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Dr. Lamm's weekly review of relevant articles and research

There is an increasing amount of information available about the gut.  Here are a few informative articles you may find valuable.

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Lymphoma & Celiac Disease

Lymphoma Risk Up in Celiac Disease
Published: Aug 5, 2013 | Updated: Aug 6, 2013, By Nancy Walsh, Staff Writer, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Patients with celiac disease have an elevated risk for lymphoproliferative malignancies, particularly if they have persistent villous atrophy, a population-based cohort study found.

Compared with the general population, the standardized incidence ratio for lymphoproliferative malignancy among patients with celiac disease was 2.81 (95% CI 2.10-3.67), according to Benjamin Lebwohl, MD, of Columbia University in New York, and colleagues. And for those who continued to have villous atrophy of the intestinal mucosa, the standardized incidence ratio was 3.78 (95% CI 2.71-5.12), the researchers reported in the August 6 issue of Annals of Internal Medicine.

Previous studies have suggested that patients with celiac disease are atincreased risk for lymphomas, and although the precise reason for this isn't clear, it may relate to ongoing villous atrophy in some patients, particularly those who fail to adhere to a gluten-free diet.

Because current guidelines don't clarify whether patients should have a follow-up biopsy to confirm mucosal healing, and to estimate the risk for malignancy among those with persistent villous atrophy, Lebwohl and colleagues analyzed data and biopsy reports from Sweden's pathology departments for the years 1969 to 2008.

They identified 7,625 patients who had a follow-up biopsy between 6 months and 5 years after having had an initial diagnostic biopsy.

Almost two-thirds were women, and the median age at the time of diagnosis was 25.

A total of 43% had evidence of ongoing villous atrophy on the second biopsy.

During a median follow-up time of 9 years after the second biopsy, 53 patients (0.7%) were diagnosed with a lymphoproliferative malignancy. The incidence in the overall group was 67.9 per 100,000 patient-years.

In contrast, the incidence in those with ongoing villous atrophy was 102.4 per 100,000, the researchers reported.

Multivariate analysis adjusting for age, sex, education, and duration of disease found a hazard ratio for lymphoproliferative malignancy of 2.26 (95% CI 1.18-4.34) among those with ongoing mucosal disease compared with those who had healing of the intestinal mucosa.

Among these patients with persistent villous atrophy, the higher risk was most prominent during the first 12 months after the follow-up biopsy, with a hazard ratio of 3.67 (95% CI 0.80-16.86), decreasing to 1.99 (95% CI 0.79-4.97) after 5 years.

"In some patients, persistent villous atrophy may reflect a gradual healing process, and a future biopsy may show mucosal healing," the researchers explained.
Specific subtypes of disease that were associated with higher risk when villous atrophy persisted were non-Hodgkin's lymphoma (HR 2.82, 95% CI 1.29-6.17, P=0.009) and unspecified non-Hodgkin's lymphoma (HR 4.31, 95% CI 1.27-14.61, P=0.019).

There also was an increase in risk, although nonsignificant, for T-cell lymphoma (HR 3.51, 95% CI 0.75-16.34, P=0.110).

An additional factor that was associated with greater risk was biopsy evidence of total or subtotal villous atrophy (HR 3.96, 95% CI 1.65-9.50), which was particularly pronounced in patients with T-cell lymphoma, who had nine times the risk (HR 9.23, 95% CI 1.66-51.34).

"Our finding of an association between persistent villous atrophy and risk for [lymphoproliferative malignancy] supports the practice of performing follow-up biopsy as a complement to dietary assessment," Lebwohl and colleagues observed.

"This study shows that the results of the follow-up biopsy matter," Lebwohl told MedPage Today.

"The result of the follow-up biopsy may spur the patient to improve dietary adherence, which will eventually diminish the increased risk," they suggested.

The study did have limitations, including a lack of information about gluten avoidance and the possibility of inadequate statistical power and reverse causality.

The researchers also didn't consider the economic effects of repeat biopsies, "and a cost-benefit analysis about this approach is warranted."

Nonetheless, "these findings should prompt further evaluation of mucosal healing as a goal for patients with [celiac disease] to reduce their risk for [lymphoproliferative malignancy]," the researchers concluded.

The study was supported by various organizations including the National Institutes of Health, the Swedish Research Council, the Celiac Sprue Association, and the Swedish Research Council.

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