Elective surgery for peptic ulcer disease has been largely abandoned, and bleeding or obstructing ulcers can be managed safely by endoscopic treatment in most cases. However, surgeons will continue to encounter patients with peptic ulcer disease for emergency surgery. Currently, laparoscopic surgery has no proven advantage in peptic ulcer surgery.
Knowledge of the neurochemical coding of submucosal neurones in the human gut is important to assess neuronal changes under pathological conditions. We therefore investigated transmitter colocalization patterns in rectal submucosal neurones in normal tissue (n=11) and in noninflamed tissue of Crohn's disease (CD) patients (n=17). Neurone-specific enolase (NSE), choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), substance P (SP), nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) were detected immunohistochemically in whole-mount preparations from rectal biopsies. The neuronal marker NSE revealed no differences in the number of cells per ganglion (controls 5.0; CD 5.1). Four cell populations with distinct neurochemical codes were identified. The sizes of the populations ChAT/VIP (58% vs. 55%), ChAT/SP (8% vs. 8%), and ChAT/- (22% vs. 22%) were similar in control and CD. The population VIP/- was significantly increased in CD (12% vs. 2% in controls). Unlike in controls, all NOS neurones colocalized ChAT in CD. Thickened CGRP-fibres occurred in CD. We identified neurochemically distinct populations in the human submucous plexus. The increase in the VIP/- population, extensive colocalization of ChAT and NOS and hypertrophied CGRP fibres indicated adaptive changes in the enteric nervous system in noninflamed rectum of CD patients.
Background
Intestinal fibrosis and subsequent stricture formation represent frequent complications of Crohn’s disease (CD). In many organs, fibrosis develops as a result of epithelial to mesenchymal transition (EMT). Recent studies suggested that EMT could be involved in intestinal fibrosis as a result of chronic inflammation. Here, we investigated whether EMT might be involved in stricture formation in CD patients.
Methods
Human colonic tissue specimens from fibrotic areas of 18 CD and 10 non-IBD control patients were studied. Immunohistochemical staining of CD68 (marker for monocytes/macrophages), transforming growth factor-β
1
(TGFβ
1
), β-catenin, SLUG, E-.cadherin, α-smooth muscle actin and fibroblast activation protein (FAP) were performed using standard techniques.
Results
In fibrotic areas in the intestine of CD patients, a large number of CD68-positive mononuclear cells was detectable suggesting an inflammatory character of the fibrosis. We found stronger expression of TGFβ
1
, the most powerful driving force for EMT, in and around the fibrotic lesions of CD patients than in non-IBD control patients. In CD patients membrane staining of β-catenin was generally weaker than in control patients and more cells featured nuclear staining indicating transcriptionally active β-catenin, in fibrotic areas. In these regions we also detected nuclear localisation of the transcription factor, SLUG, which has also been implicated in EMT pathogenesis. Adjacent to the fibrotic tissue regions, we observed high levels of FAP, a marker of reactive fibroblasts.
Conclusions
We demonstrate the presence of EMT-associated molecules in fibrotic lesions of CD patients. These findings support the hypothesis that EMT might play a role for the development of CD-associated intestinal fibrosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s40169-015-0046-5) contains supplementary material, which is available to authorized users.
A total of 36 rectal advancement flap repairs were performed in 32 patients with perianal Crohn's disease. There were 12 anovaginal and 20 trans-sphincteric fistulas. Patients were followed prospectively for a mean of 19.5 months to evaluate postoperative recurrence rate. The prognostic influence of fistula type, rectal disease, intestinal disease and faecal diversion on recurrence was assessed. Four of 36 repairs showed primary failure, the operated fistula recurred in 11 patients after a median of 7 months, and a new fistula developed in six patients. The fistula recurrence rate was higher in patients with anovaginal fistula or Crohn's colitis but did not correlate with disease activity. Transitory mild incontinence of stool was observed in one patient only. Although rectal advancement flap repair does not cure perianal fistulas in most patients with Crohn's disease, those without Crohn's colitis may have long-term benefit. Short-term improvement of symptoms justifies this simple procedure even in patients with anovaginal fistula.
Correct comparison of our results with functional outcome after anterior rectal resection is impossible. We feel, however, that functional results after TEM are likely to be superior to those after anterior resection for rectal tumors.
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