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.

Diagnostic Accuracy of the Combination of Clinical Symptoms and CT or MR Angiography in Patients With Chronic Gastrointestinal Ischemia.

BACKGROUND: No golden diagnostic standard is available to diagnose chronic gastrointestinal ischemia (CGI). GOALS: We aimed to establish an accurate prediction model for CGI, based on clinical symptoms and radiologic evaluation of the amount of stenosis in the celiac artery (CA) and superior mesenteric artery (SMA) by means of computed tomography-angiography or magnetic resonance (MR)-angiography. STUDY: We prospectively included 436 consecutive patients with clinical suspicion of CGI in a tertiary referral center. Predictors for CGI were obtained by comparing clinical parameters to the diagnosis of CGI. Multivariable logistic regression was used to combine the strongest predictors in a model. A score chart based on the prediction model was provided to calculate the risk of CGI. RESULTS: CGI was present in 171/436 (39%) patients (67 y; range, 54 to 74 y; 27% male). Strongest predictors for CGI were female gender [odds ratio (OR)=1.44; 95% confidence interval (CI), 0.85-2.43], weight loss (OR=1.63, 95% CI, 0.98-2.72), concomitant cardiovascular disease (OR=1.70, 95% CI, 1.04-2.78), duration of symptoms (OR=0.88, 95% CI, 0.79-0.99), and stenosis of CA and SMA (50% to 70% stenosis CA: OR=1.33, 95% CI, 0.56-3.19; >70% stenosis CA: OR=5.79, 95% CI, 3.42-9.81; 50% to 70% stenosis SMA: OR=3.21, 95% CI, 0.81-12.74; >70% stenosis SMA: OR=4.39, 95% CI, 2.30-8.41). A model based on clinical symptoms alone showed limited discriminative ability for diagnosing CGI (c-statistic 0.62). Adding radiologic imaging of the mesenteric arteries improved the discriminative ability (c-statistic 0.79). CONCLUSIONS: Clinical symptoms alone are insufficient to predict the risk of CGI. Radiologic evaluation of the mesenteric arteries is essential. This tool may be useful for clinicians to assess the risk of CGI and to decide whether further diagnostic work-up for CGI is needed.

GI ischemia in patients with portal vein thrombosis: a prospective cohort study.

BACKGROUND AND AIMS: GI ischemia is a concerning adverse event of portal vein thrombosis (PVT). Minimally invasive techniques, such as visible light spectroscopy (VLS), have greatly improved the ability to diagnose GI ischemia. The aim of this study was to assess the clinical presentation and characteristics of GI ischemia in patients with PVT. METHODS: Patients with noncirrhotic, nonmalignant PVT were included in this prospective cohort study. Clinical symptoms of GI ischemia were assessed by a structured questionnaire, VLS, and radiologic evaluation of the mesenteric vasculature. VLS measurements were compared with those in patients with cirrhosis and with a reference population. RESULTS: We included 15 patients with chronic PVT and 1 patient with acute PVT (median age 46.1 years [interquartile range [IQR], 30.9-53.7]; 44% male). Decreased mucosal oxygenation in at least 1 location of the GI tract was found in 12 patients (75%). Compared with the reference population (median 60.0 [IQR, 56.2-61.7]), VLS measurements were mostly decreased in the descending duodenum in patients with PVT (median 55.5 [IQR, 52.3-58.8]; P = .02) and patients with cirrhosis (median 52.0 [IQR, 46.5-54.0], P = .003). Symptoms typical for GI ischemia, such as postprandial pain and exercise-induced pain, were reported in 10 patients (63%) with PVT. In patients with extension of thrombosis into the superior mesenteric vein and splenic vein and/or presence of hypercoagulability, decreased VLS measurements were observed compared with historical control subjects. CONCLUSIONS: In patients with chronic PVT, GI ischemia is frequent. VLS enables objective and quantitative determination of GI mucosal ischemia. Onset of abdominal symptoms such as postprandial pain should prompt the physician to re-evaluate extent, cause, and treatment of PVT.

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.

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.

Validation of a score chart to predict the risk of chronic mesenteric ischemia and development of an updated score chart.

