T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence

Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 1961-1970 ◽  
Author(s):  
Matthieu Allez ◽  
Claire Auzolle ◽  
Marjolaine Ngollo ◽  
Hugo Bottois ◽  
Victor Chardiny ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
High Throughput Sequencing ◽  
Area Under The Curve ◽  
Postoperative Recurrence ◽  
Ileal Mucosa ◽  
Surgical Specimen ◽  
Endoscopic Recurrence ◽  
Tcr Repertoire

T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection.MethodsT cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively.ResultsTCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment.ConclusionClonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven.Trial registration numberNCT03458195.

scholarly journals Capsule Endoscopy, Magnetic Resonance Enterography, and Small Bowel Ultrasound for Evaluation of Postoperative Recurrence in Crohn’s Disease: Systematic Review and Meta-Analysis

2017 ◽  
Vol 24 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Diana E Yung ◽  
Ofir Har-Noy ◽  
Yuen Sau Tham ◽  
Shomron Ben-Horin ◽  
Rami Eliakim ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Magnetic Resonance ◽  
Crohn's Disease ◽  
Capsule Endoscopy ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Postoperative Recurrence ◽  
Magnetic Resonance Enterography ◽  
Ileocecal Resection ◽  
Endoscopic Recurrence

Abstract Background Anastomotic recurrence is frequent in patients with Crohn’s disease (CD) following ileocecal resection. The degree of endoscopic recurrence, quantified by the Rutgeerts score (RS), is correlated with the risk of clinical and surgical recurrence. Noninvasive modalities such as capsule endoscopy (CE), magnetic resonance enterography (MRE), and intestinal ultrasound (US) may yield similar information without the need for ileocolonoscopy (IC). The aim of our meta-analysis was to evaluate the accuracy of those modalities for detection of endoscopic recurrence in postoperative CD patients. Methods We performed a systematic literature search for studies comparing the accuracy of CE, MRE, and US with IC for detection of postoperative recurrence in CD. We calculated pooled diagnostic sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for each comparison. Results A total of 135 studies were retrieved; 14 studies were eligible for analysis. For CE, the pooled sensitivity was 100% (95% CI, 91%–100%), specificity was 69% (95% CI, 52%–83%), DOR was 30.8 (95% CI, 6.9–138), and AUC was 0.94. MRE had pooled sensitivity of 97% (95% CI, 89%–100%), specificity of 84% (95% CI, 62%–96%), DOR of 129.5 (95% CI, 16.4–1024.7), and AUC of 0.98. US had pooled sensitivity of 89% (95% CI, 85%–92%), specificity of 86% (95% CI, 78%–93%), DOR of 42.3 (95% CI, 18.6–96.0), and AUC 0.93. Conclusions CE, MRE, and US provide accurate assessment of postoperative endoscopic recurrence in CD. These modalities should gain wider use for detection of postoperative recurrence; the prognostic value of those diagnostic findings merits evaluation in further prospective studies.

The Correlation between Vitamin D Levels and the Risk of Postoperative Recurrence in Crohn’s Disease

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Akihiro Yamada ◽  
Yuga Komaki ◽  
Fukiko Komaki ◽  
Haider Haider ◽  
Dejan Micic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Postoperative Recurrence ◽  
Recurrence Rates ◽  
Reactive Protein ◽  
Endoscopic Recurrence ◽  
Vitamin D Levels ◽  
Endoscopic Remission ◽  
The University

<b><i>Background and Aims:</i></b> Vitamin D deficiency has been associated with disease activity in Crohn’s disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. <b><i>Methods:</i></b> CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6–12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. <b><i>Results:</i></b> Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of &#x3c;15, 15–30, and &#x3e;30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; <i>p</i> = 0.028). On multivariate analysis, vitamin D &#x3e;30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07–0.66, <i>p</i> = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08–0.83, <i>p</i> = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (<i>p</i> = 0.17, 0.55, 0.062, respectively). <b><i>Conclusion:</i></b> In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.

