Scharl Michael, Rogler Gerhard, Biedermann Luc
Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Clin Transl Gastroenterol. 2017 Jul 13;8(7):e106. doi: 10.1038/ctg.2017.33.
Fistulas still represent one of the most important complications in patients with Crohn's disease (CD). At least one third of CD patients suffer from fistulas during their disease course and amongst them longstanding remission of complex fistulas occurs only in about one third. So far, fistula pathogenesis is only partially understood. From a histopathological view, a fistula is a tube covered by flat epithelial cells. Current research suggests that the driving force for fistula development is epithelial-to-mesenchymal transition (EMT). Around the fistula, high levels of tumor necrosis factor (TNF), IL-13, and TGFβ can be detected and recent studies indicated an involvement of the intestinal microbiota. Fistula diagnosis requires clinical and surgical assessment, radiologic investigations, e.g., magnet resonance imaging and endoscopy. Routine medical treatment of fistulas includes antibiotics, immunosuppressives, and anti-TNF antibodies. There is no well-established role for calcineurin inhibitors in fistula treatment, corticosteroids appear to be even contra-productive. A promising novel approach might be the application of adipose tissue-derived or bone marrow-derived mesenchymal stem cells that have been studied recently. Due to insufficient efficacy of medical treatment and recurrence of fistulas, surgical interventions are frequently necessary. Further research is needed to better understand fistula pathogenesis aiming to develop novel treatment option for our patients.
瘘管仍然是克罗恩病(CD)患者最重要的并发症之一。至少三分之一的CD患者在病程中会出现瘘管,其中复杂瘘管的长期缓解仅发生在约三分之一的患者中。到目前为止,瘘管的发病机制仅得到部分理解。从组织病理学角度来看,瘘管是由扁平上皮细胞覆盖的管道。目前的研究表明,瘘管形成的驱动力是上皮-间质转化(EMT)。在瘘管周围,可以检测到高水平的肿瘤坏死因子(TNF)、IL-13和TGFβ,最近的研究表明肠道微生物群也参与其中。瘘管诊断需要临床和手术评估、放射学检查,如磁共振成像和内镜检查。瘘管的常规药物治疗包括抗生素、免疫抑制剂和抗TNF抗体。钙调神经磷酸酶抑制剂在瘘管治疗中没有明确的作用,皮质类固醇似乎甚至有反作用。一种有前景的新方法可能是应用最近研究的脂肪组织来源或骨髓来源的间充质干细胞。由于药物治疗效果不佳和瘘管复发,手术干预经常是必要的。需要进一步研究以更好地理解瘘管发病机制,旨在为我们的患者开发新的治疗选择。