Covered versus bare-metal stenting of the mesenteric arteries in patients with chronic mesenteric ischaemia (CoBaGI): a multicentre, patient-blinded and investigator-blinded, randomised controlled trial.

BACKGROUND: Mesenteric artery stenting with a bare-metal stent is the current treatment for atherosclerotic chronic mesenteric ischaemia. Long-term patency of bare-metal stents is unsatisfactory due to in-stent intimal hyperplasia. Use of covered stents might improve long-term patency. We aimed to compare the patency of covered stents and bare-metal stents in patients with chronic mesenteric ischaemia. METHODS: We conducted a multicentre, patient-blinded and investigator-blinded, randomised controlled trial including patients with chronic mesenteric ischaemia undergoing mesenteric artery stenting. Six centres in the Netherlands participated in this study, including two national chronic mesenteric ischaemia expert centres. Patients aged 18 years or older were eligible for inclusion when an endovascular mesenteric artery revascularisation was scheduled and a consensus diagnosis of chronic mesenteric ischaemia was made by a multidisciplinary team of gastroenterologists, interventional radiologists, and vascular surgeons. Exclusion criteria were stenosis length of 25 mm or greater, stenosis caused by median arcuate ligament syndrome or vasculitis, contraindication for CT angiography, or previous target vessel revascularisation. Digital 1:1 block randomisation with block sizes of four or six and stratification by inclusion centre was used to allocate patients to undergo stenting with bare-metal stents or covered stents at the start of the procedure. Patients, physicians performing follow-up, investigators, and radiologists were masked to treatment allocation. Interventionalists performing the procedure were not masked. The primary study outcome was the primary patency of covered stents and bare-metal stents at 24 months of follow-up, evaluated in the modified intention-to-treat population, in which stents with missing data for the outcome were excluded. Loss of primary patency was defined as the performance of a re-intervention to preserve patency, or 75% or greater luminal surface area reduction of the target vessel. CT angiography was performed at 6 months, 12 months, and 24 months post intervention to assess patency. The study is registered with ClinicalTrials.gov (NCT02428582) and is complete. FINDINGS: Between April 6, 2015, and March 11, 2019, 158 eligible patients underwent mesenteric artery stenting procedures, of whom 94 patients (with 128 stents) provided consent and were included in the study. 47 patients (62 stents) were assigned to the covered stents group (median age 69·0 years [IQR 63·0-76·5], 28 [60%] female) and 47 patients (66 stents) were assigned to the bare-metal stents group (median age 70·0 years [63·5-76·5], 33 [70%] female). At 24 months, the primary patency of covered stents (42 [81%] of 52 stents) was superior to that of bare-metal stents (26 [49%] of 53; odds ratio [OR] 4·4 [95% CI 1·8-10·5]; p<0·0001). A procedure-related adverse event occurred in 17 (36%) of 47 patients in the covered stents group versus nine (19%) of 47 in the bare-metal stent group (OR 2·4 [95% CI 0·9-6·3]; p=0·065). Most adverse events were related to the access site, including haematoma (five [11%] in the covered stents group vs six [13%] in the bare-metal stents group), pseudoaneurysm (five [11%] vs two [4%]), radial artery thrombosis (one [2%] vs none), and intravascular closure device (none vs one [2%]). Six (13%) patients in the covered stent group versus one (2%) in the bare-metal stent group had procedure-related adverse events not related to the access site, including stent luxation (three [6%] vs none), major bleeding (two (4%) vs none), mesenteric artery perforation (one [2%] vs one [2%]), mesenteric artery dissection (one [2%] vs one [2%]), and death (one [2%] vs none). INTERPRETATION: The findings of this trial support the use of covered stents for mesenteric artery stenting in patients with chronic mesenteric ischaemia. FUNDING: Atrium Maquet Getinge Group.

MRI-based pre- and postprandial flow in the mesenteric vasculature of patients with suspected chronic mesenteric ischemia.

