Increased lymphatic vessel (LV) density has been found in uninflamed intestinal wall of patients with Crohn's disease (CD). The goal of the study was to search for an association between LV density ...in the proximal ileal resection margin at the time of surgery and endoscopic recurrence.
Ileocolonic resection specimens were obtained from 28 CD patients and 10 control subjects. The ileal proximal uninflamed section was used for the histological quantification of LV using immunohistochemistry with D2-40 antibody in the mucosa and submucosa. Quantification of LV was performed in 8 consecutive fields and was blinded to recurrence score. Patients were divided into 2 groups based on the presence (Rutgeerts score, i3/i4) (R+) or absence (Rutgeerts score, i0/i1) (R-) of endoscopic recurrence 1 year after the surgery. All patients were free of immunomodulators or biologics between surgery and postoperative endoscopy.
Median LV density was lower in control subjects than in CD patients in the mucosa (4.5%; interquartile range IQR, 3.6-5.3 versus 5.9%; IQR, 4.2-8.5; P = 0.04) and submucosa (2.4%; IQR, 1.9-3.6 versus 5.7%; IQR, 4.3-6.9; P < 0.01). R- patients had a higher LV density in the proximal resection margin at surgery than R+ patients, both in the mucosa (8.5%; IQR, 6.5-10.3 versus 4.4%; IQR, 3.1-6.1; P < 0.01) and in the submucosa (6.3%; IQR, 5.5-9.3 versus 5.3%; IQR, 3.4-5.9; P = 0.03). Mucosal LV density greater than 7% predicted the absence of endoscopic recurrence at 1 year, with a sensitivity of 81% and a specificity of 75%.
Decreased LV density is associated with high risk of endoscopic recurrence after surgery. Therapies that improve lymphatic flow in the gut may reduce the incidence of endoscopic recurrence.
The precise diagnosis of colitis cannot always be established with the available diagnostic tools. The subgroup of patients with an uncertain diagnosis has been classified as “indeterminate colitis” ...(IC). The definition of “indeterminate,” however, has changed over the years. Originally, IC was proposed by pathologists for colectomy specimens, usually from patients operated on for severe colitis, showing overlapping features of ulcerative colitis (UC) and Crohn's disease (CD). Later, the same terminology was used for patients showing no clear clinical, endoscopic, histologic, and other features allowing a diagnosis of either UC or CD. Therefore, it is difficult to compare different studies. An International Organization of Inflammatory Bowel Diseases (IOIBD) working party confirmed 1) the ambiguous nature of the term, and 2) proposes an updated classification for the category of patients with an unclear diagnosis. According to this, the term IBD unclassified (IBDU) is confirmed, as suggested by the Montreal Working Party 2005 for patients with clinically chronic colitis, that clearly have IBD but when definitive features of CD or UC are absent. In resected specimens the term “colitis of uncertain type or etiology” (CUTE) is preferred. It is accepted that most of the time this may have a prefix, such as severe, chronic. The classification of IBD varies when based only on biopsies rather than on a colectomy specimen. The vast majority of these have severe colitis. For those that cannot bear to abandon the highly ambiguous term IC, if it is used at all, this is where it can be used parenthetically.
(Inflamm Bowel Dis 2007)
Environmental factors may play a key role in the pathogenesis of inflammatory bowel disease (IBD). Whether vaccination is associated causally with IBD is controversial. We performed a meta-analysis ...of case-control and cohort studies on the association between vaccination and the risk for IBD.
Studies and abstracts investigating the relationship between vaccination and subsequent risk for developing IBD were reviewed. Childhood or adult immunizations with any vaccine type, at any dose, and with any vaccine schedule were used as inclusion criteria.
Eleven studies were included in the systematic review and meta-analysis: 8 case-control studies and 3 cohort studies. Studied vaccines were bacille Calmette-Guérin), vaccines against diphtheria, tetanus, smallpox, poliomyelitis, pertussis, H1N1, measles, rubella, mumps, and the combined measles, mumps, and rubella vaccine. Only a few details about vaccine type or route of administration were found in studies. Overall, there was no association between childhood immunization and risk for developing IBD: bacille Calmette-Guérin, relative risk (RR) of 1.04 (95% confidence interval CI, 0.78-1.38), diphtheria, RR of 1.24 (95% CI, 0.80-1.94), tetanus, RR of 1.27 (95% CI, 0.77-2.08), smallpox, RR of 1.08 (95% CI, 0.70-1.67), poliomyelitis, RR of 1.79 (95% CI, 0.88-3.66), an measles containing vaccines, RR of 1.33 (95% CI, 0.31-5.80) in cohort studies, and RR of 0.85 (95% CI, 0.60-1.20) in case-control studies. Subgroup analysis for Crohn's disease (CD) and ulcerative colitis (UC) found an association between the poliomyelitis vaccine and risk for developing CD (RR, 2.28; 95% CI, 1.12-4.63) or UC (RR, 3.48; 95% CI, 1.2-9.71). The RR of developing IBD after H1N1 vaccination was 1.13 (95% CI, 0.97-1.32).
Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD. The association between the poliomyelitis vaccine and the risk for CD or UC should be analyzed with caution because of study heterogeneity.
Abstract
Background
Many patients with Crohn’s disease (CD) require fecal diversion. To understand the long-term outcomes, we performed a multicenter review of the experience with retained excluded ...rectums.
Methods
We reviewed the medical records of all CD patients between 1990 and 2014 who had undergone diversionary surgery with retention of the excluded rectum for at least 6 months and who had at least 2 years of postoperative follow-up.
