Colonoscopy-guided therapy for the prevention of post-operative recurrence of Crohn's disease.
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ABSTRACT:
SUBMITTER: Candia R
PROVIDER: S-EPMC8094885 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:In Crohn's disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-?1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD. METHODS:Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry. RESULTS:Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-?-secreting cells. CONCLUSIONS:Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.
| S-EPMC7574182 | biostudies-literature
Project description:To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn's disease following intestinal resection.In the "POCER" study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care (6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin (FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 mo.Sixty patients (active care n = 43, standard care n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those in remission [$26347 (IQR 25045-27485) vs $2729 (IQR 1182-5215), P < 0.001]. FC to select patients for colonoscopy could reduce cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence prevented.Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated.
| S-EPMC4814750 | biostudies-literature
Project description:BackgroundThe gut microbiome is altered in Crohn's disease. Although individual taxa have been correlated with post-operative clinical course, global trends in microbial diversity have not been described in this context.MethodsWe collected mucosal biopsies from the terminal ileum and ascending colon during surgery and post-operative colonoscopy in 6 Crohn's patients undergoing ileocolic resection (and 40 additional Crohn's and healthy control patients undergoing either surgery or colonoscopy). Using next-generation sequencing technology, we profiled the gut microbiota in order to identify changes associated with remission or recurrence of inflammation.ResultsWe performed 16S ribosomal profiling using 101 base-pair single-end sequencing on the Illumina GAIIx platform with deep coverage, at an average depth of 1.3 million high quality reads per sample. At the time of surgery, Crohn's patients who would remain in remission were more similar to controls and more species-rich than Crohn's patients with subsequent recurrence. Patients remaining in remission also exhibited greater stability of the microbiota through time.ConclusionsThese observations permitted an association of gut microbial profiles with probability of recurrence in this limited single-center study. These results suggest that profiling the gut microbiota may be useful in guiding treatment of Crohn's patients undergoing surgery.
| S-EPMC3848607 | biostudies-literature
Project description:This study prompted by growing evidence of the relationship between the yeast Candida albicans and Crohn's disease (CD) was intended to assess the effect of a 6-month course of the antifungal fluconazole (FCZ) on post-operative recurrence of CD. Mycological samples (mouth swabs and stools) and serum samples were collected from 28 CD patients randomized to receive either FCZ (n = 14) or placebo (n = 14) before surgical resection. Serological analysis focused on levels of calprotectin, anti-glycan antibodies, and antibody markers of C. albicans pathogenic transition. Levels of galectin-3 and mannose binding lectin (MBL) involved in C. albicans sensing and inflammation were also measured. 1, 2, 3, and 6 months after surgery, endoscopy revealed recurrence in 5/12 (41.7%) patients in the FCZ group and 5/9 (55.6%) in the placebo group, the small cohort preventing any clinical conclusions. In both groups, surgery was followed by a marked decrease in C. albicans colonization and biomarkers of C. albicans pathogenic transition decreased to non-significant levels. Anti-glycan antibodies also decreased but remained significant for CD. Galectin-3 and calprotectin also decreased. Conversely, MBL levels, which inversely correlated with anti-C. albicans antibodies before surgery, remained stable. Building biostatistical multivariate models to analyze he changes in antibody and lectin levels revealed a significant relationship between C. albicans and CD. Several combinations of biomarkers of adaptive and innate immunity targeting C. albicans were predictive of CD recurrence after surgery, with area under the curves (AUCs) as high as 0.86. FCZ had a positive effect on biomarkers evolution. ClinicalTrials.gov ID: NCT02997059, 19 December 2016. University Hospital Lille, Ministry of Health, France. Effect of Fluconazole on the Levels of Anti-Saccharomyces cerevisiae Antibodies (ASCA) After Surgical Resection for Crohn's Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo.
