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Wu Y, Jia Y, Jiang M, Zhang H. Case report: Successful therapy with recombinant human vascular endostatin in an elderly man with colon telangiectasia and idiopathic thrombocytopenic purpura. Front Med (Lausanne) 2025; 11:1511513. [PMID: 39882531 PMCID: PMC11774923 DOI: 10.3389/fmed.2024.1511513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 12/30/2024] [Indexed: 01/31/2025] Open
Abstract
An 83-year-old male presented to our Digestive System Department with a 5-day history of severe gastrointestinal (GI) bleeding and a 14-year history of idiopathic thrombocytopenic purpura (ITP) with low platelet levels. Colonoscopy revealed extensive telangiectasias throughout the colon, particularly in the transverse and ascending segments. Standard treatment with proton-pump inhibitors and somatostatin proved ineffective. Additionally, conventional therapies such as estrogen and thalidomide were contraindicated due to the comorbidity of ITP. Endoscopic hemostasis was also difficult to perform because of the widespread nature of the lesions. However, after the innovative use of four courses of recombinant human vascular endostatin (Endostar) therapy, the colon telangiectasia was completely resolved, and the patient reported no GI bleeding for 2 years. Managing severe GI bleeding with a rare etiology is particularly challenging, especially in patients with contraindications to conventional treatments due to comorbidities. In this case, a vascular endothelial growth factor (VEGF) inhibitor was successfully applied to treat a refractory and rare GI bleeding, which may offer a novel therapeutic approach for similar cases.
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Affiliation(s)
- Yushan Wu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yongbin Jia
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Mingshan Jiang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Hu Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China
- Lab of Inflammatory Bowel Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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Lu MC, Huang TY, Chen PJ, Chen HW, Yang CW, Lin JC, Huang WC, Lin HH, Shih YL, Hsieh TY, Chen BC. Predictors of active and recurrent bleeding in upper gastrointestinal angiodysplasia: Results from 10-year esophagogastroduodenoscopy of a tertiary center in Taiwan. Medicine (Baltimore) 2024; 103:e40921. [PMID: 39686487 PMCID: PMC11651466 DOI: 10.1097/md.0000000000040921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 11/14/2024] [Indexed: 12/18/2024] Open
Abstract
Upper gastrointestinal angiodysplasia (UGIA) is a unique mucosal vascular lesion that causes acute or recurrent gastrointestinal bleeding. Despite the increasing incidence of UGIA, the risk factors for bleeding in this condition remain unclear. We investigated the predictors of active and recurrent bleeding among patients with UGIA. We conducted a retrospective cohort study of 104,086 patients who underwent esophagogastroduodenoscopy (EGD) at the Tri-Service General Hospital in Taiwan between October 2011 and September 2021. UGIA was diagnosed in 112 patients, and the data from these patients were comprehensively analyzed. EGD documented UGIA in 112 patients, which corresponded with an overall diagnostic yield of 1.1%. Active bleeding was documented in 28 (25%) patients. Patients in the active bleeding group were older than the patients in the asymptomatic group (71.6 ± 11.7-years vs 61.3 ± 18.5-years). Most of the UGIA lesions were singular and measured 2 to 5 mm. Nearly 1-quarter of the patients (24.1%) underwent endoscopic hemostasis, and rebleeding occurred in 6 (21.4%) patients during the follow-up period. Multivariate analysis identified diabetes mellitus (DM), chronic kidney disease (CKD), and lesions in the duodenum as significant risk factors for active bleeding (P = .019; P = .006; P = .004). Our cohort study provided real-world data on the clinical and endoscopic features of UGIA. DM, CKD, and lesions in the duodenum were independent predictors of active bleeding.
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Affiliation(s)
- Meng-Chuan Lu
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tien-Yu Huang
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Peng-Jen Chen
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Hsuan-Wei Chen
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Wei Yang
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Jung-Chun Lin
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Chen Huang
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Hsuan-Hwai Lin
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Lueng Shih
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tsai-Yuan Hsieh
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Bao-Chung Chen
- Department of Internal Medicine, Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Gries JJ, Namjouyan K, Ul Hassan Virk H, Alam M, Jneid H, Krittanawong C. Evaluating the Relationship Between Gastrointestinal Bleeding and Valvular Heart Disease: A Systematic Review of Clinical Studies. GASTROINTESTINAL DISORDERS 2024; 6:916-946. [DOI: 10.3390/gidisord6040065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Background: Gastrointestinal angiodysplasia is a significant vascular anomaly characterized by dilated, tortuous blood vessels in the gastrointestinal tract. The current literature extensively documents the association between angiodysplasia and aortic stenosis, known as Heyde syndrome, characterized by the triad of aortic stenosis, GIB, and acquired von Willebrand syndrome. However, other valvular diseases, including mitral and tricuspid regurgitation, have also been implicated. This comprehensive systematic review aims to investigate the spectrum of valvular abnormalities, exploring the intricate mechanisms by which they contribute to gastrointestinal bleeding. Furthermore, it will evaluate the available surgical and nonsurgical treatment modalities, assessing their efficacy in mitigating the incidence of such bleeding. Methods: A comprehensive search of the Pubmed/MEDLINE database was conducted to identify relevant studies to retrieve relevant articles from August 2014 to August 2024. A combination of Medical Subject Heading (MeSH) terms and text words related to cardiac valvular diseases and GIB were used. MeSH terms included “gastrointestinal bleeding”, “heart valve diseases”, “hematochezia”, “heart valve prosthesis”, “bioprosthesis”, “native valve diseases”, and “mechanical valve”. Results: Forty-five papers met the inclusion criteria. Twenty-seven studies covered GIB in aortic valve disease, ten on mitral valve disease, two on tricuspid valve disease, and six on multiple valves. Conclusions: This systematic review demonstrates the association between angiodysplasia and aortic stenosis and highlights mitral regurgitation and tricuspid regurgitation as potential etiologies. Definitive management with valvuloplasty or valve replacement is vital to preventing the onset or recurrence of GIB in patients with valvular disease.
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Affiliation(s)
- Jacob J. Gries
- Department of Medicine, Geisinger Medical Center, Danville, PA 17822, USA
| | - Kamran Namjouyan
- Department of Medicine, Geisinger Medical Center, Danville, PA 17822, USA
| | - Hafeez Ul Hassan Virk
- Department of Cardiology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Mahboob Alam
- Department of Cardiology, The Texas Heart Institute, Baylor College of Medicine, Houston, TX 77030, USA
| | - Hani Jneid
- Department of Cardiology, University of Texas Medical Branch, Houston, TX 77030, USA
| | - Chayakrit Krittanawong
- Department of Cardiology, NYU Langone Health and NYU School of Medicine, New York, NY 10016, USA
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Maksić M, Corović I, Stanisavljević I, Radojević D, Veljković T, Todorović Ž, Jovanović M, Zdravković N, Stojanović B, Marković BS, Jovanović I. Heyde Syndrome Unveiled: A Case Report with Current Literature Review and Molecular Insights. Int J Mol Sci 2024; 25:11041. [PMID: 39456826 PMCID: PMC11507012 DOI: 10.3390/ijms252011041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 09/23/2024] [Accepted: 09/26/2024] [Indexed: 10/28/2024] Open
Abstract
Heyde syndrome, marked by aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome, is often underreported. Shear stress from a narrowed aortic valve degrades von Willebrand factor multimers, leading to angiodysplasia formation and von Willebrand factor deficiency. This case report aims to raise clinician awareness of Heyde syndrome, its complexity, and the need for a multidisciplinary approach. We present a 75-year-old man with aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. The patient was successfully treated with argon plasma coagulation and blood transfusions. He declined further treatment for aortic stenosis but was in good overall health with improved laboratory results during follow-up. Additionally, we provide a comprehensive review of the molecular mechanisms involved in the development of this syndrome, discuss current diagnostic and treatment approaches, and offer future perspectives for further research on this topic.
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Affiliation(s)
- Mladen Maksić
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (M.M.); (D.R.); (Ž.T.); (M.J.); (N.Z.)
| | - Irfan Corović
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (I.C.); (I.S.); (I.J.)
| | - Isidora Stanisavljević
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (I.C.); (I.S.); (I.J.)
| | - Dušan Radojević
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (M.M.); (D.R.); (Ž.T.); (M.J.); (N.Z.)
| | - Tijana Veljković
- Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia;
| | - Željko Todorović
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (M.M.); (D.R.); (Ž.T.); (M.J.); (N.Z.)
| | - Marina Jovanović
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (M.M.); (D.R.); (Ž.T.); (M.J.); (N.Z.)
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (I.C.); (I.S.); (I.J.)
| | - Nataša Zdravković
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (M.M.); (D.R.); (Ž.T.); (M.J.); (N.Z.)
| | - Bojan Stojanović
- Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia;
| | - Bojana Simović Marković
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (I.C.); (I.S.); (I.J.)
| | - Ivan Jovanović
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia; (I.C.); (I.S.); (I.J.)
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Zhang QW, Lin XL, Dai ZH, Zhao R, Hou YC, Liang Q, Zhang Y, Ge ZZ. Hypoxia and low-glucose environments co-induced HGDILnc1 promote glycolysis and angiogenesis. Cell Death Discov 2024; 10:132. [PMID: 38472215 DOI: 10.1038/s41420-024-01903-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 02/26/2024] [Accepted: 03/01/2024] [Indexed: 03/14/2024] Open
Abstract
Small bowel vascular malformation disease (SBVM) commonly causes obscure gastrointestinal bleeding (OGIB). However, the pathogenetic mechanism and the role of lncRNAs in SBVM remain largely unknown. Here, we found that hypoxia and low-glucose environments co-augment angiogenesis and existed in SBVM. Mechanistically, hypoxia and low-glucose environments supported angiogenesis via activation of hypoxia and glucose deprivation-induced lncRNA (HGDILnc1) transcription by increasing binding of the NeuroD1 transcription factor to the HGDILnc1 promoter. Raised HGDILnc1 acted as a suppressor of α-Enolase 1 (ENO1) small ubiquitin-like modifier modification (SUMOylation)-triggered ubiquitination, and an activator of transcription of Aldolase C (ALDOC) via upregulation of Histone H2B lysine 16 acetylation (H2BK16ac) level in the promoter of ALDOC, and consequently promoting glycolysis and angiogenesis. Moreover, HGDILnc1 was clinically positively correlated with Neurogenic differentiation 1 (NeuroD1), ENO1, and ALDOC in SBVM tissues, and could function as a biomarker for SBVM diagnosis and therapy. These findings suggest that hypoxia and low-glucose environments were present in SBVM tissues, and co-augmented angiogenesis. Hypoxia and low-glucose environments co-induced HGDILnc1, which is higher expressed in SBVM tissue compared with normal tissue, could promoted glycolysis and angiogenesis.
