Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model.

Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.

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.

Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study. METHODS: Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API ('GRS+API', composite endpoint) and for GRS and API separately. RESULTS: 202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081). CONCLUSIONS: Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS. TRIAL REGISTRATION NUMBER: The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465).

Gamma-Glutamyl Transferase: A Friend against Cholestatic Itch? A Retrospective Observational Data Analysis in Patients with Extrahepatic Cholestasis.

Methods: We included 235 patients with chronic extrahepatic cholestasis due to pancreatic cancer, cholangiocarcinoma, or papillary carcinoma. Results: GGT was significantly higher in patients without pruritus (median 967, IQR 587-1571) compared to patients with pruritus (median 561 IQR 266-1084 IU/l) (p < 0.01). In contrast, median alkaline phosphatase (AP) was 491 U/L (IQR; 353-684) in patients with pruritus and was not significantly different from 518 U/L (IQR; 353-726) in patients without pruritus (p = 0.524). Direct bilirubin was significantly higher in patients with pruritus compared to patients without pruritus (168 µmol/L (IQR; 95-256) vs. 120 µmol/L (IQR; 56.75-185.5)) (p < 0.01). After correcting for the extent of cholestasis via direct bilirubin, the negative association between GGT and pruritus remained significant and became stronger (p < 0.001). Conclusion: Serum GGT activity is inversely associated with the presence of cholestatic itch in patients with chronic extrahepatic cholestasis.

Systematic Review of the Efficacy of Treatment for Median Arcuate Ligament Syndrome.

OBJECTIVE: Since the first description of the median arcuate ligament syndrome (MALS), the existence for the syndrome and the efficacy of treatment for it have been questioned. METHODS: A systematic review conforming to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted, with a broader view on treatment for MALS including any kind of coeliac artery release, coeliac plexus resection, and coeliac plexus blockage, irrespective of age. Online databases were used to identify papers published between 1963 and July 2021. The inclusion criteria were abdominal symptoms, proof of MALS on imaging, and articles reporting at least three patients. Primary outcomes were symptom relief and quality of life (QoL). RESULTS: Thirty-eight studies describing 880 adult patients and six studies describing 195 paediatric patients were included. The majority of the adult studies reported symptom relief of more than 70% from three to 228 months after treatment. Two adult studies showed an improved QoL after treatment. Half of the paediatric studies reported symptom relief of more than 70% from six to 62 months after laparoscopic coeliac artery release, and four studies reported an improved QoL. Thirty-five (92%) adult studies and five (83%) paediatric studies scored a high or unclear risk of bias for the majority of the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) items. The meaning of coeliac plexus resection or blockage could not be substantiated. CONCLUSION: This systematic review suggests a sustainable symptom relief of more than 70% after treatment for MALS in the majority of adult and paediatric studies; however, owing to the heterogeneity of the inclusion criteria and outcome parameters, the risk of bias was high and a formal meta-analysis could not be performed. To improve care for patients with MALS the next steps would be to deal with reporting standards, outcome definitions, and consensus descriptions of the intervention(s), after which an appropriate randomised controlled trial should be performed.

Non-classical clinical presentation at diagnosis by male celiac disease patients of older age.

BACKGROUND: . In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients. OBJECTIVES: To identify which factors contribute to diagnosis later in life and whether diagnostic delay influences improvement of symptoms after starting a gluten-free diet (GFD). METHODS: . We performed a questionnaire study in 211 CeD patients (67:144, male:female) with median age at diagnosis of 41.8 years (interquartile range: 25-58) and at least Marsh 2 histology. RESULTS: . Classical symptoms (diarrhea, fatigue, abdominal pain and/or weight loss) were more frequent in women than men, but sex was not significantly associated with age at diagnosis. In a multivariate analysis, a non-classical presentation (without any classical symptoms) and a negative family history of CeD were significant predictors of older age at diagnosis (coefficients of 8 and 12 years, respectively). A delay of >3 years between first symptom and diagnosis was associated with slower improvement of symptoms after start of GFD, but not with sex, presentation of classical symptoms or age at diagnosis. CONCLUSION: . Non-classical CeD presentation is more prevalent in men and is associated with a diagnosis of CeD later in life. Recognizing CeD sooner after onset of symptoms is important because a long diagnostic delay is associated with a slower improvement of symptoms after starting a GFD.

The Incidence of Chronic Mesenteric Ischemia in the Well-Defined Region of a Dutch Mesenteric Ischemia Expert Center.

