Published online Aug 6, 2020. doi: 10.12998/wjcc.v8.i15.3218
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
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.
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.
To evaluate thalidomide as a treatment option for patients who suffer from refractory GIB due to GIVM.
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.
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).
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.
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.