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Affiliation(s)
- Qing-Wei Zhang
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xiao-Lu Lin
- Department of Digestive Endoscopy Center, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Zi-Hao Dai
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Ran Zhao
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yi-Chao Hou
- Department of Gastroenterology, Shanghai Nineth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qian Liang
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yan Zhang
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Zhi-Zheng Ge
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
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Ashley RL, Trigo EM, Ervin JM. Placental insufficiency and heavier placentas in sheep after suppressing CXCL12/CXCR4 signaling during implantation†. Biol Reprod 2023; 109:982-993. [PMID: 37724932 PMCID: PMC10724462 DOI: 10.1093/biolre/ioad122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/28/2023] [Accepted: 09/15/2023] [Indexed: 09/21/2023] Open
Abstract
During implantation, trophoblast cell invasion and differentiation is predominantly important to achieving proper placental formation and embryonic development. The chemokine, C-X-C motif chemokine ligand 12 (CXCL12) working through its receptor C-X-C motif chemokine receptor 4 (CXCR4) is implicated in implantation and placentation but precise roles of this axis are unclear. Suppressing CXCL12/CXCR4 signaling at the fetal-maternal interface in sheep reduces trophoblast invasion, disrupts uterine remodeling, and diminishes placental vascularization. We hypothesize these negative impacts during implantation will manifest as compromised fetal and placental growth at midgestation. To test, on day 12 postbreeding, osmotic pumps were surgically installed in 30 ewes and delivered intrauterine CXCR4 inhibitor or saline for 7 or 14 days. On day 90, fetal/maternal tissues were collected, measured, weighed, and maternal (caruncle) and fetal (cotyledon) placenta components separated and analyzed. The objectives were to determine if (i) suppressing CXCL12/CXCR4 during implantation results in reduced fetal and placental growth and development and (ii) if varying the amount of time CXCL12/CXCR4 is suppressed impacts fetal/placental development. Fetal weights were similar; however greater placental weight and placentome numbers occurred when CXCL12/CXCR4 was suppressed for 14 days. In caruncles, greater abundance of fibroblast growth factor 2, vascular endothelial growth factor A, vascular endothelial growth factor A receptor 1 (FLT-1), and placental growth factor were observed after suppressing CXCL12/CXCR4. Similar results occurred in cotyledons except less vascular endothelial growth factor in 7 day group and less fibroblast growth factor in 14 day group. Our data underscore the importance of CXCL12/CXCR4 signaling during placentation and provide strong evidence that altering CXCL12-mediated signaling induces enduring placental effects manifesting later in gestation.
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Affiliation(s)
- Ryan L Ashley
- Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA
| | - Elisa M Trigo
- Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA
| | - Jacqueline M Ervin
- Department of Animal and Range Sciences, New Mexico State University, Las Cruces, NM, USA
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Jiang T, Cai Z, Mu M, Zhao Z, Shen C, Zhang B. The Global Burden of Vascular Intestinal Disorders in 204 Countries and Territories From 1990 to 2019: Global Burden of Diseases Study. Int J Public Health 2023; 68:1606297. [PMID: 37822566 PMCID: PMC10562586 DOI: 10.3389/ijph.2023.1606297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 08/21/2023] [Indexed: 10/13/2023] Open
Abstract
Objectives: Assess the prevalence, mortality, and disability-adjusted life years (DALYs) of vascular intestinal disorders (VID) from 1990 to 2019. Methods: This study conducted a secondary data analysis utilizing the Global Burden of Diseases Study 2019. The prevalence, mortality and DALYs of VID were analyzed by sex, age and socio-demographic index (SDI), respectively. Analyses were performed by using R software. Results: Globally, the number of prevalent VID cases increased from 100,158 (95% uncertainty interval: 89,428-114,013) in 1,990-175,740 (157,941-198,969) in 2019. However, the age-standardized rates (ASR) of VID prevalence declined from 2.47 (95% uncertainty interval: 2.24-2.76) per 100,000 population to 2.21 (1.98-2.48) per 100,000 population between 1990 and 2019. Furthermore, the ASR of mortality also decreased from 1990 to 2019. Between 1990 and 2019, the regions with high and high-middle level exhibited the highest diseases burden. Conclusion: Globally, the diseases burden associated with VID demonstrated a decline from 1990 to 2019. However, concerted efforts are still required to enhance measures to combat VID within countries categorized as high and high-middle SDI.
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Affiliation(s)
- Tianxiang Jiang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhaolun Cai
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Mingchun Mu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhou Zhao
- Department of Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China
| | - Chaoyong Shen
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Zhang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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Pezzoli A, Guarino M, Fusetti N, Pizzo E, Simoni M, Simone L, Cifalà V, Solimando R, Perna B, Testino G, Pellicano R, Caio G, Lungaro L, Caputo F, Zoli G, Merighi A, DE Giorgio R. Efficacy and safety of capsule endoscopy in octogenarian patients: a retrospective study. Minerva Gastroenterol (Torino) 2023; 69:388-395. [PMID: 35708039 DOI: 10.23736/s2724-5985.22.03220-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Abstract
BACKGROUND Life expectancy and the number of ultra-octogenarians increased significantly, thus making crucial the appropriateness of several endoscopic procedures in elderly patients. The aim of our study was to provide a retrospective analysis of the efficacy and safety of capsule endoscopy (CE) in patients aged over 80 years. METHODS In this single-centre study, 900 patients underwent capsule endoscopy between 2002 and 2015 for different indications; of these 106 patients aged ≥80 years (group A) and 99 patients aged 40-60 years (control group B) were retrospectively selected. RESULTS Occult gastrointestinal bleeding accounted for 62.1% of all indications for capsule endoscopy in group B, compared to 95.2% in group A (P<0.001). Although not statistically significant, the diagnostic yield was higher in group A (71%) vs. group B (62%). The percentages of reaching the cecum and the median gastric transit time were uniform within the two groups. In contrast, small bowel transit time was longer in group A vs. B. Small bowel preparation was similar in the two groups. The exam was generally well tolerated in both groups, with capsule aspiration being one of the main adverse events, which occurred in two elderly patients. CONCLUSIONS Our data expand previous findings confirming that capsule endoscopy can be performed safely even in very old patients and show that the diagnostic yield is similar to that of younger patients.
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Affiliation(s)
- Alessandro Pezzoli
- Department of Gastroenterology and Gastrointestinal Endoscopy, University Hospital of Ferrara, Ferrara, Italy
| | - Matteo Guarino
- Department of Translational Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Nadia Fusetti
- Department of Gastroenterology and Gastrointestinal Endoscopy, University Hospital of Ferrara, Ferrara, Italy
| | - Elena Pizzo
- Department of Applied Health Research, University College of London, London, UK
| | - Marzia Simoni
- Epidemiological Unit of CNR Institute of Clinical Physiology, Pisa, Italy
| | - Loredana Simone
- Department of Gastroenterology and Gastrointestinal Endoscopy, University Hospital of Ferrara, Ferrara, Italy
| | - Viviana Cifalà
- Department of Gastroenterology and Gastrointestinal Endoscopy, University Hospital of Ferrara, Ferrara, Italy
| | - Riccardo Solimando
- Department of Gastroenterology and Gastrointestinal Endoscopy, University Hospital of Ferrara, Ferrara, Italy
| | - Benedetta Perna
- Department of Translational Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Gianni Testino
- Unit of Addiction and Hepatology, Regional Centre on Alcohol, ASL3 San Martino Hospital, Genoa, Italy
| | | | - Giacomo Caio
- Department of Translational Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Lisa Lungaro
- Department of Translational Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Fabio Caputo
- Department of Translational Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Giorgio Zoli
- Department of Translational Medicine, University Hospital of Ferrara, Ferrara, Italy
| | - Alberto Merighi
- Department of Gastroenterology and Gastrointestinal Endoscopy, University Hospital of Ferrara, Ferrara, Italy
| | - Roberto DE Giorgio
- Department of Translational Medicine, University Hospital of Ferrara, Ferrara, Italy
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Sugino S, Inoue K, Zen K, Yashige M, Kobayashi R, Takamatsu K, Ito N, Iwai N, Hirose R, Doi T, Dohi O, Yoshida N, Uchiyama K, Takagi T, Ishikawa T, Konishi H, Matoba S, Itoh Y. Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde's Syndrome. Digestion 2023; 104:468-479. [PMID: 37619533 DOI: 10.1159/000533237] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 07/22/2023] [Indexed: 08/26/2023]
Abstract
INTRODUCTION Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.
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Affiliation(s)
- Satoshi Sugino
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan,
- Department of Gastroenterology and Hepatology, Asahi University Hospital, Gifu, Japan,
| | - Ken Inoue
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kan Zen
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Masaki Yashige
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Reo Kobayashi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuaki Takamatsu
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Nobuyasu Ito
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Naoto Iwai
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ryohei Hirose
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Toshifumi Doi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Osamu Dohi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Naohisa Yoshida
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuhiko Uchiyama
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomohisa Takagi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Ishikawa
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hideyuki Konishi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoaki Matoba
- Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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10
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Oommen A, Gautam K, Kumar A. Beyond Acquired Von Willebrand Deficiency: Exploring Alternative Mechanisms of Heyde's Syndrome. Cureus 2023; 15:e41494. [PMID: 37551240 PMCID: PMC10404466 DOI: 10.7759/cureus.41494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/06/2023] [Indexed: 08/09/2023] Open
Abstract
Heyde's syndrome (HS) is a complex condition characterized by the coexistence of severe aortic stenosis (AS) and gastrointestinal (GI) angiodysplasia. The prevailing belief has been that acquired von-Willebrand factor deficiency (AVWD) is the underlying cause of HS. However, the validity of this theory remains contentious, as there have been reports of bleeding angiodysplasia in the setting of AS despite normal von-Willebrand factor (vWF) activity. Here, we present a compelling case of HS with negative diagnostic testing for AVWD. A 61-year-old female with a history of end-stage renal disease on hemodialysis, AS, and a history of recurrent GI bleeding presented with dyspnea. Prior to arrival, she reported multiple episodes of melena and hematochezia and was found to have a hemoglobin of 6 g/dL. Notable exam findings included melenic stool on digital rectal exam and a grade three systolic crescendo-decrescendo murmur that radiated up to the carotids. A transthoracic echocardiogram demonstrated evidence of severe AS. Considering the recurrent GI bleeding and severe AS, HS was suspected. To investigate this further, a vWF disease panel was sent, revealing a normal multimeric pattern. Given hemodynamic stability, she was discharged but had multiple readmissions soon after with recurrent GI bleeding requiring endoscopic intervention. On her last visit, she underwent transcatheter aortic valve replacement (TAVR) with notable resolution in her GI bleeds thereafter. The prevailing theory regarding the etiology of HS is acquired vWF deficiency. However, the validity of this theory remains a topic of debate, as a growing body of evidence suggests that the absence of AVWD does not necessarily rule out the diagnosis. The absence of AVWD in our patient raises questions about its prevalence in HS and its status as a key feature and highlights the importance of considering HS events without AVWD, given the risk of recurrent life-threatening GI bleeds.
