Introduction

Irritable bowel syndrome (IBS) is a complex multifactorial disorder characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. Patients with IBS often complain of extra-intestinal symptoms resulting in impaired related quality of life. Growing evidence support the hypothesis that intestinal barrier dysfunction has a central role in the pathophysiology of IBS being the interface between the gut lumen and the deeper intestinal layers as well as the brain.

Aims & Methods

The aims of this study were: to characterize the epithelial and vascular barriers; to correlate molecular, morphological and functional aspects of epithelial and vascular barriers with IBS symptoms. 66 healthy subjects (AC) and 223 patients with IBS (112 IBS-D, 58 IBS-C and 53 IBS-M) were enrolled in the study. Rome IV criteria, Bowel disease questionnaire, Short Form 36, Hospital Anxiety Depression Scale were used to phenotype patients. Sugar test was used to evaluate in vivo permeability. The vascular barrier was characterized by using immunohistochemistry, western blot and electron microscopy. Vascular permeability was evaluated by assessing two markers: plasmalemma vesicle–associated protein-1 (PV1) and vascular endothelial cadherin (VEC). A translational model based on Caco-2 cells or HUVEC was used to evaluate permeability changes induced by mediators spontaneously released by mucosal biopsies and to highlight the underlying molecular mechanisms. Correlation analyses have been performed among experimental and clinical data.

Results

Compared to AC, lactulose (P<0.05), sucralose (P<0.01), sucrose (P<0.01) excretion and the L/M ratio (P<0.01) were significantly increased in IBS patients. Soluble mediators released by mucosal biopsies of IBS patients increased Caco-2 permeability compared to AC mediators (P<0.05) via a down-regulation of tight junction gene expression. Blood vessels were significantly increased by 1.5 fold in the colonic mucosa of IBS patients compared to AC (P<0.01). PV1 expression was increased (P<0.01) while VEC expression was decreased in the colonic mucosa of IBS group compared to AC (P<0.05). IBS mucosal mediators increased HUVEC permeability compared to AC mediators. The HUVEC changes associated with IBS samples were mediated by a protease-activated receptor (PAR)2 dependent mechanism resulting in VEC down-regulation. Significant correlations emerged among permeability changes and intestinal, extra-intestinal symptoms and health-related quality of life reported by IBS patients.

Conclusion

Epithelial and vascular barriers are compromised in IBS and are likely involved in symptom development.

Disclosure

Nothing to disclose

Introduction

Data evaluating the utility of Blue light Imaging (BLI) and Linked Color Imaging (LCI) in the diagnosis of gastric intestinal metaplasia (IM) and atrophic gastritis (AG) is limited.

Aims & Methods

We aimed to evaluate and compare the diagnostic accuracy of BLI and LCI without magnification for the detection of IM and AG.
Single centre prospective study involving consecutive patients aged ≥18 years undergoing diagnostic upper gastrointestinal endoscopy (UGIE), endoscopic follow-up of intestinal metaplasia or gastric cancer screening. Exclusion criteria: previous gastrectomy, contraindication to UGIE due to comorbidities, no gastric mucosal biopsies, refusal of consent. Endoscopy was initially performed with white light image (WLI), followed by BLI and LCI. Standardized photodocumentation of stomach was performed with WLI, BLI and LCI. Imaging features suggestive of IM: lavender color sign and whitish flat elevation with LCI, and light blue crest and white opaque substance with BLI. EGGIM and Kimura-Takamoto Classification (KTC) were applied when IM and AG were suspected. Systematic random biopsies of the antrum, incisura angularis and corpus along with targeted biopsies of suspicious gastric mucosal lesions were obtained. Histology was considered gold standard. Performance of endoscopic imaging in the detection of IM, AG and EGC was evaluated.
Initially, 134 patients were evaluated and 64 were excluded: previous gastrectomy-22, pending histology-20, non-BLI imaging-15, intolerance to UGIE-3, refusal of consent-1, esophageal stenosis-1 and contra-indication to biopsies-2. Final sample included 70 patients.
Qualitative data expressed as percentage were compared with Chi-square test. A p value of <0.05 was considered significant.

