a 50% or greater reduction in the number of days with fecal incontinence.

Looking at anorectal function, Dr. Bharucha found that the drug did not significantly affect anal resting or squeeze pressures, rectal capacity, compliance, or sensation assessed by sensory thresholds, or visual analog scale scores during rectal distention, compared with baseline measurements.

Further, "Correlations of changes during treatment in symptoms (that is, number of days and episodes of fecal incontinence, rectal urgency, and stool consistency) separately with rectal compliance and capacity and sensory thresholds were not significant," they added.

Meanwhile, looking at adverse effects, the overall incidence was significantly higher among clonidine patients, who especially reported dry mouth.

"In our prior uncontrolled study (Aliment. Pharmacol. Ther. 2010;32:681-8) with a similar dose (0.2 mg/d) of transdermal clonidine, overall effects on anorectal functions were not significant," the authors wrote.

However, that study did find that symptom relief was correlated with effects on rectal compliance and sensation in a dose-dependent manner, leading the authors to speculate that the failure of the current study might be due to inadequate dosing.

The authors stated that they had no conflicts of interest to disclose. They added that the study was supported by the National Institutes of Health.

Clonidine was not better than placebo for fecal incontinence despite previous reports to the contrary.

The finding, reported in the May issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.06.035), gives further weight to a 2010 Cochrane review, which concluded that there was "limited evidence to guide clinicians in the selection of drug therapies for fecal incontinence," wrote Dr. Adil E. Bharucha and his colleagues. Clonidine, a centrally acting adrenergic agent, is approved to treat high blood pressure and is sometimes used to treat attention-deficit/hyperactivity disorder, dysmenorrhea, and Tourette’s syndrome.

In a placebo-controlled, double-blind study of 44 women with fecal incontinence, Dr. Bharucha of the Mayo Clinic, in Rochester, Minn., randomized 22 subjects to 0.1 mg oral clonidine twice daily or placebo.

For inclusion in the study, all subjects had to have taken the Fecal Incontinence and Continence Assessment (FICA) and reported that they were "often" or "usually" incontinent because they had "great urgency and could not reach the toilet on time."

Patients with current or prior organic colonic or anorectal diseases, including rectal cancer, were excluded, as were patients with neurologic disorders including spinal cord injury and Parkinson’s disease.

Initially, all participants underwent 4 weeks without treatment, recording their bowel habits, to establish a baseline.

That was then followed by 4 weeks of treatment with either placebo or clonidine 0.1 mg twice daily.

Patients also underwent anorectal sensorimotor function assessment at the conclusion of both the baseline period and the 4-week study period.

Dr. Bharucha found that both placebo and clonidine patients experienced an overall reduction in the number of days with at least one episode of fecal incontinence during the treatment period.

Indeed, placebo patients reported a decrease from 16 days with at least one incontinence episode during the baseline recording phase to 11 days during treatment, while clonidine patients reported a drop from 13 days during baseline to 8 days while on the drug, a difference that was not significant.

Both groups also reported a similar drop in the mean weekly FICA symptom severity score, from 9.1 to 7.6 for placebo patients and from 8.1 to 6.5 in the treatment group.

Finally, a total of eight placebo patients and seven clonidine patients reported a 50% or greater reduction in the number of days with fecal incontinence.

Looking at anorectal function, Dr. Bharucha found that the drug did not significantly affect anal resting or squeeze pressures, rectal capacity, compliance, or sensation assessed by sensory thresholds, or visual analog scale scores during rectal distention, compared with baseline measurements.

Further, "Correlations of changes during treatment in symptoms (that is, number of days and episodes of fecal incontinence, rectal urgency, and stool consistency) separately with rectal compliance and capacity and sensory thresholds were not significant," they added.

Meanwhile, looking at adverse effects, the overall incidence was significantly higher among clonidine patients, who especially reported dry mouth.

"In our prior uncontrolled study (Aliment. Pharmacol. Ther. 2010;32:681-8) with a similar dose (0.2 mg/d) of transdermal clonidine, overall effects on anorectal functions were not significant," the authors wrote.

However, that study did find that symptom relief was correlated with effects on rectal compliance and sensation in a dose-dependent manner, leading the authors to speculate that the failure of the current study might be due to inadequate dosing.

The authors stated that they had no conflicts of interest to disclose. They added that the study was supported by the National Institutes of Health.

As many as 6% of colorectal cancers are discovered between 6 and 60 months of colonoscopy – usually in the proximal colon, and usually in patients whose index colonoscopy revealed adenomas, according to Dr. N. Jewel Samadder and colleagues.

While the investigators speculated that "differences in the biology of interval versus detected cancers" might be to blame, "suboptimal management of precancerous lesions (such as incomplete polypectomy) likely also plays a role," they wrote. The report is in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.013).

Dr. Samadder of the University of Utah, Salt Lake City, and colleagues looked at data from 126,851 patients who underwent colonoscopies between 1995 and 2009. The two centers in this analysis serve more than 85% of the state’s population. Patients with a history of colorectal cancer before 1995 were excluded, the researchers wrote.

Overall, 2,659 patients were diagnosed with colorectal cancer during the study period, mostly at initial, index colonoscopy – the investigators referred to these as "detected" cancers.

However, 159 of these cases (6%) were diagnosed between 6 and 60 months of the index colonoscopy, and were therefore classified as "interval" cancers.

Interval cancer patients had a mean age of 67 years at index colonoscopy (range, 34-92 years), identical to that of detected cancer patients; both cohorts were split evenly between men and women.

The authors found that compared with detected cancers, the interval cancers were much more commonly discovered in the proximal colon – indeed, proximal cancers made up 55% of the cohort, with the remainder split evenly between the distal colon and the recto-rectosigmoid junction.

In comparison, only 39% of detected cancers were found in the proximal colon (P less than .001).

Patients with an adenoma or villous adenoma discovered at index colonoscopy were significantly more likely to develop interval cancer, compared with patients whose cancers were detected earlier (for adenoma, the odds ratio was 2.96, 95% confidence interval = 2.0-4.28; for villous adenoma, OR = 2.04, 95% CI = 1.34-3.11).

A family history also conferred an odds ratio of 2.27 for interval cancer, compared with detected cancers (95% CI, 1.24-4.16).

Finally, interval cancers were more likely to be associated with polypectomy or a biopsy at index colonoscopy (84.3%), compared with patients who did not undergo these procedures (51.8%).

According to the authors, "the association of proximal tumor location, earlier stage at diagnosis, and survival advantage compared with detected colorectal cancers suggests that tumor biology may play an important role in the pathogenesis of these lesions."

On the other hand, a 2010 study showing a much higher interval cancer rate suggests that inexpert polypectomy may be at least partially to blame, since most colonoscopies in that study were performed by nongastroenterologists (Am. J. Gastroenterol. 2010;105:2588-96).

The National Cancer Institute, the American Society for Gastrointestinal Endoscopy, the American College of Gastroenterology, the Huntsman Cancer Foundation, the Utah Department of Health, and the University of Utah funded the study. Dr Samadder and a coauthor disclosed consulting for Cook Medical, Covidien, and Myriad Genetics.

As many as 6% of colorectal cancers are discovered between 6 and 60 months of colonoscopy – usually in the proximal colon, and usually in patients whose index colonoscopy revealed adenomas, according to Dr. N. Jewel Samadder and colleagues.

While the investigators speculated that "differences in the biology of interval versus detected cancers" might be to blame, "suboptimal management of precancerous lesions (such as incomplete polypectomy) likely also plays a role," they wrote. The report is in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.013).

Dr. Samadder of the University of Utah, Salt Lake City, and colleagues looked at data from 126,851 patients who underwent colonoscopies between 1995 and 2009. The two centers in this analysis serve more than 85% of the state’s population. Patients with a history of colorectal cancer before 1995 were excluded, the researchers wrote.

Overall, 2,659 patients were diagnosed with colorectal cancer during the study period, mostly at initial, index colonoscopy – the investigators referred to these as "detected" cancers.