INTRODUCTION: This study aimed to determine the incidence of chronic mesenteric ischemia (CMI) and to examine the influence of the etiological cause, location, and severity of a mesenteric artery stenosis on the probability of having CMI. METHODS: A prospective database, containing the details of all patients with suspected CMI referred to a renowned CMI expert center, was used. Patients residing within the expert centers' well-defined region, between January 2014 and October 2019, were included. CMI was diagnosed when patients experienced sustained symptom improvement after treatment. RESULTS: This study included 358 patients, 75 had a ≥50% atherosclerotic stenosis of 1 vessel (CMI 16%), 96 of 2 or 3 vessels (CMI 81%), 81 celiac artery compression (CMI 25%), and 84 no stenosis (CMI 12%). In total, 138 patients were diagnosed with CMI, rendering a mean incidence of 9.2 (95% confidence interval [CI] 6.2-13.7) per 100,000 inhabitants. Atherosclerotic CMI was most common, with a mean incidence of 7.2 (95% CI 4.6-11.3), followed by median arcuate ligament syndrome 1.3 (95% CI 0.5-3.6) and chronic nonocclusive mesenteric ischemia 0.6 (95% CI 0.2-2.6). The incidence of CMI was highest in female patients (female patients 12.0 [95% CI 7.3-19.6] vs male patients 6.5 [95% CI 3.4-12.5]) and increased with age. CMI was more prevalent in the presence of a ≥70% atherosclerotic single-vessel stenosis of the superior mesenteric artery (40.6%) than the celiac artery (5.6%). DISCUSSION: The incidence of CMI is higher than previously believed and increases with age. Probability of CMI seems highest in suspected CMI patients with multivessel disease or a ≥70% atherosclerotic single-vessel superior mesenteric artery stenosis.

European guidelines on chronic mesenteric ischaemia - joint United European Gastroenterology, European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Gastrointestinal and Abdominal Radiology, Netherlands Association of Hepatogastroenterologists, Hellenic Society of Gastroenterology, Cardiovascular and Interventional Radiological Society of Europe, and Dutch Mesenteric Ischemia Study group clinical guidelines on the diagnosis and treatment of patients with chronic mesenteric ischaemia.

Chronic mesenteric ischaemia is a severe and incapacitating disease, causing complaints of post-prandial pain, fear of eating and weight loss. Even though chronic mesenteric ischaemia may progress to acute mesenteric ischaemia, chronic mesenteric ischaemia remains an underappreciated and undertreated disease entity. Probable explanations are the lack of knowledge and awareness among physicians and the lack of a gold standard diagnostic test. The underappreciation of this disease results in diagnostic delays, underdiagnosis and undertreating of patients with chronic mesenteric ischaemia, potentially resulting in fatal acute mesenteric ischaemia. This guideline provides a comprehensive overview and repository of the current evidence and multidisciplinary expert agreement on pertinent issues regarding diagnosis and treatment, and provides guidance in the multidisciplinary field of chronic mesenteric ischaemia.

Volatile organic compounds in breath can serve as a non-invasive diagnostic biomarker for the detection of advanced adenomas and colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer diagnosis in the Western world. AIM: To evaluate exhaled volatile organic compounds (VOCs) as a non-invasive biomarker for the detection of CRC and precursor lesions using an electronic nose. METHODS: In this multicentre study adult colonoscopy patients, without inflammatory bowel disease or (previous) malignancy, were invited for breath analysis. Two-thirds of the breath tests were randomly assigned to develop training models which were used to predict the diagnosis of the remaining patients (external validation). In the end, all data were used to develop final-disease models to further improve the discriminatory power of the algorithms. RESULTS: Five hundred and eleven breath samples were collected. Sixty-four patients were excluded due to an inadequate breath test (n = 51), incomplete colonoscopy (n = 8) or colitis (n = 5). Classification was based on the most advanced lesion found; CRC (n = 70), advanced adenomas (AAs) (n = 117), non-advanced adenoma (n = 117), hyperplastic polyp (n = 15), normal colonoscopy (n = 125). Training models for CRC and AAs had an area under the curve (AUC) of 0.76 and 0.71 and blind validation resulted in an AUC of 0.74 and 0.61 respectively. Final models for CRC and AAs yielded an AUC of 0.84 (sensitivity 95% and specificity 64%) and 0.73 (sensitivity and specificity 79% and 59%) respectively. CONCLUSIONS: This study suggests that exhaled VOCs could potentially serve as a non-invasive biomarker for the detection of CRC and AAs. Future studies including more patients could further improve the discriminatory potential of VOC analysis for the detection of (pre-)malignant colorectal lesions. (https://clinicaltrials.gov Identifier NCT03488537).