PURPOSE: The physiological increase of mesenteric blood flow after a meal is impaired in patients with occlusive chronic mesenteric ischemia (CMI). This principle could be used to develop a highly desired diagnostic test assessing the sufficiency of the collateral mesenteric circulation. This study assesses the potential to identify CMI patients using two-dimensional time-resolved phase-contrast magnetic resonance imaging (2D PC-MRI) flow measurements. METHOD: This prospective cohort study included patients with suspected CMI, based on: typical history, imaging, and functional testing. Cardiac gated 2D PC-MRI flow measurements (expressed as ml/min/kg) were performed in mesenteric arteries and veins during inspiration and expiration, after six hours of fasting and 20, 30, and 40 min after a meal challenge with a high caloric drink. RESULTS: Flow measurements were obtained in 19 patients: 8 CMI and 11 non-CMI. CMI patients showed a significantly smaller increase in postprandial blood flow in the superior mesenteric artery (SMA) at 30 and 40 min (30 min CMI 1.27(0.12-2.44) vs. non-CMI 7.82(6.28-10.90); 40 min CMI 0.30(-0.26-3.16) vs. non-CMI 7.94(6.32-10.90)) and a lower total arterial flow at 40 min (CMI 3.21(-0.72-5.05) vs. non-CMI 9.31(5.58-13.83)). Repeated flow measurements showed normalization of impaired postprandial venous flow after mesenteric artery stenting in one patient. CONCLUSIONS: The significantly lower increase in postprandial mesenteric blood flow in CMI patients confirms the promise of mesenteric blood flow measurements, before and 30-40 min after a meal, as a future diagnostic test to identify CMI patients among patients with a high clinical suspicion of CMI and mesenteric artery stenosis.

Early risk stratification of patients with suspected chronic mesenteric ischaemia using a symptom and mesenteric artery calcium score based score chart.

BACKGROUND: The mesenteric artery calcium score (MACS) identifies patients with possible chronic mesenteric ischaemia (CMI) using standard computed tomography (CT) imaging. The MACS does not necessitate a dedicated computed tomography angiography (CTA) which is required for evaluation of mesenteric artery patency. This study aimed to test the use of a symptom and MACS based score chart to facilitate the selection of patients with a low probability of CMI, in whom further diagnostic workup can be omitted, and to validate the CTA-based score chart proposed by van Dijk et al. which guides treatment decisions in patients with suspected CMI. METHODS: This retrospective study included consecutive patients with suspected CMI. The Agatston definition was used to calculate the MACS. Multivariable logistic regression analysis was used to create a MACS score chart, which was applied in all patients to determine its discriminative ability. The score chart by van Dijk et al. was validated in this independent external patient series. RESULTS: Hundred-ninety-two patients were included, of whom 49 had CMI. The MACS score chart composed of the variables weight loss, postprandial abdominal pain, history of cardiovascular disease, and MACS, showed an excellent discriminative ability (area under the curve [AUC] 0.87). CMI risks were 2.1% in the low-risk group (0-4 points) and 39.1% in the increased risk group (5-10 points); sensitivity (97.8%) and negative predictive value (NPV; 97.9%) were high. The CTA-based score chart by van Dijk et al. showed an excellent discriminative ability (AUC 0.89). CONCLUSION: The MACS score chart shows promise for early risk stratification of patients with suspected CMI based on a near-perfect NPV. It is complementary to the CTA-based score chart by van Dijk et al., which showed excellent external validity and is well suited to guide subsequent (invasive) treatment decisions in patients with suspected CMI.

Endovascular Pressure Measurements to Assess the Functional Severity of Mesenteric Arterial Stenoses.

PURPOSE: To assess the ability of pressure measurements to discriminate clinically significant celiac artery (CA) or superior mesenteric artery (SMA) stenosis in patients with suspected chronic mesenteric ischemia (CMI). MATERIALS AND METHODS: Single-center, retrospective cohort study of 41 intra-arterial pressure measurements during mesenteric angiography with intended revascularization, performed in 37 patients (mean age 67.7 ± 10.8 years, 62% female) between April 2015 and May 2017. Simultaneous prestenotic and poststenotic pressure measurements had been obtained before and after intra-arterial administration of nitroglycerin. Revascularization was performed in 38 of 41 procedures. Definitive diagnosis of CMI was defined as patient-reported symptom relief or improvement after successful revascularization. RESULTS: Pressure gradients obtained after vasodilator administration were significantly higher in CAs and SMAs with ≥50% stenosis. Pressure ratios (pressure distal [Pd]/pressure aorta [Pa]) obtained after vasodilator administration were significantly higher in CAs with ≥50% stenosis. Subgroup analysis of 22 patients with a ≥50% stenosis of either CA or SMA showed significantly higher pressure gradients and Pd/Pa ratios after vasodilator administration in CMI patients (median pressure gradient: CMI [interquartile ratio] 36 [21-40] mm Hg versus no-CMI 20 [9-21] mm Hg, P = 0.041; Pd/Pa: CMI 0.703 [0.598-0.769] versus no-CMI 0.827 [0.818-0.906], P = .009). A ≤0.8 Pd/Pa cutoff value after administration of a vasodilator best identified a clinically relevant stenosis, with 86% sensitivity and 83% specificity. Complications related to the pressure measurements were not observed. CONCLUSIONS: Intra-arterial pressure measurements are feasible and safe. Low Pd/Pa ratios were associated with clinically relevant CA or SMA stenosis.