scholarly journals P274 The clinical significance of anastomotic ulcers after ileocolic resection to predict postoperative recurrence of Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S288-S288
Author(s):  
J Y Kim ◽  
S H Park ◽  
Y J Kim ◽  
J C Park ◽  
S Noh ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Significance ◽  
Multivariable Analysis ◽  
Postoperative Recurrence ◽  
Ileocolic Resection ◽  
Single Centre ◽  
Endoscopic Recurrence ◽  
Endoscopic Remission

Abstract Background The Rutgeerts score (RS) is used to predict postoperative recurrence in Crohn’s disease (CD) patients after ileocolic resection primarily based on endoscopic finding at the neoterminal ileum. However, assessing anastomotic ulcers (AUs) is still a matter of debate. Our aim was to investigate the clinical significance of AUs on endoscopic recurrence in postoperative CD patients. Methods This was a single-centre retrospective study analysing postoperative CD patients with the RS of i0 to i1 at the first ileocolonoscopy within 1 year after ileocolic resection between 2000 and 2016 and those who underwent subsequent ileocolonoscopic follow-up. The study outcome was the clinical significance of AUs predicting endoscopic recurrence (RS ≥ i2b). Results Among 116 patients who were in endoscopic remission at the index postoperative ileocolonoscopy, 84.5% (98/116) underwent subsequent ileocolonoscopies. During the 30.0 months (interquartile ranges, 21.3–53.3) of median follow-up periods after the index ileocolonoscopy, 56.1% (55/98) showed endoscopic recurrence. Furthermore, 65.8% (48/73) with AUs and 75.5% (40/53) with major AUs defined as ulcer occupying ≥ 1/4 of the circumference or ≥ 3 ulcers confined to anastomotic ring, or any ulcers extended to ileocolic mucosa showed endoscopic recurrence. On multivariable analysis, the presence of AUs (adjusted hazard ratio [aHR], 4.33; 95% confidence interval [CI], 1.87–10.0; p &lt; 0.001) and major AUs (aHR, 3.64; 95% CI, 1.95–6.79; p &lt; 0.001) were associated with endoscopic recurrence, respectively. Conclusion AUs are associated with a significantly higher risk of endoscopic recurrence in postoperative CD patient who are in endoscopic remission.

scholarly journals Bacterial Mucosa-associated Microbiome in Inflamed and Proximal Noninflamed Ileum of Patients With Crohn’s Disease

2020 ◽  
Vol 27 (1) ◽  
pp. 12-24
Author(s):  
Maya Olaisen ◽  
Arnar Flatberg ◽  
Atle van Beelen Granlund ◽  
Elin Synnøve Røyset ◽  
Tom Christian Martinsen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Beta Diversity ◽  
Ileocecal Valve ◽  
Alpha Diversity ◽  
Normal Mucosa ◽  
Ileocecal Resection ◽  
Ileal Mucosa ◽  
Terminal Ileitis ◽  
Endoscopic Recurrence

Abstract Background Microbiota is most likely essential in the pathogenesis of Crohn’s disease (CD). Fecal diversion after ileocecal resection (ICR) protects against CD recurrence, whereas infusion of fecal content triggers inflammation. After ICR, the majority of patients experience endoscopic recurrence in the neoterminal ileum, and the ileal microbiome is of particular interest. We have assessed the mucosa-associated microbiome in the inflamed and noninflamed ileum in patients with CD. Methods Mucosa-associated microbiome was assessed by 16S rRNA sequencing of biopsies sampled 5 and 15 cm orally of the ileocecal valve or ileocolic anastomosis. Results Fifty-one CD patients and forty healthy controls (HCs) were included in the study. Twenty CD patients had terminal ileitis, with endoscopic inflammation at 5 cm, normal mucosa at 15 cm, and no history of upper CD involvement. Crohn’s disease patients (n = 51) had lower alpha diversity and separated clearly from HC on beta diversity plots. Twenty-three bacterial taxa were differentially represented in CD patients vs HC; among these, Tyzzerella 4 was profoundly overrepresented in CD. The microbiome in the inflamed and proximal noninflamed ileal mucosa did not differ according to alpha diversity or beta diversity. Additionally, no bacterial taxa were differentially represented. Conclusions The microbiome is similar in the inflamed and proximal noninflamed ileal mucosa within the same patients. Our results support the concept of CD-specific microbiota alterations and demonstrate that neither ileal sublocation nor endoscopic inflammation influence the mucosa-associated microbiome.