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Affiliation(s)
- Alvin Oommen
- Internal Medicine, Montefiore Medical Center, New York, USA
| | - Kripali Gautam
- Internal Medicine, New York University (NYU) Langone Health, New York, USA
| | - Akash Kumar
- Gastroenterology, Montefiore Medical Center, New York, USA
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11
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Ocran E, Chornenki NLJ, Bowman M, Sholzberg M, James P. Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations. Expert Rev Hematol 2023; 16:575-584. [PMID: 37278227 DOI: 10.1080/17474086.2023.2221846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 06/01/2023] [Indexed: 06/07/2023]
Abstract
INTRODUCTION Severe and recurrent gastrointestinal (GI) bleeding caused by angiodysplasia is a significant problem in patients with von Willebrand disease (VWD) and in those with acquired von Willebrand syndrome (AVWS). At present, angiodysplasia-related GI bleeding is often refractory to standard treatment including replacement therapy with von Willebrand factor (VWF) concentrates and continues to remain a major challenge and cause of significant morbidity in patients despite advances in diagnostics and therapeutics. AREAS COVERED This paper reviews the available literature on GI bleeding in VWD patients, examines the molecular mechanisms implicated in angiodysplasia-related GI bleeding, and summarizes existing strategies in the management of bleeding GI angiodysplasia in patients with VWF abnormalities. Suggestions are made for further research directions. EXPERT OPINION Bleeding from angiodysplasia poses a significant challenge for individuals with abnormal VWF. Diagnosis remains a challenge and may require multiple radiologic and endoscopic investigations. Additionally, there is a need for enhanced understanding at a molecular level to identify effective therapies. Future studies of VWF replacement therapies using newer formulations as well as other adjunctive treatments to prevent and treat bleeding will hopefully improve care.
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Affiliation(s)
- Edwin Ocran
- Department of Medicine, Queen's University, Kingston, Canada
| | | | | | - Michelle Sholzberg
- Division of Hematology-Oncology, St. Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Canada
| | - Paula James
- Department of Medicine, Queen's University, Kingston, Canada
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12
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Molineros Barón C, Roa Ballestas PA. Epidemiología, diagnóstico y tratamiento de las angiectasias gastrointestinales. UNIVERSITAS MÉDICA 2023. [DOI: 10.11144/javeriana.umed64-1.edta] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Las angiectasias son las malformaciones vasculares mas comunes en el tracto gastrointestinal en la población general. Hasta el momento, la patogénesis de este tipo de malformaciones vasculares no ha esclarecida totalmente. Su incidencia ha venido en aumento debido a la mayor disponibilidad de métodos diagnósticos en gastroenterología, principalmente la videocápsula endoscópica (VCE) y la enteroscopia profunda asistida para el estudio del intestino delgado.
La terapia endoscópica es la estrategia de tratamiento inicial más efectiva, sin embargo existen otras alternativas terapéuticas como lo son la terapia farmacológica, la angiografía más embolización selectiva o la resección quirúrgica.
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13
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Del Cueto-Aguilera Á, García-Compeán D, Jiménez-Rodríguez A, Borjas-Almaguer O, Wah-Suárez M, González-González J, Maldonado-Garza H. Efficacy of octreotide in bleeding recurrence from small bowel angioectasia: A comparative study. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:411-419. [DOI: 10.1016/j.rgmxen.2022.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 02/05/2021] [Indexed: 02/07/2023] Open
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14
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Iio S, Oka S, Sumioka A, Tsuboi A, Tanaka H, Yamashita K, Hiyama Y, Kotachi T, Takigawa H, Hayashi R, Yuge R, Urabe Y, Tanaka S. Characteristics and Treatment Outcomes of Small-bowel Angioectasia in Systemic Sclerosis Patients: A Retrospective Observational Study. Intern Med 2022; 61:615-622. [PMID: 34433725 PMCID: PMC8943382 DOI: 10.2169/internalmedicine.8034-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Objective Systemic sclerosis (SSc) is defined as an autoimmune disease presenting with fibrosis of various organs and vascular endothelial damage. Vascular lesions, including small-bowel angioectasias, are also frequently detected in SSc patients. Polidocanol injection (PDI) is a safe and effective hemostatic treatment for gastrointestinal bleeding. We evaluated the outcomes of PDI for small-bowel angioectasia in SSc patients. Methods We retrospectively evaluated 65 consecutive SSc patients (61 women; mean age, 64.3 years old) who underwent capsule endoscopy (CE) and/or double-balloon endoscopy at Hiroshima University Hospital between April 2012 and December 2019. Patients Patients were stratified according to the presence of small-bowel angioectasia. Among patients who underwent CE during the same period, those with small-bowel angioectasia without concomitant diseases were compared with SSc patients with small-bowel angioectasia. Clinical and endoscopic characteristics, treatment outcomes, and the incidence of metachronous small-bowel angioectasia after PDI were evaluated. Results SSc patients with small-bowel angioectasia exhibited significantly lower hemoglobin levels and a significantly higher incidence of skin telangiectasia than those without small-bowel angioectasia. On a multivariate analysis of the presence of small-bowel angioectasia, anemia and skin telangiectasia were significant independent factors. SSc patients with small-bowel angioectasia included a higher proportion of women and exhibited a significantly higher incidence of metachronous small-bowel angioectasia than X. The characteristics of small-bowel angioectasia and outcomes of PDI were not significantly different between the two groups. No post-treatment rebleeding cases or adverse events were noted. Conclusion CE should be performed for SSc patients with anemia and/or skin telangiectasia. PDI is effective for SSc patients with small-bowel angioectasia.
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Affiliation(s)
- Sumio Iio
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Japan
| | - Shiro Oka
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Japan
| | - Akihiko Sumioka
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Japan
| | - Akiyoshi Tsuboi
- Department of Endoscopy, Hiroshima University Hospital, Japan
| | - Hidenori Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Japan
| | - Ken Yamashita
- Department of Endoscopy, Hiroshima University Hospital, Japan
| | - Yuichi Hiyama
- Department of Endoscopy, Hiroshima University Hospital, Japan
| | | | | | - Ryohei Hayashi
- Department of Endoscopy, Hiroshima University Hospital, Japan
| | - Ryo Yuge
- Department of Endoscopy, Hiroshima University Hospital, Japan
| | - Yuji Urabe
- Department of Regeneration and Medicine Center for Translational and Clinical Research, Hiroshima University Hospital, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Japan
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15
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Del Cueto-Aguilera Á, García-Compeán D, Jiménez-Rodríguez A, Borjas-Almaguer O, Wah-Suárez M, González-González J, Maldonado-Garza H. Eficacia del octreótido sobre la recurrencia hemorrágica de las angiectasias del intestino delgado. Estudio comparativo. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2022. [DOI: 10.1016/j.rgmx.2021.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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16
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Shaw MYV, Asokkumar R, Tan Kwong Wei EJ, Seow-En I. Colonic angiodysplasia: a culprit of obscure gastrointestinal bleeding in a patient with Heyde syndrome. BMJ Case Rep 2022; 15:15/1/e247595. [PMID: 35027388 PMCID: PMC8762101 DOI: 10.1136/bcr-2021-247595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
A 77-year-old woman presented with obscure gastrointestinal bleeding requiring multiple hospitalisations and blood transfusions. The patient underwent repeated investigations over four hospital admissions across a span of two months. These included upper and lower gastrointestinal endoscopy, video capsule endoscopy as well as CT enterography, without definitive localisation or treatment of the source of bleeding. Finally, a technetium-99m-labelled red blood cell scan demonstrated a ‘blush’ at the proximal transverse colon on delayed imaging. Targeted colonoscopic evaluation showed a subcentimetre angiodysplastic lesion in the corresponding spot at the proximal transverse colon with slow persistent oozing. Endoscopic clips were applied with successful haemostasis. The patient recovered well without further symptom recurrence 5 months postdischarge. We review the literature on colonic angiodysplasias and discuss the diagnostic challenges in obscure gastrointestinal bleeding.
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Affiliation(s)
| | | | | | - Isaac Seow-En
- General Surgery, Singapore General Hospital, Singapore
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17
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Abstract
Low flow and suction alarms are provided to alert caregivers of changes in left ventricular assist device pump function but may be reset in clinical practice. We investigated the incidence and underlying causes of these alarms as well as their prognostic significance. HeartWare ventricular assist device patients (n = 113) were divided into quartiles based on their frequency of low flow and suction alarms. Survival and adverse events (thrombus, stroke, bleeding, and right heart failure) were compared between quartiles. Low flow alarms peaked in the first few months of pump support before dropping down to near negligible levels. Suction alarm frequency remained relatively constant throughout pump support. Although pump speeds (p < 0.001) and flow (p = 0.01) decreased over time, there was an increase in suction alarm frequency (p = 0.018), with no changes in low flow alarms. Patients with smaller body size (p = 0.016) and lower pump flows (p = 0.008) had higher frequencies of low flow alarms on multiple regression (p < 0.001). Patients with the highest low flow alarm frequency demonstrated poorer survival (p = 0.026). There was no relationship between suction alarm frequency and survival. There was also no relationship between either low flow or suction alarm frequency with strokes, gastrointestinal bleeds, pump thrombus, or right ventricular failure. Duration of alarm and intervention in response to the alarm was not assessed in this study. Further studies examining alarm duration and responses may inform future pump alarm algorithms.
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18
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Xu L, Xu F, Wang Q, Ke X. Hereditary hemorrhagic telangiectasia with liver cirrhosis: a case report. BMC Gastroenterol 2021. [PMID: 34488642 DOI: 10.1186/s12876-021-01913-3.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hereditary hemorrhagic telangiectasia is an autosomal dominant hereditary hemorrhagic disease. Its main feature is an abnormal structure of the blood vessel wall. Cirrhosis of the liver is a common chronic progressive disease with one or more causes in which diffuse liver damage occurs after long-term or repeated injury. Liver cirrhosis can cause dilation of gastrointestinal capillaries. Many patients with hereditary hemorrhagic telangiectasia accompanied by gastrointestinal vascular malformations and liver cirrhosis may be diagnosed only with liver cirrhosis if the clinician does not pay attention to physical examination findings and family history. Moreover, general treatment measures, such as blood transfusion, iron supplementation, and application of hemostatic drugs, are less effective for bleeding in patients with hereditary hemorrhagic telangiectasia than in those with liver cirrhosis alone. CASE PRESENTATION Here, we report the rare case of a 75-year-old Chinese man who was admitted to the hospital with repeated melena and epistaxis. He was diagnosed with unexplained liver cirrhosis, which was later confirmed as hereditary hemorrhagic telangiectasia. Subsequently, we implemented the treatment intervention of oral thalidomide combined with gastrointestinal argon plasma coagulation. A follow-up of more than 8 months showed that the treatment effect was excellent. CONCLUSIONS If patients with liver cirrhosis and gastrointestinal vascular malformations also have a family history of epistaxis, special attention should be paid to targeted physical examination results, and the possibility of hereditary hemorrhagic telangiectasia should be considered. Moreover, for patients with hereditary hemorrhagic telangiectasia and both gastrointestinal bleeding caused by gastrointestinal capillaries and repeated epistaxis, when other general treatment measures are ineffective, thalidomide combined with gastrointestinal argon plasma coagulation may be an effective intervention.
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Affiliation(s)
- Linxia Xu
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China
| | - Feng Xu
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China
| | - Xiquan Ke
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China.