Results
From all the CD patients in the institutions’ databases, there were 197 who met all our inclusion criteria. A total of 92 (46.7%) of 197 patients ultimately underwent subsequent proctectomy, while 105 (53.3%) still had retained rectums at time of last follow-up. Among these 105 patients with retained rectums, 50 (47.6%) underwent reanastomosis, while the other 55 (52.4%) retained excluded rectums. Of these 55 patients whose rectums remained excluded, 20 (36.4%) were symptom-free, but the other 35 (63.6%) were symptomatic. Among the 50 patients who had been reconnected, 28 (56%) were symptom-free, while 22(44%) were symptomatic. From our entire cohort of 197 cases, 149 (75.6%) either ultimately lost their rectums or remained symptomatic with retained rectums, while only 28 (14.2%) of 197, and only 4 (5.9%) of 66 with initial perianal disease, were able to achieve reanastomosis without further problems. Four patients developed anorectal dysplasia or cancer.
Conclusions
In this multicenter cohort of patients with CD who had fecal diversion, fewer than 15%, and only 6% with perianal disease, achieved reanastomosis without experiencing disease persistence.
Lay Summary
Patients with distal Crohn’s disease often undergo colon resection with a stoma to divert the intestinal stream from the rectum in hopes of achieving sufficient healing to allow ultimate re-establishment of intestinal continuity. Patients and practitioners alike should be aware of the long-term success rates of this procedure. Our retrospective study of 197 patients found that half required later proctectomy and an additional one-quarter remained symptomatic with excluded rectums. Only 14% remained symptom-free after reanastomosis, and only 6% if perianal disease was the initial surgical indication. These data provide estimation of long-term surgical outcomes.
Intestinal microbial community is involved in the pathogenesis of Crohn's disease, but knowledge of its potential abnormalities has been limited by the impossibility to grow many dominant intestinal ...bacteria. Using sequence analysis of randomly cloned bacterial 16S ribosomal DNA, the dominant faecal species from four Crohn's disease patients and four controls were compared. Whereas marked inter-individual differences were observed in the faecal microflora of patients, three remained distantly related to controls on the basis of their operational taxonomic unit composition.
Bacteroides vulgatus and closely related organisms represented the only molecular species shared by all patients and exhibited an unusually high rate of occurrence.
Escherichia coli clones were isolated only in two patients with ileocolonic Crohn's disease. Moreover, numerous clones belonged to phylogenetic groups or species that are commonly not dominant in the faecal microflora of healthy subjects:
Pectinatus,
Sutterella,
Verrucomicrobium,
Fusobacterium,
Clostridium disporicum,
Clostridium glycolicum,
Clostridium ramosum,
Clostridium innocuum and
Clostridium perfringens.
Anti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance-enteroclysis (MRE) ...offers excellent imaging of transmural and peri-enteric lesions in Crohn's ileitis and we aimed to study its responsiveness to anti TNF therapy.
In this multi-center prospective trial, anti TNF naïve patients with ileal Crohn's disease and with increased CRP and contrast enhanced wall thickening received infliximab 5mg/kg at weeks 0, 2 and 6, and q8 weeks maintenance MRE was performed at baseline, 2 weeks and 6 months and assessed based on a predefined MRE score of severity in ileal Crohn's Disease.
Twenty patients were included; of those, 18 patients underwent MRE at week 2 and 15 patients at weeks 2 and 26 as scheduled. Inflammatory components of the MRE index decreased by ≥2 points and by ≥50% at week 26 (primary endpoint) in 40% and 32% of patients (per protocol and intention to treat analysis, respectively). The MRE index improved in 44% at week 2 and in 80% at week 26. Complete absence of inflammatory lesions was observed in 0/18 at week 2 and 13% (2/15) at week 26. The obstructive elements did not change. Clinical and CRP improvement occurred as early as wk 2, but only CDAI correlated with the MRE index.
Improvement of MRE occurs from 2 weeks after infliximab therapy onwards and correlates with clinical response but normalization of MRE is rare.
Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).
To evaluate variation in the overall endoscopic assessment of ...severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.
A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors.
There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR(2), Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity).
The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.
We sought to determine the efficacy of certolizumab pegol reinduction in patients with active Crohn's disease who respond to induction therapy with certolizumab pegol and then relapse during ...continuous or interrupted maintenance therapy.
In the Pegylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial, 428 patients who responded to induction therapy with certolizumab pegol at week 6 were randomized to continuous therapy with certolizumab pegol or placebo (drug interruption) during weeks 6 to 26. Patients who relapsed before week 26 could enter PRECiSE 4, an ongoing open-label extension trial in which patients on continuous therapy underwent recapture with a single extra 400-mg dose of certolizumab pegol, and patients who relapsed after drug interruption underwent reinduction with certolizumab pegol 400 mg at weeks 0, 2, and 4 followed by maintenance with certolizumab pegol 400 mg every 4 weeks. Disease activity was measured by the Harvey-Bradshaw Index.
During PRECiSE 2, 124 patients had disease relapse and entered PRECiSE 4; 49 patients had received continuous therapy and 75 patients had drug interruption. At week 4 of PRECiSE 4, response rates were 63% in patients who relapsed on continuous therapy and 65% after drug interruption. Response was maintained in 55% and 59% of these responders, respectively, through week 52.
Administration of 1 additional dose of certolizumab pegol to patients who relapsed on continuous maintenance therapy, and certolizumab pegol reinduction to those who relapsed after drug interruption, are effective strategies for treating patients who have relapsed after successful induction therapy with certolizumab pegol.
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