However, 159 of these cases (6%) were diagnosed between 6 and 60 months of the index colonoscopy, and were therefore classified as "interval" cancers.

Interval cancer patients had a mean age of 67 years at index colonoscopy (range, 34-92 years), identical to that of detected cancer patients; both cohorts were split evenly between men and women.

The authors found that compared with detected cancers, the interval cancers were much more commonly discovered in the proximal colon – indeed, proximal cancers made up 55% of the cohort, with the remainder split evenly between the distal colon and the recto-rectosigmoid junction.

In comparison, only 39% of detected cancers were found in the proximal colon (P less than .001).

Patients with an adenoma or villous adenoma discovered at index colonoscopy were significantly more likely to develop interval cancer, compared with patients whose cancers were detected earlier (for adenoma, the odds ratio was 2.96, 95% confidence interval = 2.0-4.28; for villous adenoma, OR = 2.04, 95% CI = 1.34-3.11).

A family history also conferred an odds ratio of 2.27 for interval cancer, compared with detected cancers (95% CI, 1.24-4.16).

Finally, interval cancers were more likely to be associated with polypectomy or a biopsy at index colonoscopy (84.3%), compared with patients who did not undergo these procedures (51.8%).

According to the authors, "the association of proximal tumor location, earlier stage at diagnosis, and survival advantage compared with detected colorectal cancers suggests that tumor biology may play an important role in the pathogenesis of these lesions."

On the other hand, a 2010 study showing a much higher interval cancer rate suggests that inexpert polypectomy may be at least partially to blame, since most colonoscopies in that study were performed by nongastroenterologists (Am. J. Gastroenterol. 2010;105:2588-96).

The National Cancer Institute, the American Society for Gastrointestinal Endoscopy, the American College of Gastroenterology, the Huntsman Cancer Foundation, the Utah Department of Health, and the University of Utah funded the study. Dr Samadder and a coauthor disclosed consulting for Cook Medical, Covidien, and Myriad Genetics.

As many as 6% of colorectal cancers are discovered between 6 and 60 months of colonoscopy – usually in the proximal colon, and usually in patients whose index colonoscopy revealed adenomas, according to Dr. N. Jewel Samadder and colleagues.

While the investigators speculated that "differences in the biology of interval versus detected cancers" might be to blame, "suboptimal management of precancerous lesions (such as incomplete polypectomy) likely also plays a role," they wrote. The report is in the April issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.013).

Dr. Samadder of the University of Utah, Salt Lake City, and colleagues looked at data from 126,851 patients who underwent colonoscopies between 1995 and 2009. The two centers in this analysis serve more than 85% of the state’s population. Patients with a history of colorectal cancer before 1995 were excluded, the researchers wrote.

Overall, 2,659 patients were diagnosed with colorectal cancer during the study period, mostly at initial, index colonoscopy – the investigators referred to these as "detected" cancers.

However, 159 of these cases (6%) were diagnosed between 6 and 60 months of the index colonoscopy, and were therefore classified as "interval" cancers.

Interval cancer patients had a mean age of 67 years at index colonoscopy (range, 34-92 years), identical to that of detected cancer patients; both cohorts were split evenly between men and women.

The authors found that compared with detected cancers, the interval cancers were much more commonly discovered in the proximal colon – indeed, proximal cancers made up 55% of the cohort, with the remainder split evenly between the distal colon and the recto-rectosigmoid junction.

In comparison, only 39% of detected cancers were found in the proximal colon (P less than .001).

Patients with an adenoma or villous adenoma discovered at index colonoscopy were significantly more likely to develop interval cancer, compared with patients whose cancers were detected earlier (for adenoma, the odds ratio was 2.96, 95% confidence interval = 2.0-4.28; for villous adenoma, OR = 2.04, 95% CI = 1.34-3.11).

A family history also conferred an odds ratio of 2.27 for interval cancer, compared with detected cancers (95% CI, 1.24-4.16).

Finally, interval cancers were more likely to be associated with polypectomy or a biopsy at index colonoscopy (84.3%), compared with patients who did not undergo these procedures (51.8%).

According to the authors, "the association of proximal tumor location, earlier stage at diagnosis, and survival advantage compared with detected colorectal cancers suggests that tumor biology may play an important role in the pathogenesis of these lesions."

On the other hand, a 2010 study showing a much higher interval cancer rate suggests that inexpert polypectomy may be at least partially to blame, since most colonoscopies in that study were performed by nongastroenterologists (Am. J. Gastroenterol. 2010;105:2588-96).

The National Cancer Institute, the American Society for Gastrointestinal Endoscopy, the American College of Gastroenterology, the Huntsman Cancer Foundation, the Utah Department of Health, and the University of Utah funded the study. Dr Samadder and a coauthor disclosed consulting for Cook Medical, Covidien, and Myriad Genetics.

Linaclotide is safe and effective, even in severe cases of irritable bowel syndrome with constipation, according to a post-hoc analysis of phase III trial data.

Indeed, more acute patients "responded ... just as well as, if not better than, the intent-to-treat population, which included patients with milder abdominal symptoms," wrote Dr. Satish S. C. Rao and colleagues in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1053/j.gastro.2014.01.0130).

According to Dr. Rao of Georgia Regents University, Augusta, although the guanylate cyclase-C agonist is already Food and Drug Administration approved for irritable bowel syndrome–constipation (IBS-C) subtype in 2012, it has not been explicitly tested in patients with more severe disease.

In the current study, Dr. Rao and his fellow investigators looked specifically at several symptoms common to this population: pain, cramping, bloating, fullness, and discomfort.

Patients who ranked at least one of these as being greater than or equal to 7 at baseline were scored as severe, where 0 represents no symptoms and 10 represents the worst possible symptoms.

Overall, out of a total intent-to-treat population of 1,602 patients, 376 reported severe pain, 507 reported severe discomfort, 702 reported severe bloating, 708 reported severe fullness, and 359 reported severe cramping.

Given the overlap between the pain/cramping and bloating/fullness cohorts, the investigators organized the severe IBS group into four subgroups: patients reporting severe pain as their primary complaint (including cramping), severe bloating (including fullness), severe discomfort, and those patients who reported severe symptoms in all three realms.

Demographics were similar between each subgroup and in the overall study population, "although the subpopulations tended to be younger, more female, and more non-white than the intent-to-treat population," the investigators wrote.

Patients were randomized to receive placebo or linaclotide 290 mcg once daily; primary endpoints for this study were assessed at 12 weeks.

The investigators found that, among all severe IBS patients in all subgroups, the mean changes from baseline were significantly greater for linaclotide-treated patients compared with placebo patients for pain, discomfort, bloating, fullness, and cramping (P less than .0001 for all).

Looking at the whole severe IBS cohort, the authors found that 59%-61% of linaclotide patients reported adequate relief of IBS symptoms at week 12, compared with 28%-32% of placebo patients (P less than .0001).

Of those with severe IBS, 70%-77% of linaclotide-treated patients reported being "moderately, quite, or very satisfied" with treatment at week 12, but only 41%-43% of placebo-treated patients said the same (P less than .0001).

Finally, looking specifically at severe versus more mild IBS cases, the investigators found that, overall, the severe IBS cohort reported significantly greater improvements with the drug, compared with their less severe, drug-treated counterparts in the intent-to-treat population.

The most common side effect – diarrhea – occurred in almost one-fifth of linaclotide-treated patients with severe IBS, versus an occurrence rate of 1.6%-2.1% among placebo-treated patients.

In addition to the finding that linaclotide is effective in severe IBS-C, the investigators also wrote that their finding of severe bloating and fullness in many of these patients should give clinicians pause.

"Pain or discomfort is considered a clinical hallmark of IBS," they wrote, but "the presence of bloating and fullness in patients with IBS-C may warrant greater attention in clinical practice as well as in clinical trial design."

Several of the investigators are employees of Ironwood Pharmaceuticals, maker of linaclotide. Additionally, Dr. Rao and another investigator disclosed financial relationships with the pharmaceutical company, which also funded the study.