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19
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Xu L, Xu F, Wang Q, Ke X. Hereditary hemorrhagic telangiectasia with liver cirrhosis: a case report. BMC Gastroenterol 2021; 21:343. [PMID: 34488642 PMCID: PMC8422673 DOI: 10.1186/s12876-021-01913-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 08/17/2021] [Indexed: 11/30/2022] Open
Abstract
Background Hereditary hemorrhagic telangiectasia is an autosomal dominant hereditary hemorrhagic disease. Its main feature is an abnormal structure of the blood vessel wall. Cirrhosis of the liver is a common chronic progressive disease with one or more causes in which diffuse liver damage occurs after long-term or repeated injury. Liver cirrhosis can cause dilation of gastrointestinal capillaries. Many patients with hereditary hemorrhagic telangiectasia accompanied by gastrointestinal vascular malformations and liver cirrhosis may be diagnosed only with liver cirrhosis if the clinician does not pay attention to physical examination findings and family history. Moreover, general treatment measures, such as blood transfusion, iron supplementation, and application of hemostatic drugs, are less effective for bleeding in patients with hereditary hemorrhagic telangiectasia than in those with liver cirrhosis alone. Case presentation Here, we report the rare case of a 75-year-old Chinese man who was admitted to the hospital with repeated melena and epistaxis. He was diagnosed with unexplained liver cirrhosis, which was later confirmed as hereditary hemorrhagic telangiectasia. Subsequently, we implemented the treatment intervention of oral thalidomide combined with gastrointestinal argon plasma coagulation. A follow-up of more than 8 months showed that the treatment effect was excellent. Conclusions If patients with liver cirrhosis and gastrointestinal vascular malformations also have a family history of epistaxis, special attention should be paid to targeted physical examination results, and the possibility of hereditary hemorrhagic telangiectasia should be considered. Moreover, for patients with hereditary hemorrhagic telangiectasia and both gastrointestinal bleeding caused by gastrointestinal capillaries and repeated epistaxis, when other general treatment measures are ineffective, thalidomide combined with gastrointestinal argon plasma coagulation may be an effective intervention.
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Affiliation(s)
- Linxia Xu
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China
| | - Feng Xu
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China
| | - Xiquan Ke
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China.
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20
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Johnson AM, Chovwen PE, Akpan EJ, Patel A. Aortic Valve Stenosis, a Precipitating Factor of Recurrent Bleed in Colonic Angiodysplasia: A Literature Review. Cureus 2021; 13:e15903. [PMID: 34322347 PMCID: PMC8310456 DOI: 10.7759/cureus.15903] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2021] [Indexed: 12/16/2022] Open
Abstract
Angiodysplasia (also known as angioectasia) is a lesion characterized by abnormal, dilated small blood vessels in the mucosa and submucosal layers of the GI tract. With the estimated low incidence of active GI bleeding from these lesions, angiodysplasia can be challenging to diagnose. The presence of aortic stenosis has increased the recognition rate of angiodysplasia, especially in the elderly. Despite the associations between aortic stenosis and angiodysplasia (Heyde's syndrome) revealed in several studies, the etiology of Heyde syndrome is still debatable, which has led to the proposition of several hypotheses that are reviewed in this article. This activity will help review the meaning of Heyde's syndrome, epidemiology, proposed pathophysiology, diagnosis, and management by surveying articles published between 1955 and 2021 on PubMed. We used search terms such as "colonic angiodysplasia," "arteriovenous malformation," "Heyde syndrome," "refractory gastrointestinal bleed," "aortic valve stenosis," and "acquired von Willebrand disease." Findings revealed an association between aortic stenosis and lower gastrointestinal (GI) bleed.
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Affiliation(s)
| | | | - Ezekiel J Akpan
- Medicine, All Saints University College of Medicine, Kingstown, VCT
| | - Anna Patel
- Gastroenterology and Hepatology, Community First Medical Center, Chicago, USA
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21
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Abnormalities in the Von Willebrand-Angiopoietin Axis Contribute to Dysregulated Angiogenesis and Angiodysplasia in Children With a Glenn Circulation. JACC Basic Transl Sci 2021; 6:222-235. [PMID: 33778210 PMCID: PMC7987544 DOI: 10.1016/j.jacbts.2020.12.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 12/22/2020] [Accepted: 12/22/2020] [Indexed: 02/08/2023]
Abstract
Children with a bidirectional superior cavopulmonary connection (Glenn circulation) develop dysregulated angiogenesis and pulmonary angiodysplasia in the form of arteriovenous malformations (AVMs). No targeted therapy exists. The von Willebrand factor (vWF)–angiopoietin axis plays a major role in normal angiogenesis, angiodysplasia, and AVM formation in multiple diseases. vWF and angiopoietin-2 (which destabilizes vessel formation) were abnormal in children with a Glenn circulation versus control children. Within Glenn patients, angiopoietin-1 (which stabilizes vessel formation) and angiogenesis were different in the systemic versus pulmonary circulation. Plasma angiopoietin-1 was lower in the pulmonary circulation of Glenn patients with pulmonary AVMs than Glenn patients without AVMs. In parallel, differences in multiple angiogenic and inflammatory signaling peptides were observed between Glenn patients and controls, which indicated derangements in multiple angiogenic pathways in Glenn patients. These findings support the novel hypothesis that abnormal vWF metabolism and angiopoietin signaling dysregulate angiogenesis and contribute to pulmonary AVM formation in children with a Glenn circulation. The vWF-angiopoietin axis may be a target to correct angiogenic imbalance and reduce pulmonary angiodysplasia in Glenn patients. Children with a bidirectional superior cavopulmonary (Glenn) circulation develop angiodysplasia and pulmonary arteriovenous malformations (AVMs). The von Willebrand factor (vWF)–angiopoietin axis plays a major role in AVM formation in multiple diseases. We observed derangements in global angiogenic signaling, vWF metabolism, angiopoietins, and in vitro angiogenesis in children with a Glenn circulation versus controls and within Glenn pulmonary versus systemic circulations. These findings support the novel hypothesis that abnormalities in the vWF-angiopoietin axis may dysregulate angiogenesis and contribute to Glenn pulmonary AVMs. The vWF-angiopoietin axis may be a target to correct angiogenic imbalance in Glenn patients, for whom no targeted therapy exists.
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Key Words
- ADAMTS-13, a disintegrin and metalloproteinase thrombospondin (motif) #13
- AVM, arteriovenous malformation
- EBM, endothelial basal media
- EGM, endothelial growth media
- Glenn
- HUVEC, human umbilical vein endothelial cell
- IVC, inferior vena cava
- LVAD, left ventricular assist device
- PA, pulmonary artery
- SVC, superior vena cava
- angiogenesis
- angiopoietin
- arteriovenous malformation
- vWF, von Willebrand factor
- von Willebrand factor
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22
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Mondal S, Hollander KN, Ibekwe SO, Williams B, Tanaka K. Heyde Syndrome-Pathophysiology and Perioperative Implications. J Cardiothorac Vasc Anesth 2020; 35:3331-3339. [PMID: 33132021 DOI: 10.1053/j.jvca.2020.10.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 10/02/2020] [Accepted: 10/04/2020] [Indexed: 11/11/2022]
Abstract
Gastrointestinal (GI) bleeding in patients with calcific aortic valve stenosis (AVS), termed Heyde syndrome, was first described by Edward C. Heyde. The strong association between valvular replacement and the eradication of clinically significant GI bleeding confirmed an underlying pathophysiologic relationship. The rheologic stress created by AVS increases proteolysis of von Willebrand factor (VWF), resulting in loss of predominantly high-molecular-weight VWF (Hmw VWF). Angiodysplastic vessels present in patients with AVS, coupled with the lack of functioning Hmw VWF, increase the risk for GI bleeds. Aortic valve replacement, both surgical and transcatheter-based, is often a definitive treatment for GI bleeding, leading to recovery of Hmw VWF multimers. Perioperative management of patients involves monitoring their coagulation profiles with relevant laboratory tests and instituting appropriate management. Management can be directed in the following two ways: by improving internal release of VWF or by administration of external therapeutics containing VWF. It is important for perioperative physicians to obtain an understanding of the pathophysiology of this disease process and closely monitor the bleeding pattern so that targeted therapies can be initiated.
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Affiliation(s)
- Samhati Mondal
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD.
| | - Kimberly N Hollander
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD
| | - Stephanie O Ibekwe
- Department of Anesthesiology, Cardiovascular Division, BTGH, Baylor College of Medicine, Houston, TX
| | - Brittney Williams
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD
| | - Kenichi Tanaka
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD
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23
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Sarangdhar M, Yacyshyn MB, Gruenzel AR, Engevik MA, Harris NL, Aronow BJ, Yacyshyn BR. Therapeutic Opportunities for Intestinal Angioectasia- Targeting PPARγ and Oxidative Stress. Clin Transl Sci 2020; 14:518-528. [PMID: 33048460 PMCID: PMC7993272 DOI: 10.1111/cts.12899] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 08/30/2020] [Indexed: 01/22/2023] Open
Abstract
Recurrent and acute bleeding from intestinal tract angioectasia (AEC) presents a major challenge for clinical intervention. Current treatments are empiric, with frequent poor clinical outcomes. Improvements in understanding the pathophysiology of these lesions will help guide treatment. Using data from the US Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS), we analyzed 12 million patient reports to identify drugs inversely correlated with gastrointestinal bleeding and potentially limiting AEC severity. FAERS analysis revealed that drugs used in patients with diabetes and those targeting PPARγ-related mechanisms were associated with decreased AEC phenotypes (P < 0.0001). Electronic health records (EHRs) at University of Cincinnati Hospital were analyzed to validate FAERS analysis. EHR data showed a 5.6% decrease in risk of AEC and associated phenotypes in patients on PPARγ agonists. Murine knockout models of AEC phenotypes were used to construct a gene-regulatory network of candidate drug targets and pathways, which revealed that wound healing, vasculature development and regulation of oxidative stress were impacted in AEC pathophysiology. Human colonic tissue was examined for expression differences across key pathway proteins, PPARγ, HIF1α, VEGF, and TGFβ1. In vitro analysis of human AEC tissues showed lower expression of PPARγ and TGFβ1 compared with controls (0.55 ± 0.07 and 0.49 ± 0.05). National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) RNA-Seq data was analyzed to substantiate human tissue findings. This integrative discovery approach showing altered expression of key genes involved in oxidative stress and injury repair mechanisms presents novel insight into AEC etiology, which will improve targeted mechanistic studies and more optimal medical therapy for AEC.
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Affiliation(s)
- Mayur Sarangdhar
- Department of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Mary B Yacyshyn
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, Ohio, USA
| | - Andrew R Gruenzel
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Department of Anesthesiology, Cleveland Clinic, Cleveland, Ohio, USA
| | - Melinda A Engevik
- Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, Ohio, USA.,Department of Pathology, Baylor College of Medicine, Houston, Texas, USA
| | - Nathaniel L Harris
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Bruce J Aronow
- Department of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Bruce R Yacyshyn
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, Ohio, USA.,Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky, USA
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Douglas AR, Holleran G, Smith SM, McNamara D. Shared changes in angiogenic factors across gastrointestinal vascular conditions: A pilot study. World J Gastrointest Pharmacol Ther 2020; 11:40-47. [PMID: 32844042 PMCID: PMC7416378 DOI: 10.4292/wjgpt.v11.i3.40] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/11/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neovascularisation is common to a variety of gastrointestinal (GI) disorders with differing aetiologies and presentations; usually affecting adults above 60 years. Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets. As yet, assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported.
AIM To assess serum levels of angiogenic factors in several intestinal vascular disorders.
METHODS A case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia (SBA), portal hypertensive gastropathy (PHG), gastric antral vascular ectasia (GAVE) and non-bleeding, non-anaemic controls. Using enzyme-linked immunosorbent assay, concentrations of Angiopoietin 1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) were measured from 2 serum tubes of blood following informed consent. The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups. Statistical analysis was applied using a t-test, and a P value of < 0.05 was considered significant.
