乳糜泻患者的活检结果可预测癌症风险

《内科学年鉴》(Annals of Internal Medicine)在线发表的一项瑞典研究显示，乳糜泻患者的随访肠活检结果有助于评估其发生淋巴组织增生性恶性肿瘤(LPM)的风险。

在这项研究中，纽约哥伦比亚大学乳糜泻中心的Benjamin Lebwohl医生及其同事在7625例活检证实乳糜泻(活检示存在绒毛萎缩)的患者中比较了LPM发生率，并通过随访活检观察中位时间1.3年后的愈合情况。患者诊断时的中位年龄为35岁，63%为女性；诊断后的中位随访时间为11年，随访活检后的中位随访时间为9年。

共53例(0.7%)患者在随访活检后中位4.9年发生LPM。在43%的随访活检中观察到持续绒毛萎缩。总体而言，随访活检示持续绒毛萎缩的患者的LPM风险是活检示黏膜愈合患者的2倍以上[风险比(HR) 2.26]。但在随访活检后的第1年内，持续绒毛萎缩患者的LPM风险是黏膜愈合患者的近4倍(HR, 3.67)，此后随时间推移而降低。随访活检后1~5年和活检后5年以上，持续绒毛萎缩患者的LPM风险是黏膜愈合患者的2倍(HR, 1.99)，但差异无统计学显著性。

在男性和女性中均观察到持续绒毛萎缩与LPM风险增加相关，并且在随访活检时60岁以上患者中观察到的风险较高。持续绒毛萎缩患者发生LPM的风险高于一般人群。

研究者表示，乳糜泻患者LPM风险增加的原因尚不清楚，但该研究结果表明，LPM风险增加可能受到黏膜愈合影响。该研究的局限性在于缺乏有关患者对无麸质饮食的依从性的信息，因此尚不能断定饮食依从程度是否影响LPM风险。但该研究结果应促使临床医生进一步评估黏膜愈合这一治疗目标，以降低乳糜泻患者的LPM风险。

研究者声明无经济利益冲突。

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By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network

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.

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.

No author disclosures were provided.