Linaclotide is safe and effective, even in severe cases of irritable bowel syndrome with constipation, according to a post-hoc analysis of phase III trial data.

Indeed, more acute patients "responded ... just as well as, if not better than, the intent-to-treat population, which included patients with milder abdominal symptoms," wrote Dr. Satish S. C. Rao and colleagues in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1053/j.gastro.2014.01.0130).

According to Dr. Rao of Georgia Regents University, Augusta, although the guanylate cyclase-C agonist is already Food and Drug Administration approved for irritable bowel syndrome–constipation (IBS-C) subtype in 2012, it has not been explicitly tested in patients with more severe disease.

In the current study, Dr. Rao and his fellow investigators looked specifically at several symptoms common to this population: pain, cramping, bloating, fullness, and discomfort.

Patients who ranked at least one of these as being greater than or equal to 7 at baseline were scored as severe, where 0 represents no symptoms and 10 represents the worst possible symptoms.

Overall, out of a total intent-to-treat population of 1,602 patients, 376 reported severe pain, 507 reported severe discomfort, 702 reported severe bloating, 708 reported severe fullness, and 359 reported severe cramping.

Given the overlap between the pain/cramping and bloating/fullness cohorts, the investigators organized the severe IBS group into four subgroups: patients reporting severe pain as their primary complaint (including cramping), severe bloating (including fullness), severe discomfort, and those patients who reported severe symptoms in all three realms.

Demographics were similar between each subgroup and in the overall study population, "although the subpopulations tended to be younger, more female, and more non-white than the intent-to-treat population," the investigators wrote.

Patients were randomized to receive placebo or linaclotide 290 mcg once daily; primary endpoints for this study were assessed at 12 weeks.

The investigators found that, among all severe IBS patients in all subgroups, the mean changes from baseline were significantly greater for linaclotide-treated patients compared with placebo patients for pain, discomfort, bloating, fullness, and cramping (P less than .0001 for all).

Looking at the whole severe IBS cohort, the authors found that 59%-61% of linaclotide patients reported adequate relief of IBS symptoms at week 12, compared with 28%-32% of placebo patients (P less than .0001).

Of those with severe IBS, 70%-77% of linaclotide-treated patients reported being "moderately, quite, or very satisfied" with treatment at week 12, but only 41%-43% of placebo-treated patients said the same (P less than .0001).

Finally, looking specifically at severe versus more mild IBS cases, the investigators found that, overall, the severe IBS cohort reported significantly greater improvements with the drug, compared with their less severe, drug-treated counterparts in the intent-to-treat population.

The most common side effect – diarrhea – occurred in almost one-fifth of linaclotide-treated patients with severe IBS, versus an occurrence rate of 1.6%-2.1% among placebo-treated patients.

In addition to the finding that linaclotide is effective in severe IBS-C, the investigators also wrote that their finding of severe bloating and fullness in many of these patients should give clinicians pause.

"Pain or discomfort is considered a clinical hallmark of IBS," they wrote, but "the presence of bloating and fullness in patients with IBS-C may warrant greater attention in clinical practice as well as in clinical trial design."

Several of the investigators are employees of Ironwood Pharmaceuticals, maker of linaclotide. Additionally, Dr. Rao and another investigator disclosed financial relationships with the pharmaceutical company, which also funded the study.

Linaclotide is safe and effective, even in severe cases of irritable bowel syndrome with constipation, according to a post-hoc analysis of phase III trial data.

Indeed, more acute patients "responded ... just as well as, if not better than, the intent-to-treat population, which included patients with milder abdominal symptoms," wrote Dr. Satish S. C. Rao and colleagues in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1053/j.gastro.2014.01.0130).

According to Dr. Rao of Georgia Regents University, Augusta, although the guanylate cyclase-C agonist is already Food and Drug Administration approved for irritable bowel syndrome–constipation (IBS-C) subtype in 2012, it has not been explicitly tested in patients with more severe disease.

In the current study, Dr. Rao and his fellow investigators looked specifically at several symptoms common to this population: pain, cramping, bloating, fullness, and discomfort.

Patients who ranked at least one of these as being greater than or equal to 7 at baseline were scored as severe, where 0 represents no symptoms and 10 represents the worst possible symptoms.

Overall, out of a total intent-to-treat population of 1,602 patients, 376 reported severe pain, 507 reported severe discomfort, 702 reported severe bloating, 708 reported severe fullness, and 359 reported severe cramping.

Given the overlap between the pain/cramping and bloating/fullness cohorts, the investigators organized the severe IBS group into four subgroups: patients reporting severe pain as their primary complaint (including cramping), severe bloating (including fullness), severe discomfort, and those patients who reported severe symptoms in all three realms.

Demographics were similar between each subgroup and in the overall study population, "although the subpopulations tended to be younger, more female, and more non-white than the intent-to-treat population," the investigators wrote.

Patients were randomized to receive placebo or linaclotide 290 mcg once daily; primary endpoints for this study were assessed at 12 weeks.

The investigators found that, among all severe IBS patients in all subgroups, the mean changes from baseline were significantly greater for linaclotide-treated patients compared with placebo patients for pain, discomfort, bloating, fullness, and cramping (P less than .0001 for all).

Looking at the whole severe IBS cohort, the authors found that 59%-61% of linaclotide patients reported adequate relief of IBS symptoms at week 12, compared with 28%-32% of placebo patients (P less than .0001).

Of those with severe IBS, 70%-77% of linaclotide-treated patients reported being "moderately, quite, or very satisfied" with treatment at week 12, but only 41%-43% of placebo-treated patients said the same (P less than .0001).

Finally, looking specifically at severe versus more mild IBS cases, the investigators found that, overall, the severe IBS cohort reported significantly greater improvements with the drug, compared with their less severe, drug-treated counterparts in the intent-to-treat population.

The most common side effect – diarrhea – occurred in almost one-fifth of linaclotide-treated patients with severe IBS, versus an occurrence rate of 1.6%-2.1% among placebo-treated patients.

In addition to the finding that linaclotide is effective in severe IBS-C, the investigators also wrote that their finding of severe bloating and fullness in many of these patients should give clinicians pause.

"Pain or discomfort is considered a clinical hallmark of IBS," they wrote, but "the presence of bloating and fullness in patients with IBS-C may warrant greater attention in clinical practice as well as in clinical trial design."

Several of the investigators are employees of Ironwood Pharmaceuticals, maker of linaclotide. Additionally, Dr. Rao and another investigator disclosed financial relationships with the pharmaceutical company, which also funded the study.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Wilson disease patients without cirrhosis at diagnosis generally have good long-term prognoses, but the presence of cirrhosis on diagnosis of this rare condition necessitates transplant in up to 13% of cases and is the strongest predictor of mortality, according to findings from a retrospective analysis.

The report appears in the April issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.09.025).

The finding "[reinforces] the histologic assessment of liver fibrosis to be performed in all patients suspected to have Wilson disease, regardless of whether they present with neurologic or hepatic symptoms," wrote Dr. Sandra Beinhardt of the Medical University of Vienna. She and her colleagues looked at 229 patients (48% of whom were male) who were diagnosed with Wilson disease in Austria between 1961 and 2013.

Courtesy: American Gastroenterological Association

"In patients with evaluable symptoms at diagnosis as well as reliable information on the time of the onset of symptoms" (90% of the total cohort), diagnosis of Wilson disease was established by 3 years after symptom onset in 75% of patients, the researchers noted.

Overall, 140 patients presented with predominantly hepatic symptoms; 61 with neurologic symptoms; and 23 were diagnosed by screening before any symptoms were noted.

In the remaining 5 patients, the presenting symptoms could not be determined.

Looking at long-term prognosis, the authors found that patients presenting with neurologic symptoms had a significantly longer mean follow-up period than did patients with hepatic symptoms at diagnosis (21.1 years versus 11.8 years, respectively; P less than .001).

"Nevertheless, 34% of patients predominantly presenting with neurologic symptoms at diagnosis already had developed cirrhosis," they wrote.