Postoperative Management of Crohn’s Disease: What Can We Do to Prevent Recurrence?

2016 ◽  
Vol 2 (11) ◽  
Author(s):  
Adriana Georgiana Olariu ◽  
Liliana Bordeianou
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Recurrence ◽  
Postoperative Recurrence ◽  
Postoperative Management ◽  
Chronic Inflammatory Bowel Disease ◽  
Ileocecal Resection ◽  
Endoscopic Recurrence ◽  
Relapsing Remitting ◽  
Patients Experience

<p>Crohn’s disease (CD) is a chronic inflammatory bowel disease with a relapsing, remitting course.  Approximately one in four CD patients requires surgery within five years of diagnosis. Unfortunately, surgery is rarely curative and up to 70% of CD patients experience endoscopic recurrence and 40% have clinical disease recurrence within 18 months after surgery.</p><p> </p><p>This review is aimed at providing internists and gastroenterologists a foundation for the management of patients who underwent ileocecal resection for CD. We provide an overview of the current definitions of postoperative recurrence and prognostic factors for postoperative CD recurrence. As recent studies raised concerns about the value of these factors, we examine the evidence behind the current risk stratification algorithm and pharmacologic treatment recommendations. Lastly, we discuss future directions for research.</p>

scholarly journals DOP36 Non-invasive assessment of postoperative disease recurrence in Crohn’s Disease: A multicenter, prospective cohort study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S074-S075
Author(s):  
F Furfaro ◽  
A Zilli ◽  
V Craviotto ◽  
A Aratari ◽  
C Bezzio ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Wall ◽  
Color Doppler ◽  
Disease Recurrence ◽  
Postoperative Recurrence ◽  
Fecal Calprotectin ◽  
Non Invasive ◽  
Endoscopic Recurrence ◽  
Sensitivity Specificity

Abstract Background Prevention of postoperative recurrence is a critical goal in Crohn’s disease (CD) management. Currently, postsurgical CD management and treatment are based on endoscopic monitoring performed within the first year after surgery. However, colonoscopy (CS) is an invasive and expensive procedure, unpleasant to patients. A non-invasive and patient friendly approach is required. Methods Consecutive CD patients who underwent ileo-cecal resection from July 2017 to January 2020 were prospectively enrolled in three Italian Centers and performed CS and bowel ultrasound (US) after six months from the surgery, in a blinded fashion. The patients also underwent complete clinical assessment and blood and stool samples were obtained for C-reactive protein (CRP), and fecal calprotectin (FC) measurements. The disease was considered clinically active if the Harvey–Bradshaw Index (HBI) was higher than 4. Uni- and multivariable analyses were used to assess the correlation between non-invasive parameters, including bowel US findings and FC values and endoscopic recurrence, defined by a Rutgeerts’s score (RS) &gt; 2. Sensitivity, specificity, accuracy, PPV and NPV of bowel US parameters alone and in combination with FC in assessing endoscopic recurrence were calculated. Results Seventy patients were enrolled, 45 patients (64%) had an endoscopic recurrence (RS &gt; 2) at 6 months. Thirteen out of 45 (29%) were symptomatic (HBI &gt; 4). Bowel wall thickness (BWT), bowel wall flow (BWF, presence of vascular signals at color Doppler), the presence of mesenteric hypertrophy, the presence of limph-nodes and FC values significantly correlated with the endoscopic recurrence (p &lt; 0.005). Independent predictors for endoscopic recurrence were BWT (for 1-mm increase: OR 2.63; 95% CI 1.136.12; p= 0.024), presence of lymph-nodes (OR 23.24; 95% CI 1.85291.15; p= 0.014) and FC &gt; 50 µg/g (OR 11.86; 95% CI 2.60–54.09; p= 0.001). Sensitivity, specificity, accuracy, PPV and NPV of bowel US and/or FC are showed in Table 1. Table 1: Diagnostic accuracy of Bowel US and/or FC compared to CS in assessing endoscopic activity (CI 95%): per-patient analysis Conclusion Combined use of bowel US and FC is accurate in assessing endoscopic recurrence at 6 months in CD patients and represent a valid alternative to endoscopic assessment after surgery

scholarly journals DOP17 In high-risk Crohn’s Disease patients, anastomosis configuration types have similar rates of endoscopic recurrence