| S-EPMC8146386 | biostudies-literature
Project description:BackgroundDespite major advances in the medical management of Crohn's disease (CD), a significant proportion of patients will require surgery within 5 years of diagnosis. Malnutrition is an independent risk factor for adverse post-operative outcomes following gastrointestinal surgery. Data on the value of pre-operative total parenteral nutrition (TPN) in CD patients are mixed and there is a paucity of data in the biologic era. We aimed to define the role of pre-operative TPN in this population.MethodsThis was a retrospective cohort study conducted at a tertiary referral center. CD patients who underwent major abdominal surgery were identified. Patients receiving pre-operative TPN were compared to controls. We compared the incidence of 30-day infectious and non-infectious post-operative complications between the two groups.ResultsA total of 144 CD patients who underwent major abdominal surgery between March 2007 and March 2017 were included. Fifty-five patients who received pre-operative TPN were compared to 89 controls. Twenty-one (14.6%) patients developed infectious complications (18.2% in TPN group vs 12.3% in non-TPN group, P = 0.34) and 23 (15.9%) developed non-infectious complications (14.5% in TPN group vs 16.9% in non-TPN group, P = 0.71). In a multivariate analysis, controlling for differences in baseline disease severity and malnutrition between groups, patients receiving pre-operative TPN for ≥60 days had significantly lower odds of developing non-infectious complications (odds ratio 0.07, 95% confidence interval: 0.01-0.80, P = 0.03). Weight loss of >10% in the past 6 months was a significant predictor of post-operative complications.ConclusionsIn a subset of malnourished CD patients, TPN is safe and allows comparable operative outcomes to controls. Pre-operative TPN for ≥60 days reduced post-operative non-infectious complications without associated increase in infectious complications.
| S-EPMC6454845 | biostudies-literature
Project description:There is increasing complexity in the management of patients with acute severe exacerbation of inflammatory bowel disease [IBD; Crohn's disease (CD), ulcerative colitis (UC)] with frequent requirement for urgent surgery.To determine whether a weekend effect exists for IBD care in the United States.We used data from the Nationwide Inpatient Sample (NIS) 2007, the largest all-payer hospitalisation database in the United States. Discharges with a diagnosis of CD or UC who underwent urgent intestinal surgery within 2 days of hospitalisation were identified using the appropriate ICD-9 codes. The independent effect of admission on a weekend was examined using multivariate logistic regression adjusting for potential confounders.Our study included 7,112 urgent intestinal surgeries in IBD patients, 21% of which occurred following weekend admissions. There was no difference in disease severity between weekend and weekday admissions. Post-operative complications were more common following weekend than weekday hospitalisations in UC [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.01-2.90]. The most common post-operative complication was post-operative infections (Weekend 30% vs. weekday 20%, P = 0.04). The most striking difference between weekend and weekday hospitalisations was noted for needing repeat laparotomy (OR 11.5), mechanical wound complications (OR 10.03) and pulmonary complications (OR 2.22). In contrast, occurrence of any post-operative complication in CD was similar between weekday and weekend admissions.Patients with UC hospitalised on a weekend undergoing urgent surgery within 2 days have an increased risk for post-operative complications, in particular mechanical wound complications, need for repeat laparotomy and post-operative infections.
| S-EPMC3618593 | biostudies-literature
Project description:Background and Aims: Gut microbiota recolonization after intestinal resection had been reported to be associated with post-operative recurrence in Crohn's disease (CD). However, the results of different studies are inconsistent and even contradictory. In addition, knowledge on the efficacy of microbial-based therapies in preventing post-operative recurrence of CD is limited. Therefore, the aim of this review was to investigate gut microbiota profiles in patients with CD before and after surgery and evaluate microbial-based therapies in preventing post-operative recurrence. Methods: Electronic databases were searched from inception to 31 June 2020 using predefined terms. Studies that investigated gut microbiota pre- and post-intestinal resection, and microbial-based therapies in preventing post-operative recurrence, were eligible. Study quality was assessed using either the Newcastle-Ottawa scale or Jadad scoring system. Results: Twelve studies investigating gut microbiota of CD patients suffering from operation, and other 12 studies evaluating the efficacy of antibiotics and probiotics, were included in our review. The mucosa-associated microbiota in surgical biopsy of CD patients is significantly distinct from that in normal mucosa from healthy subjects. Gut microbiota recolonization following surgery might be associated with post-operative recurrence in CD patients. Furthermore, CD patients with post-operative recurrence presented a gain in pro-inflammatory pathogenic bacteria and a loss in short-chain fatty acid-producing bacteria before and after surgery. However, no consistent bacteria or metabolites were found to predict the post-operative recurrence of CD. Additionally, microbial-based therapies are deficient and present restricted widespread clinical utility due to several deficiencies. Conclusion: Recurrence-associated bacteria observed pre- and post- operation might be promising in preventing the post-operative recurrence of CD. Furthermore, potential microbe biomarkers for predicting subsequent disease recurrence should be validated with larger sample sizes using more rigorous and standardized methodologies.