Results

Median age was 56 (19-86), with 49 (63%) female. There was family history of gastric cancer in 12(15%) and history of smoking in 35 (44%).
Histological AG was found in 15 (19%) and IM in 20 (26%) patients. WLI was suggestive of IM in 14(20%), confirmed histologically in 9 (64%). IM was suspected by LCI and BLI in 24 (34%) and 23 (32%) cases, confirmed by histology in 16 (67%) and 17 (74%), respectively.
WLI classified 56 (71%) as EGGIM 0 and after LCI and BLI, 10 (18%) and 8 (15%) of these cases had EGGIM 1 or 2. In 10 patients, EGGIM 1-2 with WLI, only 1 was upgraded to EGGIM 3-4 with LCI and BLI. In 3 (4%) EGGIM 3-4 with WLI, after LCI and BLI,1 had extensive IM (EGGIM 6). Among 19(24%) patients EGGIM 1-2 with LCI, 3(16%) had EGGIM 0 with BLI.
Atrophy was suspected by WLI and LCI in 9(12%) and 15(21%) patients, confirmed by histology in 6(67%) and 8(53%) cases, respectively. According to KTC, 5 (6%) were classified as C1, 2 (3%) as C2 and 4 (5%) as O3 with WLI. With LCI images, 8 (10%) were classified as C1, 3(4%) as C2 and 4(5%) as O3. The sensitivity (Sens), specificity (Spec), accuracy, positive predictive value (PPV), negative predictive value (NPV) of WLI, BLI and LCI in detecting AG and IM are shown in table 1.


Table 1. Sens, Spec, accuracy, PPV and NPV in detecting AG and IM with WLI, LCI and BLI.

Conclusion

Both BLI and LCI are promising advanced endoscopic imaging techniques with BLI having higher accuracy than LCI in detection of IM.

References

1. Chen H, Liu Y, Lu Y, Lin X, Wu Q, Sun J, et al. Ability of blue laser imaging with magnifying endoscopy for the diagnosis of gastric intestinal metaplasia. Lasers Med Sci. 2018 Nov 1;33(8):1757–62.
2. Ono S, Abiko S, Kato M. Linked color imaging enhances gastric cancer in gastric intestinal metaplasia. Vol. 29, Digestive Endoscopy. Blackwell Publishing; 2017. p. 230–1.
3. Ono S, Kato M, Tsuda M, Miyamoto S, Abiko S, Shimizu Y, et al. Lavender Color in Linked Color Imaging Enables Noninvasive Detection of Gastric Intestinal Metaplasia. Digestion. 2018 Nov 1;98(4):222–30.
4. Zhang G, Zheng J, Zheng L, Yu S, Jiang C, Lin W, et al. Gastric intestinal metaplasia assessment between linked color imaging based on endoscopy and pathology. Scand J Gastroenterol. 2021;56(1):103–10.
5. Shu X, Wu G, Zhang Y, Wang Y, Zheng Y, Guo Q, et al. Diagnostic value of linked color imaging based on endoscopy for gastric intestinal metaplasia: a systematic review and meta-analysis. Ann Transl Med. 2021 Mar;9(6):506–506.
6. Esposito G, Pimentel-Nunes P, Angeletti S, Castro R, Libânio D, Galli G, et al. Endoscopic grading of gastric intestinal metaplasia (EGGIM): A multicenter validation study. Endoscopy. 2019;51(6):515–21.

Clinical Case Summary

A 56-year-old male presented with postprandial vomiting and weight loss beginning three weeks after laparoscopic ulcerorraphy of a perforated pyloric ulcer. An abdominal CT showed marked gastric distension and upper GI endoscopy revealed gastric stasis and a fibrotic stenosis in the duodenal bulb in close relation with a suture stitch, only transposable with an ultra-slim gastroscope. Two sessions of balloon dilation (BD) until 20mm were performed one month apart with poor clinical/endoscopic improvement. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) was proposed to avoid surgical reintervention.
Using a standard gastroscope a 0.035´´guidewire was passed into the proximal jejunum allowing insertion of a 7-french nasobiliary drain. Jejunal distension was achieved through saline, iodate contrast and methylene blue infusion. The linear echoendoscope was used to identify a distended loop adjacent to the gastric wall and EUS-guided puncture with a 19G needle was accomplished. A 20x10mm lumen-apposing metal stent (LAMS) was deployed in distal gastric body. The flow of blue mixture to the lumen confirmed successful gastroenterostomy creation. The patient was hospitalized overnight and resumed oral feeding the day after the procedure. No symptom recurrence was observed and the gastroenterostomy remained patent during the 6 months of follow-up.
Gastric outlet obstruction (GOO) may result from several malignant and benign causes. Surgical gastroenterostomy, self-expandable metal stents (SEMS) and BD are standard therapeutic options. EUS-GE is emerging as an effective and minimally invasive alternative. EUS-GE presents high technical and clinical success with lower rates of adverse events and reduced need of reintervention when compared to surgery and other endoscopic therapies. In benign GOO, SEMS seems less adequate and BD often results in suboptimal outcomes. The authors exemplify the effectiveness of EUS-GE in a case of GOO associated with a benign condition.

References

Illustrative material:
- Endoscopic and fluoroscopic images of guidewire and nasobiliary drain passed into the proximal jejunum
- EUS image of jejunal distension previous to LAMS placement
- EUS image of LAMS placement
- Endoscopic and fluoroscopic images of LAMS in situ
- Endoscopic image of 6 months follow-up