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.

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.

Clinical management of chronic mesenteric ischemia.

This This Dutch Mesenteric Ischemia Study group consists of: Ron Balm, Academic Medical Center, Amsterdam Gert Jan de Borst, University Medical Center Utrecht, Utrecht Juliette T Blauw, Medisch Spectrum Twente, Enschede Marco J Bruno, Erasmus MC University Medical Center, Rotterdam Olaf J Bakker, St Antonius Hospital, Nieuwegein Louisa JD van Dijk, Erasmus MC University Medical Center, Rotterdam Hessel CJL Buscher, Gelre Hospitals, Apeldoorn Bram Fioole, Maasstad Hospital, Rotterdam Robert H Geelkerken, Medisch Spectrum Twente, Enschede Jaap F Hamming, Leiden University Medical Center, Leiden Jihan Harki, Erasmus MC University Medical Center, Rotterdam Daniel AF van den Heuvel, St Antonius Hospital, Nieuwegein Eline S van Hattum, University Medical Center Utrecht, Utrecht Jan Willem Hinnen, Jeroen Bosch Hospital, 's-Hertogenbosch Jeroen J Kolkman, Medisch Spectrum Twente, Enschede Maarten J van der Laan, University Medical Center Groningen, Groningen Kaatje Lenaerts, Maastricht University Medical Center, Maastricht Adriaan Moelker, Erasmus MC University Medical Center, Rotterdam Desirée van Noord, Franciscus Gasthuis & Vlietland, Rotterdam Maikel P Peppelenbosch, Erasmus MC University Medical Center, Rotterdam André S van Petersen, Bernhoven Hospital, Uden Pepijn Rijnja, Medisch Spectrum Twente, Enschede Peter J van der Schaar, St Antonius Hospital, Nieuwegein Luke G Terlouw, Erasmus MC University Medical Center, Rotterdam Hence JM Verhagen, Erasmus MC University Medical Center, Rotterdam Jean Paul PM de Vries, University Medical Center Groningen, Groningen Dammis Vroegindeweij, Maasstad Hospital, Rotterdam review provides an overview on the clinical management of chronic mesenteric ischemia (CMI). CMI is defined as insufficient blood supply to the gastrointestinal tract, most often caused by atherosclerotic stenosis of one or more mesenteric arteries. Patients classically present with postprandial abdominal pain and weight loss. However, patients may present with, atypically, symptoms such as abdominal discomfort, nausea, vomiting, diarrhea or constipation. Early consideration and diagnosis of CMI is important to timely treat, to improve quality of life and to prevent acute-on-chronic mesenteric ischemia. The diagnosis of CMI is based on the triad of clinical symptoms, radiological evaluation of the mesenteric vasculature and if available, functional assessment of mucosal ischemia. Multidisciplinary consensus on the diagnosis of CMI is of paramount importance to adequately select patients for treatment. Patients with a consensus diagnosis of single-vessel or multi-vessel atherosclerotic CMI are preferably treated with endovascular revascularization.

Sucrose but Not Nitrate Ingestion Reduces Strenuous Cycling-induced Intestinal Injury.

PURPOSE: Strenuous exercise induces intestinal injury, which is likely related to splanchnic hypoperfusion and may be associated with gastrointestinal complaints commonly reported during certain exercise modalities. Increasing circulating nitric oxide (NO) levels or inducing postprandial hyperemia may improve splanchnic perfusion, thereby attenuating intestinal injury during exercise. Therefore, we investigated the effects of both dietary nitrate ingestion and sucrose ingestion on splanchnic perfusion and intestinal injury induced by prolonged strenuous cycling. METHODS: In a randomized crossover manner, 16 well-trained male athletes (age, 28 ± 7 yr; Wmax, 5.0 ± 0.3 W·kg) cycled 60 min at 70% Wmax after acute ingestion of sodium nitrate (NIT; 800 mg NO3), sucrose (SUC; 40 g), or a water placebo (PLA). Splanchnic perfusion was assessed by determining the gap between gastric and arterial pCO2 (gapg-apCO2) using gastric air tonometry. Plasma intestinal fatty acid-binding protein (I-FABP) concentrations, reflecting enterocyte damage, were assessed every 20 min during and up to 60 min of postexercise recovery. RESULTS: The exercise protocol resulted in splanchnic hypoperfusion, as gapg-apCO2 levels increased during exercise (P < 0.001), with no differences between treatments (P = 0.47). Although plasma I-FABP concentrations increased during exercise and postexercise recovery for all treatments (P < 0.0001), the increase was different between treatments (P < 0.0001). Post hoc comparisons showed an attenuated increase in I-FABP in SUC versus PLA (P = 0.020). In accordance, I-FABP area under the curve (AUC0-120) was significantly lower in SUC versus PLA (57,270 ± 77,425 vs 114,907 ± 91,527 pg·mL per 120 min, P = 0.002). No differences were observed between NIT and PLA (P = 0.99). CONCLUSION: Sucrose but not nitrate ingestion lowers intestinal injury evoked during prolonged strenuous cycling. These results suggest that sucrose ingestion, but not nitrate, prevents hypoperfusion-induced gastrointestinal damage during exercise and, as such, may help to lower exercise-related gastrointestinal complaints.

