Colonoscopic and Clinical Features of Colonic Angiodysplasia: A Study in 54 Patients.

OBJECTIVES: Colonic angiodysplasia is a rare disease, it is nevertheless a common cause of lower gastrointestinal (GI) bleeding in older adults. The study summarized the colonoscopic and clinical features of colonic angiodysplasia to raise awareness among endoscopists regarding this disease. MATERIALS AND METHODS: We performed a retrospective study of enrolled patients diagnosed with colonic angiodysplasia between September 2013 and April 2022. Clinical and colonoscopic features of the patients with active bleeding were analyzed and compared with those of patients without bleeding. The comparisons were also conducted between the patients with active lower GI bleeding caused by colonic angiodysplasia and those by other diseases. RESULTS: In total, 54 eligible patients were included in this study; 55.55% of the participants were aged over 60 years. Ten patients (3 men and 7 women) with colonic angiodysplasia suffered from active lower GI bleeding, which was mainly located in the left and total colon. The patients with type 2 diabetes mellitus, radiotherapy history, antiplatelet drug use, and multiple lesions were more likely to endure lower GI bleeding. The duration between bleeding and admission was longer in the colonic angiodysplasia group than in the other diseases group ( P = 0.043). In the colonic angiodysplasia group, bleeding relapsed in 3 patients, and the recurrence rate was higher than in the other diseases group ( P < 0.001). CONCLUSION: Endoscopists should perform colonoscopy scrupulously and consider colonic angiodysplasia as a differential diagnosis in patients with lower GI bleeding, especially for older women and adults with chronic diseases, such as type 2 diabetes mellitus.

Endocuff-assisted push enteroscopy increases the detection of proximal small-bowel gastrointestinal angiodysplasias.

Gastrointestinal angiodysplasias (GIADs) are the most common causes for suspected small bowel bleeding. Fifty percent of GIADs do not need treatment due to bleeding cessation, while 45% have high re-bleeding rates, that significantly impact patient outcome and health resource utilization. We suspected that this high re-bleeding rate occurs because not all lesions are detected with present standard of care. This study evaluates whether device-assisted enteroscopy (DAE) utilizing the Endocuff (EC) device could improve GIAD detection. A retrospective chart review of a prospective data collection was performed from January 2006 to December 2018 at VA Loma Linda Healthcare System (VALLHCS) on both inpatients and outpatients referred for active and chronic suspected small bowel bleeding. The patients were initially monitored for bleeding lesions via video capsule endoscopy (VCE) after negative upper and lower endoscopy. GIADs observed between 0% to 40% small bowel transit time (SBTT) were referred for push enteroscopy (PE) with and without (±) the EC device. Twenty-five consecutive patients underwent PE ± EC. No patient had VCE done after PE ± EC. Using PE-EC, GIADs were detected in 9 of 25 (36%) of patients. Importantly, PE+EC detected GIADs in 23 of 25 (92%) patients. The sum of GIADs detected without EC was 26 ± 0.06 vs. 112 ± 0.2 using EC. The average detection rate for PE without EC was significantly lower (1.04 ± 0.06, mean ± SE) as compared to PE with EC (4.48 ± 0.23, mean ± SE, p<0.0005). Additionally, a positive correlation (r=0.51) between capsule enteroscopy (CE) location of GIADs and SBTT was found. The EC device increases the detection of GIADs in the proximal small bowel. We also reconfirm that the location of bleeding GIADs are within the reach of the push enteroscope (PE). Finally, PE + EC may also reduce GIAD miss rates, which may play a role in the reduction of re-bleeding episodes.

The impact of inpatient capsule endoscopy on the need for therapeutic interventions in patients with obscure gastrointestinal bleeding.

