Real-Time In Vivo Imaging of Early Mucosal Changes during Ischemia-Reperfusion in Human Jejunum

BACKGROUND AND STUDY AIMS: Small intestinal ischemia-reperfusion (IR) is a frequent, potentially life threatening phenomenon. There is a lack of non-invasive diagnostic modalities. For many intestinal diseases, visualizing the intestinal mucosa using endoscopy is gold standard. However, limited knowledge exists on small intestinal IR-induced, early mucosal changes. The aims of this study were to investigate endoscopic changes in human jejunum exposed to IR, and to study concordance between endoscopic appearance and histology. PATIENTS AND METHODS: In 23 patients a part of jejunum, to be removed for surgical reasons, was isolated and selectively exposed to ischemia with 0, 30 or 120 minutes of reperfusion. In 3 patients, a videocapsule was inserted in the isolated segment before exposure to IR, to visualize the mucosa. Endoscopic view at several time points was related to histology (Heamatoxylin & Eosin) obtained from 20 patients. RESULTS: Ischemia was characterized by loss of villous structure, mucosal whitening and appearance of punctate lesions. This was related to appearance of subepithelial spaces and breaches in the epithelial lining in the histological view. Early during reperfusion, the lumen filled with IR-damaged, shed cells and VCE showed mucosal erosions, hemorrhage and intraluminal debris. At 60 minutes of reperfusion, the only remaining signs of IR were loss of villous structure and small erosions, indicating rapid mucosal healing. CONCLUSIONS: This study shows a unique, real-time in vivo endoscopic view of early mucosal changes during IR of the human small intestine. Future studies should evaluate its usefulness in diagnosis of patients suspected of IR

Human experimental model to study real time in vivo mucosal changes during human intestinal IR.

<p>(A) During a pylorus-preserving pancreaticoduodenectomy, a part of otherwise healthy intestine is removed for surgical reasons. A small segment (red arrowhead) of jejunum is isolated on both sides using a cutting stapler, allowing us to selectively expose it to ischemia and reperfusion. (B) Prior to induction of ischemia, a small bowel videocapsule is introduced into the isolated part of intestine via a small incision and positioned at the distal end of the isolated part of intestine (1 and 2). The part with the incision is resected using a cutting stapler (3), to rule out any possible leakage from intraluminal content towards the abdominal cavity.</p

Concordance between endoscopic and histological appearance.

<p>(A) Normal endoscopic view and histological appearance. (B) At 30 minutes of ischemia, subepithelial spaces appear (asterisks), indicating retraction of the basement membrane. This relates to the pale discoloration of mucosa in the endoscopic view. (C) At 60 minutes of ischemia, breaches in the epithelial lining can be observed (arrowhead), which relate to the appearance of punctate lesions in the endoscopic view (white arrow). (D) At 30 minutes of reperfusion, hemorrhage and shedding of IR-damaged epithelial cells becomes evident in both histological view (right panel: red arrowhead and black arrowhead, respectively), and endoscopic view (left panel: black arrow and white arrow, respectively). (E) At 60 minutes of reperfusion, villus atrophy in observed in conjunction with gaps in the epithelial lining and luminal debris. This relates to the loss of villous structure in endoscopic view, and the ‘white clouds’ of intraluminal debris.</p

Endoscopic appearance of human jejunum exposed to IR.

<p>(A) Normal endoscopic appearance of control tissue (B1) Pale discoloration of jejunal mucosa after 30 minutes of ischemia (B2) Appearance of small punctate lesions (white arrows) within the pale mucosa at 60 minutes of jejunal ischemia. (C) Within a few minutes of reperfusion, the intestinal lumen fills with a white substance (white arrowhead). (D1–D2) At 20–30 minutes of reperfusion, villous architecture in the mucosa is loss, and areas with hemorrhage (black arrows) and superficial erosions become apparent. Note the ‘white clouds’ of debris in the intestinal lumen (white arrows). (E) At 45 minutes of reperfusion, areas with hemorrhage and erosion are reduced. (F) At 60 minutes of reperfusion, the mucosa regained its initial color. Remaining signs of ischemia are the spots with hemorrhage, the intraluminal debris (white arrow), and loss of the villous structure.</p

High Percentage of IBD Patients with Indefinite Fecal Calprotectin Levels: Additional Value of a Combination Score

BACKGROUND AND AIM: Monitoring mucosal inflammation in inflammatory bowel disease (IBD) is of major importance to prevent complications and improve long-term disease outcome. The correlation of clinical activity indices with endoscopic disease activity is, however, moderate. Fecal calprotectin (FC) is a better predictor of mucosal inflammation, but values between 100 and 250 µg/g are difficult to interpret in clinical practice. We aimed to evaluate the occurrence of indefinite FC levels in a real-life IBD cohort and study the additional value of a combination of biochemical markers and clinical activity indices. METHODS: In total, 148 Crohn’s disease (CD) and 80 ulcerative colitis (UC) patients visiting the outpatient clinic were enrolled. FC, clinical disease activity scored by the Harvey–Bradshaw index or Simple Clinical Colitis Activity Index, and C-reactive protein (CRP) were assessed. In a subset of patients, endoscopic activity was scored by the simple endoscopic score-Crohn’s disease and Mayo endoscopic subscore. Clinical activity index, CRP, and FC were integrated in a combination score and compared with endoscopy. RESULTS: Indefinite FC values were present in 24% of CD and 15% of UC. In the cohort of patients with endoscopy scores available, the combination score predicted endoscopic disease activity in CD with a sensitivity of 83% and specificity of 69% [positive predictive value (PPV) 58%, negative predictive value (NPV) 89%]. In UC, this was 88 and 75% (PPV 93%, NPV 60%). CONCLUSIONS: A combination of FC with clinical activity indices or CRP may aid in classifying patients with indefinite disease activity according to FC alone

Improvements in the Long-Term Outcome of Crohn's Disease Over the Past Two Decades and the Relation to Changes in Medical Management: Results from the Population-Based IBDSL Cohort

OBJECTIVES: Medical treatment options and strategies for Crohn's disease (CD) have changed over the past decades. To assess its impact, we studied the evolution of the long-term disease outcome in the Dutch Inflammatory Bowel Disease South Limburg (IBDSL) cohort.METHODS: In total, 1,162 CD patients were included. Three eras were distinguished: 1991-1998 (n=316), 1999-2005 (n=387), and 2006-2011 (n=459), and patients were followed until 2014. Medication exposure and the rates of hospitalization, surgery, and phenotype progression were estimated using Kaplan-Meier survival analyses and compared between eras by multivariable Cox regression models. Second, propensity score matching was used to assess the relation between medication use and the long-term outcome.RESULTS: Over time, the immunomodulator exposure rate increased from 30.6% in the era 1991-1998 to 70.8% in the era 2006-2011 at 5 years. Similar, biological exposure increased from 3.1% (era 1991-1998) to 41.2% (era 2006-2011). In parallel, the hospitalization rate attenuated from 65.9% to 44.2% and the surgery rate from 42.9% to 17.4% at 5 years, respectively (both P0.05 for all analyses). Similar results were found for biological users (P&gt;0.05 for all analyses).CONCLUSIONS: Between 1991 and 2014, the hospitalization and surgery rates decreased, whereas progression to complicated disease is still common in CD. These improvements were not significantly related to the use of immunomodulators and biologicals.</p