Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease.

OBJECTIVES: Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD. METHODS: Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease. RESULTS: Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively. CONCLUSIONS: Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.

Trans-anal total mesorectal excision in low rectal cancers: Preliminary oncological results of a comparative study.

OBJECTIVE: The management of lower rectal cancers is a therapeutic challenge both from the oncological and functional viewpoints. The aim of this study is to assess the oncological results and postoperative morbidity after transanal total mesorectal excision (TaTME) for low rectal cancer. MATERIAL AND METHODS: In this monocentric retrospective study, we compared the quality of carcinologic resection and the morbidity-mortality between a group of 20 patients undergoing TaTME and 21 patients treated by abdomino-perineal resection (APR) between 2016 to 2019. RESULTS: More patients had a positive circumferential resection margin (CRM) (≤1mm) in the APR group (47.6% vs. 5%; P<0.0036). The difference in the rates of grades I-II and III-IV complications (Clavien-Dindo classification) between the two groups was not statistically significant (50% vs. 57.1% and 5% vs. 9.5% in TaTME and APR, respectively; P=0.7579, P=1.00). The median follow-up was longer in the TaTME group (20 months vs. 11 months; P=0.58). The local recurrence rate did not differ between the two groups (5% vs. 4.8%; P=1.00) CONCLUSION: TaTME provides a reliable total mesorectal resection with an acceptable CRM. However, like any new technique, it requires experience and the learning curve is long.

Two-step pull-through colo-anal anastomosis aiming to avoid stoma in rectal cancer surgery: A "real life" study in a developing country.

BACKGROUND: Delayed colo-anal anastomosis (DCA) is an underused technique rarely performed after resection of primary low rectal adenocarcinoma. The objective of this study was to compare the short-term outcomes of DCA and classical colo-anal anastomosis (CAA). METHODS: This is a retrospective comparative study carried out at two tertiary centres in Morocco and France. It included all patients who underwent colo-anal anastomosis after complete mesorectal excision for primary rectal adenocarcinoma between January 2018 and December 2019. The main outcomes were 90-day morbidity and rates completing the surgical steps of DCA and CAA. RESULTS: Among 215 rectal resections, 45 patients received colo-anal anastomosis, including 19 DCA and 26 CAA. Seventeen patients in the DCA group completed the two steps compared to 16 in the CAA group (89.5% vs. 61.5%, P=0.04). The rates of severe complications (26.9% vs. 26.3%, P=0.96) and anastomotic leakage (42.3% vs. 31.6%, P=0.46) were not different between the two groups. CONCLUSION: This study showed that DCA was associated with a higher rate of completing the two surgical steps, with no difference in overall and severe morbidity. DCA may be a strong alternative to classical colo-anal anastomosis.

Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.

Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Colon cancer in inflammatory bowel disease: recent trends, questions and answers.

Patients with chronic colitis (ulcerative colitis or colonic Crohn's disease) have an increased risk of colorectal cancer (CRC). Although most of the molecular alterations reported in sporadic CRC have also been observed in colitis-associated CRC, they do not occur at the same timing and frequency, indicating a different pathophysiology. In particular, recent work highlighted the importance of chronic mucosal inflammation as a key factor favouring colorectal carcinogenesis in these patients. This may also be one of the reasons explaining the role of 5-aminosalicylates as chemopreventive agents for CRC in inflammatory bowel disease (IBD) patients with colonic involvement. Beside chemoprevention, colonoscopic screening and surveillance have been shown to be the cornerstone for CRC prevention and early detection in this particular patients' population. Periodic surveillance colonoscopy to detect dysplasia has been shown to decrease the mortality attributed to CRC. More recently, progress in imaging techniques increased our ability to identify dysplasia, and should probably now be considered to be an integral part of surveillance colonoscopy. In the future, further improvement of our knowledge of CRC biology, refinement of imaging techniques, as well as molecular discovery (e.g. identification of specific mutations in stool DNA extracts), might lead to develop more accurate diagnostic strategies to reduce the morbidity and mortality related to CRC in patients with ulcerative colitis or colonic Crohn's disease.

Frequency and severity of ileal adenomas in familial adenomatous polyposis after colectomy.

BACKGROUND AND STUDY AIMS: The high cumulative risk of colorectal cancer in patients with familial adenomatous polyposis (FAP) justifies prophylactic colectomy with either ileorectal (IRA) or ileal-pouch-anal anastomosis (IPAA). Our aim was to evaluate retrospectively the frequency of and time interval to adenoma development in the ileal mucosa of patients with both types of surgery. PATIENTS AND METHODS: Retrospective study of 44 FAP patients with IRA (n = 21) and IPAA (n = 23). All patients were followed with a standardized procedure including chromoscopy and biopsies of visible polyps. In patients with IRA, specific attention was paid to the ileal mucosa above the anastomosis. RESULTS: In the IPAA group, 18/23 patients (78 %) presented with visible polyps [histology: 16 (70 %) had adenoma with low-grade dysplasia; 1 (4 %) had adenoma with high-grade dysplasia; 1 had normal mucosa]. The mean interval between colectomy and the diagnosis of adenoma was 4.7 +/- 3.3 years. In the IRA group, 16/21 patients (77 %) presented visible polyps in the ileal mucosa [adenoma with low-grade dysplasia in 8 patients (38 %), with high-grade dysplasia in 2 (10 %), and lymphoid nodular hyperplasia in 6]. The mean interval between colectomy and adenoma diagnosis was significantly shorter in the IPAA than in the IRA group (4.76 +/- 3.3 vs. 16.4 +/- 8.5 years, P< 0.0001). CONCLUSION: Our results show a high frequency of adenomas in the ileal mucosa of patients with IPAA and IRA (74 % and 48 % respectively), with evolution into high-grade dysplasia in 6.7 % of cases.