Background and objective: The objective of this article is to externally validate and update a recently published score chart for chronic mesenteric ischemia (CMI). Methods: A multicenter prospective cohort analysis was conducted of 666 CMI-suspected patients referred to two Dutch specialized CMI centers. Multidisciplinary consultation resulted in expert-based consensus diagnosis after which CMI consensus patients were treated. A definitive diagnosis of CMI was established if successful treatment resulted in durable symptom relief. The absolute CMI risk was calculated and discriminative ability of the original chart was assessed by the c-statistic in the validation cohort. Thereafter the original score chart was updated based on the performance in the combined original and validation cohort with inclusion of celiac artery (CA) stenosis cause. Results: In 8% of low-risk patients, 39% of intermediate-risk patients and 94% of high-risk patients of the validation cohort, CMI was diagnosed. Discriminative ability of the original model was acceptable (c-statistic 0.79). The total score of the updated chart ranged from 0 to 28 points (low risk 19% absolute CMI risk, intermediate risk 45%, and high risk 92%). The discriminative ability of the updated chart was slightly better (c-statistic 0.80). Conclusion: The CMI prediction model performs and discriminates well in the validation cohort. The updated score chart has excellent discriminative ability and is useful in clinical decision making.

Patients with chronic mesenteric ischemia have an altered sublingual microcirculation.

BACKGROUND: Little is known about the microcirculatory alterations in patients with chronic mesenteric ischemia (CMI). We hypothesized that patients with CMI have an impaired microcirculatory function and show an oral microcirculatory response after caloric challenge compared to healthy controls. METHODS: All patients and controls received the standard workup for CMI. Sublingual micro-circulation was evaluated before (T0) and 20 minutes after (T1) feeding. The total vessel density (TVD; mm/mm2), perfused vessel density (PVD; mm/mm2), proportion of perfused vessels (PPV; %) and microvascular flow index (MFI; AU) were assessed. RESULTS: We included 12 patients (63.2 years [IQR 48.8-70.4 years], 67% males) and 12 controls (32.7 years [IQR 27.7-38.1 years], 42% males). At baseline, patients with CMI had a decreased PPV of the sublingual small vessels (median 84.8% vs 95.7%, P=0.006), PPV of all vessels (PPV median 85.4% vs 95.3%, P=0.007) and microvascular flow index of all vessels (MFIa; median 3.00 vs 2.80, P=0.039) compared to healthy controls. After caloric challenge, PVD increased significantly in both small vessels (perfused vessel density of the small vessels [PVDs]) and all vessels (perfused vessel density of all vessels [PVDa]; PVDs [T0]) median 16.3 [IQR 13.3-22.1] vs [T1] median 19.9 [IQR 14.2-26.2], P=0.008; PVDa [T0] median 19.1 [IQR 16.2-23.6] vs [T1] median 22.2 [IQR 16.5-28.9], P=0.02; proportion of perfused vessels of the small vessels (PPVs; [T0] median 84.8% [IQR 75.3-90.4] vs [T1] median 91.0% [IQR 80.1-93.8], P=0.010). In contrast, no significant changes in microcirculatory parameters were observed after caloric challenge in healthy controls. CONCLUSION: Patients with CMI have an impaired sublingual microcirculation at baseline and show a significant response in the sublingual microcirculation after caloric challenge, whereas healthy controls have a normal microcirculation at baseline and show no reactive response upon a caloric challenge as seen in CMI patients. Sublingual microcirculation visualization may offer a rapid noninvasive method to identify patients at risk for having CMI.

Hypoxia-inducible factor 1-α in chronic gastrointestinal ischemia.

Chronic gastrointestinal ischemia (CGI) is the result of decreased mucosal perfusion. Typical histological characteristics are lacking which hamper its early diagnosis. Hypoxia-inducible factor-1α (HIF-1α) is expressed under acute hypoxia. We investigated HIF-1α expression in chronic ischemic and inflammatory conditions of the human gastrointestinal (GI) tract. Immunohistochemical expression of HIF-1α was analyzed in 61 patients, including patients with CGI, Helicobacter pylori gastritis, ischemic colitis (IC), infectious colitis, and inflammatory bowel disease (IBD), and 22 controls. HIF-1α expression in >10 % of the cells was regarded as positive staining, and expression <10 % of the cells was considered as negative staining. In the upper GI tract, HIF-1α expression was found in 5/20 CGI patients, but not in controls (p = 0.08). The sensitivity and specificity of HIF-1α expression for diagnosing CGI were 25 and 84%, respectively. In the lower GI tract, HIF-1α was expressed in all patients with IC and infectious colitis and in a majority of IBD patients as well as in 7/12 controls. The sensitivity and specificity of HIF-1α for diagnosing IC were 100 and 51%, respectively. HIF-1α expression was more often (p = 0.02) observed in patients with histological signs of inflammation in the lower GI tract. HIF-1α is expressed in acute and chronic ischemic tissue, but also in normal colon tissue and inflammatory disorders.