BACKGROUND/AIM: There are limited data evaluating the impact of inpatient video capsule endoscopy (VCE) on the need for therapeutic interventions in hospitalized patients with obscure gastrointestinal bleeding (OGIB). The objective of this study was to determine the impact of inpatient VCE on the need for therapeutic interventions and rehospitalization for recurrent bleeding. PATIENTS AND METHODS: Hospitalized patients who underwent VCE for OGIB indication were retrospectively included. Clinical data were collected including therapeutic interventions performed after VCE. Specific therapeutic interventions were defined as the medical, endoscopic, or surgical treatment directly targeting the cause of OGIB. Patients were followed up to determine the rate of rehospitalization. RESULTS: A total of 48 inpatient VCE were identified, of which 43 VCE were performed for OGIB indication and were included for analysis. The completion rate and the diagnostic yield were 78.5% and 55.8%, respectively. Subsequent specific therapeutic interventions were performed in 65.2% and 5.8% of patients with positive and negative VCE, respectively (P < 0.001). After a median follow up of 30 months (minimum 12, maximum 58), rehospitalization for recurrent bleeding occurred in 30.4% and 17% of patients with positive and negative VCE, respectively. Patients with angiodysplasia on VCE were significantly more likely to be readmitted (P = 0.02). Throughout the course of the follow-up, only 2 (11.7%) patients with negative VCE underwent specific therapeutic interventions. CONCLUSION: Inpatient VCE is an effective tool to identify patients who need specific therapeutic interventions. Patients with negative VCE are unlikely to be readmitted or require specific therapeutic interventions in the index admission.

[A hemostatic disorder caused by high shear stress: acquired von Willebrand syndrome].

The von Willebrand factors (VWFs) play critical role in hemostasis and thrombosis formation. VWFs are produced in and secreted as large multimers from endothelial cells, and shear stress-dependently cleaved into 2-80 multimers by their specific protease, ADATS13. Because high molecular weight VWFs play important roles in platelet aggregation, the loss of high molecular weight VWFs caused by pathological high-shear stress induces a hemostatic disorder known as acquired von Willebrand syndrome (AVWS) type IIA. The most well-known cause of this loss is aortic stenosis, which is accompanied by gastrointestinal bleeding most often as a result of angiodysplasia; this comprises a condition known as Heyde's syndrome. Additionally, various cardiovascular diseases that generate excessive high-shear stress in the blood stream, such as hypertrophic obstructive cardiomyopathy (HOCM), mitral regurgitation, pulmonary hypertension, and some congenital heart diseases, and mechanical circulatory support systems, such as left ventricular assist device (LVAD), cause AVWS.

Initial experience of video capsule endoscopy at a tertiary center in Saudi Arabia.

BACKGROUND/AIM: No prior experience with video capsule endoscopy (VCE) has been published from Saudi Arabia. In this study, we aim to report the first Saudi experience with VCE. PATIENTS AND METHODS: A prospective study was conducted between March 2013 and September 2017 at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Eligible patients underwent VCE and their data (age, sex, indication for VCE, type of obscure gastrointestinal bleeding [OGIB: overt vs occult], VCE findings, and complications) were recorded. Approval was obtained from the institutional ethics board before the study began and all patients provided verbal and signed consent for the procedure. The procedure was performed according to the established guidelines. RESULTS: During the study period, a total 103 VCE procedures were performed on 96 patients. Overall, 60 participants (62.5%) were male (mean age, 58.8 years; range, 25-97 years) and 36 (37.5%) were female (mean age, 52.8 years; range, 18-78 years). The most frequent indication for VCE was OGIB (n = 91, 88.35%; overt, n = 46, 50.55%; occult, n = 45, 49.45%). Other indications were suspected Crohn's disease (n = 4, 3.88%), suspected complicated celiac disease (n = 4, 3.88%), and unexplained chronic abdominal pain (n = 4, 3.88%). The VCE results were categorized as incomplete (n = 2, 1.94%), poor-quality (n = 7; 6.8%), normal (n = 39, 37.86%), and abnormal (n = 55, 53.4%). The completion rate was 98.06% (n = 101), and the overall diagnostic yield was 53.4%. Of the 55 patients with abnormal VCE results, 43 (78.2%) had small bowel (SB) abnormalities and 12 (21.8%) had abnormalities in the proximal or distal gut. The most frequent SB abnormalities were angiodysplasia (n = 22, 40.0%) and tumors (n = 7, 12.7%). CONCLUSION: The diagnostic yield of VCE for Saudi patients with OGIB is comparable to that reported internationally; however, data for other VCE indications, including inflammatory bowel disease, are still lacking.

Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran.

BACKGROUND AND AIM: Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. METHODS: Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). RESULTS: Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). CONCLUSIONS: In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.

Lenalidomide as a novel therapy for gastrointestinal angiodysplasia in von Willebrand disease.

INTRODUCTION: Lenalidomide is a thalidomide analog with anti-angiogenic properties. Previous case reports suggest its efficacy in preventing gastrointestinal bleeding (GIB) secondary to angiodysplasia (AD) in hereditary haemorrhagic telangiectasia and potentially in reversing AD. We present the first case series to explore lenalidomide as a treatment for AD-related GIB in patients with von Willebrand disease (VWD). METHODS: A retrospective chart review was conducted to include patients with VWD, who were evaluated from 2010 to 2013 and who had received lenalidomide to treat recurrent GIB secondary to AD. All patients had failed single-agent use of antifibrinolytic agents. Patients were observed for at least 2 years on therapy. RESULTS: Five patients (3 males; 68.2 ± 4.9 years) with VWD (3 with type 3 and 1 each with types 1 and 2a) and AD were found. Sites of AD included the stomach, duodenum, jejunum and colon. Lenalidomide was started at 5 mg oral daily. Uptitration to 10 and 15 mg in 1 patient each was necessary due to recurrence of GIB. The mean number of endoscopies performed for control of GIB post lenalidomide was significantly lower compared to pretherapy (0.25 vs 5.50; P = .001). Mean bleed-free duration on lenalidomide was 12.6 ± 4.7 months. Three patients have reported no GIB on lenalidomide. CONCLUSION: This case series demonstrates significantly reduced number of endoscopies and increased bleed-free duration with lenalidomide treatment in selected patients with VWD and recurrent GIB from AD. Prospective multicenter trials are needed to further define the role of lenalidomide in the management of GIB from angiodysplasia and VWD.

Nonisolated Small Bowel Gastrointestinal Angiodysplasias are Associated With Higher Rebleeding Rates When Compared With Isolated Small Bowel Gastrointestinal Angiodysplasia on Video Capsule Endoscopy.

BACKGROUND: Gastrointestinal angiodysplasias (GIAD) are commonly diagnosed in the small bowel but can be located in other areas of the gastrointestinal tract. About half of patients diagnosed with GIAD have more than 1 lesion and 20% of patients have GIAD in both the small bowel and a source outside of the small bowel (nonisolated to small bowel GIAD or NISGIAD). The remaining patients with GIAD have lesions isolated to the small bowel (ISGIAD). Complications including rebleeding, hospitalization and mortality rates have not been previously analyzed between these 2 groups. AIM: To compare rebleeding, hospitalization and mortality rates between ISGIAD and NISGIAD. The secondary goals were to evaluate comorbidities that may be associated with ISGIAD and/or NISGIAD, and to determine if any of these comorbidities are associated with a higher risk of rebleeding from GIAD. MATERIALS AND METHODS: This was a retrospective study that included 425 patients who underwent video capsule endoscopy between 2006 and 2013. Patients underwent esophagogastroduodenoscopy and colonoscopy before video capsule endoscopy. The primary indications for workup included obscure gastrointestinal bleeding. After exclusion criteria, 87 patients diagnosed with GIAD remained, 57 patients with ISGIAD and 30 with NISGIAD. Categorical variables were compared by the Fisher exact test or χ test and continuous data were compared using the Student T test. RESULTS: Risk factors associated with rebleeding rates included coronary artery disease, chronic kidney disease, and congestive heart failure on multivariate analysis. Odds ratios for rebleeding was found in patients with NISGIAD (odds ratio, 4.222; P=0.036). There was no difference in hospitalization rates between patients with ISGIAD and NISGIAD. There was no statistically significant difference in mortality from any cause at 30, 60, and 90 days in patients with ISGIAD and NISGIAD. CONCLUSIONS: In this retrospective analysis of GIAD at a single institution, patients with NISGIAD compared with ISGIAD had a 4 times odds of rebleeding within 1 year after capsule endoscopy. This is a novel study, as the distribution of GIAD has not been previously described as being a risk factor for rebleeding.