| S-EPMC7876235 | biostudies-literature
Project description:Abstract Background Crohn’s disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in over half of the patients following their initial operation. Although many genetic loci are implicated in Crohn’s disease, few have been associated with post-resection recurrence. Aims To identify genetic factors that predict recurrence of CD following intestinal resection. Methods A cohort of Crohn’s disease subjects who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at eight loci associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP, IFNGR2, and JAK2). Univariate and multivariate survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively. Results 191 Crohn’s disease subjects with 11.2 years mean post-operative follow-up were included. 46% experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male gender(p=0.05), and shortened time to first intestinal surgery(5.0 vs 7.3years p=0.03), while inflammatory disease behaviour was associated with a lower chance of repeat surgery(p<0.01). Of the loci assessed on multivariate analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly associated with disease recurrence(HR-1.24 CI-1.00–1.54 p<0.05). Conclusions We identify BACH2 as a susceptibility locus for post-operative recurrence of Crohn’s disease in our cohort. BACH2 is critical in the differentiation and function of T-cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in post-operative Crohn’s disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process. Funding Agencies CIHR
| S-EPMC6508141 | biostudies-literature
Project description:PurposePost-operative surveillance strategies for colorectal cancer (CRC) include periodic optical colonoscopy (OC) and abdominal-pelvic CT scan. Adherence with these recommendations is limited. For CRC screening, CT colonography (CTC) identifies larger adenomas and cancers nearly as well as OC. Most screening studies demonstrate that patients prefer CTC. However, CTC has never been compared to OC in the post-operative surveillance setting.MethodsWe hypothesized that CTC might represent an attractive substitute for the standard OC/CT scan combination. Here, 223 patients underwent CTC followed by same day OC 1 year after curative CRC resection.ResultsOf the 144/223 (64.6%) participants with a preference, 65.9% (95/144) preferred OC. This preference was more pronounced in women and in patients with polyps detected. No additional patient level factors significantly altered this primary result.ConclusionsIn contrast to CRC screening, this first study in CRC post-operative surveillance patients demonstrates a preference for OC. Assuming patient preference is an important determinant, introduction of CTC as a method to increase patient adherence with CRC surveillance is unlikely to be effective.Trial registrationClinical Trials.gov registration number: NCT02143115.
| S-EPMC7534185 | biostudies-literature
Project description:Aim: This study aimed to investigate the relationship between clinicopathological characteristics of atypical meningiomas (AM) and its post-operative recurrence. Materials and Methods: The clinicopathological characteristics and findings from follow up were retrospectively reviewed and compared between AM and benign meningioma (BM) patients. Univariate and multivariate analyses were employed to identify the factors related to the post-operative recurrence of AM. Results: More BM patients were females and received complete resection; the recurrence rate was significantly lower in BM patients as compared to AM patients. The progesterone receptor (PR), E-cadherin protein (E-Ca) and ?-catenin positive rates and Ki67 labeling index were significantly different between two groups. Univariate analysis showed the age, tumor size, tumor invasiveness, E-Ca expression, and extent of resection were related to the post-operative recurrence of AM. However, multivariate analysis showed only the extent of resection and tumor invasiveness were the independent factors associated with the post-operative recurrence of AM. Conclusions: The extent of resection and tumor invasiveness are related to the post-operative recurrence of AM. To improve the surgical procedures to maximize the tumor resection is important to improve the prognosis of AM patients.
| S-EPMC7174970 | biostudies-literature