But how many misunderstood Crohn's disease are revealed "by chance" using Capsule Endoscopy in Chronic Recurrent OGIB? Experience of a Single Italian Center and long term follow-up.

OBJECTIVE: The role of capsule endoscopy (CE) in Crohn's disease (CD) has expanded with greater understanding of the technology. The ability of CE to differentiate CD from other causes of inflammation has been questioned. Longitudinal studies are required to assess the long-term impact and significance of CE findings in suspected CD. The aim of this work is to verify in how many misunderstood cases of suspected Crohn's Disease CE was able to identify precociously and "by chance" when it is performed for recurrent obscure GI bleeding (OGIB), to evaluate how many of them were later confirmed during a median 24 months follow-up. Moreover, we observed the role of the early diagnosis in changing the clinical management of these patients. PATIENTS AND METHODS: A retrospective review was carried out on CE procedures performed for suspected OGIB. 1008 consecutive patients was enrolled and 492 included in the study. Previous investigations such as ileo-colonoscopy and/or previous small bowel imaging were documented. Only patients with at least 6 months of documented follow-up were included. A chart review was undertaken to record CE findings/correlate with subsequent diagnosis and outcome. RESULTS: 94/492 (19.1%) patients positive for suspected CD were identified. Follow-up data were available 64/94 (68%). The mean follow-up was 24 months. There was a strong positive correlation between results of CE and subsequent clinical diagnosis. The suspected CD was confirmed in 100% (94/94) of follow-up patients. CONCLUSIONS: CE appears able to identify lesions compatible with suspected Crohn's disease otherwise unacknowledged with consequently change in treatment options for the patients.

The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop.

Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

A randomized double-blind placebo-controlled clinical trial on efficacy and safety of association of simethicone and Bacillus coagulans (Colinox®) in patients with irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that affects 15-20% of the Western population. BACKGROUND: There are currently few therapeutic options available for the treatment of IBS. The aim of this study is to evaluate the efficacy and the safety of a medical device containing a combination of Simethicone and Bacillus coagulans in the treatment of IBS. PATIENTS AND METHODS: This is a monocentric double-blind, placebo-controlled parallel group clinical trial. Adult subjects suffering from IBS as defined by Rome III criteria were enrolled. Bloating, discomfort, abdominal pain were assessed as primary end point. Subjects received the active treatment or placebo 3 time a day after each meal for 4 weeks of study period. Subjects were submitted to visit at Day 0 (T1), at Days 14 (T2) and 29 (T3). RESULTS: Fifty-two patients were included into the study. Intragroup analysis showed a significant reduction of the bloating, discomfort and pain in Colinox® group (CG) compared to placebo group (PG). Between group analysis confirmed, at T1-T3, significant differences between CG and PG in bloating and discomfort. DISCUSSION: Simethicone is an inert antifoaming able to reduce bloating, abdominal discomfort. Literature offers increasing evidence linking alterations in the gastrointestinal microbiota and IBS and it is well known that probiotics are important to restore the native gut microbiota. The Colinox medical device is specifically targeted against most intrusive symptom of IBS (bloating) and it is also able to counteract the most accredited ethiopathogenetic factor in IBS (alterations of intestinal microbiota). CONCLUSIONS: This is the first randomized double-blind placebo-controlled clinical trial demonstrating the efficacy and safety of a combination of simethicone and Bacillus coagulans in treatment of IBS.

Evaluation of gastric and small bowel transit times in coeliac disease with the small bowel PillCam®: a single centre study in a non gluten-free diet adult Italian population with coeliac disease.

BACKGROUND: The mechanisms underlying bowel disturbances in coeliac disease are still relatively unclear. Past reports suggested that small bowel motor abnormalities may be involved in this pathological condition; there are no studies addressing small bowel transit in coeliac disease before and after a gluten-free diet. AIM: The objective of this study was to determine whether capsule endoscopy (CE) could serve as a test for measurement of gastric and small bowel transit times in a group of symptomatic or asymptomatic coeliac patients at the time of diagnosis with respect to a control group. PATIENTS AND METHODS: Thirty coeliac untreated patients and 30 age-, sex- and BMI-matched healthy controls underwent CE assessment of whole gut transit times. RESULTS: All subjects completed the study per protocol and experienced natural passage of the pill. No statistical significant differences between gastric emptying and small bowel transit times both in coeliac and control group were found (p = 0.1842 and p = 0.7134; C.I. 95%, respectively). No correlation was found in coeliac patients and control group between transit times and age, sex and BMI. By using the Pearson's correlation test, significant correlation emerged between gastric emptying time and small bowel transit times in coeliac disease (r = 0.1706). CONCLUSIONS: CE reveals unrecognized gender differences and may be a novel outpatient technique for gut transit times' assessment without exposure to radiation and for the evaluation of upper gut dysfunction in healthy patients suffering from constipation without evidence of intestinal malabsorption. Nevertheless, CE does not seem to be the most suitable method for studying gut transit times in untreated coeliac patients; this might be ascribed to the fact that CE consists of inert (non-digestible, non-absorbable) substances.