RESULTS To date 44 samples were tested: 10 SBA, 11 PHG, 8 GAVE and 15 controls. Mean age 60 (range 20-85) years and 20 (45%) were males. Controls were significantly younger (49 years vs 66 years, P = 0.0005). There was no difference in VEGF levels between the groups (P = 0.6). SBA, PHG and GAVE Ang-1 levels were similar and were significantly lower than controls, (P = 0.0002, 95%CI: 241 to 701). Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls (P = 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratios compared to controls. While SBA Ang-2 levels were higher than controls, this did not reach statistical significance. Neither age nor haemoglobin level, which was similar between disease groups, could explain the difference. In addition, the median Ang-1/Ang-2 ratio for all patients was found to be significantly lower compared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12.
CONCLUSION Our novel pilot study suggests common alterations in Ang-1 and Ang-2 levels across several GI vascular disorders. Differences in Ang-1/Ang-2 ratios among vascular disorders compared to controls suggest disease-specific modulation.
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Affiliation(s)
| | - Grainne Holleran
- TAGG Research Centre, School of Medicine, Trinity College Dublin, Dublin D24, Ireland
| | - Sinead M Smith
- TAGG Research Centre, School of Medicine, Trinity College Dublin, Dublin D24, Ireland
| | - Deirdre McNamara
- TAGG Research Centre, School of Medicine, Trinity College Dublin, Dublin D24, Ireland
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25
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Bayudan AM, Chen CH. Thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities. World J Clin Cases 2020; 8:3218-3229. [PMID: 32874976 PMCID: PMC7441260 DOI: 10.12998/wjcc.v8.i15.3218] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 06/15/2020] [Accepted: 07/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Refractory gastrointestinal bleeding (GIB) secondary to gastrointestinal vascular malformations (GIVM) such as gastrointestinal angiodysplasia (GIAD) and gastric antral vascular ectasia (GAVE) remains challenging to treat when endoscopic therapy fails. Recently thalidomide has been suggested as a treatment option for refractory GIB.
AIM To determine the outcome of patients treated with thalidomide for refractory GIB due to GIVM.
METHODS IRB approved, single center, 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 who had been treated with thalidomide for at least 3 mo were included. The primary endpoint was recurrence of GIB 6 mo after initiation of thalidomide.
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).
CONCLUSION Thalidomide appears to be an effective treatment for refractory GIB due to GIAD or GAVE in a Western population with significant comorbidities.
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Affiliation(s)
- 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
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26
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Lara LF, Silva R, Thakkar S, Stanich PP, Mai D, Samarasena JB. Multicenter case series of patients with small-bowel angiodysplasias treated with a small-bowel radiofrequency ablation catheter. VideoGIE 2020; 5:162-167. [PMID: 32258850 PMCID: PMC7125393 DOI: 10.1016/j.vgie.2019.11.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Background and Aims GI angiodysplasia is the most common cause of small-bowel bleeding. Argon plasma coagulation (APC) is preferred for ablation because of its availability, ease of use, and perceived safety, but it has limitations. An instrument capable of repeated use through the enteroscope, which covers more area of intestinal mucosa per treatment with low risk of damage to healthy mucosa, and which improves ablation, is desirable. A series of patients treated with a through-the-scope radiofrequency ablation (RFA) catheter is reported. Methods Patients with a previous diagnosis of small-bowel angiodysplasia (SBA) and ongoing bleeding with melena, hematochezia, or iron-deficiency anemia were eligible for treatment. A small-bowel radiofrequency ablation (SBRFA) catheter was passed through the enteroscope instrument channel. The treatment paddle was pushed against the SBA, achieving coaptive coagulation, and the SBA was treated up to 2 times at standard settings of 10 J/cm2. The patients' demographics, pretreatment and posttreatment hemoglobin levels, time to recurrence of bleeding, and need for more therapy were recorded. This study was approved by the institutional review boards of the respective institutions. Results Twenty consecutive patients were treated from March until October 2018 and followed up until March 2019. There were 6 women (average age 68 years, standard deviation ± 11.1), and 14 men (average age 73 years, standard deviation ± 10.4). All had undergone at least 1 previous EGD and colonoscopy; 14 patients (70%) had SBA on video capsule endoscopy, and 14 patients had undergone previous endoscopic treatment of SBA with APC. A median of 23 treatments were applied (range, 2-99). The median follow-up time was 195 days (range, 30-240 days). Four patients, including 3 with a left ventricular assist device (LVAD), had recurrent bleeding between 45 and 210 days after treatment, and 2 patients received repeated blood transfusions. Three of those patients underwent repeated endoscopies, including a push enteroscopy and an upper endoscopy with no treatment, and a repeated enteroscopy with SBA treated with APC, respectively. One patient with LVAD underwent arterial embolization. Conclusions In this case series, bleeding recurred in 20% of patients in a follow-up time of ≤240 days. Notably, 3 of the 4 patients who had recurrent bleeding had an LVAD. These rates compare favorably with reported bleeding recurrence after APC of SBA. More studies on the benefits of SBRFA, which may include reduced risk of recurrent bleeding or prolonging the time to recurrent bleeding, resource utilization, and factors associated with bleeding recurrence are needed.
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Affiliation(s)
- Luis F Lara
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Rogelio Silva
- Advocate Christ Medical Center, Oak Lawn, Illinois, USA
| | - Shyam Thakkar
- Allegheny Health Network, Pittsburgh, Pennsylvania, USA
| | - Peter P Stanich
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Daniel Mai
- University of California, Irvine, California USA
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27
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Intravenous bevacizumab as a novel treatment for refractory left ventricular assist device-related gastrointestinal bleeding. J Heart Lung Transplant 2020; 39:492-495. [PMID: 32173217 DOI: 10.1016/j.healun.2020.02.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 12/30/2019] [Accepted: 02/14/2020] [Indexed: 11/21/2022] Open
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28
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Patel H, Mehershahi S, Shaikh DH, Makker J, Nayudu S, Remy P, Chilimuri S. Thalidomide for the treatment of angiodysplasia-related recurrent gastrointestinal hemorrhage: Is low dose a safe and viable option? Clin Case Rep 2019; 7:2363-2367. [PMID: 31893059 PMCID: PMC6935600 DOI: 10.1002/ccr3.2501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/01/2019] [Accepted: 08/25/2019] [Indexed: 12/16/2022] Open
Abstract
Thalidomide is often used for the management of refractory gastrointestinal angiodysplasia (GIAD). The tolerance, toxic profile, and compliance of thalidomide are dose-dependent. The low-dose thalidomide (50 mg) is safe and a viable option for bleeding related to GIAD.
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Affiliation(s)
- Harish Patel
- Division of GastroenterologyBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
- Department of MedicineBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
| | - Shehriyar Mehershahi
- Division of GastroenterologyBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
- Department of MedicineBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
| | - Danial Haris Shaikh
- Division of GastroenterologyBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
- Department of MedicineBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
| | - Jasbir Makker
- Division of GastroenterologyBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
- Department of MedicineBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
| | - Sureshkumar Nayudu
- Division of GastroenterologyBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
- Department of MedicineBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
| | - Prospere Remy
- Division of GastroenterologyBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
- Department of MedicineBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
| | - Sridhar Chilimuri
- Division of GastroenterologyBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
- Department of MedicineBronxCare Hospital Center a Clinical Affiliate of Mt Sinai Health Systems and Academic affiliate of Icahn School of MedicineBronxNew York
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29
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Bartoli CR, Zhang DM, Hennessy-Strahs S, Kang J, Restle DJ, Bermudez C, Atluri P, Acker MA. Clinical and In Vitro Evidence That Left Ventricular Assist Device-Induced von Willebrand Factor Degradation Alters Angiogenesis. Circ Heart Fail 2019; 11:e004638. [PMID: 30354363 DOI: 10.1161/circheartfailure.117.004638] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background Gastrointestinal bleeding from angiodysplasia is a major problem in continuous-flow left ventricular assist device (LVAD) patients. LVAD shear stress causes pathologic degradation of VWF (von Willebrand factor). A mechanistic relationship between VWF degradation and angiodysplasia has not been explored. We tested 2 novel hypotheses: (1) clinical hypothesis: VWF fragments are elevated in LVAD patients that develop angiodysplasia and (2) in vitro hypothesis: VWF fragments generated during LVAD support alter angiogenesis, which may contribute to angiodysplasia. Methods and Results Clinical study: Paired blood samples were collected from continuous-flow LVAD patients (n=35). VWF was quantified with immunoblotting. In vitro experiments: (1) To investigate whether LVAD support alters angiogenesis, human endothelial cells were cultured with LVAD patient plasma (n=11). To investigate mechanism, endothelial cells were cultured with VWF fragments produced by exposing human VWF and ADAMTS-13 (VWF protease) to LVAD-like shear stress (175 dyne/cm2, n=8). Clinical study results: in all patients (n=35, mean support 666±430 days), LVAD support degraded high-molecular-weight VWF multimers ( P<0.0001) into low-molecular-weight VWF multimers ( P<0.0001) and VWF fragments ( P<0.0001). In patients with gastrointestinal bleeding from angiodysplasia (n=7), VWF fragments were elevated ( P=0.02) versus nonbleeders. In contrast, in patients with gastrointestinal bleeding without angiodysplasia, VWF fragments were not elevated versus nonbleeders ( P=0.96). In vitro experiments results: LVAD patient plasma caused abnormal angiogenesis with reduced tubule length ( P=0.04) and migration ( P=0.05). Similarly, endothelial cells grown with VWF degradation fragments exhibited reduced tubule length ( P<0.001) and migration ( P=0.01). Conclusions LVAD patients who bled from angiodysplasia had higher levels of VWF fragments than nonbleeders and gastrointestinal bleeders without angiodysplasia. VWF fragments caused abnormal angiogenesis in vitro. These findings suggest that VWF fragments may be a mechanistic link between LVAD support, abnormal angiogenesis, angiodysplasia, and gastrointestinal bleeding.
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Affiliation(s)
- Carlo R Bartoli
- Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia (C.R.B., S.H.-S., C.B., P.A., M.A.A.)
| | - David M Zhang
- Washington University, School of Medicine, St Louis, MO (D.M.Z.)
| | - Samson Hennessy-Strahs
- Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia (C.R.B., S.H.-S., C.B., P.A., M.A.A.)
| | - Jooeun Kang
- Vanderbilt University School of Medicine, Nashville, TN (J.K.)
| | | | - Christian Bermudez
- Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia (C.R.B., S.H.-S., C.B., P.A., M.A.A.)
| | - Pavan Atluri
- Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia (C.R.B., S.H.-S., C.B., P.A., M.A.A.)
| | - Michael A Acker
- Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia (C.R.B., S.H.-S., C.B., P.A., M.A.A.)