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S055-S056
Author(s):  
S Bachour ◽  
R Shah ◽  
R Lyu ◽  
F Rieder ◽  
B Cohen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
High Risk ◽  
Crohn's Disease ◽  
Postoperative Recurrence ◽  
Endoscopic Recurrence ◽  
Preoperative Risk Factors ◽  
Younger Age ◽  
Risk Patients ◽  
Ileocolonic Anastomosis

Abstract Background There is conflicting data on the influence of surgical anastomosis configuration on endoscopic postoperative recurrence (POR) of Crohn’s disease (CD) following ileocolonic resection (ICR). Furthermore, whether this relationship differs by preoperative risk factors for POR has not been studied. We aimed to assess the role of ileocolonic anastomosis type on the rate and time to POR by preoperative POR risk. Methods Retrospective cohort study of adult CD patients who underwent ICR between 2009–2020 at a quaternary IBD referral center. Patients with a primary or secondary anastomosis and ≥1 postoperative colonoscopy were included. Endoscopic activity was assessed by modified Rutgeerts’ scoring. POR was defined as Rutgeerts’ ≥ i2b. Patients were categorized by anastomosis type: end-to-end (ETE), end-to-side (ETS), or side-to-side (STS). High-risk CD patients were defined by ≥1: age ≤ 30 years, active smoker, or ≥2 ICR for penetrating disease. Results 548 CD patients (52.6% female, age 35 y, 15.5% &gt; 1 prior ICR, 19.7% on biologic prophylaxis, 74.8% high-risk for POR) were included in the study (Figure 1). The majority received a STS (52.0%, N=285), 27.2% ETS, and 20.8% ETE. Patients with an ETE were diagnosed with CD at a younger age (p=0.04), had more penetrating disease (p=0.01), hand-sewn anastomoses (p &lt;0.001), and diverting loop ileostomies (p=0.02). There were no differences in prior ICR, smoking, biologic prophylaxis, or in median time from ICR to first post-operative colonoscopy (388.5 days, p=0.41) or POR detection (905 days, p=0.8) by anastomosis type. ETS patients had a shorter median follow-up time (3.9 y, p=0.02). The majority (55.7%) of all patients experienced POR (57% ETS; 55.4% STS; 54.4% ETE). Overall, there was no significant association between anastomosis type and POR rate (p=0.91) or time to POR (p=0.32). However, in high-risk CD patients, ETS was significantly associated with more rapid time to POR on log-rank (p=0.03) and multivariable Cox modeling (HR=1.51; p=0.04). Postoperative prophylactic biologic therapy initiated within 3 months of ICR significantly delayed POR in the overall cohort (HR=0.64; p=0.012) and the high-risk CD subgroup (HR=0.67; p=0.047). High-risk CD patients on prophylactic biologics had no difference in time to POR by anastomosis type (p=0.66). Conclusion In post-operative CD patients, there is no difference in rates of endoscopic recurrence by anastomosis configuration regardless of risk stratification. In high-risk patients, ETS was associated with more rapid endoscopic recurrence compared to other configurations, however prophylactic postoperative biologics may protect against this effect. Figure 2: KM Survival analysis of time (days) to POR

scholarly journals Expression of T cell receptors αβ and γδ in the ileal mucosa of patients with Crohn's disease and with spondylarthropathy

2008 ◽  
Vol 90 (2) ◽  
pp. 275-279 ◽  
Author(s):  
C. A. CUVELIER ◽  
N. WEVER ◽  
H. MIELANTS ◽  
M. VOS ◽  
E. M. VEYS ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
T Cell Receptors ◽  
Ileal Mucosa ◽  
Cell Receptors
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