BACKGROUND: Sub-occlusions are frequent complications of Crohn's disease (CD).They are usually caused by stenosis, which can be due to recurrent CD or ischemic anastomosis.Through-the-scope balloon dilation (TTS) is the only alternative to intestinal resection or stricturoplasty for the treatment of intestinal strictures.Previous studies have reported a long-term symptomatic benefit of TTS balloon dilation in CD ranging from 48% and 66%.The aim of this study is to evaluate safety and efficacy of repeated TTS balloon dilations in CD strictures.PATIENTS AND METHODS: We retrospectively analyzed consecutive endoscopy protocols of all CD patients who underwent colonoscopy or rectosigmoidoscopy with TTS balloon dilation between 2000 and 2007, in the hospital databases of University Hospital of Lausanne and Kantonspital St Gallen, Switzerland.All patients had histologically proven CD that did not improve under medical CD treatment, including 5-amino salicylic acid, azathioprine, 6-mercaptopurine, methotrexate, budesonide, prednisone or anti-TNFα.Hydrostatic TTS balloon dilation was performed using Wilson Cook/Boston Scientific balloons progressively inflated to maximal pressure for 60 seconds.RESULTS: Sixty-one consecutive patients (33 females, 28 males), mean age 37±11 years, underwent dilation for a total of 237 dilations.Mean balloon diameter was 18mm (range 10-25mm).An inflammatory activity was observed in 75% of strictures, 129 dilations were performed on anastomotic strictures (54%), the other dilations were performed on surgically naïve bowel (21 in terminal ileum, 11 at the ileo-cecal valve,4 in the right colon, 21 in the left colon, 51 in the rectoanal region).Mean number of dilations was 2.25 (interval range 1 to 21) per stricture.All patients had symptoms relief post dilation, mean time before repeated dilation was 132 days (range: 3-1495 days).One perforation occured, which required surgery.CONCLUSION: TTS balloon dilation is a safe and effective treatment of CD strictures.It can be used to treat anastomotic as well as disease-induced stenosis, independently of inflammatory status.Multiple TTS balloon dilations of the same stenosis is often required to improve symptoms.Repeated TTS dilations did not increase the risk of complications.

During infliximab treatment of perianal Crohn’s disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10±2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4±8.8 months (range 3–28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25±5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.

43severe active luminal CD, agreed upon by the panel experts (acute flare, hospitalized patient, without documented fistula or stenosis and who did not undergo surgery for abscess drainage or a fistulectomy).The various treatments were analyzed to determine the appropriateness of the medical decision, according to the EPACT criteria.Results: 84 (20%) patients met the inclusion criteria.Considering at least one appropriate (A) treatment as appropriate: 60 patients (71%) received an appropriate treatment, 24 patients (29%) an inappropriate treatment (I).Furthermore, in 87% of the cases with one appropriate treatment an additional mostly inappropriate treatment was added or continued.Detailed results are indicated in the table. Conclusion:In the EC-IBD IBD cohort, the treatment for severe active luminal CD was appropriate for more than 70% of the patients, but frequently an inappropriate treatment was continued or added, thus increasing the risk of adverse reactions, drugs interactions and costs

Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel disease (IBD). Although their etiology is still unknown, the pathogenic mechanisms underlying intestinal inflammation have made impressive progress in our understanding. In particular, the abnormalities underlying IBD pathogenesis are not restricted to those mediated by classical immune cells such as T and B lymphocytes, macrophages and dendritic cells, but also nonimmune cells. Interestingly, endothelium has become one of the major areas of investigation in gut inflammation.