Overall, 30 patients received liver transplants between 1986 and 2013, because of fulminant hepatic failure in 11 patients, neurologic worsening in 1 patient, and decompensated liver cirrhosis in the remaining 18.

As for mortality, among the 17 patients who died during the study period, the researchers reported that most of the deaths could be attributed to Wilson disease. Seven patients died of liver failure, four died of complications resulting from the liver transplant.

One patient died of suicide, reportedly following severe depression stemming from the Wilson disease diagnosis.

That translated to an overall 20-year cumulative survival rate of 0.920 by Kaplan-Meier analysis. However, that figure dipped to 0.84 for patients with cirrhosis on diagnosis (compared with 0.97 for all others, P = .008).

Indeed, "By univariate logistic regression analysis, liver cirrhosis at diagnosis was the best predictor for the need of liver transplant (odds ratio, 0.07; 95% confidence interval, 0.016-0.307; P less than .001) as well as for death (OR, 6.8; 95% CI, 1.5-31.03; P = .013)," wrote the authors.

The cohort they studied represents nearly all cases of Wilson disease that could have been expected to occur in Austria during the study period, given an incidence of 30 cases per million people in that nation of 8 million inhabitants, they wrote.

And while the retrospective nature of their study limits analysis, because of the rarity of Wilson disease, "prospective studies with reasonably large sample sizes are almost impossible to perform," they noted.

Nevertheless, "the long-term prognosis in patients with Wilson disease surviving more than 10 years after diagnosis and treatment initiation is excellent," especially if the diagnosis is early, wrote Dr. Beinhardt and her colleagues.

The authors stated that they had no conflicts of interest.

Patients with chronic pancreatitis have a life expectancy that is roughly 8 years shorter than that of the general population.

Indeed, the "beyond a doubt" finding of a mortality rate up to five times higher in this cohort illustrates "the great impact the presence of this disease has on the accompanying complications," wrote Dr. Ulrich Christian Bang. The report appears in the April issue of Gastroenterology (doi:10.1053/j.gastro.2013.12.033).

Dr. Bang, of Copenhagen University Hospital Hvidovre, looked at 11,972 patients (33.5% were women) with a primary diagnosis of chronic pancreatitis between 1995 and 2010, and 119,720 age- and sex-matched controls. Median age was 54 years.

Alcoholic pancreatitis was present in just over half (52.7%) of chronic pancreatitis cases.

The primary endpoint was mortality, but the authors also assessed all inpatient and outpatient diagnoses accumulated during the study period.

Overall, the age at death was significantly lower for pancreatitis patients compared with controls (63.7 years versus 72.1 years for controls; P less than .0001).

Indeed, per 1,000 patient-years, mortality rates were 77.4 among cases (95% confidence interval, 75.4-79.5) and 16.9 among controls (95% CI, 16.7-17.2) translating to an adjusted hazard ratio of 5.0 (95% CI, 4.8-5.2).

Although mortality rates predictably increased with age for both cases and controls, "the adjusted relative risks of death were significantly higher for the younger chronic pancreatitis cases than among older patients (P less than .0001)," wrote Dr. Bang and colleagues.

Fatal diseases of the alimentary tract were the most common cause of death in cases (10.6%), followed closely by cancer (10.2%) and circulatory system diseases (5.5%).

In comparison, 0.4% of controls had mortality associated with gastrointestinal disease (adjusted HR for cases, 26.1); 3.3% developed a fatal malignancy (HR for cases, 1.4), and 3.2% had mortality caused by diseases of the circulatory system (HR for cases, 1.9).

Looking generally at all comorbidities, the researchers found that the proportion of patients with any morbidity excluding chronic pancreatitis was significantly higher among cases (78%) compared with controls (38%) (P less than .0001). That included the presence of cerebrovascular disease (adjusted HR for cases, 1.3; 94% CI, 1.2-1.4), chronic pulmonary disease (adjusted HR for cases, 1.9; 95% CI, 1.8-2.1), and chronic kidney disease (adjusted HR for cases, 1.7; 95% CI, 1.5-1.9) as well as diabetes and ulcer disease.

Only the incidence of myocardial infarction was not elevated among cases, compared with controls; in fact, after adjustment for socioeconomic status, chronic pulmonary disease, and diabetes, cases had a trend toward a slightly lower risk, at 0.9 (95% CI, 0.8-1.0).

According to the authors, one of the weaknesses of their study was that they were unable to control for lifestyle factors such as smoking and drinking, which may especially contribute to the higher mortality among younger patients with chronic pancreatitis.

"Older age groups may be able to compensate for more advanced chronic pancreatitis accompanied by fat malabsorption and secondary diabetes by adopting a healthier lifestyle including tobacco and alcohol cessation as well as better compliance with routine follow-up evaluation and medication," they added.

Copenhagen University Hospital Hvidovre funded the study. The authors stated that they had no conflicts of interest.

Patients with chronic pancreatitis have a life expectancy that is roughly 8 years shorter than that of the general population.

Indeed, the "beyond a doubt" finding of a mortality rate up to five times higher in this cohort illustrates "the great impact the presence of this disease has on the accompanying complications," wrote Dr. Ulrich Christian Bang. The report appears in the April issue of Gastroenterology (doi:10.1053/j.gastro.2013.12.033).

Dr. Bang, of Copenhagen University Hospital Hvidovre, looked at 11,972 patients (33.5% were women) with a primary diagnosis of chronic pancreatitis between 1995 and 2010, and 119,720 age- and sex-matched controls. Median age was 54 years.

Alcoholic pancreatitis was present in just over half (52.7%) of chronic pancreatitis cases.

The primary endpoint was mortality, but the authors also assessed all inpatient and outpatient diagnoses accumulated during the study period.

Overall, the age at death was significantly lower for pancreatitis patients compared with controls (63.7 years versus 72.1 years for controls; P less than .0001).

Indeed, per 1,000 patient-years, mortality rates were 77.4 among cases (95% confidence interval, 75.4-79.5) and 16.9 among controls (95% CI, 16.7-17.2) translating to an adjusted hazard ratio of 5.0 (95% CI, 4.8-5.2).

Although mortality rates predictably increased with age for both cases and controls, "the adjusted relative risks of death were significantly higher for the younger chronic pancreatitis cases than among older patients (P less than .0001)," wrote Dr. Bang and colleagues.

Fatal diseases of the alimentary tract were the most common cause of death in cases (10.6%), followed closely by cancer (10.2%) and circulatory system diseases (5.5%).

In comparison, 0.4% of controls had mortality associated with gastrointestinal disease (adjusted HR for cases, 26.1); 3.3% developed a fatal malignancy (HR for cases, 1.4), and 3.2% had mortality caused by diseases of the circulatory system (HR for cases, 1.9).

Looking generally at all comorbidities, the researchers found that the proportion of patients with any morbidity excluding chronic pancreatitis was significantly higher among cases (78%) compared with controls (38%) (P less than .0001). That included the presence of cerebrovascular disease (adjusted HR for cases, 1.3; 94% CI, 1.2-1.4), chronic pulmonary disease (adjusted HR for cases, 1.9; 95% CI, 1.8-2.1), and chronic kidney disease (adjusted HR for cases, 1.7; 95% CI, 1.5-1.9) as well as diabetes and ulcer disease.

Only the incidence of myocardial infarction was not elevated among cases, compared with controls; in fact, after adjustment for socioeconomic status, chronic pulmonary disease, and diabetes, cases had a trend toward a slightly lower risk, at 0.9 (95% CI, 0.8-1.0).

According to the authors, one of the weaknesses of their study was that they were unable to control for lifestyle factors such as smoking and drinking, which may especially contribute to the higher mortality among younger patients with chronic pancreatitis.

"Older age groups may be able to compensate for more advanced chronic pancreatitis accompanied by fat malabsorption and secondary diabetes by adopting a healthier lifestyle including tobacco and alcohol cessation as well as better compliance with routine follow-up evaluation and medication," they added.

Copenhagen University Hospital Hvidovre funded the study. The authors stated that they had no conflicts of interest.

