Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 6, 2020; 8(15): 3218-3229
Published online Aug 6, 2020. doi: 10.12998/wjcc.v8.i15.3218
Thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities
Alexis Mae Bayudan, Chien-Huan Chen
Alexis Mae Bayudan, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63108, United States
Chien-Huan Chen, Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
Author contributions: Chen CH designed the research; Bayudan AM performed database generation; all authors performed statistical analysis and wrote the paper. Both authors approved the final version.
Institutional review board statement: The study was reviewed and approved by the Washington University Institutional Review Board.
Informed consent statement: As this is a retrospective study, all participants were waived of written informed consent by our IRB.
Conflict-of-interest statement: Both authors have no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Chien-Huan Chen, MD, PhD, Professor, Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Ave, Box 8124, St. Louis, MO 63110, United States. chen330@wustl.edu
Received: February 8, 2020
Peer-review started: February 8, 2020
First decision: May 22, 2020
Revised: June 15, 2020
Accepted: July 15, 2020
Article in press: July 15, 2020
Published online: August 6, 2020
Processing time: 179 Days and 12.4 Hours
ARTICLE HIGHLIGHTS
Research background

Gastrointestinal vascular malformations (GIVM) consist of several types such as gastrointestinal angiodysplasias (GIAD) and gastric antral vascular ectasias (GAVE). GIAD are abnormal, dilated, tortuous vessels within the mucosal and submucosal layers and are the most common GIVM seen throughout the gastrointestinal tract. GAVE is generally found in patients with chronic illnesses, such as liver disease, connective tissue diseases, and chronic renal failure. Refractory gastrointestinal bleeding (GIB) secondary to GIVM remains challenging to treat when endoscopic therapy fails. Endoscopic therapy with argon plasma coagulation (APC) is the mainstay of treatment for GIVM. However, GIVM refractory to endoscopic treatment is common and medications such as octreotide, tranexamic acid, hormonal therapy such as estrogen-progesterone, and thalidomide have all been studied in the management of recurrent GIB refractory to endoscopic therapy. Thalidomide, known to have antiangiogenic properties by suppressing VEGF, has been suggested recently as a treatment option for refractory GIB.

Research motivation

Only one randomized control trial demonstrating the efficacy of thalidomide for treating refractory GIB due to GIVM has been published in 2011 in a Chinese population. However, the study had extensive exclusion criteria and it is unclear whether the results of the study can be extrapolated to other patient populations. We therefore decided to conduct a retrospective study of thalidomide in treating refractory GIB from GIVM in a Western population with significant comorbidities at a tertiary medical center.

Research objectives

To evaluate thalidomide as a treatment option for patients who suffer from refractory GIB due to GIVM.

Research methods

Single center, IRB approved, retrospective review of electronic medical records from January 2012 to November 2018. Patients age > 18 years old, who had > 3 episodes of GIB refractory to medical or endoscopic therapy and documented to be due to GIVM, and who had been treated with thalidomide for at least 3 months were included. Refractory bleeding was defined as recurrent bleeding requiring > 2 transfusions after failing 2 treatments with endoscopic therapy using APC or medical therapies, such as octreotide, estrogen, or aminocaproic acid. The primary endpoint was recurrence of GIB 6 mo after initiation of thalidomide. The secondary endpoints were the number of hospitalizations, blood transfusion requirements, and endoscopic treatments.

Research results

Fifteen patients were included in the study, all with significant cardiac, hepatic, or renal comorbidities. The cause of GIB was GIAD in 10 patients and GAVE in 5 patients. Two patients were lost to follow up. Of the 13 patients followed, 38.5% (n = 5) had no recurrent GIB or transfusion requirement after treatment with thalidomide. Furthermore, 84.6% (n = 11) of patients had a reduction in transfusion requirements and hospitalizations for GIB. Thalidomide was discontinued in 2 patients due to cost (n = 1) and medication interaction (n = 1). Reported adverse reactions included fatigue (n = 3), neuropathy (n = 2), dizziness (n = 1), and constipation (n = 1). Six patients died during follow up due to unknown cause (n = 4) and sepsis (n = 2).

Research conclusions

Our results demonstrated that thalidomide appears to be an effective medical therapy for refractory GIB due to GIVM. The response rate in this study was 84.6%, comparable to other previous studies. The patients in our study represent the most challenging recurrent GIB patients in a tertiary referral medical center, as evidenced by their multiple comorbidities, and the average number of admissions (5.5) and transfusions (31 units of PRBC) one year before the initiation of thalidomide. Our study demonstrated that thalidomide remains an effective treatment for refractory GIB from GIVM in a Western population, including patients with severe comorbidities such as left ventricular assist device, cirrhosis, and end-stage renal disease on dialysis.

Research perspectives

Based on the results of this study, future research should include prospective randomized control trial with a larger patient population so that we can examine the effect of thalidomide on each comorbidity with sufficient power.