Histopathology of Calciphylaxis: Cohort Study With Clinical Correlations.

Calciphylaxis is a rare, painful, and life-threatening condition with a high mortality rate. Although the etiology of calciphylaxis is not well understood, it has been proposed that calcium deposition within and around subcutaneous vessels restricts blood flow chronically, thereby predisposing the patient to acute pannicular and dermal thrombosis. Given increasing recognition of the role of hypercoagulability in calciphylaxis, this retrospective cohort study sought to evaluate the presence of thromboses and dermal angioplasia in calciphylaxis. Moreover, we aimed to validate previous observations about the histopathology of calciphylaxis compared with skin biopsies from patients with end-stage renal disease but without calciphylaxis. After a meticulous clinical chart review, we assessed the corresponding skin biopsies for the presence of vessel calcification, thromboses, and dermal angioplasia in skin biopsies from patients with calciphylaxis (n = 57) and compared with those from patients with end-stage renal disease but without calciphylaxis (n = 26). Histopathologic findings were correlated with clinical features such as chronic kidney disease, diabetes, or associated malignancy. Our results validated a prior observation that calciphylaxis was significantly more likely to show calcification of dermal vessels and diffuse dermal thrombi. This study reports the frequent finding of dermal angioplasia, a potential marker of chronic low-grade ischemia, as another frequent microscopic finding in calciphylaxis. Among cases of calciphylaxis, histopathologic changes in patients with chronic kidney disease were indistinguishable from those in patients without chronic kidney disease, thereby implying a final common pathogenic pathway in both uremic and nonuremic calciphylaxis. In future, larger, prospective studies may be useful in validating these findings.

Continuous-Flow LVAD Support Causes a Distinct Form of Intestinal Angiodysplasia.

RATIONALE: The objective of this autopsy study was to determine whether gastrointestinal angiodysplasia develops during continuous-flow left ventricular assist device (LVAD) support. OBJECTIVE: LVAD support causes pathologic degradation of von Willebrand factor (vWF) and bleeding from gastrointestinal angiodysplasia at an alarming rate. It has been speculated that LVAD support itself may cause angiodysplasia. The relationship to abnormal vWF metabolism is unknown. We tested the hypothesis that abnormal gastrointestinal vascularity develops during continuous-flow LVAD support. METHODS AND RESULTS: Small bowel was obtained from deceased humans, cows, and sheep supported with a continuous-flow LVAD (n=9 LVAD, n=11 control). Transmural sections of jejunum were stained with fluorescein isothiocyanate-conjugated isolectin-B4 for endothelium to demarcate vascular structures and quantify intestinal vascularity. Paired plasma samples were obtained from humans before LVAD implantation and during LVAD support (n=41). vWF multimers and degradation fragments were quantified with agarose and polyacrylamide gel electrophoresis and immunoblotting. Abnormal vascular architecture was observed in the submucosa of the jejunum of human patients, cows, and sheep supported with a continuous-flow LVAD. Intestinal vascularity was significantly higher after LVAD support versus controls (5.2±1.0% versus 2.1±0.4%, P=0.004). LVAD support caused significant degradation of high-molecular-weight vWF multimers (-9±1%, P<0.0001) and accumulation of low-molecular-weight vWF multimers (+40±5%, P<0.0001) and vWF degradation fragments (+53±6%, P<0.0001). CONCLUSIONS: Abnormal intestinal vascular architecture and LVAD-associated vWF degradation were consistent findings in multiple species supported with a continuous-flow LVAD. These are the first direct evidence that LVAD support causes gastrointestinal angiodysplasia. Pathologic vWF metabolism may be a mechanistic link between LVAD support, abnormal angiogenesis, gastrointestinal angiodysplasia, and bleeding.

