Hemorrhagic angiodysplasia of the digestive tract: pathogenesis, diagnosis, and management

Becq, Aymeric; Rahmi, Gabriel; Perrod, Guillaume; Cellier, Christophe

doi:10.1016/j.gie.2017.05.018

Cited by 56 publications

(55 citation statements)

References 147 publications

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“…Small bowel vascular malformation (SBVM) accounts for 30-40% of cases of small bowel bleeding (also called obscure gastrointestinal bleeding, OGIB), which is the most common cause of OGIB in people older than 40 years of age [1]. A 13-year follow-up study showed that 16-64% of cases would lead to iron deficiency anemia or require a blood transfusion, which undoubtedly is a major burden [2]. Histologically, SBVM is characterized by dilated communication between veins and capillaries, and usually, these vessels are thin and immature, without a smooth muscle layer [1].…”

Section: Introductionmentioning

confidence: 99%

Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation

Tang

Zhang

et al. 2020

Cell. Mol. Life Sci.

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Background Small bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide. Methods We took advantage of SBVM plasma and tissue samples and compared the expression of EGFL6 between SBVM patients and healthy people via ELISA and Immunohistochemistry. We elucidated the underlying function of EGFL6 in SBVM in vitro and by generating a zebrafish model that overexpresses EGFL6, The cycloheximide (CHX)-chase experiment and CoIP assays were conducted to demonstrate that thalidomide can promote the degradation of EGFL6 by targeting CRBN. Results The analysis of SBVM plasma and tissue samples revealed that EGFL6 was overexpressed in the patients compared to healthy people. Using in vitro and in vivo assays, we demonstrated that an EMT pathway triggered by the EGFL6/PAX6 axis is involved in the pathogenesis of SBVM. Furthermore, through in vitro and in vivo assays, we elucidated that thalidomide can function as anti-angiogenesis medicine through the regulation of EGFL6 in a proteasome-dependent manner. Finally, we found that CRBN can mediate the effect of thalidomide on EGFL6 expression and that the CRBN protein interacts with EGFL6 via a Lon N-terminal peptide. Conclusion Our findings revealed a key role for EGFL6 in SBVM pathogenesis and provided a mechanism explaining why thalidomide can cure small bowel bleeding resulting from SBVM.

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Section: Introductionmentioning

confidence: 99%

Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation

Tang

Zhang

et al. 2020

Cell. Mol. Life Sci.

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“…27 Trials were conducted using anti-VEGF agents such as thalidomide, which showed a significant reduction in the incidence of bleeding episodes and the need for blood transfusions. 28 However, this response was only observed in one third of the patients. Other concerns regarding thalidomide include an unknown optimal dose and duration and neurotoxicity with long-term administration.…”

Section: Thalidomide and Bevacizumabmentioning

confidence: 98%

“…Other concerns regarding thalidomide include an unknown optimal dose and duration and neurotoxicity with long-term administration. 28 Intravenous bevacizumab was used effectively to control refractory GI bleeding in patients with hereditary hemorrhagic telangiectasia. 29 It was also used in patients with gastric antral vascular ectasias and small bowel angioectasias that were unresponsive to other therapeutic modalities.…”

Section: Thalidomide and Bevacizumabmentioning

confidence: 99%

Roles of Capsule Endoscopy and Balloon-Assisted Enteroscopy in the Optimal Management of Small Bowel Bleeding

Abutalib

Yano

Shinozaki³

et al. 2020

Clin Endosc

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The small bowel had long been considered a dark unapproachable tunnel until the invention of capsule endoscopy and doubleballoon enteroscopy in the 21st century, which revolutionized the diagnosis and management of small bowel diseases, including bleeding. Various imaging modalities such as computed tomographic enterography, angiography, capsule endoscopy, and balloonassisted enteroscopy play vital roles in the diagnosis and management of small bowel bleeding. The choice of modality to use and timing of application differ according to the availability of the modalities, patient's history, and physician's experience. Small bowel bleeding is managed using different strategies as exemplified by medical treatment, interventional radiology, endoscopic therapy, or surgical intervention. Balloon-assisted enteroscopy enables endoscopic interventions to control small bowel bleeding, including electrocautery, argon plasma coagulation, clip application, and tattooing as a prelude to surgery. In this article, we clarify the recent approaches to the optimal diagnosis and management of patients with small bowel bleeding.

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“…A decrease of at least 30% of pRBC transfusion was obtained in 83% with pasireotide-LAR compared to 25% with placebo. New is the emerging role of thalidomide in the treatment of patients with challenging gastrointestinal bleeding [8] (Fig. 3).…”

Section: Suggested Readingmentioning

confidence: 99%

Gastro Update Europe 2018

Tytgat

2019

Dig Dis

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Hemorrhagic angiodysplasia of the digestive tract: pathogenesis, diagnosis, and management

Cited by 56 publications

References 147 publications

Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation

Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation

Roles of Capsule Endoscopy and Balloon-Assisted Enteroscopy in the Optimal Management of Small Bowel Bleeding

Gastro Update Europe 2018

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