A nomogram incorporating ileal and anastomotic lesions separately to predict the long-term outcome of Crohn’s disease after ileocolonic resection
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PROVIDER: S-EPMC10503285 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Surgery remains an important treatment modality in the multidisciplinary management of patients with Crohn's disease (CD). To illustrate the recent advances in the management of postoperative CD we outline the contemporary approach to treatment: diagnosing disease recurrence using endoscopy or noninvasive methods and risk stratification underlying decisions to institute treatment. Endoscopic scoring indices are being refined to guide treatment decisions by accurately estimating the risk of recurrence based on endoscopic appearance. The original Rutgeerts score has been modified to separate anastomotic lesions from lesions in the neoterminal ileum. Two further indices, the REMIND score and the POCER index, were recently developed with the same intention. Noninvasive monitoring for recurrence using a method with high negative predictive value has the potential to simplify management algorithms and only perform ileocolonoscopy in a subset of patients. Fecal calprotectin, intestinal ultrasound, and magnetic resonance enterography are all being evaluated for this purpose. The use of infliximab for the prevention of postoperative recurrence is well supported by data, but management decisions are fraught with uncertainty for patients with previous exposure to biologics. Data on the use of ustekinumab and vedolizumab for postoperative CD are emerging, but controlled studies are lacking.
| S-EPMC9693828 | biostudies-literature
Project description:There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease.MethodsRetrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence.ResultsOne hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86).ConclusionPost-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.
| S-EPMC9677520 | biostudies-literature
Project description:Ileocecal resection (ICR) is frequently performed in Crohn's disease (CD). NOD2 mutations are risk factors for CD. Nod2 knockout (ko) mice show impaired anastomotic healing after extended ICR. We further investigated the role of NOD2 after limited ICR. C57B16/J (wt) and Nod2 ko littermates underwent limited ICR including 1-2 cm terminal ileum and were randomly assigned to vehicle or MDP treatment. Bursting pressure was measured on POD 5, and the anastomosis was analyzed for matrix turn-over and granulation tissue. Wound fibroblasts from subcutaneously implanted sponges were used for comparison. The M1/M2 macrophage plasma cytokines were analyzed. Mortality was not different between groups. Bursting pressure was significantly decreased in ko mice. This was associated with less granulation tissue but was not affected by MDP. However, anastomotic leak (AL) rate tended to be lower in MDP-treated ko mice (29% vs. 11%, p = 0.07). mRNA expression of collagen-1α (col1 α), collagen-3α (col3 α), matrix metalloproteinase (mmp)2 and mmp9 was increased in ko mice, indicating increased matrix turn-over, specifically in the anastomosis. Systemic TNF-α expression was significantly lower in ko mice. Ileocolonic healing is impaired in Nod2 ko mice after limited ICR by local mechanisms maybe including local dysbiosis.
| S-EPMC10219437 | biostudies-literature
Project description:Background and aimsMultiple factors are suggested to place Crohn's disease patients at risk of recurrence after ileocolic resection with conflicting associations. We aimed to identify clinical predictors of recurrence at first [early] and further [late] postoperative colonoscopy.MethodsCrohn's disease patients undergoing ileocolic resection were prospectively recruited at six North American centres. Clinical data were collected and endoscopic recurrence was defined as Rutgeerts score ≥i2. A multivariable model was fitted to analyse variables independently associated with recurrence.ResultsA total of 365 patients undergoing 674 postoperative colonoscopies were included with a median age of 32 years, 189 [51.8%] were male, and 37 [10.1%] were non-Whites. Postoperatively, 133 [36.4%] used anti-tumour necrosis factor [anti-TNF] and 30 [8.2%] were smokers. At first colonoscopy, 109 [29.9%] had recurrence. Male gender (odds ratio [OR] = 1.95, 95% confidence interval [CI] 1.12-3.40), non-White ethnicity [OR = 2.48, 95% CI 1.09-5.63], longer interval between surgery and colonoscopy [OR = 1.09, 95% CI 1.002-1.18], and postoperative smoking [OR = 2.78, 95% CI 1.16-6.67] were associated with recurrence, while prophylactic anti-TNF reduced the risk [OR = 0.28, 95% CI 0.14-0.55]. Postoperative anti-TNF prophylaxis had a protective effect on anti-TNF experienced patients but not on anti-TNF naïve patients. Among patients without recurrence at first colonoscopy, Rutgeerts score i1 was associated with subsequent recurrence [OR = 4.43, 95% CI 1.73-11.35].ConclusionsWe identified independent clinical predictors of early and late Crohn's disease postoperative endoscopic recurrence. Clinical factors traditionally used for risk stratification failed to predict recurrence and need to be revised.