Single-Center Retrospective Comparative Analysis of Transradial, Transbrachial, and Transfemoral Approach for Mesenteric Arterial Procedures.

PURPOSE: To assess feasibility and safety of transradial access (TRA) compared with transfemoral access (TFA) and transbrachial access (TBA) for mesenteric arterial endovascular procedures. MATERIALS AND METHODS: A retrospective cohort analysis was performed including all consecutive patients who underwent a mesenteric arterial procedure in a tertiary referral center between May 2012 and February 2018. Exclusion criteria were absence of data and lost to follow-up within 24 hours after the procedure. During the study period, 103 patients underwent 148 mesenteric arterial procedures (TBA, n = 52; TFA, n = 39; TRA, n = 57). Mean patient age was 64.3 years ± 13.3, and 91 patients (62%) were women. Primary outcomes were vascular access specified technical success rate and access site complication rate, as reported in hospital records. RESULTS: Technical success rate specified for the vascular access technique did not differ between the 3 approaches (TBA 96%, TFA 87%, TRA 91%; TRA vs TBA, P = .295; TBA vs TFA, P = .112; TRA vs TFA, P = .524), and overall access site complication rate was not different between the 3 approaches (TBA 42%, TFA 23%, TRA 35%; TRA vs TBA, P = .439; TBA vs TFA, P = .055; TRA vs TFA, P = .208). However, more major access site complications were reported for TBA than for TRA or TFA (TBA 17%, TFA 3%, TRA 2%; TRA vs TBA, P = .005; TBA vs TFA, P = .026; TRA vs TFA, P = .785). CONCLUSIONS: TRA is a safe and feasible approach for mesenteric arterial procedures comparable to TFA, but with a significantly lower major access site complication rate than TBA.

Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI): study protocol for a randomized controlled trial.

BACKGROUND: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly higher patency rates for covered stents (CS). The Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI) trial is designed to prospectively assess the patency of CS versus BMS in patients with atherosclerotic CMI. METHODS/DESIGN: The CoBaGI trial is a randomized controlled, parallel-group, patient- and investigator-blinded, superiority, multicenter trial conducted in six centers of the Dutch Mesenteric Ischemia Study group (DMIS). Eighty-four patients with a consensus diagnosis of atherosclerotic CMI are 1:1 randomized to either a balloon-expandable BMS (Palmaz Blue with rapid-exchange delivery system, Cordis Corporation, Bridgewater, NJ, USA) or a balloon-expandable CS (Advanta V12 over-the-wire, Atrium Maquet Getinge Group, Hudson, NH, USA). The primary endpoint is the primary stent-patency rate at 24 months assessed with CT angiography. Secondary endpoints are primary stent patency at 6 and 12 months and secondary patency rates, freedom from restenosis, freedom from symptom recurrence, freedom from re-intervention, quality of life according the EQ-5D-5 L and SF-36 and cost-effectiveness at 6, 12 and 24 months. DISCUSSION: The CoBaGI trial is designed to assess the patency rates of CS versus BMS in patients treated for CMI caused by atherosclerotic mesenteric stenosis. Furthermore, the CoBaGI trial should provide insights in the quality of life of these patients before and after stenting and its cost-effectiveness. The CoBaGI trial is the first randomized controlled trial performed in CMI caused by atherosclerotic mesenteric artery stenosis. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02428582 . Registered on 29 April 2015.

Oxygen-dependent delayed fluorescence of protoporphyrin IX measured in the stomach and duodenum during upper gastrointestinal endoscopy.

Protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) is a method used to measure oxygen (PO2 ) in human cells. The aim of this study was to assess the technical feasibility and safety of measuring oxygen-dependent delayed fluorescence of 5-aminolevulinic acid (ALA)-induced PpIX during upper gastrointestinal (GI) endoscopy. Endoscopic delayed fluorescence measurements were performed 4 hours after oral administration of ALA in healthy volunteers. The ALA dose administered was 0, 1, 5 or 20 mg/kg. Measurements were performed at three mucosal spots in the gastric antrum, duodenal bulb and descending duodenum with the catheter above the mucosa and while applying pressure to induce local ischemia and monitor mitochondrial respiration. During two endoscopies, measurements were performed both before and after intravenous administration of butylscopolamine. Delayed fluorescence measurements were successfully performed during all 10 upper GI endoscopies. ALA dose of 5 mg/kg showed adequate signal-to-noise ratio (SNR) values >20 without side effects. All pressure measurements showed significant prolongation of delayed fluorescence lifetime compared to measurements performed without pressure (P < .001). Measurements before and after administration of butylscopolamine did not differ significantly in the duodenal bulb and descending duodenum. Measurements of oxygen-dependent delayed fluorescence of ALA-induced PpIX in the GI tract during upper GI endoscopy are technically feasible and safe.