Patients with chronic pancreatitis have a life expectancy that is roughly 8 years shorter than that of the general population.

Indeed, the "beyond a doubt" finding of a mortality rate up to five times higher in this cohort illustrates "the great impact the presence of this disease has on the accompanying complications," wrote Dr. Ulrich Christian Bang. The report appears in the April issue of Gastroenterology (doi:10.1053/j.gastro.2013.12.033).

Dr. Bang, of Copenhagen University Hospital Hvidovre, looked at 11,972 patients (33.5% were women) with a primary diagnosis of chronic pancreatitis between 1995 and 2010, and 119,720 age- and sex-matched controls. Median age was 54 years.

Alcoholic pancreatitis was present in just over half (52.7%) of chronic pancreatitis cases.

The primary endpoint was mortality, but the authors also assessed all inpatient and outpatient diagnoses accumulated during the study period.

Overall, the age at death was significantly lower for pancreatitis patients compared with controls (63.7 years versus 72.1 years for controls; P less than .0001).

Indeed, per 1,000 patient-years, mortality rates were 77.4 among cases (95% confidence interval, 75.4-79.5) and 16.9 among controls (95% CI, 16.7-17.2) translating to an adjusted hazard ratio of 5.0 (95% CI, 4.8-5.2).

Although mortality rates predictably increased with age for both cases and controls, "the adjusted relative risks of death were significantly higher for the younger chronic pancreatitis cases than among older patients (P less than .0001)," wrote Dr. Bang and colleagues.

Fatal diseases of the alimentary tract were the most common cause of death in cases (10.6%), followed closely by cancer (10.2%) and circulatory system diseases (5.5%).

In comparison, 0.4% of controls had mortality associated with gastrointestinal disease (adjusted HR for cases, 26.1); 3.3% developed a fatal malignancy (HR for cases, 1.4), and 3.2% had mortality caused by diseases of the circulatory system (HR for cases, 1.9).

Looking generally at all comorbidities, the researchers found that the proportion of patients with any morbidity excluding chronic pancreatitis was significantly higher among cases (78%) compared with controls (38%) (P less than .0001). That included the presence of cerebrovascular disease (adjusted HR for cases, 1.3; 94% CI, 1.2-1.4), chronic pulmonary disease (adjusted HR for cases, 1.9; 95% CI, 1.8-2.1), and chronic kidney disease (adjusted HR for cases, 1.7; 95% CI, 1.5-1.9) as well as diabetes and ulcer disease.

Only the incidence of myocardial infarction was not elevated among cases, compared with controls; in fact, after adjustment for socioeconomic status, chronic pulmonary disease, and diabetes, cases had a trend toward a slightly lower risk, at 0.9 (95% CI, 0.8-1.0).

According to the authors, one of the weaknesses of their study was that they were unable to control for lifestyle factors such as smoking and drinking, which may especially contribute to the higher mortality among younger patients with chronic pancreatitis.

"Older age groups may be able to compensate for more advanced chronic pancreatitis accompanied by fat malabsorption and secondary diabetes by adopting a healthier lifestyle including tobacco and alcohol cessation as well as better compliance with routine follow-up evaluation and medication," they added.

Copenhagen University Hospital Hvidovre funded the study. The authors stated that they had no conflicts of interest.

Endoscopic resection for mucosal esophageal adenocarcinoma is safe and highly effective, and should be the new standard of care.

That’s according to Dr. Oliver Pech, whose study in the March issue of Gastroenterology showed a complete remission rate of 93.8% over nearly 5 years of follow-up (doi: 10.1053/j.gastro.2013.11.006).

Dr. Pech, of the University of Regensburg, Germany, and his colleagues looked at 1,000 consecutive patients (mean age, 69 years; 861 men) with mucosal adenocarcinoma of the esophagus, who were referred to a single center between October 1996 and September 2010.

All patients had mucosal Barrett’s carcinoma; lesions judged resectable were first subjected to diagnostic endoscopic resection for staging, even when the macroscopic appearance suggested submucosal disease. Patients with low-grade dysplasia, high-grade dysplasia, and submucosal or more advanced cancer (T1 or greater) were excluded.

In total, 481 patients had short-segment Barrett’s esophagus, and the remainder had long-segment Barrett’s. The majority (n = 493) had intraepithelial adenocarcinoma, according to staging by endoscopic resection, while 240 patients had adenocarcinoma invading the tunica propria, 124 had invasion of the first layer of the muscularis mucosae, and the remaining 143 had disease of the second layer of the muscularis mucosae.

En bloc resection was performed in 508 patients and piecemeal resection in the rest.

The authors found that complete remission, defined as an R0 resection plus one normal surveillance endoscopy, was achieved in 963 (96.3%) of the 1,000 patients in the study.

Among these, recurrence of neoplasia (high-grade dysplasia or adenocarcinoma) was detected in 14.5% of the patients (140 out of the 963) after a median 26.5 months; 115 were successfully retreated with additional endoscopic resection.

That translated to a long-term complete remission rate of 93.8% (mean, 56.6 months) and a 5-year survival rate of 91.5%.

Looking at safety, Dr. Pech reported that 15 patients experienced major complications, including bleeding with a corresponding drop in hemoglobin of at least 2 g/dL (in 14 cases) and perforation (in 1).

He added that the relatively minor complication of stenosis requiring dilation occurred in 13 cases, all of which were managed endoscopically. Finally, in an analysis of which patients were more likely to have successful endoscopic treatment, the authors determined that long-segment Barrett’s as well as poorly differentiated mucosal adenocarcinoma (as opposed to well-differentiated lesions) had a significantly higher risk for failure (P less than .0001 for both).

The authors conceded that referral bias cannot be excluded in this cohort, "because it is possible that only patients with early Barrett’s carcinoma that was endoscopically well treatable may have been referred."

Additionally, over the long course of the study, best practices for Barrett’s esophagus and high grade-dysplasia have evolved considerably, "moving away from multimodal therapy for early Barrett’s carcinoma using a combination of [endoscopic resection], photodynamic therapy, [argon plasma coagulation], and laser toward a strict and purely resectional form of treatment."

Nevertheless, "the data presented here on the largest series published to date on endoscopic therapy for mucosal adenocarcinomas in 1,000 patients confirm the safety of endoscopic resection," the authors wrote.

"Endoscopic therapy for mucosal Barrett’s carcinoma should therefore become the international gold standard for treatment," they added.

The authors stated that they had no conflicts of interest to disclose. They disclosed no funding.

Endoscopic resection for mucosal esophageal adenocarcinoma is safe and highly effective, and should be the new standard of care.

That’s according to Dr. Oliver Pech, whose study in the March issue of Gastroenterology showed a complete remission rate of 93.8% over nearly 5 years of follow-up (doi: 10.1053/j.gastro.2013.11.006).

Dr. Pech, of the University of Regensburg, Germany, and his colleagues looked at 1,000 consecutive patients (mean age, 69 years; 861 men) with mucosal adenocarcinoma of the esophagus, who were referred to a single center between October 1996 and September 2010.

All patients had mucosal Barrett’s carcinoma; lesions judged resectable were first subjected to diagnostic endoscopic resection for staging, even when the macroscopic appearance suggested submucosal disease. Patients with low-grade dysplasia, high-grade dysplasia, and submucosal or more advanced cancer (T1 or greater) were excluded.

In total, 481 patients had short-segment Barrett’s esophagus, and the remainder had long-segment Barrett’s. The majority (n = 493) had intraepithelial adenocarcinoma, according to staging by endoscopic resection, while 240 patients had adenocarcinoma invading the tunica propria, 124 had invasion of the first layer of the muscularis mucosae, and the remaining 143 had disease of the second layer of the muscularis mucosae.

En bloc resection was performed in 508 patients and piecemeal resection in the rest.

The authors found that complete remission, defined as an R0 resection plus one normal surveillance endoscopy, was achieved in 963 (96.3%) of the 1,000 patients in the study.

