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Different clinical outcomes in Crohn's disease patients with esophagogastroduodenal, jejunal, and proximal ileal disease involvement: is L4 truly a single phenotype?

ABSTRACT: Background:The Montreal classification defines L4 Crohn's disease (CD) as any disease location proximal to the terminal ileum, which anatomically includes L4-esophagogastroduodenal (EGD), L4-jejunal, and L4-proximal ileal involvement. L4-jejunal disease was established to be associated with poor prognosis. However, the outcome of patients with L4-proximal ileal disease or L4-EGD remains to be clarified. Our study aimed to investigate whether the outcome differs among CD patients with L4-EGD, L4-jejunal, and L4-proximal ileal disease. Methods:In our retrospective cohort study, 483 patients with confirmed CD were included. The primary outcome was intestinal surgery. Demographic features and outcomes were compared among L4-EGD, L4-jejunal, and L4-proximal ileal disease. Results:Thirty-nine (8.1%) patients had isolated L4 disease, whereas 146 patients had L4 as well as concomitant L1, L2, or L3 disease. During a median follow up of 5.8 years, L4 patients were more likely to have intestinal surgeries compared to non-L4 patients (31% versus 16%, p < 0.001). The percentage of L4-jejunal patients who underwent surgery was higher than that of L4-proximal ileal (66% versus 28%, p < 0.001), and both of these subtypes of L4 were at higher risk for intestinal resection compared to L4-EGD patients (66% and 28% versus 9%, respectively, p < 0.001 and p < 0.05). On multi-variable analysis, L4-jejunal (HR 3.08; 95% CI 1.30-7.31) and L4-proximal ileal disease (HR 1.83; 95% CI 1.07-3.15) were independent predictors for intestinal resection. Conclusions:L4 disease had worse prognosis compared to non-L4 disease. Within L4 disease, phenotype of L4-jejunal and L4-proximal ileal disease indicated higher risk for intestinal surgery. It might be justified to further characterize the L4 phenotype of the Montreal classification into three specific subgroups including L4-EGD, L4-jejunal, and L4-proximal ileal disease, similar to the Paris classification of pediatric patients.

SUBMITTER: Mao R

PROVIDER: S-EPMC5990878 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Different clinical outcomes in Crohn's disease patients with esophagogastroduodenal, jejunal, and proximal ileal disease involvement: is L4 truly a single phenotype?

Mao Ren R Tang Rui-Han RH Qiu Yun Y Chen Bai-Li BL Guo Jing J Zhang Sheng-Hong SH Li Xue-Hua XH Feng Rui R He Yao Y Li Zi-Ping ZP Zeng Zhi-Rong ZR Eliakim Rami R Ben-Horin Shomron S Chen Min-Hu MH

Therapeutic advances in gastroenterology 20180605

<h4>Background</h4>The Montreal classification defines L4 Crohn's disease (CD) as any disease location proximal to the terminal ileum, which anatomically includes L4-esophagogastroduodenal (EGD), L4-jejunal, and L4-proximal ileal involvement. L4-jejunal disease was established to be associated with poor prognosis. However, the outcome of patients with L4-proximal ileal disease or L4-EGD remains to be clarified. Our study aimed to investigate whether the outcome differs among CD patients with L4- ...[more]

PMID: 29899757

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Project description:Background: In the Montreal classification, L4 Crohn's disease (CD) is defined as an ileal disease, including L4-esophagogastric duodenum (EGD), L4-jejunum, and L4-proximal ileal involvement. According to the previous studies, the prognosis of L4 disease was worse than that of non-L4 disease. Among L4 diseases, the phenotypes of L4-jejunum and L4-proximal ileum indicated that the risk of abdominal surgery was higher. However, the prognosis of L4-esophagogastroduodenal remains largely elusive. Therefore, we aim to investigate whether the prognosis differs between CD patients with and without esophagogastroduodenal involvement. Methods: In this study, patients with L4-EGD phenotype (n = 74) who underwent gastroscopy, ileocolonoscopy, biopsies, and CTE from 2018 to 2020 were compared with L4 non-EGD controls (n = 148) who were randomly selected at a ratio of 1:2 in the same period. Demographic information inclusive of disease conduct and location, important points of the surgery, and hospitalization have been collected. The distinction between L4-EGD patients and non-L4-EGD patients was identified by way of multivariable logistic regression analysis. The Kaplan-Meier technique was used to consider the possibility of abdominal surgical operation and complications, observed by means of Cox percentage hazard fashions to decide if L4 EGD independently estimated the endpoints inclusive of the abdominal surgery and the occurrences of complications. Results: L4-EGD group (n = 74) had a lower proportion of intestinal fistula than the control group (n = 148) (17.6% versus 34.5%; p = 0.009), and the probabilities of requiring abdominal surgery and multiple abdominal surgeries were also lower (21.6% versus 36.5%; p = 0.025), (6.8% versus 18.9%; p = 0.016), respectively. The frequency of hospitalization was lower in the L4-EGD group than in the control group (3-7 versus 4-9; p = 0.013). L4-EGD phenotype was found to be an independent protective factor for abdominal surgery and intestinal fistula in the Cox regression model, with HRs of 0.536 (95%CI: 0.305-0.940; p = 0.030) and 0.478 (95%CI: 0.259-0.881; p = 0.018), respectively. Conclusion: Our data suggest that the L4-EGD phenotype may have a better prognosis compared to the Non-L4-EGD phenotype. Our data may advocate a revision of the Montreal classification including separate designations for L4-EGD disease.