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Tsuchiya S, Matsumoto Y, Doman T, Fujiya T, Sugisawa J, Suda A, Sato K, Ikeda S, Shindo T, Kikuchi Y, Hao K, Takahashi J, Hatta W, Koike T, Masamune A, Saiki Y, Horiuchi H, Shimokawa H. Disappearance of Angiodysplasia Following Transcatheter Aortic Valve Implantation in a Patient with Heyde's Syndrome: A Case Report and Review of the Literature. J Atheroscler Thromb 2019; 27:271-277. [PMID: 31378751 PMCID: PMC7113142 DOI: 10.5551/jat.49239] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
An 83-year-old woman with severe aortic stenosis was admitted to our hospital due to heart failure with refractory anemia requiring blood transfusions. She had repetitive bleeding episodes from endoscopically proven angiodysplasia in the stomach. Moreover, she repeatedly underwent endoscopic argon plasma coagulation for hemostasis. Importantly, she had a deficiency of the high-molecular-weight (HMW) multimers of von Willebrand factor (VWF), and she was diagnosed with Heyde's syndrome.After she underwent transcatheter aortic valve implantation (TAVI), aortic valve area and mean left ventricular aorta pressure gradient improved. Notably, endoscopy showed cessation of bleeding at 10 days after TAVI and the disappearance of angiodysplasia at 4 months after TAVI. Even at 2 years after TAVI, follow-up endoscopy showed remaining free of angiodysplasia in the stomach. She experienced no episodes of anemia since TAVI procedure. Additionally, analysis of HMW multimers demonstrated immediate and lasting recovery after TAVI.Recovery of HMW multimers of VWF with cessation of gastrointestinal bleeding following aortic valve replacement has been previously reported in a patient diagnosed with Heyde's syndrome. To the best our knowledge, this is the first case to demonstrate that angiodysplasia disappears after TAVI for a long term with endoscopic images in a patient with Heyde's syndrome. Here, we summarized case reports of patients with Heyde's syndrome that required aortic valve intervention. Cessation of gastrointestinal bleeding and anemia after aortic valve intervention for severe aortic stenosis may be attributed not only to recovery of HMW multimers of VWF but also to the disappearance of angiodysplasia.
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Affiliation(s)
- Satoshi Tsuchiya
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Yasuharu Matsumoto
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Tsuyoshi Doman
- Department of Molecular and Cellular Biology, Institute of Development, Aging, and Cancer, Tohoku University
| | - Taku Fujiya
- Department of Gastroenterology, Tohoku University Graduate School of Medicine
| | - Jun Sugisawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Akira Suda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Koichi Sato
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Shohei Ikeda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Tomohiko Shindo
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Yoku Kikuchi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Kiyotaka Hao
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Jun Takahashi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Waku Hatta
- Department of Gastroenterology, Tohoku University Graduate School of Medicine
| | - Tomoyuki Koike
- Department of Gastroenterology, Tohoku University Graduate School of Medicine
| | - Atsushi Masamune
- Department of Gastroenterology, Tohoku University Graduate School of Medicine
| | - Yoshikatsu Saiki
- Department of Cardiovascular Surgery, Tohoku University Graduate school of Medicine
| | - Hisanori Horiuchi
- Department of Molecular and Cellular Biology, Institute of Development, Aging, and Cancer, Tohoku University
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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Sakai E, Ohata K, Nakajima A, Matsuhashi N. Diagnosis and therapeutic strategies for small bowel vascular lesions. World J Gastroenterol 2019; 25:2720-2733. [PMID: 31235995 PMCID: PMC6580356 DOI: 10.3748/wjg.v25.i22.2720] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 04/21/2019] [Accepted: 05/03/2019] [Indexed: 02/06/2023] Open
Abstract
Small bowel vascular lesions, including angioectasia (AE), Dieulafoy’s lesion (DL) and arteriovenous malformation (AVM), are the most common causes of obscure gastrointestinal bleeding. Since AE are considered to be venous lesions, they usually manifest as a chronic, well-compensated condition. Subsequent to video capsule endoscopy, deep enteroscopy can be applied to control active bleeding or to improve anemia necessitating blood transfusion. Despite the initial treatment efficacy of argon plasma coagulation (APC), many patients experience re-bleeding, probably because of recurrent or missed AEs. Pharmacological treatments can be considered for patients who have not responded well to other types of treatment or in whom endoscopy is contraindicated. Meanwhile, a conservative approach with iron supplementation remains an option for patients with mild anemia. DL and AVM are considered to be arterial lesions; therefore, these lesions frequently cause acute life-threatening hemorrhage. Mechanical hemostasis using endoclips is recommended to treat DLs, considering the high re-bleeding rate after primary APC cauterization. Meanwhile, most small bowel AVMs are large and susceptible to re-bleeding therefore, they usually require surgical resection. To achieve optimal diagnostic and therapeutic approaches for each type of small bowel lesion, the differences in their epidemiology, pathology and clinical presentation must be understood.
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Affiliation(s)
- Eiji Sakai
- Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan
- Division of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Ken Ohata
- Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan
| | - Atsushi Nakajima
- Division of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Nobuyuki Matsuhashi
- Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo 141-8625, Japan
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García-Compeán D, Del Cueto-Aguilera ÁN, Jiménez-Rodríguez AR, González-González JA, Maldonado-Garza HJ. Diagnostic and therapeutic challenges of gastrointestinal angiodysplasias: A critical review and view points. World J Gastroenterol 2019; 25:2549-2564. [PMID: 31210709 PMCID: PMC6558444 DOI: 10.3748/wjg.v25.i21.2549] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/19/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal angiodysplasias (GIADs), also called angioectasias, are the most frequent vascular lesions. Its precise prevalence is unknown since most of them are asymptomatic. However, the incidence may be increasing since GIADs affect individuals aged more than 60 years and population life expectancy is globally increasing worldwide. They are responsible of about 5% to 10% of all gastrointestinal bleeding (GIB) cases. Most GIADs are placed in small bowel, where are the cause of 50 to 60% of obscure GIB diagnosed with video capsule endoscopy. They may be the cause of fatal severe bleeding episodes; nevertheless, recurrent overt or occult bleeding episodes requiring repeated expensive treatments and disturbing patient’s quality-of-life are more frequently observed. Diagnosis and treatment of GIADs (particularly those placed in small bowel) are a great challenge due to insidious disease behavior, inaccessibility to affected sites and limitations of available diagnostic procedures. Hemorrhagic causality out of the actively bleeding lesions detected by diagnostic procedures may be difficult to establish. No treatment guidelines are currently available, so there is a high variability in the management of these patients. In this review, the epidemiology and pathophysiology of GIADs and the status in the diagnosis and treatment, with special emphasis on small bowel angiodysplasias based on multiple publications, are critically discussed. In addition, a classification of GIADs based on their endoscopic characteristics is proposed. Finally, some aspects that need to be clarified in future research studies are highlighted.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Ángel N Del Cueto-Aguilera
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Alan R Jiménez-Rodríguez
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Héctor J Maldonado-Garza
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
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Horiuchi H, Doman T, Kokame K, Saiki Y, Matsumoto M. Acquired von Willebrand Syndrome Associated with Cardiovascular Diseases. J Atheroscler Thromb 2019; 26:303-314. [PMID: 30867356 PMCID: PMC6456452 DOI: 10.5551/jat.rv17031] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The blood glycoprotein von Willebrand factor (VWF) plays an important role in hemostasis and thrombosis. VWF is produced and secreted as large multimers by endothelial cells and megakaryocytes. It is then cleaved in a sheer-stress dependent manner by a specific protease, ADAMTS13, into multimers consisting of 2–80 subunits. Among VWF multimers, high molecular weight (HMW) multimers play important roles in platelet aggregation. Therefore, their loss induces a hemostatic disorder known as von Willebrand disease (VWD) type 2A. Various cardiovascular diseases, such as aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), and several congenital structural diseases, as well as mechanical circulatory support systems, generate excessive high shear stress in the bloodstream. These cause excessive cleavage of VWF multimers resulting in a loss of HMW multimers, known as acquired von Willebrand syndrome (AVWS), a hemostatic disorder similar to VWD type 2A. Bleeding often occurs in the gastrointestinal tract since a fragile angiodysplasia develops associated with these diseases. Radical treatment for AVWS is to remove the pathological high shear causing AVWS.
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Affiliation(s)
- Hisanori Horiuchi
- Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University
| | - Tsuyoshi Doman
- Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University
| | - Koichi Kokame
- Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center
| | - Yoshikatsu Saiki
- Division of Cardiovascular Surgery, Tohoku University Graduate School of Medicine
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A Risk Assessment of Factors for the Presence of Angiodysplasias During Endoscopy and Factors Contributing to Symptomatic Bleeding and Rebleeds. Dig Dis Sci 2019; 64:2923-2932. [PMID: 31190204 PMCID: PMC6744377 DOI: 10.1007/s10620-019-05683-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 05/23/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Few studies have assessed factors associated with angiodysplasias during endoscopy or factors associated with symptomatic disease. AIMS To evaluate risk factors for the presence of and contribution to symptomatic disease in patients with angiodysplasias. METHODS We performed a systematic MEDLINE, EMBASE and Cochrane Library search according to the PRISMA guidelines for studies assessing risk factors involved in angiodysplasias detected during endoscopy and factors that lead to anemia or overt bleeding. Study quality was assessed with the Newcastle-Ottawa scale. A risk assessment was performed by selecting risk factors identified by two independent studies and/or by a large effect size. RESULTS Twenty-three studies involving 92,634 participants were included. The overall quality of the evidence was moderate. Risk factors for the diagnosis of angiodysplasias during endoscopy confirmed by at least two studies were increasing age (OR 1.09 per year, 95% CI 1.04-1.1), chronic kidney disease (OR 4.5, 95% CI 1.9-10.5) and cardiovascular disease (2.9, 95% CI 1.4-6.2). The risk of rebleeds was higher in the presence of multiple lesions (OR 4.2, 95% CI 1.1-16.2 and 3.8, 95% CI 1.3-11.3 and 8.6, 95% CI 1.4-52.6), liver cirrhosis (OR 4.0, 95% 1.1-15.0) and prothrombin time < 30% (OR 4.2, 95% 1.1-15.4) with a moderate effect size. Multiple comorbidities were associated with an increased in-hospital mortality (OR 2.29, 95% CI 1.2-4.3). CONCLUSIONS This systematic review identified age, chronic kidney disease and cardiovascular disease as the most important risk factors for the diagnosis of angiodysplasias during endoscopy. Multiple lesions increase the risk of recurrent bleeding.
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Abstract
Gastrointestinal angiodysplasias (GIADs) have a wide variety of presentations, which can be significant and debilitating in a subset of patients. Endoscopic ablation is currently the most effective treatment for GIADs, however re-bleeding rates are high. Several medical have been used for GIADs and reported in the literature, however these medications have significant side effect profiles and randomized controlled trials are lacking. A relatively poor understanding of the pathophysiology of GIAD formation has limited the development of more effective treatments and improved diagnostic and prognostic markers for GIAD. However, recent advances in research in the area of angiogenesis have identified a potential role for certain angiogenic factors including Angiopoeitin 1 and 2, in the pathophysiology of GIAD. Areas covered: We performed an extensive pubmed search of all articles mentioning GIAD and summarized our findings focussing on patient management and prospects. We summarize the available literature regarding the medical, endoscopic, and radiological management of GIAD and the value of clinical prognostic factors. Expert commentary: Although the area of angiogenesis is a novel area of research in GIAD, it represents an exciting avenue for development with the potential to improve diagnostic and prognostic tools to improve patient outcome.