Evaluation of endoscopic visible light spectroscopy: comparison with microvascular oxygen tension measurements in a porcine model.

BACKGROUND: Visible light spectroscopy (VLS) is a technique used to measure the mucosal oxygen saturation during upper gastrointestinal endoscopy to evaluate mucosal ischemia, however in vivo validation is lacking. We aimed to compare VLS measurements with a validated quantitative microvascular oxygen tension (µPO2) measurement technique. METHODS: Simultaneous VLS measurements and µPO2 measurements were performed on the small intestine of five pigs. First, simultaneous measurements were performed at different FiO2 values (18%-100%). Thereafter, the influence of bile was assessed by comparing VLS measurements in the presence of bile and without bile. Finally, simultaneous VLS and µPO2 measurements were performed from the moment a lethal dose potassium chloride intravenously was injected. RESULTS: In contrast to µPO2 values that increased with increasing FiO2, VLS values decreased. Both measurements correlated poorly with R2 = 0.39, intercept 18.5, slope 0.41 and a bias of - 16%. Furthermore, the presence of bile influenced VLS values significantly (median (IQR)) before bile application 57.5% (54.8-59.0%) versus median with bile mixture of the stomach 73.5% (66.8-85.8), p = < 2.2 * 10-16; median with bile mixture of small bowel 47.6% (41.8-50.8) versus median after bile removal 57.0% (54.7-58.6%), p = < 2.2 * 10-16). Finally, the VLS mucosal oxygen saturation values did not decrease towards a value of 0 in the first 25 min of asystole in contrast to the µPO2 values. CONCLUSIONS: These results suggest that VLS measures the mixed venous oxygen saturation rather than mucosal capillary hemoglobin oxygen saturation. Further research is needed to establish if the mixed venous compartment is optimal to assess gastrointestinal ischemia.

Detection of mesenteric ischemia by means of endoscopic visible light spectroscopy after luminal feeding.

BACKGROUND AND AIMS: Endoscopic visible light spectroscopy (VLS) enables measurement of mucosal oxygen saturation during upper GI endoscopy and is used in the diagnostic work-up of chronic mesenteric ischemia (CMI). Currently, VLS is performed when the patient has fasted. We aimed to determine whether food challenge improves the diagnostic performance of VLS measurements for the diagnosis of CMI. METHODS: This was a single-center prospective study of healthy controls and consecutive patients suspected of having CMI and referred to a Dutch specialized CMI center for standardized diagnostic CMI work-up. Immediately after conventional fasting, VLS measurements were taken, luminal feeding was administered, and VLS measurements were repeated 45 minutes later. Patients were classified as CMI if a multidisciplinary expert-based consensus diagnosis of CMI was established and successful revascularization therapy resulted in symptom relief. Patients were classified as no-CMI when consensus diagnosis was not reached or when symptom relief did not occur after technically successful treatment. RESULTS: We included 60 patients with suspected CMI and 16 healthy controls. Duodenal oxygen saturation was significantly higher postprandially compared with the fasting state: healthy controls: median (interquartile range) pre 54% (49%-56%), post 56% (53%-58%), P = .02), no-CMI patients (pre 55% (51%-57%), post 57% (53%-59%), P > .01); CMI patients: pre 51% (48%-53%), post 54% (50%-58%), P = .01. Mucosal oxygen saturation did not significantly increase postprandially in the duodenal bulb or antrum of the stomach. Absolute postprandial oxygen measurements and the absolute or relative difference between preprandial versus postprandial oxygen measurements did not provide additional discriminative ability for the diagnosis of CMI. CONCLUSIONS: Postprandial VLS measurements have no added benefit for the diagnosis of CMI.

Intraobserver and interobserver reliability of visible light spectroscopy during upper gastrointestinal endoscopy.