Among these, recurrence of neoplasia (high-grade dysplasia or adenocarcinoma) was detected in 14.5% of the patients (140 out of the 963) after a median 26.5 months; 115 were successfully retreated with additional endoscopic resection.

That translated to a long-term complete remission rate of 93.8% (mean, 56.6 months) and a 5-year survival rate of 91.5%.

Looking at safety, Dr. Pech reported that 15 patients experienced major complications, including bleeding with a corresponding drop in hemoglobin of at least 2 g/dL (in 14 cases) and perforation (in 1).

He added that the relatively minor complication of stenosis requiring dilation occurred in 13 cases, all of which were managed endoscopically. Finally, in an analysis of which patients were more likely to have successful endoscopic treatment, the authors determined that long-segment Barrett’s as well as poorly differentiated mucosal adenocarcinoma (as opposed to well-differentiated lesions) had a significantly higher risk for failure (P less than .0001 for both).

The authors conceded that referral bias cannot be excluded in this cohort, "because it is possible that only patients with early Barrett’s carcinoma that was endoscopically well treatable may have been referred."

Additionally, over the long course of the study, best practices for Barrett’s esophagus and high grade-dysplasia have evolved considerably, "moving away from multimodal therapy for early Barrett’s carcinoma using a combination of [endoscopic resection], photodynamic therapy, [argon plasma coagulation], and laser toward a strict and purely resectional form of treatment."

Nevertheless, "the data presented here on the largest series published to date on endoscopic therapy for mucosal adenocarcinomas in 1,000 patients confirm the safety of endoscopic resection," the authors wrote.

"Endoscopic therapy for mucosal Barrett’s carcinoma should therefore become the international gold standard for treatment," they added.

The authors stated that they had no conflicts of interest to disclose. They disclosed no funding.

Endoscopic resection for mucosal esophageal adenocarcinoma is safe and highly effective, and should be the new standard of care.

That’s according to Dr. Oliver Pech, whose study in the March issue of Gastroenterology showed a complete remission rate of 93.8% over nearly 5 years of follow-up (doi: 10.1053/j.gastro.2013.11.006).

Dr. Pech, of the University of Regensburg, Germany, and his colleagues looked at 1,000 consecutive patients (mean age, 69 years; 861 men) with mucosal adenocarcinoma of the esophagus, who were referred to a single center between October 1996 and September 2010.

All patients had mucosal Barrett’s carcinoma; lesions judged resectable were first subjected to diagnostic endoscopic resection for staging, even when the macroscopic appearance suggested submucosal disease. Patients with low-grade dysplasia, high-grade dysplasia, and submucosal or more advanced cancer (T1 or greater) were excluded.

In total, 481 patients had short-segment Barrett’s esophagus, and the remainder had long-segment Barrett’s. The majority (n = 493) had intraepithelial adenocarcinoma, according to staging by endoscopic resection, while 240 patients had adenocarcinoma invading the tunica propria, 124 had invasion of the first layer of the muscularis mucosae, and the remaining 143 had disease of the second layer of the muscularis mucosae.

En bloc resection was performed in 508 patients and piecemeal resection in the rest.

The authors found that complete remission, defined as an R0 resection plus one normal surveillance endoscopy, was achieved in 963 (96.3%) of the 1,000 patients in the study.

Among these, recurrence of neoplasia (high-grade dysplasia or adenocarcinoma) was detected in 14.5% of the patients (140 out of the 963) after a median 26.5 months; 115 were successfully retreated with additional endoscopic resection.

That translated to a long-term complete remission rate of 93.8% (mean, 56.6 months) and a 5-year survival rate of 91.5%.

Looking at safety, Dr. Pech reported that 15 patients experienced major complications, including bleeding with a corresponding drop in hemoglobin of at least 2 g/dL (in 14 cases) and perforation (in 1).

He added that the relatively minor complication of stenosis requiring dilation occurred in 13 cases, all of which were managed endoscopically. Finally, in an analysis of which patients were more likely to have successful endoscopic treatment, the authors determined that long-segment Barrett’s as well as poorly differentiated mucosal adenocarcinoma (as opposed to well-differentiated lesions) had a significantly higher risk for failure (P less than .0001 for both).

The authors conceded that referral bias cannot be excluded in this cohort, "because it is possible that only patients with early Barrett’s carcinoma that was endoscopically well treatable may have been referred."

Additionally, over the long course of the study, best practices for Barrett’s esophagus and high grade-dysplasia have evolved considerably, "moving away from multimodal therapy for early Barrett’s carcinoma using a combination of [endoscopic resection], photodynamic therapy, [argon plasma coagulation], and laser toward a strict and purely resectional form of treatment."

Nevertheless, "the data presented here on the largest series published to date on endoscopic therapy for mucosal adenocarcinomas in 1,000 patients confirm the safety of endoscopic resection," the authors wrote.

"Endoscopic therapy for mucosal Barrett’s carcinoma should therefore become the international gold standard for treatment," they added.

The authors stated that they had no conflicts of interest to disclose. They disclosed no funding.

Cardiovascular complications and sepsis are two major concerns after liver transplant for nonalcoholic steatohepatitis, more so than after liver transplant for other indications.

The finding comes from what the authors called the first systematic review and meta-analysis to investigate the cumulative clinical experience of liver transplant for NASH, wrote Dr. Xiaofei Wang and colleagues in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2013.09.023).

In their analysis, Dr. Wang, of the Affiliated Hospital of North Sichuan Medical College, Nanchong, China, and colleagues performed a search of PubMed, Embase, the Cochrane Library, and the Web of Science for studies published through Sept. 1, 2012, that looked at liver transplant for nonalcoholic fatty liver disease (NAFLD) or NASH. Reviews were excluded, as were studies in which NASH patients could not be separated out from non-NASH liver transplant recipients.

Courtesy Wikimedia Commons/ Nephron/ Creative Commons License

Overall, nine studies were analyzed, all of which measured outcomes after liver transplant for NASH. Other indications for transplant included primary biliary cirrhosis/primary sclerosing cholangitis, alcoholic liver disease, hepatitis C, hepatitis B, and cryptogenic cirrhosis.

The researchers found that, on the whole, survival rates at post-transplant years 1, 3, and 5 did not significantly differ between NASH patients and their non-NASH counterparts (1-year odds ratio, 0.77; 95% confidence interval, 0.59-1.00; P = .05; 3-year OR, 0.97; 95% CI, 0.67-1.40; P = .86; 5-year OR, 1.09; 95% CI, 0.77-1.56; P = .63).

Nevertheless, NASH patients registered more deaths due to "cardiovascular events" compared with non-NASH liver transplant recipients, the authors wrote (OR, 1.65; 95% CI, 1.01-2.70; P = .05).

The authors also found that NASH patients were significantly more likely to die of sepsis post transplant than were non-NASH patients (OR, 1.71; 95% CI, 1.17-2.50; P = .006).

On the other hand, NASH patients had fewer deaths caused by graft failure than did patients undergoing liver transplant for other indications (OR, 0.21; 95% CI, 0.05-0.89; P = .03).

In an attempt to explain their findings, the authors pointed out that while cardiovascular events are the top cause of non–graft-related mortality in all liver transplants, NASH patients might be especially susceptible, given that their diagnosis is "frequently associated" with cardiovascular risk factors such as obesity, diabetes, and hypertension. Indeed, these same characteristics might also predispose these patients to postoperative infection and sepsis, they added.

And regarding the finding that graft-related mortality is actually lower among NASH patients, Dr. Wang and colleagues postulated that this may be due to the "lower likelihood of disease recurrence, and this may mean lower rates of graft failure compared with other liver diseases, such as hepatitis C virus and hepatitis B virus infection."

The authors conceded that there were several limitations to their analysis, not the least being heterogeneity between included studies. Moreover, two large population-based studies using national databases were ultimately excluded due to patient duplication and poor accuracy with regard to the cause of death.

In any case, the current analysis shows that "more attention and careful consideration are required in selecting patients with NASH for liver transplant, along with aggressive management of cardiovascular complications and sepsis after transplantation."