Fluid hydration to prevent post-ERCP pancreatitis in average- to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial): study protocol for a randomized controlled trial.

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP. METHODS: The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness. DISCUSSION: The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs. TRIAL REGISTRATION: EudraCT: 2015-000829-37 . Registered on 18 February 2015. ISRCTN: 13659155 . Registered on 18 May 2015.

Colon ischemia: Right-sided colon involvement has a different presentation, etiology and worse outcome. A large retrospective cohort study in histology proven patients.

BACKGROUND: Colon ischemia (CI), is generally considered a non-occlusive mesenteric ischemia disorder that usually runs a benign course, but right-sided involvement (RCI) has been associated with worse outcome. The poor outcome of RCI has been associated with comorbidity, but more recently also with occlusions of the mesenteric arteries. We performed a retrospective analysis of a large cohort of CI-patients to assess differences in presentation, etiology, and comorbidity between right-sided colon ischemia (RCI) and non-right-sided colon ischemia (NRCI), and their relation to outcome. METHODS: We performed a retrospective cohort study in two centers from 2000 to 2011 for CI and analyzed clinical presentation, etiology, treatment and outcome. Diagnosis was based on full colonoscopy and/or surgical findings and confirmed by histopathology. RESULTS: 239 patients were included (mean age 69, 52% female). RCI was found in 48% and NRCI in 52%. Patients with NRCI presented more often with rectal bleeding (87% vs. 45%; p<0.001). In RCI more nausea (58% vs. 39%; p=0.013), weight loss (56% vs. 19%; p<0.001), paralytic ileus (32% vs. 18%; p=0.018) and peritoneal signs (27% vs. 7%; p<0.001) was observed compared to NRCI. The cause of CI was more often idiopathic in NRCI (46% vs. 26%; p=0.002); an occlusive cause was seen more often in RCI (26.3 vs 2.4%, p<0.0001). RCI patients had longer hospital stay (15 vs. 8 days, p<0.001), need for surgery (61% vs. 34%, p<0.001), and trend toward higher 30-day in-hospital mortality (20% vs. 12%, p=0.084). CONCLUSIONS: RCI ischemia has different etiology, presentation, and outcome. The series shows a high proportion of - treatable - vessel occlusion. It reinforces the advice to perform CT angiography in RCI as means to improve its poor outcome.

Diagnosis and treatment of chronic mesenteric ischemia: An update.

Although the prevalence of mesenteric artery stenoses (MAS) is high, symptomatic chronic mesenteric ischemia (CMI) is rare. The collateral network in the mesenteric circulation, a remnant of the extensive embryonal vascular network, serves to prevent most cases of ischemia. This explains the high incidence of MAS and relative rarity of cases of CMI. The number of affected vessels is the major determinant in CMI development. Most subjects with single vessel mesenteric stenosis do not develop ischemic complaints. Our experience is that most subjects with CA and SMA stenoses with abdominal complaints have CMI. A special mention should be made on patients with median arcuate ligament compression (MALS). There is ongoing debate whether the intermittent compression, caused by respiration movement, can cause ischemic complaints. The arguments pro and con treatment of MALS will be discussed. The clinical presentation of CMI consists of postprandial pain, weight loss, and an adapted eating pattern caused by fear of eating. In end-stage disease more continuous pain, diarrhea or a dyspepsia-like presentation can be observed. Workup of patients suspected for CMI consists of three elements: the anamnesis, the vascular anatomy and proof of ischemia. The main modalities to establish mesenteric vessel patency are duplex ultrasound, CT angiography or MR angiography. Assessing actual ischemia is still challenging, with only tonometry and visual light spectroscopy as tested candidates. Treatment consists of limiting metabolic demand, treatment of the atherosclerotic process and endovascular or operative revascularisation. Metabolic demand can be reduced by using smaller and more frequent meals, proton pump inhibition. Treatment of the atherosclerotic process consists of cessation of smoking, treatment of dyslipidemia, hypertension, hyperglycaemia, and medication with trombocyte aggregation inhibitors.