BACKGROUND: Visible light spectroscopy (VLS) performed during upper gastrointestinal endoscopy allows measuring mucosal oxygen saturation levels to determine gastrointestinal ischemia. We aimed to determine the observer variability of VLS. METHODS: This is a single-center prospective study of 24 patients planned for usual care upper endoscopy. To test intraobserver variability, VLS measurements were performed in duplicate by a single endoscopist in 12 patients. For interobserver variability analysis, in another 12 patients VLS measurements were repeatedly and independently performed by two endoscopists in the same patient during the same endoscopy session. Observer variability was assessed with intraclass correlation coefficient (ICC) and clinical disagreement defined as >5% difference between first and second set of VLS measurements. RESULTS: The intraobserver reliability was excellent (ICC antrum 0.77, duodenal bulb 0.81 and duodenum 0.84) with clinical disagreement only in antrum (3% of all intraobserver measurements). The interobserver reliability was good for the duodenal bulb (ICC 0.70) without clinical disagreement; however, interobserver reliability was fair for duodenum (ICC 0.49) and antrum (ICC 0.56) with clinical disagreement occurring in 11% of all interobserver measurements. CONCLUSIONS: The observer reliability of VLS is fair to good with intraobserver reliability being better than interobserver reliability. This supports the use of VLS for detection of gastrointestinal ischemia.

[A man with abdominal bloating]. / Een man met een opgeblazen gevoel.

A 73-year-old man with an aneurysm of the abdominal aorta (AAA) presented with abdominal bloating. CT-angiography showed compression of the duodenum between the AAA and the pancreas and superior mesenteric artery with dilatation of the descending duodenum, leading to the diagnosis of mechanical duodenal obstruction due to compression by an AAA.

Persistent symptom relief after revascularization in patients with single-artery chronic mesenteric ischemia.

OBJECTIVE: An isolated stenosis of the celiac artery (CA) or the superior mesenteric artery (SMA) is frequently detected in patients with abdominal complaints. The dilemma is whether these patients suffer from chronic mesenteric ischemia (CMI) and whether they will benefit from revascularization. We evaluated the long-term clinical success rates for single CA or SMA revascularization in patients with gastrointestinal symptoms and confirmed mucosal ischemia. METHODS: This was a retrospective cohort analysis of 59 consecutive patients with gastrointestinal symptoms and a single atherosclerotic mesenteric artery stenosis who were referred to our tertiary care institution between 2006 and 2010 for standardized diagnostic workup of CMI, including measurement of mucosal ischemia with visible light spectroscopy or gastric-jejunal tonometry. Patients with multidisciplinary consensus diagnosis of CMI underwent surgical or endovascular revascularization. The primary outcome was clinical response to revascularization, defined as relief of presenting symptoms as experienced by the patient. RESULTS: Consensus diagnosis of CMI was obtained in 37 of 59 patients. Isolated CA stenosis was present in 30 of 37 patients (81%) and isolated SMA stenosis in seven patients. After a mean follow-up of 5.0 ± 3.0 years, 27 of 37 patients (73%) experienced sustained symptom relief after revascularization. Response was not related to lesion localization (CA, 73%; SMA, 71%; P = .919). CONCLUSIONS: Revascularization of the CA or SMA provides persistent symptom relief in 73% of patients diagnosed with CMI due to single atherosclerotic mesenteric artery stenosis.

Vascular imaging of the mesenteric vasculature.

Imaging of the mesenteric vasculature is crucial in diagnosing vascular disease of the gastro-intestinal tract such as acute or chronic mesenteric ischemia caused by arterial stenosis, embolism or thrombosis, mesenteric vein thrombosis and mesenteric aneurysm or dissection. The reference standard for imaging of the mesenteric vasculature is digital subtraction angiography. However, modalities as duplex ultrasonography, computed tomography angiography and magnetic resonance angiography are developing rapidly and may provide accurate imaging non-invasively. This review provides an up-to-date overview of the anatomic resolution, clinical application, emerging techniques and future perspectives of these four radiological modalities for imaging of the mesenteric vasculature.

A young woman with a jejuno-jejunal intussusception.

A 27-year-old woman presented at the emergency department, with pain in the epigastric region. Because physical examination, blood results, urine tests and an X-ray of the thorax showed no abnormalities, she was discharged. Twelve hours later, she presented again at the emergency department, with intense abdominal pain. The blood results, an X-ray and ultrasound of the abdomen were now aberrant. A CT of the abdomen showed an extensive intussusception. During an emergency laparotomy, the intussusception of the proximal jejunum was confirmed. Owing to gangrene of the proximal jejunum, a resection was inevitable. A polyp in the resected part of the jejunum was the lead point of the intussusception. This case report shows the challenges of diagnosing an 'intussusception' and gives a short overview of this condition in adults.