The authors disclosed no conflicts of interest related to this study. They wrote that funding was provided by the scientific research development project of North Sichuan Medical College.

Cardiovascular complications and sepsis are two major concerns after liver transplant for nonalcoholic steatohepatitis, more so than after liver transplant for other indications.

The finding comes from what the authors called the first systematic review and meta-analysis to investigate the cumulative clinical experience of liver transplant for NASH, wrote Dr. Xiaofei Wang and colleagues in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2013.09.023).

In their analysis, Dr. Wang, of the Affiliated Hospital of North Sichuan Medical College, Nanchong, China, and colleagues performed a search of PubMed, Embase, the Cochrane Library, and the Web of Science for studies published through Sept. 1, 2012, that looked at liver transplant for nonalcoholic fatty liver disease (NAFLD) or NASH. Reviews were excluded, as were studies in which NASH patients could not be separated out from non-NASH liver transplant recipients.

Courtesy Wikimedia Commons/ Nephron/ Creative Commons License

Overall, nine studies were analyzed, all of which measured outcomes after liver transplant for NASH. Other indications for transplant included primary biliary cirrhosis/primary sclerosing cholangitis, alcoholic liver disease, hepatitis C, hepatitis B, and cryptogenic cirrhosis.

The researchers found that, on the whole, survival rates at post-transplant years 1, 3, and 5 did not significantly differ between NASH patients and their non-NASH counterparts (1-year odds ratio, 0.77; 95% confidence interval, 0.59-1.00; P = .05; 3-year OR, 0.97; 95% CI, 0.67-1.40; P = .86; 5-year OR, 1.09; 95% CI, 0.77-1.56; P = .63).

Nevertheless, NASH patients registered more deaths due to "cardiovascular events" compared with non-NASH liver transplant recipients, the authors wrote (OR, 1.65; 95% CI, 1.01-2.70; P = .05).

The authors also found that NASH patients were significantly more likely to die of sepsis post transplant than were non-NASH patients (OR, 1.71; 95% CI, 1.17-2.50; P = .006).

On the other hand, NASH patients had fewer deaths caused by graft failure than did patients undergoing liver transplant for other indications (OR, 0.21; 95% CI, 0.05-0.89; P = .03).

In an attempt to explain their findings, the authors pointed out that while cardiovascular events are the top cause of non–graft-related mortality in all liver transplants, NASH patients might be especially susceptible, given that their diagnosis is "frequently associated" with cardiovascular risk factors such as obesity, diabetes, and hypertension. Indeed, these same characteristics might also predispose these patients to postoperative infection and sepsis, they added.

And regarding the finding that graft-related mortality is actually lower among NASH patients, Dr. Wang and colleagues postulated that this may be due to the "lower likelihood of disease recurrence, and this may mean lower rates of graft failure compared with other liver diseases, such as hepatitis C virus and hepatitis B virus infection."

The authors conceded that there were several limitations to their analysis, not the least being heterogeneity between included studies. Moreover, two large population-based studies using national databases were ultimately excluded due to patient duplication and poor accuracy with regard to the cause of death.

In any case, the current analysis shows that "more attention and careful consideration are required in selecting patients with NASH for liver transplant, along with aggressive management of cardiovascular complications and sepsis after transplantation."

The authors disclosed no conflicts of interest related to this study. They wrote that funding was provided by the scientific research development project of North Sichuan Medical College.

Cardiovascular complications and sepsis are two major concerns after liver transplant for nonalcoholic steatohepatitis, more so than after liver transplant for other indications.

The finding comes from what the authors called the first systematic review and meta-analysis to investigate the cumulative clinical experience of liver transplant for NASH, wrote Dr. Xiaofei Wang and colleagues in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2013.09.023).

In their analysis, Dr. Wang, of the Affiliated Hospital of North Sichuan Medical College, Nanchong, China, and colleagues performed a search of PubMed, Embase, the Cochrane Library, and the Web of Science for studies published through Sept. 1, 2012, that looked at liver transplant for nonalcoholic fatty liver disease (NAFLD) or NASH. Reviews were excluded, as were studies in which NASH patients could not be separated out from non-NASH liver transplant recipients.

Courtesy Wikimedia Commons/ Nephron/ Creative Commons License

Overall, nine studies were analyzed, all of which measured outcomes after liver transplant for NASH. Other indications for transplant included primary biliary cirrhosis/primary sclerosing cholangitis, alcoholic liver disease, hepatitis C, hepatitis B, and cryptogenic cirrhosis.

The researchers found that, on the whole, survival rates at post-transplant years 1, 3, and 5 did not significantly differ between NASH patients and their non-NASH counterparts (1-year odds ratio, 0.77; 95% confidence interval, 0.59-1.00; P = .05; 3-year OR, 0.97; 95% CI, 0.67-1.40; P = .86; 5-year OR, 1.09; 95% CI, 0.77-1.56; P = .63).

Nevertheless, NASH patients registered more deaths due to "cardiovascular events" compared with non-NASH liver transplant recipients, the authors wrote (OR, 1.65; 95% CI, 1.01-2.70; P = .05).

The authors also found that NASH patients were significantly more likely to die of sepsis post transplant than were non-NASH patients (OR, 1.71; 95% CI, 1.17-2.50; P = .006).

On the other hand, NASH patients had fewer deaths caused by graft failure than did patients undergoing liver transplant for other indications (OR, 0.21; 95% CI, 0.05-0.89; P = .03).

In an attempt to explain their findings, the authors pointed out that while cardiovascular events are the top cause of non–graft-related mortality in all liver transplants, NASH patients might be especially susceptible, given that their diagnosis is "frequently associated" with cardiovascular risk factors such as obesity, diabetes, and hypertension. Indeed, these same characteristics might also predispose these patients to postoperative infection and sepsis, they added.

And regarding the finding that graft-related mortality is actually lower among NASH patients, Dr. Wang and colleagues postulated that this may be due to the "lower likelihood of disease recurrence, and this may mean lower rates of graft failure compared with other liver diseases, such as hepatitis C virus and hepatitis B virus infection."

The authors conceded that there were several limitations to their analysis, not the least being heterogeneity between included studies. Moreover, two large population-based studies using national databases were ultimately excluded due to patient duplication and poor accuracy with regard to the cause of death.

In any case, the current analysis shows that "more attention and careful consideration are required in selecting patients with NASH for liver transplant, along with aggressive management of cardiovascular complications and sepsis after transplantation."

The authors disclosed no conflicts of interest related to this study. They wrote that funding was provided by the scientific research development project of North Sichuan Medical College.

The risk of colorectal cancer is greatly reduced for up to 10 years following even nonscreening colonoscopies, such as those performed in the setting of a positive fecal occult blood test or abdominal symptoms, a study showed.

Cancer risk was also lowered in the right colon, regardless of the indication for the colonoscopy, reported Dr. Hermann Brenner and his colleagues in the March issue of Gastroenterology (doi:10.1053/j.gastro.2013.09.001).

The finding is mostly good news for patients and practitioners. However, the investigators pointed out that as the use of diagnostic colonoscopy becomes more widespread in the United States and beyond, future researchers risk "contamination by taking diagnostic colonoscopies into account in the design and analysis of results from screening endoscopy randomized controlled trials."

Dr. Brenner of the University of Heidelberg (Germany) looked at 2,516 patients with a first diagnosis of colorectal cancer and 2,284 healthy controls culled from the DACHS study, a population-based case-control study conducted in the Rhine-Neckar region of Germany since 2003.

Patients were excluded if they were younger than 50 years old (in which case screening colonoscopy is not generally recommended) and if they had any history of inflammatory bowel disease, which requires frequent colonoscopies.

The median age was 70 years; 59% of all participants were men.

Overall, reported the authors, slightly more than a third (38.3%) of controls had a previous colonoscopy, most commonly for screening (12.0%) followed by abdominal symptoms (9.1%).

The other possible indications were screening, a positive fecal occult blood test result, surveillance, rectal bleeding, or "other."

Looking at both cases and controls, the investigators said that although only a small fraction of colonoscopies conducted until 2002 were performed for screening, screening was the most common indication for colonoscopies conducted from 2003 on.