Advance in diagnosis and treatment of small bowel tumors: a single-center report.

BACKGROUND: The past decade has seen significant advances in the evaluation of the small bowel, long considered as the "black box" in gastroenterology. The development of several endoscopic techniques, including capsule endoscopy (CE) and double (DBE)- and single (SBE)-balloon enteroscopy, has improved the evaluation of this part of the gut and led to reach a more precise preoperative diagnosis of small-bowel tumors. These rare tumors were previously diagnosed only after laparotomy, although laparoscopic advanced surgery can be used for minimally invasive therapeutic approach in these patients. This study was designed to evaluate the diagnostic and therapeutic impact of endoscopic procedures on small-bowel tumors. METHODS: During October 2010, 148 SBE procedures were performed; in 14 patients (7 males and 7 females, mean age 58.8 years; range 37-82 years) who suffered from obscure gastrointestinal bleeding, with previous negative upper and lower GI endoscopy, a diagnosis of small-bowel tumor was suspected according to CT scan (7 cases) and/or CE (11 patients). Then, an enteroscopy was performed. RESULTS: Multiple biopsies were taken in 9 cases; endoscopic tattoos were performed in 11 cases. After endoscopic procedures, histological examination showed melanoma in one case, adenocarcinoma in seven, and adenoma in one case. In 11 of 14 patients, a laparoscopic partial resection of small bowel involved was possible due to endoscopic tattoos. In one patient, the involvement of colic segment precluded a laparoscopic resection. In two patients, the laparoscopic resection was not possible for technical problems. Histological findings on resected specimens were indicative for melanoma in one case, gastrointestinal stromal tumor (GIST) in four cases, gastrointestinal autonomic nerve tumor (GANT) in one case, adenoma in one, and adenocarcinoma in seven cases. CONCLUSIONS: New development of different endoscopic approaches to the small bowel has led to reach an earlier diagnosis of small-bowel tumors and a preoperative diagnosis with consequent minimally invasive surgical approach.

Helicobacter pylori infection: is sequential therapy superior to standard triple therapy? A single-centre Italian study in treatment-naive and non-treatment-naive patients.

BACKGROUND: Clarithromycin resistance has decreased the eradication rates of Helicobacter pylori. AIMS: To determine whether a 10-day course of sequential therapy (ST) is more effective at eradicating H pylori infection than triple therapy (TT) in the first or second line, and to assess side effects and compliance with therapy. METHODS: One hundred sixty treatment-naive and 40 non-treatment-naive patients who were positive for H pylori infection by ¹³C-urea breath test or endoscopy were enrolled. Eighty of 160 patients underwent TT, while 80 of 160 underwent ST with omeprazole (20 mg) plus amoxicillin (1 g) twice/day for five days, followed by omeprazole (20 mg) with tinidazole (500 mg) twice/day and clarithromycin (500 mg) twice/day for five consecutive days. H pylori eradication was evaluated by ¹³C-urea breath test no sooner than four weeks after the end of treatment. RESULTS: Eradication was achieved in 59 of 80 treatment-naive patients treated with TT (74%), in 74 of 80 patients treated with ST (93%), and in 38 of 40 non-treatment-naive patients (95%). Eradication rates in treatment-naive patients with ST were statistically significantly higher than TT (92.5% versus 73.7%; P=0.0015; OR 4.39 [95% CI 1.66 to 11.58]). Mild adverse effects were reported for both regimens. CONCLUSIONS: ST appears to be a well-tolerated, promising therapy; however, randomized controlled trials with larger and more diverse sample populations are needed before it can be recommended as a first-line treatment.

Single-balloon push-and-pull enteroscopy system: does it work? A single-center, 3-year experience.