The introduction of biological treatments like monoclonal anti TNF-a antibodies (infliximab), is changing the clinical history of Crohn's disease (CD). The effects of these therapies are monitored emplying clinical indexes of active disease, laboratory parameters, endoscopy and histology, and also with imaging techniques. A new ultrasound contrast agent, SonoVue (Bracco SpA, Milano, Italy), is opening new perspectives in the study of microvasculature of several organs. Aim of this study is to evaluate by SonoVue enhanced ultrasonography (US) the occurrence of modifications in bowel wall microvasculature of CD patients and to correlate them with parameters of disease activity and to follow up the findings during infliximab therapy. After performing a basal color-doppler ultrasonography, the study of the affected bowel loop is performed after i.v. injection of SonoVue and the enhancement is evaluated on a qualitative basis. We report on the preliminary results obtained in twenty patients, eight of which have been treated with three infusions of infliximab (induction cycle) and evaluated at baseline and after the treatment. While at baseline we describe a positive correlation of SonoVue enhancement of the affected bowel loop with CRP, alpha1-glycoprotein and white blood cell number, after infliximab treatment in 6/8 cases a definite improvement was detected. Ultrasonographic evaluation of the changes of bowel wall enhancement after i.v. SonoVue during infliximab therapy might represent an useful, not invasive and relatively low cost imaging modality for the clinical monitoring of activity of small bowel Crohn's disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Arterial and venous system may be involved. Moreover, mesenteric microvascular thrombosis has been hypothesised as a contributing factor in the pathogenesis of IBD. Early atherosclerosis is a clinical feature common to several inflammatory and immunological diseases in which atherothrombotic complication represents one of the most important cause of mortality and morbidity. We investigate the prevalence and the entity of the early stages of vascular disease in a population of IBD patients without the classical cardiovascular risk factors, by measuring the intima-media thickness (IMT) of the common carotid artery. We found that IBD patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid IMT and that homocysteine levels and age were independently associated with the increased arterial wall thickness.

The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFalpha by peripheral blood mononuclear cells (PBMC) and the levels of NF-kappaB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFalpha was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kB subunit Rel-A, and its inhibitors IKBalpha and IkappaBgamma was performed on intestinal biopsies and PBMC. The TNFalpha production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IkappaBalpha and IkappaBgamma inhibitor levels in intestinal biopsies after treatment. An increase of IkappaB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-kappaB activity and exerts its anti-inflammatory effects.

BACKGROUND:Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease.AIM:To assess the extent of subclinical atherosclerosis in inflammatory bowel disease by measuring the intima-media thickness of the common carotid artery.METHODS:Fifty-two patients were enrolled in the study. Patients aged >45 years, with a history of cardiovascular disease and known risk factors for atherosclerosis were excluded from the study. Twenty healthy subjects were studied as controls. Carotid ultrasonography was performed in all patients and controls. intima-media thickness was measured proximal to the carotid bifurcation over both right and left common carotid arteries. The clinical characteristics and the laboratory parameters relevant to disease activity were recorded for all inflammatory bowel disease patients. In particular, plasma homocysteine, a well-known risk factor for thrombosis, was assessed.RESULTS:Common carotid artery intima-media thickness was significantly higher in inflammatory bowel disease patients (0.63 +/- 0.15 mm) compared with controls (0.53 +/- 0.08 mm). Multiple regression analysis revealed a significant association of carotid intima-media thickness with homocysteine levels and age.CONCLUSIONS:Inflammatory bowel disease patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid intima-media thickness. Homocysteine levels and age resulted independently associated with the increased arterial wall thickness.

