Roberto I1, D’Introno A1*, Semeraro S1, Ingravallo G2, Vicenti L3, Ciracì E1 and Gatti P4 1Internal Medicine Unit, Ostuni Hospital Ostuni (Brindisi), Italy 2Department of Emergency and Organ Transplantation (DETO) Pathology Sectio, University Hospital “Policlinico” of Bari, Bari, Italy 3General Surgery Unit “Ospedaliera”, University Hospital “Policlinico” of Bari, Bari, Italy 4Internal Medicine Unit, “Perrino” Hospital, Brindisi – Italy

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

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.

Mucosal endothelium has become one of the major areas of investigation in gut inflammation. It is now well recognised that it plays an active role in the pathogenesis of both forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis, since endothelial cells regulate mucosal immune homeostasis, acting as "gatekeepers", controlling leukocyte accumulation in the interstitial compartment. This process is mediated by leukocyte-endothelial adhesion molecules. This paper reviews the major molecules that mediate leukocyte-endothelial interactions, and summarises the results of the most recent clinical trials targeting adhesion molecules in inflammatory bowel disease.

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.

Intercellular adhesion molecule (ICAM)-1 is a single-chain cell surface glycoprotein that plays an important role in the recruitment of leukocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease (IBD). ICAM-1 gene lies on chromosome 19p13, implicated in determining susceptibility to IBD. The human ICAM-1 gene contains two polymorphic sites in codon 241 (G241R) and 469 (K469E) which have been implicated in the susceptibility to a range of degenerative and inflammatory diseases. Recently, several reports have shown discordant data regarding the association of these polymorphisms with IBD. In particular, we found an association of IBD with the E/E genotype while allele E469 was associated with a subgroup of patients with more extensive location of Crohn's disease and penetrating behaviour. However, other studies reached different conclusions. A possible explanation for the discrepancy of results is probably the influence of the different geographic distribution of the genetic mutations.

Up to 70% of patients with typical symptoms of gastroesophageal reflux disease (GERD) have neither definite endoscopic oesophageal breaks nor Barrett's oesophagus at upper endoscopy. These patients suffer from non-erosive reflux disease (NERD), also termed endoscopy-negative reflux disease or symptomatic GERD. NERD patients appear as a heterogeneous population with multiple and substantially different mechanisms implicated in the genesis of symptoms. In fact, patients with NERD may be divided into 3 groups on the basis of 24-hour pH monitoring: 1) patients with an abnormal acid exposure time (AET); 2) patients who demonstrate a normal AET, but in whom symptoms and reflux events are significantly correlated (hypersensitive oesophagus) and 3) patients with typical reflux symptoms but in whom all parameters of the pH study are normal. There is no gold standard for the diagnosis of NERD but a well-taken history can be, usually, sufficient to confirm the diagnosis and begin therapy. Thus, the more sensitive tool for the diagnosis of NERD is proton pump-inhibitor (PPI) test. The aims of NERD treatment are: symptoms relieve, restore quality of life and maintain clinical remission. Proton pump-inhibitors (PPIs) in full doses represent the treatment of choice of NERD patients, even if overall, clinical trials showed a lower efficacy in symptoms control when compared to patients with erosive oesophagitis. Patients with NERD often need long-term therapy for symptoms control. ''On demand'' PPI therapy has been considered as the most cost-effective strategy for the long-term treatment of NERD. In conclusion, many data indicate that NERD is a disorder in its own right that shares symptoms with other GERD groups. However further studies are needed to better define the natural history and improve the treatment of this disorder.

BACKGROUNDS AND OBJECTIVE:Aim of the present study was to evaluate the clinical correlates of small bowel CT patterns in patients with Crohn's disease (CD), as compared to barium studies and endoscopic findings, as far as parameters of disease activity are concerned.MATERIAL AND METHODS:Thirty five patients with pathologically proven CD were studied by means of helical single detector CT (13) or multidetector CT (22), after administration of low density contrast by mouth (13) or by nasojeunal tube (22). Eight hours later, all patients were studied with barium administered by mouth (13) or with barium and methilcellulose administered by nasojeunal tube (22). Clinical activity was assessed by CDAI score, ESR, CRP, alpha1 glycoprotein and fibrinogen levels. In twenty one patients, colonoscopy was also performed.RESULTS:Sensitivity of small bowel CT versus endoscopy was of 88% while sensitivity of barium studies was of 77% versus endoscopic findings, and it reached 100% for the combination of both exams. We found positive correlations between the detection at CT of "target sign" and a CDAI score > 150 or abnormal values of CRP, ESR, alpha1 glycoprotein. Abnormal ESR or fibrinogen levels were correlated with the detection of fistulas at CT scans. The diameter of enlarged mesenteric lymph nodes was correlated with alpha1 glycoprotein values. No similar correlations were detected for contrast radiology findings.DISCUSSION:This study underscores the clinical usefulness of performing small bowel CT in adjunct to conventional diagnostic studies in Crohn's disease patients. CT findings (either by oral route or nasojeunal tube) correlate with parameters of disease activity.