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

Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal and extra-intestinal cancers. Specific therapies used to control inflammation in IBD may have a different impact on cancer risk. However, there are no long-term studies investigating cancer risk in patients with IBD.

Aims & Methods

In the present study we aimed to quantify the overall risk for of developing cancer and to identify specific risk factors for the occurrence of intestinal and extra-intestinal cancers in 560 consecutive patients with Crohn's disease (CD, N=310) or ulcerative colitis (UC, N=250) referred to our outpatient department between January 2021 and February 2022. Demographic data, smoking status, alcohol consumption, age at IBD diagnosis, disease location and course, therapies, and cancer development after IBD diagnosis were recorded. Odds ratios (OR) were estimated by logistic regression analysis. Standardized Incidence Ratios (SIRs) were estimated compared with the general population.

Results

During a median follow-up interval or time of 10 years (range 1-26 years), 6.6% of patients (37/550, female 65 %, mean age 51 years) developed cancer (SIR 1.94, 95%CI 1.4-2.6). The most common cancers were colorectal (12.3%), skin (8.2%), and breast cancer (7.2%). Female patients had an increased risk for all cancers (SIR 3.11, 95%CI 2.06-4.3), melanoma (SIR 5.6, 95%CI 1.14-16.2) and colorectal cancer (SIR 7.59, 95%CI 3-15.4). Male patients had an increased risk of lymphoma (SIR 26.15, 95%CI 3.2-95.7). Younger age at diagnosis of CD (A1 Montreal classification, OR 37.9, 95%CI 10-14), immunosuppressive monotherapy (OR 5.5, 95%CI 2.65- 11) or in combination with anti-TNFα (OR 9.9, 95%CI 3.3-29.09) were associated with an increased risk of cancer in the study population.

Conclusion

We have identified subgroups of IBD patients who would particularly benefit from screening programs. Our findings need to be validated in independent cohorts.

Introduction

Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data on outcomes are derived from Asian studies. Therefore, we aimed to evaluate the short- and long-term outcomes of ESD for patients with early ESCC in a Western cohort.

Aims & Methods

In this retrospective cohort study, patients with early ESCC amendable for ESD were included in four tertiary referral hospitals in the Netherlands between 2012 and 2017. All procedures were performed by experienced endoscopists who were specifically trained in ESD. The decision for and choice of additional treatment following ESD was made on a per-patient basis. For this study, dedicated research fellows collected all relevant data by reviewing the electronic patients files. Data concerning long-term outcomes were checked with general practitioners or referral hospitals, when applicable. Outcomes included technical success, R0 resection (i.e. tumor-free lateral and vertical margins), curative resection (i.e. en-bloc radical resection with histology no more advanced than T1sm1, good differentiation and absence of lymphovascular invasion) and recurrence rates, as well as ESCC-specific and overall survival.

Results

We included 68 patients (34 males; mean age 69) with a median tumor size of 3cm (range 1-12) and circumferential extent of 50% (range 10-100), in whom ESD was technically successful in 66/68 patients (97%). While en-bloc resection was achieved in 64/66 technically successful ESDs (97%), R0 resection was accomplished in 54/66 patients (82%). Overall, a curative resection was achieved in only 34/66 patients (52%). Among the patients with a non-curative resection, 16/32 (50%) underwent additional treatment receiving either argon plasma coagulation for tumor-positive resection margins (n=1), selective lymph node dissection (n=1), definite chemoradiation therapy (n=4) or esophagectomy ± neoadjuvant chemoradiation therapy (n=10). Endoscopic surveillance was preferred in the other half of patients with a non-curative resection (16/32; 50%) based on significant comorbidities or patient choice. During a median follow-up of 66 months (p25-p75 43-88), 12/66 patients (18%) developed a local recurrence which could be treated endoscopically in most cases (10/12; 83%). Locoregional lymph node metastasis and distant metastasis were observed in 6 (6/66; 9%) and 3 (3/66; 5%) patients, respectively. A total of 30 patients (30/66; 45%) died during follow-up, of which the minority (7/30; 23%) was ESCC-related deaths. The 5-year overall and ESCC-specific survival probability were 64% (95% CI 53-76%) and 88% (95% CI 79-97%), respectively. More importantly, overall survival did not significantly differ between patients with and without curative resections (p = 0.69). In addition, no significant difference was seen for ESCC-specific survival between patients with or without additional treatment after a non-curative resection (p = 0.07).

Conclusion

In this Western cohort with long-term follow-up, the efficacy and safety of ESD for early ESCC was confirmed although the rate of non-curative resections was substantial. Irrespective of non-curative or curative resection, the long-term prognosis of these patients was limited mainly due to competing mortality. Considering additional treatment after a non-curative resection did not influence survival, the potential benefit of adjuvant therapy should be carefully balanced against the risk of dying from another cause than esophageal cancer on an individual basis.

Disclosure

C.N. Frederiks has received speaker's fee from Pentax Medical.
R.E. Pouw is a consultant for MicroTech, and has received speaker’s fee from Medtronic.
J.J.G.H.M. Bergman is a consultant for Medtronic, Cook Medical, and Boston Scientific, and has received research funding from Pentax Medical, C2 Therapeutics, Medtronic, Aqua Medical, Olympus Endoscopy, and Fuji-film.
B.L.A.M. Weusten has received research funding from Pentax Medical, C2 Therapeutics, and Aqua Medical. The remaining authors declare to have no disclosures relevant to this manuscript.

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.