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Affiliation(s)
- Grainne Holleran
- a Department of Gastroenterology and Clinical Medicine , Trinity Centre for Health Sciences' Tallaght Hospital , Dublin , Ireland
| | - Deirdre McNamara
- a Department of Gastroenterology and Clinical Medicine , Trinity Centre for Health Sciences' Tallaght Hospital , Dublin , Ireland
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Randi AM, Smith KE, Castaman G. von Willebrand factor regulation of blood vessel formation. Blood 2018; 132:132-140. [PMID: 29866817 PMCID: PMC6182264 DOI: 10.1182/blood-2018-01-769018] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 04/18/2018] [Indexed: 02/06/2023] Open
Abstract
Several important physiological processes, from permeability to inflammation to hemostasis, take place at the vessel wall and are regulated by endothelial cells (ECs). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for von Willebrand factor (VWF), a large glycoprotein best known for its critical role in hemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularization, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth EC (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel-Palade bodies, such as angiopoietin-2 and galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor signaling. Recent studies suggest that the roles of VWF may be tissue specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding resulting from vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high-molecular-weight multimers in regulating angiogenesis, and review the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome.
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Affiliation(s)
- Anna M Randi
- Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom; and
| | - Koval E Smith
- Vascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom; and
| | - Giancarlo Castaman
- Center for Bleeding Disorders and Coagulation, Department of Oncology, Careggi University Hospital, Florence, Italy
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Nardone G, Compare D, Martino A, Rocco A. Pharmacological treatment of gastrointestinal bleeding due to angiodysplasias: A position paper of the Italian Society of Gastroenterology (SIGE). Dig Liver Dis 2018; 50:542-548. [PMID: 29610020 DOI: 10.1016/j.dld.2018.02.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 01/11/2018] [Accepted: 02/08/2018] [Indexed: 02/08/2023]
Abstract
Angioectasias (AD) belong to benign vascular malformations of the gastrointestinal tract and are responsible for about 4-7% of upper non variceal bleeding, 30-40% of small bowel occult bleeding and 3-40% of colonic bleeding episodes. Gastrointestinal haemorrhage secondary to AD represents an important diagnostic and therapeutic problem that negatively impacts on the quality of life of patients and heath care costs. Endoscopic interventions are the mainstay in both diagnosis and treatment of vascular malformations. However, in a substantial percentage of the cases, age of the patients, comorbidities, clinical severity of anaemia and blood loss as well as size, site and number of lesions prevent this therapeutic approach. Hormonal therapy, thalidomide and somatostatin analogues have been investigated for their potential role as rescue therapies in controlling AD bleeding although, thus far, no recommendations have been provided on their use in this clinical setting. In order to implement appropriate prescription of pharmacological agents to manage gastrointestinal bleeding due to ADs, the Italian Society of Gastroenterology (SIGE) nominated a panel of experts who reviewed the available clinical literature and produced practical clinical recommendations.
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Affiliation(s)
- Gerardo Nardone
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy.
| | - Debora Compare
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
| | - Alberto Martino
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
| | - Alba Rocco
- Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
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McFarlane M, O’Flynn L, Ventre R, Disney BR. Emerging role of thalidomide in the treatment of gastrointestinal bleeding. Frontline Gastroenterol 2018; 9:98-104. [PMID: 29588836 PMCID: PMC5868454 DOI: 10.1136/flgastro-2017-100870] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 09/22/2017] [Accepted: 10/18/2017] [Indexed: 02/04/2023] Open
Abstract
Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.
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Affiliation(s)
- Michael McFarlane
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Lauren O’Flynn
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Rachel Ventre
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Benjamin R Disney
- Department of Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
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Aoyama T, Fukumoto A, Shigita K, Asayama N, Mukai S, Nagata S. Arteriosclerosis Is a Major Predictor of Small Bowel Vascular Lesions. Dig Dis Sci 2018; 63:723-730. [PMID: 29372478 DOI: 10.1007/s10620-018-4930-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 01/11/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Most studies have focused on evaluating the association between the presence of small bowel vascular lesions (SBVLs) and patients' comorbidities. AIMS We sought to uncover a more fundamental indicator that may predict the presence of SBVLs by considering atherosclerosis qualitatively and quantitatively. METHODS We enrolled 79 consecutive patients with obscure gastrointestinal bleeding who had undergone computed tomography (CT) and capsule endoscopy or double-balloon endoscopy from January 2015 to June 2017. The SBVL frequency, type, and location, and the relationship between the presence of SBVLs and the patients' clinical characteristics were evaluated. Arterial wall calcification was assessed on unenhanced CT images, and a modified Agatston scoring system was used to determine the abdominal aorta calcium scores. RESULTS Of the 27 (34%) patients with SBVLs, 15 (19%) had type 1a, 12 (15%) had type 1b, and 2 (3%) had type 2a SBVLs. Most of the lesions were located in the jejunum. Cardiovascular disease (P = .017), chronic kidney disease (P = .025), and arteriosclerosis (P = .0036) were associated with the presence of SBVLs. Subsequent multivariate analysis revealed that arteriosclerosis (odds ratio [OR] 7.29; 95% confidence interval [CI] 1.13-143.9) and superior mesenteric artery calcification (OR 16.3; 95% CI 3.64-118.6) were independent predictors of the presence of SBVLs. The modified Agatston score was significantly higher in SBVL cases than in non-SBVL cases (6384 vs. 2666, P = .0023). CONCLUSIONS Arteriosclerosis, especially increased superior mesenteric artery calcification, is associated with an increased likelihood of SBVLs.
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Affiliation(s)
- Taiki Aoyama
- Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabe-minami, Asakita-ku, Hiroshima, 731-0293, Japan.
| | - Akira Fukumoto
- Department of Endoscopy, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabe-minami, Asakita-ku, Hiroshima, 731-0293, Japan
| | - Kenjiro Shigita
- Department of Endoscopy, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabe-minami, Asakita-ku, Hiroshima, 731-0293, Japan
| | - Naoki Asayama
- Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabe-minami, Asakita-ku, Hiroshima, 731-0293, Japan
| | - Shinichi Mukai
- Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabe-minami, Asakita-ku, Hiroshima, 731-0293, Japan
| | - Shinji Nagata
- Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabe-minami, Asakita-ku, Hiroshima, 731-0293, Japan
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Benamouzig R, Benallaoua M, Saurin JC, Boubaya M, Cellier C, Laugier R, Vincent M, Boustière C, Gincul R, Samaha E, Grandval P, Aparicio T, Airinei G, Bejou B, Bon C, Raynaud JJ, Levy V, Sautereau D. Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study. Therap Adv Gastroenterol 2018; 11:1756283X18756260. [PMID: 29479375 PMCID: PMC5818089 DOI: 10.1177/1756283x18756260] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 10/31/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Gastrointestinal angiodysplasias (GIADs) could be responsible for recurrent bleeding and severe anemia. Somatostatin analogs could reduce transfusion requirements in these patients but no randomized controlled study is available. The main objective of the ANGIOPAS phase II double-blinded randomized, noncomparative study was to assess the effectiveness of pasireotide-LAR in reducing transfusion requirements in patients with refractory GIADs bleeding. METHODS A total of 22 patients with transfusion requirements ⩾6 units of packed red blood cells (pRBCs) during the 6 months prior to inclusion were randomized to receive pasireotide-LAR 60 mg (n = 10) or placebo (n = 12) every 28 days for 6 months. Patients were then followed for an additional 6 months after stopping treatment. RESULTS The pasireotide-LAR and placebo groups were equivalent for age, sex, comorbidities and transfusion requirement during the reference period (median 13 and 9.5 pRBCs). A 50 and 83% success rate (success defined as a decrease of at least 30% of transfused pRBCs) was observed in the pasireotide-LAR arm in the Intent to Treat (ITT) and per protocol (PP) analysis respectively. The need for transfusion during the intervention period was 3 pRBC units in the pasireotide-LAR group (range 0-26) and 11.5 pRBC units in the placebo group (range 0-23). Overall, three cases with glycemic control impairment were observed in the pasireotide-LAR group including one de novo diabetes. CONCLUSION This double-blinded noncomparative randomized phase II study suggests, for the first time, the effectiveness of pasireotide-LAR 60 mg every 28 days to decrease the transfusion requirement in patients with recurrent bleeding due to GIADs.
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Affiliation(s)
| | | | | | | | | | - René Laugier
- Gastroenterology Unit, Timone Hospital, Marseille, France
| | | | | | - Rodica Gincul
- Gastroenterology Unit, Edouard Herriot Hospital, Lyon, France
| | - Elia Samaha
- Gastroenterology Unit, Georges-Pompidou Hospital, Paris, France
| | | | | | | | - Bakhtiar Bejou
- Gastroenterology Unit, Avicenne Hospital, Bobigny, France
| | - Cyriaque Bon
- Gastroenterology Unit, Avicenne Hospital, Bobigny, France
| | | | - Vincent Levy
- Clinical Research Unit, Avicenne Hospital, Bobigny, France
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Grooteman KV, van Geenen EJM, Drenth JPH. Tranexamic acid in treatment-resistant chronic transfusion-dependent gastrointestinal angiodysplasia bleeding. BMJ Case Rep 2017; 2017:bcr-2017-221832. [PMID: 29092972 DOI: 10.1136/bcr-2017-221832] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
A small proportion of gastrointestinal angiodysplasia bleeding leads to chronic blood cell transfusion dependency. There are no guidelines supporting decision-making among various treatments in patients with gastrointestinal angiodysplasia bleeding. When endoscopic argon plasma coagulation is ineffective, the angiogenesis inhibitors thalidomide and octreotide can be considered. We describe a 77-year-old woman who had side effects of these angiogenesis inhibitors, which caused her to have continued bleeding. She was successfully treated with tranexamic acid with a substantial decrease in need for red blood cell transfusions.
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Affiliation(s)
| | | | - Joost P H Drenth
- Gastroenterology and Hepatology, Radboudumc, Nijmegen, Netherlands
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Becq A, Rahmi G, Perrod G, Cellier C. Hemorrhagic angiodysplasia of the digestive tract: pathogenesis, diagnosis, and management. Gastrointest Endosc 2017; 86:792-806. [PMID: 28554655 DOI: 10.1016/j.gie.2017.05.018] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 05/18/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Aymeric Becq
- Gastroenterology and Endoscopy division, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris-Descartes Sorbonne-Paris Cité, Paris, France
| | - Gabriel Rahmi
- Gastroenterology and Endoscopy division, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris-Descartes Sorbonne-Paris Cité, Paris, France
| | - Guillaume Perrod
- Gastroenterology and Endoscopy division, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris-Descartes Sorbonne-Paris Cité, Paris, France
| | - Christophe Cellier
- Gastroenterology and Endoscopy division, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, University Paris-Descartes Sorbonne-Paris Cité, Paris, France
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Vuddanda V, Jazayeri MA, Turagam MK, Lavu M, Parikh V, Atkins D, Bommana S, Yeruva MR, Di Biase L, Cheng J, Swarup V, Gopinathannair R, Olyaee M, Ivaturi V, Natale A, Lakkireddy D. Systemic Octreotide Therapy in Prevention of Gastrointestinal Bleeds Related to Arteriovenous Malformations and Obscure Etiology in Atrial Fibrillation. JACC Clin Electrophysiol 2017; 3:1390-1399. [PMID: 29759670 DOI: 10.1016/j.jacep.2017.04.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 04/05/2017] [Accepted: 04/11/2017] [Indexed: 12/14/2022]
Abstract
OBJECTIVES The present study describes the use of octreotide (OCT) in patients with atrial fibrillation (AF) receiving oral anticoagulation (OAC) who have gastrointestinal (GI) bleeding related to arteriovenous malformations (AVMs), as well as its effect on OAC tolerance and subsequent rebleeding. BACKGROUND AVMs cause significant GI bleeding, especially in patients with AF who are receiving OAC for stroke prevention. OCT has been shown to minimize recurrent GI bleeds related to AVMs. METHODS In a multicenter, observational study, 38 AF patients with contraindications to OAC because of AVM-related GI bleeding were started on 100 μg of subcutaneous OCT twice daily. OAC was resumed in all patients within 48 h. Incidence of recurrent GI bleeds was calculated, and hemoglobin levels were recorded at enrollment and at 3 and 6 months' follow-up. RESULTS After a median follow-up of 8 months, 36 patients (mean age 69 ± 8.0 years; mean CHA2DS2-VASc score 3 ± 1 and mean HAS-BLED score 3 ± 1) were available for analysis. All were able to successfully resume OAC, and 28 of 36 (78%) remained on OAC at the conclusion of the study, whereas 8 underwent left atrial appendage closure with subsequent OAC discontinuation. No systemic thromboembolic events occurred in follow-up. Of the 28 patients who continued receiving OAC, 19 (68%) were free of recurrent GI bleed, 4 had minor GI bleeds, 4 required transfusion, and 1 required colectomy for GI bleeding. Mean hemoglobin levels in all patients receiving OAC were significantly higher at 3- and 6-month follow-up than at baseline (p < 0.001). CONCLUSIONS Subcutaneous OCT therapy is an attractive option in AF patients receiving OAC who have AVM-related GI bleeds. It allows successful reinitiation of OAC as a bridge to left atrial appendage exclusion or short-term relief from bleeding.