Functional testing in the diagnosis of chronic mesenteric ischemia.

Chronic mesenteric ischemia (CMI) results from insufficient oxygen delivery or utilization to meet metabolic demand. Two main mechanisms may lead to mesenteric ischemia: occlusion in the arteries or veins of the gastrointestinal tract, or reduced blood flow from shock states or increased intra-abdominal pressure, so-called non-occlusive mesenteric ischemia. Severe stenoses in the three main mesenteric vessels as demonstrated with CT-angiography or MR-angiography are sufficient to proof mesenteric ischemia, for example in patients who present with weight loss, postprandial pain and diarrhea. Still in many clinical situations mesenteric ischemia is only one of many possible explanations. Especially in patients with a single vessel stenosis in the celiac artery or superior mesenteric artery with postprandial pain, mesenteric ischemia remains a diagnosis of probability or assumption without functional proof of actual ischemia. This review is aimed to provide an overview of all past, present and future ways to functionally proof CMI.

Clinical significance of mesenteric arterial collateral circulation in patients with celiac artery compression syndrome.

OBJECTIVE: Although extensive collateral arterial circulation will prevent ischemia in most patients with stenosis of a single mesenteric artery, mesenteric ischemia may occur in these patients, for example, in patients with celiac artery compression syndrome (CACS). Variation in the extent of collateral circulation may explain the difference in clinical symptoms and variability in response to therapy; however, evidence is lacking. The objective of the study was to classify the presence of mesenteric arterial collateral circulation in patients with CACS and to evaluate the relation with clinical improvement after treatment. METHODS: Collateral mesenteric circulation was classified on the basis of angiographic findings. Collaterals were categorized in three groups: no visible collaterals (grade 0), collaterals seen on selective angiography only (grade 1), and collaterals visible on nonselective angiography (grade 2). Surgical release of the celiac artery in patients with suspected CACS was performed by arcuate ligament release. Clinical success after surgical revascularization was defined as an improvement in abdominal pain. RESULTS: Between 2002 and 2013, there were 135 consecutive patients with suspected CACS who were operated on. In 129 patients, preoperative angiograms allowed classification of collateral circulation. Primary assisted anatomic success was 93% (120/129). In patients with grade 0 collaterals, clinical success was 81% (39 of 48 patients); with grade 1 collaterals, 89% (25 of 28 patients); and with grade 2 collaterals, 52% (23 of 44 patients; P < .001). CONCLUSIONS: Patients with CACS and with extensive collateral mesenteric arterial circulation are less likely to benefit from arcuate ligament release than are patients without this type of collateral circulation. The classification of the extent of mesenteric collateral circulation may predict and guide shared decision-making in patients with CACS.

Chronic mesenteric ischemia: when and how to intervene on patients with celiac/SMA stenosis.

BACKGROUND: Studies that compared open surgical mesenteric artery repair (OSMAR) with percutaneous mesenteric artery stenting (PMAS) in patients with chronic mesenteric ischemia (CMI) are based on merely older studies in which only a minority of patients received PMAS. This does not reflect the current PMAS-first choice treatment paradigm. This article focused on the present opinions and changes in outcomes of OSMAR for CMI in the era of preferred use of PMAS. METHODS: Patients who received OSMAR for CMI from 1997 until 2014 in a tertiary referral centre for chronic mesenteric ischemia were included in this report. Patients were divided into two groups, the historical OSMAR preferred group and present PMAS preferred group. RESULTS: Patient characteristics, SVS comorbidity severity score, clinical presentation and number of diseased mesenteric arteries were not significantly changed after the widespread introduction of PMAS. In the present PMAS first era there were trends of less open surgical mesenteric artery multivessel repair, less antegrade situated bypasses, decreased clinical success but improved survival after OSMAR. CONCLUSIONS: Elective OSMAR should only be used in patients with substantial physiologic reserve and who have unfavourable mesenteric lesions, failed PMAS or multiple recurrences of in-stent stenosis/occlusion. PMAS in CMI patients is evolved from "bridge to surgery" to nowadays first choice treatment and "bridge to repeated PMAS" in almost all patients with CMI.