Faecal bacterial mass and energetic losses in healthy humans and patients with a short bowel syndrome.

OBJECTIVE: In addition to non-digested nutrients, human stools contain endogenous substrates, among which bacteria are a major component, whose growth may be stimulated when more dietary nutrients are available for bacterial fermentation, as in patients with malabsorption syndrome. We assessed the energy content and composition of both stools and faecal bacteria in healthy volunteers and patients with a short bowel and colon in continuity (SBC). Our goal was to clarify the magnitude of error introduced by the faecal bacteria in the measurement of the digestibility of ingested energy and nutrients. SUBJECTS AND METHODS: We studied six healthy volunteers and six patients with a SBC under free oral intake. The bacterial mass of stools was isolated. In the bacterial fractions and fresh stools, calorie, fat, nitrogen and short-chain fatty acid contents were determined. The Wilcoxon signed rank or the Mann-Whitney tests were used for comparison. RESULTS: In healthy volunteers and patients with SBC, faecal bacterial mass accounted for 44 and 35% of faecal dry weight, and contained 50 and 34% of total faecal energy. In healthy volunteers, the apparent digestibilities when corrected by bacterial constituents (88-97% according to nutrients) were significantly higher than the apparent non-corrected digestibilities (84-94%). In patients with SBC, the corrected apparent digestibilities (69-89% according to nutrients) were significantly higher than the apparent non-corrected digestibilities (54-83%). CONCLUSION: The error introduced by the faecal bacterial fraction when assessing the extent of nutrient digestibility is small in healthy volunteers; it is more pronounced in patients with SBC, reaching 18% for the digestibility of ingested fat.

Effect of short-chain fatty acids and acidification on the phasic and tonic motor activity of the human colon.

BACKGROUND: The effects of bacterial fermentation on human colonic motor activity could be explained by colonic acidification or short-chain fatty acid (SCFA) production. We compared in healthy volunteers the colonic motor effects of intracolonic infusion of neutral or acidic saline solutions and then of neutral or acidic solutions containing an SCFA mixture. METHODS: 20 healthy volunteers swallowed a probe (with an infusion catheter, 6 perfused catheters and a balloon connected to a barostat) that migrated into the colon. Colonic motor activity was recorded in fasting basal state (1 h), during (3 h) and after (2 h) intracolonic infusion in a random order on two consecutive days of 750 mL of NaCl at pH 7.0 (neutral saline) or 4.5 (acidic saline) in 10 volunteers (first experiment) and of an SCFA mixture (acetic acid 66%, propionic acid 24% and butyric acid 10%; 100 mM) at pH 7.0 or 4.5 in 10 other volunteers (second experiment). We determined for each hour a global motility index (reflecting phasic activity recorded by all catheters), the mean balloon volume (reflecting tonic activity), and the mean number of high-amplitude-propagated contractions (HAPCs). KEY RESULTS: Intracolonic infusion of neutral or acidic solutions containing saline or an SCFA mixture did not change the global motility index, the barostat balloon volume, or the HAPC number compared with basal values. CONCLUSIONS & INFERENCES: Under our experimental conditions, these findings suggest that the stimulation of colonic motor activity induced by carbohydrate fermentation is not explained by the acidification of the colonic contents or the resulting production of SCFAs.

Urinary neopterin is a valuable tool in monitoring Crohn's disease activity.

BACKGROUND: The aim was to investigate the relation between urinary neopterin and the Crohn's Disease Activity Index (CDAI) and to compare its ability to discriminate active versus inactive CD with serum C-reactive protein (CRP). METHODS: In all, 217 urinary samples for neopterin measurement were obtained in a cohort of 93 consecutive patients with CD and 66 samples in 33 healthy volunteers. Clinical parameters were recorded and blood samples for CRP were collected as well. RESULTS: Whereas patients with inactive CD showed similar levels of urinary neopterin excretion than healthy volunteers (163 +/- 8 versus 142 +/- 7 nmol/mol of creatinine, respectively; P = 0.1), urinary neopterin excretion from mild to severe active CD was significantly higher (302 +/- 15 nmol/mol of creatinine; P < 0.001). Serum CRP levels were higher in active CD (14.8 +/- 2.1 mg/L) compared with inactive CD (5.6 +/- 0.8 mg/L; P < 0.001). Urinary neopterin excretion, and to a lesser degree CRP, were positively and significantly correlated with CDAI (r = 0.64 and 0.43, respectively, P < 0.001). Based on the cutoff of 183 nmol/mol of creatinine for urinary neopterin, the sensitivity and specificity of urinary neopterin to discriminate between active and inactive CD were 73% and 82%, respectively, and the positive and negative predictive values were 80% and 78%, respectively. CONCLUSIONS: Urinary neopterin excretion is an objective, valuable, simple, and noninvasive biomarker to detect and follow fluctuations of CD activity. Further work is warranted to study its clinical value and relation to mucosal healing.