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Affiliation(s)
- Venkat Vuddanda
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Mohammad-Ali Jazayeri
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Mohit K Turagam
- Division of Cardiology, University of Missouri, Columbia, Missouri
| | - Madhav Lavu
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Valay Parikh
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Donita Atkins
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Sudharani Bommana
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Madhu Reddy Yeruva
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Luigi Di Biase
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas
| | - Jie Cheng
- Texas Heart Institute, St. Luke's Hospital, Houston, Texas
| | | | | | - Mojtaba Olyaee
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas
| | - Vijay Ivaturi
- Department of Pharmacy Practice and Science University of Maryland, Baltimore
| | - Andrea Natale
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas
| | - Dhanunjaya Lakkireddy
- Cardiovascular Research Institute, University of Kansas Hospital, Kansas City, Kansas.
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Abstract
Vascular anomalies comprise a spectrum of diseases that are broadly classified as tumors and malformations. Diagnosis is often challenging, given a wide range of clinical presentations with overlapping signs and symptoms. Accurate diagnosis is critical to determine prognosis and to generate a management plan, which frequently involves multiple subspecialists during different phases of treatment. An updated classification system provides structure and clear, consistent terminology, allowing for improved diagnosis, provider communication, and collaboration. Historically, treatment of vascular anomalies was primarily surgical and medical therapies were limited or ineffective. Recent discoveries of pharmacologic agents effective in treating vascular anomalies have broadened our medical therapeutic options, limiting the need for unnecessary or high-risk procedures and improving patients' quality of life.
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Affiliation(s)
- Kiersten W Ricci
- Division of Hematology, Hemangioma and Vascular Malformation Center, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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45
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Chetcuti Zammit S, Sanders DS, Sidhu R. Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre. Scand J Gastroenterol 2017; 52:962-968. [PMID: 28506132 DOI: 10.1080/00365521.2017.1325929] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs. METHOD Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes. RESULTS Twelve patients (67% males, mean age 74 SD ± 15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60 mg (42%), 90 mg (33%) or 120 mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD ± 14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis. There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131-166 g/L, p = .012). The mean number of bleeding episodes (4.18 versus 1.09, p = .010) and packed red cells (323 versus 152, p = .006) received improved. Patients required less DBEs ± APCs after starting lanreotide (19 versus 11 p = .048). CONCLUSION Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.
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Affiliation(s)
- S Chetcuti Zammit
- a Department of Gastroenterology , Royal Hallamshire Hospital , Sheffield, UK
| | - D S Sanders
- a Department of Gastroenterology , Royal Hallamshire Hospital , Sheffield, UK
| | - R Sidhu
- a Department of Gastroenterology , Royal Hallamshire Hospital , Sheffield, UK
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46
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Abstract
BACKGROUND Gastrointestinal angioectasias (AEs) represent the most common vascular malformation within the gastrointestinal tract. This study sought to characterize epidemiologic/comorbid risk factors for AEs, rebleeding, and patterns of anatomic distribution within the small intestine. STUDY This retrospective observational cohort study included 158 patients with AEs on capsule endoscopy (CE) from 2007 to 2015. Epidemiologic/comorbid data were collected and incorporated into final analysis. Each AE was categorized by location using a small bowel transit time-based quartile system. Rebleeding was evaluated following CE. Multivariate logistic regression was applied to statistically significant factors on univariate analysis to determine independent risk factors for rebleeding. RESULTS Most lesions were found in the first quartile (67.1%). Rebleeding occurred in 46 (29.7%) of the 156 patients for whom data were available. Rates of rebleeding were significantly higher among older patients (74.4 vs. 67.7 y, P=0.001), those with active bleeding on CE (41.3% vs. 16.5%, P=0.001), those with a history of aortic stenosis (21.7% vs. 9.2%, P=0.033), and those with AEs presents in quartile 3 (26.1% vs. 8.3%, P=0.003). Age, active bleeding on CE, and AE presence in quartile 3 were independently associated with rebleeding in multivariate analysis (P=0.009, 0.023, and 0.008, respectively). CONCLUSIONS These data help improve our knowledge of AEs regarding risk factors for rebleeding, and utilizes a novel small bowel transit time-based quartile localization method that may simplify future research and comparisons of anatomic distribution and behavior of small bowel AEs.
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47
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Selvam S, James P. Angiodysplasia in von Willebrand Disease: Understanding the Clinical and Basic Science. Semin Thromb Hemost 2017; 43:572-580. [PMID: 28476066 DOI: 10.1055/s-0037-1599145] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Severe and intractable gastrointestinal bleeding caused by angiodysplasia is a debilitating problem for up to 20% of patients with von Willebrand disease (VWD). Currently, the lack of an optimal treatment for this recurrent problem presents an ongoing challenge for many physicians in their management of affected patients. Over the past few years, studies have pointed to a regulatory role for the hemostatic protein, von Willebrand factor (VWF), in angiogenesis, providing a novel target for the modulation of vessel development. This article will review the clinical implications and molecular pathology of angiodysplasia in VWD.
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Affiliation(s)
- Soundarya Selvam
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, Canada
| | - Paula James
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, Canada.,Department of Medicine, Queen's University, Kingston, Canada
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48
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Nennstiel S, Machanek A, von Delius S, Neu B, Haller B, Abdelhafez M, Schmid RM, Schlag C. Predictors and characteristics of angioectasias in patients with obscure gastrointestinal bleeding identified by video capsule endoscopy. United European Gastroenterol J 2017; 5:1129-1135. [PMID: 29238592 DOI: 10.1177/2050640617704366] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Accepted: 03/12/2017] [Indexed: 12/13/2022] Open
Abstract
Background In obscure gastrointestinal bleeding, angioectasias are common findings in video capsule endoscopy (VCE). Objective The objective of this study was to identify predictors and characteristics of small bowel angioectasias. Methods Video capsule examinations between 1 July 2001 and 31 July 2011 were retrospectively reviewed. Patients with obscure gastrointestinal bleeding were identified, and those with small bowel angioectasia were compared with patients without a definite bleeding source. Univariate and multivariable statistical analyses for possible predictors of small bowel angioectasia were performed. Results From a total of 717 video capsule examinations, 512 patients with obscure gastrointestinal bleeding were identified. Positive findings were reported in 350 patients (68.4%) and angioectasias were documented in 153 of these patients (43.7%). These angioectasias were mostly located in the proximal small intestine (n = 86, 56.6%). Patients' age >65 years (odds ratio (OR) 2.15, 95% confidence interval (CI) 1.36-3.38, p = .001) and overt bleeding type (OR 1.89, 95% CI 1.22-2.94, p = .004) were identified as significant independent predictors of small bowel angioectasia. Conclusion Angioectasias are the most common finding in VCE in patients with obscure gastrointestinal bleeding. They are mostly located in the proximal small bowel and are associated with higher age and an overt bleeding type.
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Affiliation(s)
- Simon Nennstiel
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Annkathrin Machanek
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Stefan von Delius
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Bruno Neu
- Medizinische Klinik II, Krankenhaus Landshut-Achdorf, Academic Teaching Hospital, Technische Universität München, Landshut, Germany
| | - Bernhard Haller
- Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Mohamed Abdelhafez
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Roland M Schmid
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Christoph Schlag
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
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49
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Beg S, Ragunath K. Review on gastrointestinal angiodysplasia throughout the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2017; 31:119-125. [PMID: 28395783 DOI: 10.1016/j.bpg.2016.11.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2016] [Revised: 11/27/2016] [Accepted: 11/29/2016] [Indexed: 01/31/2023]
Abstract
Gastrointestinal angiodysplasia are rare but clinically important vascular aberrations found within the gastrointestinal mucosa and submucosa. Their clinical impact varies from being an asymptomatic incidental finding, to causing life threatening bleeding. In this review we critically appraise the key findings from the current literature on the pathology, clinical presentation and management of these lesions.
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Affiliation(s)
- Sabina Beg
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, Department of Gastroenterology, Queen Medical Centre, Nottingham, United Kingdom.
| | - Krish Ragunath
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, Department of Gastroenterology, Queen Medical Centre, Nottingham, United Kingdom.
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50
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Randi AM, Laffan MA. Von Willebrand factor and angiogenesis: basic and applied issues. J Thromb Haemost 2017; 15:13-20. [PMID: 27778439 DOI: 10.1111/jth.13551] [Citation(s) in RCA: 128] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Indexed: 12/11/2022]
Abstract
The recent discovery that von Willebrand factor (VWF) regulates blood vessel formation has opened a novel perspective on the function of this complex protein. VWF was discovered as a key component of hemostasis, capturing platelets at sites of endothelial damage and synthesized in megakaryocytes and endothelial cells (EC). In recent years, novel functions and binding partners have been identified for VWF. The finding that loss of VWF in EC results in enhanced, possibly dysfunctional, angiogenesis is consistent with the clinical observations that in some patients with von Willebrand disease (VWD), vascular malformations can cause severe gastrointestinal (GI) bleeding. In vitro and in vivo studies indicate that VWF can regulate angiogenesis through multiple pathways, both intracellular and extracellular, although their relative importance is still unclear. Investigation of these pathways has been greatly facilitated by the ability to isolate EC from progenitors circulating in the peripheral blood of normal controls and patients with VWD. In the next few years, these will yield further evidence on the molecular pathways controlled by VWF and shed light on this novel and fascinating area of vascular biology. In this article, we will review the evidence supporting a role for VWF in blood vessel formation, the link between VWF dysfunction and vascular malformations causing GI bleeding and how they may be causally related. Finally, we will discuss how these findings point to novel therapeutic approaches to bleeding refractory to VWF replacement therapy in VWD.
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Affiliation(s)
- A M Randi
- National Heart and Lung Institute, Imperial College, London, UK
| | - M A Laffan
- Department of Haematology, Imperial College, London, UK
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