| S-EPMC11037109 | biostudies-literature
Project description:BackgroundNucleotide-binding oligomerization domain-containing protein 2 (NOD2) mutations are a genetic risk factor for Crohn disease. Ileocecal resection is the most often performed surgery in Crohn disease. We investigated the effect of Nod2 knockout (KO) status on anastomotic healing after extended ileocecal resection (ICR) in mice.MethodsMale C57BL6/J wild-type and Nod2 KO mice underwent an 11 cm resection of the terminal ileum including the cecum. An end-to-end jejuno-colostomy was performed. Animals were killed after 5 days investigating bursting pressure, hydroxyproline content, and expression of matrix metabolism genes, key cytokines, and histology of the anastomosis.ResultsMortality was higher in the Nod2 KO group but not because of local or septic complications. Bursting pressure was significantly reduced in the Nod2 KO mice (32.5 vs 78.0 mmHg, P < 0.0024), whereas hydroxyprolin content was equal. The amount of granulation tissue at the anastomosis was similar but more unstructured in the Nod2 KO mice. Gene expression measured by real-time polymerase chain reaction showed significantly increased expression for Collagen 1alpha and for collagen degradation as measured by matrix metalloproteinase-2, -9, and -13 in the Nod2 KO mice. Gelatinase activity from anastomotic tissue was enhanced by Nod2 status. Gene expression of arginase I, tumor necrosis factor-α, and transforming growth factor-ß but not inducible nitric oxide synthase were also increased at the anastomosis in the Nod2 KO mice compared with the control mice.ConclusionsWe found that Nod2 deficiency results in significantly reduced bursting pressure after ileocecal resection. This effect is mediated via an increased matrix turnover. Patients with genetic NOD2 variations may be prone to anastomotic failure after bowel resection.
| S-EPMC8376130 | biostudies-literature
Project description:BackgroundMost Crohn's disease [CD] patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impacts of ileocolectomy-induced bile acid [BA] perturbations on intestinal microbiota and inflammation are unknown. We characterized the relationships between ileocolectomy, stool BAs, microbiota and intestinal inflammation in inflammatory bowel disease [IBD].MethodsValidated IBD clinical and endoscopic assessments were prospectively collected. Stool primary and secondary BA concentrations were compared based on ileocolectomy and ileitis status. Primary BA thresholds for ileitis were evaluated. Metagenomic sequencing was use to profile microbial composition and function. Relationships between ileocolectomy, BAs and microbiota were assessed.ResultsIn 166 patients, elevated primary and secondary BAs existed with ileocolectomy. With ileitis, only primary BAs [795 vs 398 nmol/g, p = 0.009] were higher compared to without ileitis. The optimal primary BA threshold [≥228 nmol/g] identified ileitis on multivariable analysis [odds ratio = 2.3, p = 0.04]. Microbial diversity, Faecalibacterium prausnitzii and O-acetylhomoserine aminocarboxypropyltransferase [MetY] were decreased with elevated primary BAs. Amongst ileocolectomy patients, only those with elevated primary BAs had diversity, F. prausnitzii and MetY reductions. Those with both ileocolectomy and intermediate [p = 0.002] or high [≥228 nmol/g, p = 9.1e-11]] primary BA concentrations had reduced F. prausnitzii compared to without ileocolectomy. Those with ileocolectomy and low [<29.2 nmol/g] primary BA concentrations had similar F. prausnitzii to those without ileocolectomy [p = 0.13]. MetY was reduced with ileitis [p = 0.02].ConclusionsElevated primary BAs were associated with ileitis, and reduced microbial diversity, F. prausnitzii abundance and enzymatic abundance of MetY [acetate and l-methionine-producing enzyme expressed by F. prausnitzii], and were the only factors associated with these findings after ileocolectomy.
| S-EPMC10155745 | biostudies-literature
Project description:BackgroundPrediction of endoscopic postoperative recurrence (POR) and prophylactic treatment based on clinical risk profile have thus far been inconclusive. This study aimed to examine the association between clinical risk profile and the development of endoscopic POR in a Crohn's disease population without postoperative treatment and to identify individual risk factors of endoscopic POR.MethodsMedical records of 142 patients with Crohn's disease during follow-up after ileocecal or ileocolonic resection without prophylactic treatment at 3 referral centers were reviewed. Endoscopic POR was defined as a modified Rutgeerts score ≥i2b. Clinical risk profiles were distilled from current guidelines. Both uni- and multivariate logistic regression analysis were used to assess the relationship between risk profiles and endoscopic POR.ResultsEndoscopic POR was observed in 68 out of 142 (47.9%) patients. Active smoking postsurgery (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.24-7.34; P = 0.02), a Montreal classification of A3 (OR, 3.05; 95% CI, 1.07-8.69; P = 0.04), and previous bowel resections (OR, 2.58; 95% CI, 1.07-6.22; P = 0.03) were significantly associated with endoscopic POR. No significant association was observed between endoscopic POR and any guideline defined as a high-/low-risk profile. However, patients with a combination of any 3 or more European Crohns & Colitis Organisation- (OR, 4.87; 95% CI, 1.30-18.29; P = 0.02) or British Society of Gastroenterology-defined (OR 3.16; 95% CI, 1.05-9.49; P = 0.04) risk factors showed increased odds of developing endoscopic POR.ConclusionsOur results suggest that patients with a combination of any 3 or more European Crohns & Colitis Organisation- or British Society of Gastroenterology-defined risk factors would probably benefit from immediate prophylactic treatment.