Introduction: Coeliac Disease (CD) is an immuno-mediated enteropathy based on genetic factors, induced by gluten and characterized by malabsorption syndrome and villous atrophy. Capsule Endoscopy (CE), is a new tool that allows a complete morphological examination of small bowel mucosa in addiction to tradional endoscopic procedures. Aim & Methods: Aim of the study is to verify the usefulness of CE in diagnosing CD in correlation to a routine upper endoscopy, and to detect eventually the presence of associated diseases or complications. Ten patients were investigate for a clinical suspicion of CD from January to October 2004. In all of them the diagnosis of CD was confirmed by serological markers and duodenal biopsies. The endoscopic examination was conducted untill the third duodenal portion. The histological findings were classified by Oberhuber score. All the coeliac histologically proven patients, underwent to CE. Results: The quality of the images was good or execellent in all the patients. CE showed the same endoscopic signs observed during upper endoscopy in 8/10 patients. In 2 patients CE improved the diagnostic yeald acquiring pathological findings not observed in routine endoscopy: a scalloped valvulae in DII and micronodular appearance in the duodenal cup. In 2 patients CE shoved micropolips lesions, probably of inflammatory origin, in distal jejunum;another patient had a flat polips in the third jejunal loop. In 1 patient mucosa erosion was found from the distal jejunum to the ileum. Finally CE found a progressive reduction of mucosal lesion from the distal jejunum to the ileum in all the patients, but in 2 (progressive appearance of micropilyps or erosive jejunitis) Conclusions: CE is a simple and very effective tool in studing the CD patients. It seems to be complementary to routine endoscopy (and to histological picture), first to confirm the lenght of mucosal damage and second to verify the synchronous presence of complications (erosive jejunitis) or other associated diseases (pre and malignant lesions). On the basis of our preliminary report, we emphasize that today is possible and important (mandatory?) to “stage” CD at the time of the diagnosis.

The treatment with infliximab is employed successfully in Crohn's disease (CD) but predictors of efficacy are lacking. Activation of the transcription factor NF-kB has been demonstrated in CD and its inhibition is one of the mechanisms by which anti-inflammatory agents exert their effects. We evaluated the production of TNFalpha by peripheral blood mononuclear cells (PBMC) and the levels of NF-kappaB family molecules in the intestinal mucosa during infliximab therapy in 12 patients. TNFalpha was assayed on supernatants of PBMC culture stimulated with PHA or LPS. Immunohistochemistry was also done on intestinal biopsies. In six patients, Western blot analysis of the NF-kappaB subunit Rel-A, and its inhibitors IkappaBalpha and IkappaBgamma was performed on intestinal biopsies and PBMC. The TNFalpha production by LPS stimulated PBMC showed mild changes, while it was increased by PHA-stimulated PBMC after treatment. The number of inflammatory cells in the intestinal mucosa was reduced (p<0.002) by the treatment. In five out of six cases we detected an increase of the IkappaBalpha and IkappaBgamma)inhibitor levels in intestinal biopsies after treatment. An increase of IkappaB inhibitors levels could be one of the mechanisms by which infliximab decreases NF-kappaB activity and exerts its anti-inflammatory effects.

Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations, complications, and other autoimmune disorders. Indeed, physicians who care for patients with ulcerative colitis and Crohn's disease, the two major forms of IBD, face a new clinical challenge every day, worsened by the very frequent rate of extraintestinal complications. The goal of this review is to provide an overview and an update on the extraintestinal complications occurring in IBD. Indeed, this paper highlights how virtually almost every organ system can be involved, principally eyes, skin, joints, kidneys, liver and biliary tracts, and vasculature (or vascular system) are the most common sites of systemic IBD and their involvement is dependent on different mechanisms.

To our knowledge there are only a few reports showing a role of eradication therapy for H. pylori in the treatment of low-grade MALT-lymphoma, of stage EI2. We report a rare case of MALT-lymphoma, invading all of the gastric wall, which regressed after eradication of H. pylori. The regression was well documented by endoscopic ultrasonography (EUS). A 70-year-old man was referred to us for upper endoscopy that showed a single ulcer of 3cm in diameter at the gastric angulus. Histology, immunohistochemistry and PCR analyses diagnosed a low-grade MALT-lymphoma in the presence of H. pylori infection. EUS showed a tumor invasion of all the gastric wall. The serosa layer, also, appeared irregular and interrupted in some points. The lymph nodes around the duodenum and the stomach were not involved. An anti-H. pylori therapy was started. After 1 year from the diagnosis, EUS showed the reappearance of the normal layers of the stomach. The patient is actually disease free. This result suggests that in EI2-stage gastric lymphoma of MALT type, in the absence of both high-grade malignancy foci and t(11;18)(q21;q21) chromosomal translocation, an eradication treatment may be considered as a first therapeutic option.