Angiodysplasia in von Willebrand Disease: Understanding the Clinical and Basic Science.

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.

The impact of hospitalization on the performance of capsule endoscopy (CE).

BACKGROUND: For proper evaluation of capsule endoscopy (CE), a complete examination is necessary. AIM: We evaluated risk factors of an incomplete CE with focus on patient hospitalization. METHODS: We retrospectively evaluated 161 consecutive patients who underwent CE between 01.07.2013 and 13.03.2016. Main indications were active bleeding, iron deficiency anemia (IDA), inflammatory bowel disease (IBD), abdominal pain, and familial adenomatous polyposis (FAP). RESULTS: We report the results of 103 in-patients and 56 out-patients. Eighty-two patients were male, average age was 58.9 years (range 18-90). Indications for CE were active bleeding (103 patients), IDA and IBD (16 patients), and FAP, abdominal pain and others (eight examinations each). All FAP patients were out-patients, but showed the longest small bowel transit time (SBTT) of 443.6min (p=0.0001). The shortest SBTT was found in out-patients without FAP (267.5min, p<0.05). In the in-patient group, nine endoscopies did not record the entire small bowel (8.7%) due to battery depletion, compared with only one incomplete examination in the out-patients (1.8%, p=0.036). We found pathologic lesions in the last 30min of the SBTT in 43 patients, and this indicates the necessity for complete examination. Thirteen of these 43 patients showed major lesions such as ulcers or angiodysplasia in this last region alone. CONCLUSION: In-patients might require special treatment to ensure complete examination, since a considerable amount of pathologies can only be found in the ileum.

Haemoglobin responses to transfusion in severe iron deficiency anaemia: potential impact of gastrointestinal disorders.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) transfusion may be justified in iron deficiency anaemia (IDA) when an increase in oxygen delivery is needed, as sometimes occurs in subjects with haemoglobin <8·0 mg/dL, serious comorbidities or at risk of cardiovascular instability. Earlier investigations showed that some patients with severe IDA requiring transfusion had lower than expected post-transfusion haemoglobin levels with poorer clinical outcomes than other patients. After hypothesizing that haemoglobin responses to transfusion were different and that the underlying gastrointestinal (GI) disorders causing IDA could be a confounder explaining this association, these responses were analysed in a prospective cohort of IDA adults referred for outpatient GI investigation. MATERIALS AND METHODS: Transfused patients with proven IDA, baseline haemoglobin at referral <9·0 g/dL and no extraintestinal bleeding were eligible. To assess a homogeneous population, only GI disorders known to cause occult bleeding were considered. Haemoglobin increments per 100 mL of RBCs were investigated. RESULTS: In total, 2818 patients were enrolled over 10·5 years. On multivariable regression, diffuse angiodysplasias and GI cancer independently predicted for reduced increments in post-transfusion haemoglobin [adjusted regression coefficients: -0·082 (95% confidence interval, -0·093 to -0·072) and -0·073 (95% confidence interval, -0·081 to -0·066), respectively, P < 0·001 in both]. Haemoglobin responses in the remaining bleeding disorders were adequate and agreed with the principle that one RBC unit increases the haemoglobin an average of 1 g/dL. CONCLUSION: The potential differential impact of GI disorders on changes in haemoglobin levels after RBC transfusion could be useful for transfusing physicians, especially for diagnostic purposes.