Project description:BackgroundThe diagnosis of proximal small bowel involvement in Crohn's disease (CD) can be challenging at magnetic resonance enterography (MRE). The inflammatory process in CD can be associated with peri-intestinal inflammatory reactions, including the presence of inflamed mesenteric lymph nodes.ObjectivesTo evaluate the significance of inflamed mesenteric lymph nodes adjacent to the jejunum at MRE in CD and the association with proximal bowel disease as detected by video capsule endoscopy (VCE).DesignThis retrospective study was performed in two tertiary medical centres, and included 64 patients with CD who underwent MRE as well as VCE within 1 year.MethodsData were collected for examinations performed between August 2013 and February 2021. MRE images were independently reviewed by radiologists who were blinded to the clinical data. Association between the presence of mesenteric lymph nodes adjacent to jejunum at MRE and disease activity according to VCE Lewis scores of proximal small bowel was examined.ResultsVCE detected proximal disease in 24/64 patients (37.5%). Presence of regional lymph nodes in the jejunal mesentery was significantly associated with jejunal disease as seen on VCE (p < 0.001). Of the 20 patients who had proximal mesenteric lymph nodes at MRE, 15 (75%) had jejunal disease at VCE (sensitivity, 62.5%; specificity, 87.5%; and negative and positive predictive values, 79.5 and 75%, respectively). The number of regional lymph nodes was positively correlated with jejunal disease (mean: 2.63 ± 2.90 versus 0.78 ± 2.60, p = 0.01). Other MRE features of lymph nodes were not significantly predictive of jejunal CD.ConclusionIn patients with CD, inflamed regional lymph nodes in the jejunal mesentery at MRE can be valuable to suggest proximal small bowel disease, even when bowel wall features at imaging do not suggest disease involvement.Plain language summaryThe diagnosis of proximal small bowel involvement in Crohn's disease (CD) can be challenging at magnetic resonance enterography (MRE). We analysed MRE examinations in patients with CD for the presence of lymph nodes adjacent to the proximal small bowel. We included 64 patients with CD who had MRE examinations and video capsule endoscopy (VCE) examinations within 1 year. Of 64 patients, 24 had proximal small bowel disease according to VCE. We found that of 20 patients who had regional mesenteric lymph nodes in the jejunal mesentery at MRE, 15 had proximal bowel disease involvement. We also found that patients with jejunal disease had a larger number of regional lymph nodes compared to patients without jejunal disease. All but one patient had normal appearing bowel at MRE. But, using regional mesenteric lymphadenopathy at MRE as an indicator for disease, 15/24 (62.5%) patients with proximal small bowel disease were detected. We therefore conclude that regional mesenteric lymph nodes assessment at MRE can aid diagnose proximal bowel disease, even when the proximal bowel looks normal at imaging. Presence of proximal mesenteric lymph nodes at MRE in patients with CD possibly warrant further investigation of the proximal small bowel by endoscopic measures.

Project description:BACKGROUND: Endoplasmic reticulum (ER) stress has been suggested to play a role in inflammatory bowel disease (IBD). The three branches (ATF6, IRE1 and PERK) of the unfolded protein response (UPR) have different roles and are not necessarily activated simultaneously. METHODOLOGY/PRINCIPAL FINDINGS: Expression of UPR-related genes was investigated in colonic and ileal biopsies of 23 controls, 15 ulcerative colitis (UC) and 54 Crohn's disease (CD) patients. This expression was confirmed at protein level in colonic and ileal samples of five controls, UC and CD patients. HSPA5, PDIA4 and XBP1s were significantly increased in colonic IBD at mRNA and/or protein levels, indicating activation of the ATF6 and IRE1 branch. Colonic IBD was associated with increased phosphorylation of EIF2A suggesting the activation of the PERK branch, but subsequent induction of GADD34 was not observed. In ileal CD, no differential expression of the UPR-related genes was observed, but our data suggested a higher basal activation of the UPR in the ileal mucosa of controls. This was confirmed by the increased expression of 16 UPR-related genes as 12 of them were significantly more expressed in ileal controls compared to colonic controls. Tunicamycin stimulation of colonic and ileal samples of healthy individuals revealed that although the ileal mucosa is exhibiting this higher basal UPR activation, it is still responsive to ER stress, even more than colonic mucosa. CONCLUSIONS/SIGNIFICANCE: Activation of the three UPR-related arms is seen in colonic IBD-associated inflammation. However, despite EIF2A activation, inflamed colonic tissue did not increase GADD34 expression, which is usually involved in re-establishment of ER homeostasis. This study also implies the presence of a constitutive UPR activation in healthy ileal mucosa, with no further activation during inflammation. Therefore, engagement of the UPR differs between colon and ileum and this could be a factor in the development of ileal or colonic disease.

Dataset Information

Different clinical outcomes in Crohn's disease patients with esophagogastroduodenal, jejunal, and proximal ileal disease involvement: is L4 truly a single phenotype?

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Different clinical outcomes in Crohn's disease patients with esophagogastroduodenal, jejunal, and proximal ileal disease involvement: is L4 truly a single phenotype?

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