The authors found that even though there was a stronger risk reduction in colorectal cancer among patients who underwent screening colonoscopy between 1 and 10 years prior (and this reduction was profound, with an odds ratio of 0.09 and a 95% confidence interval of 0.07-0.13), there was still a significant reduction after colonoscopies performed for other indications, including a positive fecal occult blood test result (OR, 0.33; 95% CI, 0.19-0.57), surveillance after a preceding colonoscopy (OR, 0.33; 95% CI, 0.24-0.45), rectal bleeding (OR, 0.28; 95% CI, 0.20-0.40), and abdominal symptoms (OR, 0.15; 95% CI, 0.10-0.21).

Unspecified other indications were associated with an odds ratio of 0.21 for cancer (95% CI, 0.14-0.30).

"All risk reductions were substantially less pronounced (and partly not statistically significant) for cancer in the right colon compared with cancer in the left colon and rectum," wrote the authors.

Nevertheless, colonoscopy was also associated with a reduced risk of cancer in the right colon regardless of the indication, although the effect was more pronounced specifically after a screening exam (OR for screening colonoscopy, 0.22; 95% CI, 0.14-0.33).

"To our knowledge, only two case-control studies from Canada and the United States have previously provided separate estimates of colorectal cancer risk after diagnostic and screening colonoscopy," wrote the authors.

"However, with ORs of 0.69 and 0.81, risk reduction was much less pronounced in the Canadian study than in the U.S. study and our study."

The authors disclosed no conflicts of interest related to this study; they stated that funding was provided by the German Research Council as well as the German Federal Ministry of Education and Research.

The risk of colorectal cancer is greatly reduced for up to 10 years following even nonscreening colonoscopies, such as those performed in the setting of a positive fecal occult blood test or abdominal symptoms, a study showed.

Cancer risk was also lowered in the right colon, regardless of the indication for the colonoscopy, reported Dr. Hermann Brenner and his colleagues in the March issue of Gastroenterology (doi:10.1053/j.gastro.2013.09.001).

The finding is mostly good news for patients and practitioners. However, the investigators pointed out that as the use of diagnostic colonoscopy becomes more widespread in the United States and beyond, future researchers risk "contamination by taking diagnostic colonoscopies into account in the design and analysis of results from screening endoscopy randomized controlled trials."

Dr. Brenner of the University of Heidelberg (Germany) looked at 2,516 patients with a first diagnosis of colorectal cancer and 2,284 healthy controls culled from the DACHS study, a population-based case-control study conducted in the Rhine-Neckar region of Germany since 2003.

Patients were excluded if they were younger than 50 years old (in which case screening colonoscopy is not generally recommended) and if they had any history of inflammatory bowel disease, which requires frequent colonoscopies.

The median age was 70 years; 59% of all participants were men.

Overall, reported the authors, slightly more than a third (38.3%) of controls had a previous colonoscopy, most commonly for screening (12.0%) followed by abdominal symptoms (9.1%).

The other possible indications were screening, a positive fecal occult blood test result, surveillance, rectal bleeding, or "other."

Looking at both cases and controls, the investigators said that although only a small fraction of colonoscopies conducted until 2002 were performed for screening, screening was the most common indication for colonoscopies conducted from 2003 on.

The authors found that even though there was a stronger risk reduction in colorectal cancer among patients who underwent screening colonoscopy between 1 and 10 years prior (and this reduction was profound, with an odds ratio of 0.09 and a 95% confidence interval of 0.07-0.13), there was still a significant reduction after colonoscopies performed for other indications, including a positive fecal occult blood test result (OR, 0.33; 95% CI, 0.19-0.57), surveillance after a preceding colonoscopy (OR, 0.33; 95% CI, 0.24-0.45), rectal bleeding (OR, 0.28; 95% CI, 0.20-0.40), and abdominal symptoms (OR, 0.15; 95% CI, 0.10-0.21).

Unspecified other indications were associated with an odds ratio of 0.21 for cancer (95% CI, 0.14-0.30).

"All risk reductions were substantially less pronounced (and partly not statistically significant) for cancer in the right colon compared with cancer in the left colon and rectum," wrote the authors.

Nevertheless, colonoscopy was also associated with a reduced risk of cancer in the right colon regardless of the indication, although the effect was more pronounced specifically after a screening exam (OR for screening colonoscopy, 0.22; 95% CI, 0.14-0.33).

"To our knowledge, only two case-control studies from Canada and the United States have previously provided separate estimates of colorectal cancer risk after diagnostic and screening colonoscopy," wrote the authors.

"However, with ORs of 0.69 and 0.81, risk reduction was much less pronounced in the Canadian study than in the U.S. study and our study."

The authors disclosed no conflicts of interest related to this study; they stated that funding was provided by the German Research Council as well as the German Federal Ministry of Education and Research.

The risk of colorectal cancer is greatly reduced for up to 10 years following even nonscreening colonoscopies, such as those performed in the setting of a positive fecal occult blood test or abdominal symptoms, a study showed.

Cancer risk was also lowered in the right colon, regardless of the indication for the colonoscopy, reported Dr. Hermann Brenner and his colleagues in the March issue of Gastroenterology (doi:10.1053/j.gastro.2013.09.001).

The finding is mostly good news for patients and practitioners. However, the investigators pointed out that as the use of diagnostic colonoscopy becomes more widespread in the United States and beyond, future researchers risk "contamination by taking diagnostic colonoscopies into account in the design and analysis of results from screening endoscopy randomized controlled trials."

Dr. Brenner of the University of Heidelberg (Germany) looked at 2,516 patients with a first diagnosis of colorectal cancer and 2,284 healthy controls culled from the DACHS study, a population-based case-control study conducted in the Rhine-Neckar region of Germany since 2003.

Patients were excluded if they were younger than 50 years old (in which case screening colonoscopy is not generally recommended) and if they had any history of inflammatory bowel disease, which requires frequent colonoscopies.

The median age was 70 years; 59% of all participants were men.

Overall, reported the authors, slightly more than a third (38.3%) of controls had a previous colonoscopy, most commonly for screening (12.0%) followed by abdominal symptoms (9.1%).

The other possible indications were screening, a positive fecal occult blood test result, surveillance, rectal bleeding, or "other."

Looking at both cases and controls, the investigators said that although only a small fraction of colonoscopies conducted until 2002 were performed for screening, screening was the most common indication for colonoscopies conducted from 2003 on.

The authors found that even though there was a stronger risk reduction in colorectal cancer among patients who underwent screening colonoscopy between 1 and 10 years prior (and this reduction was profound, with an odds ratio of 0.09 and a 95% confidence interval of 0.07-0.13), there was still a significant reduction after colonoscopies performed for other indications, including a positive fecal occult blood test result (OR, 0.33; 95% CI, 0.19-0.57), surveillance after a preceding colonoscopy (OR, 0.33; 95% CI, 0.24-0.45), rectal bleeding (OR, 0.28; 95% CI, 0.20-0.40), and abdominal symptoms (OR, 0.15; 95% CI, 0.10-0.21).

Unspecified other indications were associated with an odds ratio of 0.21 for cancer (95% CI, 0.14-0.30).

"All risk reductions were substantially less pronounced (and partly not statistically significant) for cancer in the right colon compared with cancer in the left colon and rectum," wrote the authors.

Nevertheless, colonoscopy was also associated with a reduced risk of cancer in the right colon regardless of the indication, although the effect was more pronounced specifically after a screening exam (OR for screening colonoscopy, 0.22; 95% CI, 0.14-0.33).

"To our knowledge, only two case-control studies from Canada and the United States have previously provided separate estimates of colorectal cancer risk after diagnostic and screening colonoscopy," wrote the authors.

"However, with ORs of 0.69 and 0.81, risk reduction was much less pronounced in the Canadian study than in the U.S. study and our study."

The authors disclosed no conflicts of interest related to this study; they stated that funding was provided by the German Research Council as well as the German Federal Ministry of Education and Research.