BACKGROUND: The last decade has seen significant advances in the evaluation of the small bowel. Several endoscopic techniques have been developed in recent years: capsule endoscopy (CE), double-balloon enteroscopy (DBE), and, more recently, the single-balloon enteroscopy (SBE). The aim of this study was to evaluate diagnostic and therapeutic impact, safety, and feasibility of the SBE procedure after a 3-year experience. METHODS: A total of 73 SBE procedures were performed from July 2006 to July 2009. The starting insertion route (oral or anal) of SBE was chosen according to the estimated location of the suspected lesions based on the clinical presentation and, in 48 patients, on the findings of CE. A total of 70 patients with obscure gastrointestinal bleeding (31), suspected malabsorption syndrome (12), polyposis syndromes (11), suspected Crohn's disease (9), and suspected gastrointestinal tumors (7) were recruited. RESULTS: The SBE was not carried out in four patients because of technical problems. Multiple angiodysplasias were found and treated in 9 patients; Peutz-Jeghers syndrome, familial adenomatous polyposis (FAP), and multiple polypectomies were carried out in 8 patients; endoscopic tattoos were performed in 2 patients due to the large diameter of the polyps; and multiple biopsies was performed in only one patient. SBE diagnosed Crohn's disease in four patients, malabsorption syndromes in two, lymphangiectasia in two, eosinophilic enteritis in one, melanoma in one, and nonspecific inflammation in eight. A total of seven small-bowel tumors were diagnosed (all were tattooed). In 23/70 patients the exam was negative. No major complications occurred. CONCLUSION: Single-balloon enteroscopy seems to be safe, useful, and highly effective in the diagnosis and therapy of several small-bowel diseases.

Spontaneous right ventricular thrombus in a patient with active ulcerative colitis and protein C deficiency: a review with a case report.

BACKGROUND: Inflammatory bowel disease (IBD) is an idiopathic condition of gastrointestinal tract whose pathogenesis results from the complex interaction of genetic susceptibility and environmental influences. Is well known how IBD patients have an increased risk of thrombosis. OBJECTIVES: To assess the frequency and characteristics of thromboembolic events (TEE) in IBD and the role of certain etiopathological factors in such thrombotic patients. MATERIAL AND METHODS: We report the case of a young woman affected by protein C deficiency, who during a clinical recurrence of ulcerative colitis (UC), developed a spontaneous right ventricular thrombus and pulmonary embolism. Then, we made a review of literature that documented thromboembolic events in IBD patients. RESULTS: A search using the PubMed database identified 65 case reports documenting thromboembolic events in patients with known UC and 7 documenting thromboembolic events in known Crohn's disease. DISCUSSION: The data of the literature confirm that IBD patients have an approximately three fold greater risk for developing a TEE compared with the general population. The risk for thrombosis correlates well with disease activity in Crohn's disease, and to lesser extent in ulcerative colitis.

Active thymopoiesis in idiopathic chronic pancreatitis.

BACKGROUND/AIMS: Cellular immunity has a pivotal role in the pathogenesis of chronic pancreatitis (CP), resulting in pancreas infiltration by T-cells. Studies on systemic immunity are few and contradictory. One study reported a decrease of naive CD45RA+ cells. The presence of naive T cells, detected as recent thymic emigrants (RTEs), is evaluated with a new molecular technique by using real-time PCR to detect the T-cell receptor excision circles (TREC). To elucidate the role of naive T-cells in the pathogenesis of CP, we investigated the percentage of sj-TREC in CP patients. PATIENTS: Thirty CP patients were studied and compared to 30 sex- and age-matched healthy volunteers. METHODS: Genomic DNA was isolated from peripheral blood mononuclear cells (PBMC) of each patient. RTEs were evaluated by measuring sj-TREC by real-time PCR. RESULTS: The mean percentage of sj-TREC+ cells present in CP was not significantly different from that of control group (0.02319% vs 0.02338%, respectively). CONCLUSION: Our data show that naive TREC+ cells are normally represented in CP. The presence of active thymopoiesis may be the underlying mechanism resulting in continuous production of T-cells, responsible of maintaining the inflammatory process.

Early atherosclerosis in patients with inflammatory bowel 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.

Increased carotid intima-media thickness in patients with inflammatory bowel disease.

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.

Prevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease.

BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.

Intercellular adhesion molecule 1 gene polymorphisms in inflammatory bowel disease.

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.

Clinical correlations of small bowel CT and contrast radiology findings in Crohn's disease.

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.

Pathophysiology, diagnosis and treatment of non-erosive reflux disease (NERD).

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.