| S-EPMC8730683 | biostudies-literature
Project description:Background and study aims Recent evidence supports the use of pan-enteric capsule endoscopy (CE) for the diagnosis and follow-up of Crohn's disease (CD). The aim of this study was to examine the agreement between CE and ileocolonoscopy (IC) for determining the severity and classification of lesions in ileocolonic CD. Patients and methods In a prospective blinded multicenter study, patients with suspected CD were examined with CE and IC within 2 weeks. Ninety-nine participants with a full IC and CE were included in the analysis. The ileocolonic disease severity was assessed with the Simple Endoscopic Score for Crohn's Disease (SES-CD). Results CD was diagnosed in 30 patients with IC and CE. The mean SES-CD was 9.8 (CI 7.9-11.8) and 10.6 (CI 8.2-13.1), respectively ( P = 0.69). There was a substantial agreement (ICC 0.83, CI 0.68-0.92) and a strong correlation between SES-CD assessed with IC and CE (r s = 0.78, P < 0.001). 55 bowel segments had ulcerations with both modalities (terminal ileum 24, right colon 12, transverse colon eight, left colon eight and rectum three). Mean sub-scores for ulcer size, area of ulcerated surface and area of affected surface did not differ between modalities. The inter-modality agreement (κ) was 0.46, 0.34 and 0.43, respectively ( P < 0.001). Conclusions There is a strong correlation between IC and CE for the severity of ileocolonic CD. The agreement for SES-CD sub-scores is fair to moderate. CE could be an alternative to IC for the assessment of endoscopic severity in selected patients with suspected CD.
| S-EPMC9812649 | biostudies-literature
Project description:BackgroundThe proliferation marker Ki67 is associated with the progression and prognosis of melanoma. However, its prognostic impact on acral melanoma (AM) remains unclear.MethodsA total of 314 AM patients were enrolled from a cohort of 5758 patients with melanoma at Peking University Cancer Hospital between 2006 and 2018. The patients were divided into Ki67 high- and low-expressing groups using a cut-off value of 30%. The associations between Ki67 and clinicopathologic characteristics as well as survival were analyzed. Cox proportional regression analysis was used to establish a nomogram to predict the survival probabilities of AM.ResultsAmong 314 patients, the Ki67-high group (Ki67 ≥ 30%) included 49.4% of patients at diagnosis. Patients in the Ki67-high group had lower median melanoma-specific survival (MSS) than those in the Ki67-low group (60.7 months vs. not reached, p < 0.001). In multivariate analyses, Ki67, lymph node metastasis and primary site were independent prognostic factors for MSS. The nomogram showed that Ki67 had the fourth greatest impact on survival, following Breslow thickness, lymph node metastasis and primary site. The C-index of the nomogram was 0.765 and 0.758 in the training and validation cohort, respectively. Area under the curve values were both near 0.8 in the training and validation cohorts. Net reclassification improvement and integrated discrimination improvement demonstrated that the predictive nomogram performed better than the traditional AJCC staging system.ConclusionKi67 expression is an independent prognostic factor for MSS in AM. A predictive model incorporating Ki67 and clinical factors was constructed to predict the prognosis of AM.
| S-EPMC10587210 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).MethodsThis phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease (ulceration in ?2 intestinal segments with a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ?8 points). Patients received subcutaneous CZP 400 mg at weeks 0, 2 and 4 and every 4 weeks up to week 52. Endoscopic evaluations were performed at weeks 0, 10 and 54. The primary outcome was mean change in CDEIS score at week 10; secondary outcome measures included endoscopic response (decrease in CDEIS score >5 points), remission (CDEIS score <6), complete remission (CDEIS score <3) and mucosal healing (no ulcer) at weeks 10 and 54.ResultsIn the intention-to-treat population (n=89) the mean±SD CDEIS score was 14.5±5.3 at baseline; the mean decrease in CDEIS score at week 10 was 5.7 (95% CI 4.6 to 6.8, p<0.0001). Rates of endoscopic response, endoscopic remission, complete endoscopic remission and mucosal healing at week 10 were 54%, 37%, 10% and 4%, respectively. At week 54 the corresponding rates were 49%, 27%, 14% and 8%, respectively. The safety profile was consistent with that of previous CZP trials.ConclusionsFollowing CZP treatment in patients with active CD, endoscopic lesions were improved as shown by the decrease in mean CDEIS score and by endoscopic response and remission rates. These benefits were achieved as early as week 10 and were generally maintained through week 54.Clinical trial registration numberNCT00297648.
| S-EPMC3551215 | biostudies-literature