Temporary diverting stoma in therapy-refractory luminal colonic Crohn's disease: an alternative to immediate colorectal resection?

AIM: Creation of a diverting stoma in patients with Crohn's disease (CD) can counteract luminal inflammation. The clinical utility of a diverting stoma with the prospect of restoration of gastrointestinal continuity warrants further investigation. The aim of this work was to evaluate the long-term effects of creation of a diverting stoma on the disease course in patients with luminal colonic CD. METHOD: In this retrospective, multicentre cohort study we investigated the disease course of patients who received a diverting stoma in the biological era. Clinical characteristics, medication use and surgical course were assessed at the time of creation of the diverting stoma and during follow-up. The primary outcome was the rate of successful and lasting reestablishment of gastrointestinal continuity. RESULTS: Thirty six patients with refractory luminal CD from four institutions underwent creation of a diverting stoma. Of the overall cohort, 20 (56%) patients had their gastrointestinal continuity reestablished after initial stoma creation and 14 (39%) who had their stoma reversed remained stoma-free during a median of 3.3 years follow-up (interquartile range 2.1-6.1 years). Absence of stoma reversal was associated with the presence of proctitis (p = 0.02). Colorectal resection after creation of a diverting stoma was performed in 28 (78%) patients, with 7 (19%) having a less extensive resection and 6 (17%) having a more extensive resection compared with the surgical plan before stoma creation. CONCLUSION: A diverting stoma could potentially be an alternative to immediate definitive stoma placement in specific populations consisting of patients with luminal colonic CD, especially in the absence of proctitis.

Genomic and Expression Analyses Identify a Disease-Modifying Variant for Fibrostenotic Crohn's Disease.

Background and Aims: Crohn's disease [CD] is a chronic inflammatory disease with unpredictable behaviour. More than half of CD patients eventually develop complications such as stenosis, for which they then require endoscopic dilatation or surgery, as no anti-fibrotic drugs are currently available. We aim to identify disease-modifying genes associated with fibrostenotic CD. Methods: We performed a within-case analysis comparing 'extreme phenotypes' using the Immunochip and replication of the top single nucleotide polymorphisms [SNPs] with Agena Bioscience in two independent case-control cohorts totalling 322 cases with fibrostenotis [recurrent after surgery] and 619 cases with purely inflammatory CD. Results: Combined meta-analysis resulted in a genome-wide significant signal for SNP rs11861007 [p = 6.0910-11], located on chromosome 16, in lncRNA RP11-679B19.1, an lncRNA of unknown function, and close to exon 9 of the WWOX gene, which codes for WW domain-containing oxidoreductase. We analysed mRNA expression of TGF-ß and downstream genes in ileocecal resection material from ten patients with and without the WWOX risk allele. Patients carrying the risk allele [A] showed enhanced colonic expression of TGF-ß compared to patients homozygous for the wild-type [G] allele [p = 0.0079]. Conclusion: We have identified a variant in WWOX and in lncRNA RP11-679B19.1 as a disease-modifying genetic variant associated with recurrent fibrostenotic CD and replicated this association in an independent cohort. WWOX can potentially play a crucial role in fibrostenosis in CD, being positioned at the crossroads of inflammation and fibrosis.

Outcome of pancreas transplantation from donation after circulatory death compared to donation after brain death.

INTRODUCTION: To overcome the gap of organ shortage grafts from donation after circulatory death (DCD) can be used. This review evaluates the outcomes after DCD pancreas donation compared to donation after brain death (DBD). MATERIALS AND METHODS: A literature search was performed using Medline, Embase, and PubMed databases. All comparative cohort studies reporting the outcome after DCD and DBD pancreas transplantation were included. All data were assessed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. To evaluate the event rates, pooled odds ratios (ORs) as well as the 95% confidence intervals (CI) were calculated. Since the number of studies is small we used the random-effects model only to overcome heterogeneity. RESULTS: There is no difference in 1-year pancreas graft survival (OR 1.092, CI 95% 0.649-1.837, P = 0.741) or patient survival (OR 0.699, CI 95% 0.246-1.985, P = 0.502). Simultaneous pancreas-kidney (SPK) transplantation showed significantly higher graft survival rates compared to pancreas transplantation alone (87.2% vs. 76.6%, P < 0.001 in DBD and 86.5% vs. 74.9%, P < 0.001 in DCD). DCD SPK grafts show a higher delayed kidney graft function rate compared to DBD SPK-grafts (OR 0.209, CI 95% 0.104-0.421, P < 0.001). There is significantly less pancreas graft thrombosis after DBD-donation (OR 0.567, CI 95% 0.340-0.946, P = 0.030). We found no difference in the HbA1c level at 1-year follow-up with a median of 5.4% in both groups and a mean of 5.63% (DCD) vs 5.43% (DBD). DISCUSSION: DCD pancreas transplantation has comparable patient and 1-year graft survival rates and should be considered a safe alternative for DBD pancreas transplantation.

Thiopurines are associated with a reduction in surgical re-resections in patients with Crohn's disease: a long-term follow-up study in a regional and academic cohort.

BACKGROUND: Combination therapy of thiopurines and anti-tumor necrosis factor alpha (TNF-α) antibodies is the most effective medical treatment of Crohn's disease (CD). Data on thiopurines and anti-TNF-α antibodies in preventing surgical recurrence (need for re-resection) of CD are scarce. Therefore, we analyzed which factors were involved in surgical recurrence of CD in a large cohort of patients with CD operated in a regional and a university hospital. METHODS: This is a retrospective cohort study of 567 patients who underwent surgery for CD. Clinical data and risk factors for surgical recurrence were analyzed, focusing on medical therapy and hospital type. RESULTS: Overall, 237 (41.8%) patients developed a surgical recurrence, after a median of 70 (2-482) months. Before surgical recurrence, 235 patients (41.4%) and 116 patients (20.5%) used thiopurines and anti-TNF-α antibodies, respectively. Multivariate analysis identified 3 independent risk factors associated with surgical recurrence of CD. A higher risk was seen in patients with colonic disease compared with patients with ileal disease (hazard ratio, 1.56; 95% confidence interval, 1.10-2.21; P = 0.012) and in patients using multiple types of medication (hazard ratio, 1.38; 95% confidence interval, 1.25-1.54; P < 0.001). However, a lower risk was seen in patients using thiopurines (hazard ratio, 0.51; 95% confidence interval, 0.34-0.77; P = 0.001). CONCLUSIONS: Thiopurines are effective in preventing surgical recurrence of CD. The role of anti-TNF-α antibodies seems promising as well. Combination therapy of thiopurines and anti-TNF-α antibodies for prevention of surgical recurrence of CD should be studied in a randomized trial.