Biopsy as follow-up not standard care
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Biopsy results in celiac disease patients may predict cancer risk

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

[email protected]

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For celiac disease, we have robust evidence for testing and diagnosis, but the evidence base for how best to follow our patients with celiac disease is decidedly weak. It is generally accepted that patients with celiac disease should see their gastroenterologist and dietician on a regular basis and that celiac serologies and nutritional studies should be performed.

However, while duodenal biopsy remains the nearly uncontested gold standard for diagnosis, the utility of routine endoscopy for monitoring hovers somewhere between controversial and contentious. This recent work by Lebwohl and Ludvigsson is an important contribution. In an earlier study, this group utilized the Swedish National Registry to evaluate the effect of persistent enteropathy on mortality and found no difference (Aliment. Pharmacol. Ther. 2013;37:332-9).

In this follow-up study, they looked only at LPM and found that individuals with persistent entero-pathy are at significantly higher risk of lymphoma than celiac disease individuals with mucosal healing (Ann. Intern. Med. 2013;159:169-75).

So what are we to do at this point? Barring a randomized, controlled trial of endoscopic monitoring of celiac disease or at least good evidence that repeat endoscopy provides actionable information resulting in a higher proportion of patients achieving mucosal remission, it is still not clear that we have the level of evidence necessary to make repeat endoscopy the standard of care for follow-up of celiac disease.

On the other hand, this paper serves to remind us and our patients that celiac disease is not a benign disorder and that there are significant long-term risks, at least in a proportion of this growing population. Repeat endoscopy, generally 1-2 years after diagnosis, is one of a number of tests that patients with celiac disease should discuss with their gastroenterologist.

Dr. Daniel A. Leffler, director of clinical research, the Celiac Center at BIDMC, director of quality assurance, division of gastroenterology, Beth Israel Deaconess Medical Center. He has received consulting and/or research support from Alvine Pharma-ceuticals, Alba Therapeutics, Shire Pharmaceuticals, and Inova Diagnostics.

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For celiac disease, we have robust evidence for testing and diagnosis, but the evidence base for how best to follow our patients with celiac disease is decidedly weak. It is generally accepted that patients with celiac disease should see their gastroenterologist and dietician on a regular basis and that celiac serologies and nutritional studies should be performed.

However, while duodenal biopsy remains the nearly uncontested gold standard for diagnosis, the utility of routine endoscopy for monitoring hovers somewhere between controversial and contentious. This recent work by Lebwohl and Ludvigsson is an important contribution. In an earlier study, this group utilized the Swedish National Registry to evaluate the effect of persistent enteropathy on mortality and found no difference (Aliment. Pharmacol. Ther. 2013;37:332-9).

In this follow-up study, they looked only at LPM and found that individuals with persistent entero-pathy are at significantly higher risk of lymphoma than celiac disease individuals with mucosal healing (Ann. Intern. Med. 2013;159:169-75).

So what are we to do at this point? Barring a randomized, controlled trial of endoscopic monitoring of celiac disease or at least good evidence that repeat endoscopy provides actionable information resulting in a higher proportion of patients achieving mucosal remission, it is still not clear that we have the level of evidence necessary to make repeat endoscopy the standard of care for follow-up of celiac disease.

On the other hand, this paper serves to remind us and our patients that celiac disease is not a benign disorder and that there are significant long-term risks, at least in a proportion of this growing population. Repeat endoscopy, generally 1-2 years after diagnosis, is one of a number of tests that patients with celiac disease should discuss with their gastroenterologist.

Dr. Daniel A. Leffler, director of clinical research, the Celiac Center at BIDMC, director of quality assurance, division of gastroenterology, Beth Israel Deaconess Medical Center. He has received consulting and/or research support from Alvine Pharma-ceuticals, Alba Therapeutics, Shire Pharmaceuticals, and Inova Diagnostics.

Body

For celiac disease, we have robust evidence for testing and diagnosis, but the evidence base for how best to follow our patients with celiac disease is decidedly weak. It is generally accepted that patients with celiac disease should see their gastroenterologist and dietician on a regular basis and that celiac serologies and nutritional studies should be performed.

However, while duodenal biopsy remains the nearly uncontested gold standard for diagnosis, the utility of routine endoscopy for monitoring hovers somewhere between controversial and contentious. This recent work by Lebwohl and Ludvigsson is an important contribution. In an earlier study, this group utilized the Swedish National Registry to evaluate the effect of persistent enteropathy on mortality and found no difference (Aliment. Pharmacol. Ther. 2013;37:332-9).

In this follow-up study, they looked only at LPM and found that individuals with persistent entero-pathy are at significantly higher risk of lymphoma than celiac disease individuals with mucosal healing (Ann. Intern. Med. 2013;159:169-75).

So what are we to do at this point? Barring a randomized, controlled trial of endoscopic monitoring of celiac disease or at least good evidence that repeat endoscopy provides actionable information resulting in a higher proportion of patients achieving mucosal remission, it is still not clear that we have the level of evidence necessary to make repeat endoscopy the standard of care for follow-up of celiac disease.

On the other hand, this paper serves to remind us and our patients that celiac disease is not a benign disorder and that there are significant long-term risks, at least in a proportion of this growing population. Repeat endoscopy, generally 1-2 years after diagnosis, is one of a number of tests that patients with celiac disease should discuss with their gastroenterologist.

Dr. Daniel A. Leffler, director of clinical research, the Celiac Center at BIDMC, director of quality assurance, division of gastroenterology, Beth Israel Deaconess Medical Center. He has received consulting and/or research support from Alvine Pharma-ceuticals, Alba Therapeutics, Shire Pharmaceuticals, and Inova Diagnostics.

Title
Biopsy as follow-up not standard care
Biopsy as follow-up not standard care

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

[email protected]

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

[email protected]

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Biopsy results in celiac disease patients may predict cancer risk
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intestinal biopsies, celiac disease, lymphoproliferative malignancies, LPM, biopsy, villous atrophy, Dr. Benjamin Lebwohl
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Major finding: The risk of developing a lymphoproliferative malignancy (LPM) was about twofold higher among patients with celiac disease who had persistent villous atrophy on a follow-up biopsy than among those whose biopsies showed mucosal healing – an association that was highest in the year after the biopsy and diminished over time.

Data source: A population-based cohort study of intestinal biopsy results in 7,625 patients with celiac disease in Sweden.

Disclosures: The study was funded by the National Institutes of Health, the American-Scandinavian Foundation, Celiac Sprue Association, Oresbro University Hospital, Karolinska Institutet, Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr. Lebwohl disclosed ties

with the National Institutes of Health, the American Scandinavian Foundation,

and the Celiac Sprue Association, which funded the study along with Oresbro

University Hospital, Karolinska Institutet, the Swedish Society of Medicine,

Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a

coauthor, received grants from the NIH.