Pre-illness changes in dietary habits and diet as a risk factor for inflammatory bowel disease: a case-control study.

AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an age-matched healthy control group. METHODS: Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease) and 160 healthy controls were studied. Portions per week of 34 foods and beverages before onset of symptoms were recorded using a validated questionnaire. Duration of symptoms before IBD diagnosis, presence of specific symptoms and their impact on subjective changes in usual dietary habits were also recorded. The association between diet and IBD was investigated by multiple logistic regression and dietary patterns were assessed by factor analysis. RESULTS: Changes in dietary habits, due to the presence of symptoms, were reported by 38.6% of patients and were not significantly related to specific symptoms, rather to long duration of symptoms, only in Crohn's disease patients. In IBD patients who did not change dietary habits, moderate and high consumption of margarine (OR = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high consumption of red meat (OR = 7.8) and high intake of cheese were associated with Crohn's disease. CONCLUSION: More than one third of IBD patients change dietary habits before diagnosis. Margarine, red meat and cheese increase the risk of ulcerative colitis and Crohn's disease.

Isolated ampullary adenoma causing biliary obstruction.

This is an interesting case of an isolated ampullary adenoma causing biliary obstruction that required surgical excision. We describe a patient who presented with a six month history of recurrent attacks of typical biliary pain radiating from the right upper quadrant of the abdomen to the back, nausea and vomiting, which we attributed to a large pedunculated tubulovillous adenoma. Abdominal ultrasound and endoscopic ultrasonography provided useful information in the diagnostic assessment of ampullary adenoma. Sporadic duodenal adenomas are an increasingly recognized condition in those with familial adenomatous polyposis syndromes as well as sporadic cases.

Over-the-catheter precut to gain access to the biliary duct during ERCP rendezvous.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) rendezvous during laparoscopic cholecystectomy is an efficient and safe method to treat cholecystocholedocholithiasis. Advancing a guidewire through the cystic duct into the duodenum and withdrawing it in the accessory channel of duodenoscope may be, however, laborious. Moreover, rendezvous performed in the typical manner needs the use of several costly accessories. We herein describe a simpler and cheaper method to gain access to the biliary duct at rendezvous. METHODS: Twenty-four consecutive patients undergoing ERCP rendezvous during laparoscopic cholecystectomy were considered. A catheter was introduced in the cystic duct and advanced into the duodenum. Access to the bile duct was than achieved by means of a precut sphincterotomy performed over the catheter emerging from the papilla. RESULTS: Cannulation was successful in all but two patients, in whom ERCP was performed in the conventional manner. The only complication was a case of mild post-sphincterotomy bleeding. In comparison with the typical rendezvous technique our procedure allowed savings of about 250, since its performance only requires a catheter and a knife sphincterotome. CONCLUSIONS: Over-the-catheter precut during ERCP rendezvous is a feasible and safe method which avoids the need for the manipulation of several accessories and guidewires, and thus results in money and time savings.

Bowel ultrasound in Crohn's disease: surgical perspective.

BACKGROUND: Bowel ultrasound has been proven to be a useful tool in the management of Crohn's disease, particularly in the assessment of intra-abdominal complications, most of which require surgery. MATERIALS AND METHODS: The National Library of Medicine has been searched for articles on the use of bowel ultrasound in Crohn's disease focusing on aspects of interest to the surgeon. RESULTS AND CONCLUSIONS: Several studies have demonstrated that bowel ultrasound may be useful to reduce the risk of unnecessary laparotomy in patients presenting acute abdomen with suspected chronic inflammatory bowel disease. Bowel ultrasound has been proven to be of value in the follow-up of Crohn's disease patients since allowing early diagnosis of intra-abdominal complications and, therefore, optimising the diagnostic and surgical approach. At followup, bowel ultrasound may accurately diagnose early postoperative complications and long-term disease recurrence. In patients submitted to conservative surgery, ultrasonography reveals changes in diseased bowel walls that may be predictive of recurrence of the disease, and hence determinant in the choice of medical treatment.

Prevalence of pancreatic insufficiency in inflammatory bowel diseases. Assessment by fecal elastase-1.

Pancreatic insufficiency (PI) may be an extraintestinal manifestation of inflammatory bowel diseases (IBD). We report the results of a cross-sectional study that was carried out to investigate both the prevalence of PI in IBD patients and its clinical course over a 6-month follow-up period. In total, 100 Crohn's disease (CD) patients, 100 ulcerative colitis (UC) patients, and 100 controls were screened for PI by the fecal elastase-1 (FE-1) test. The decision limits employed were: < or =200 microg/g stool for PI and < or =100 microg/g for severe PI. Patients with abnormal FE-1 values were re-tested after 6 months. Odds ratios (OR) for PI were estimated by unconditional logistic regression analysis. PI was found in 22 UC and 14 CD patients. The OR for the FE-1 test < or =200 microg/g was 10.5 [95% confidence interval (CI): 2.5-44.8] for IBD patients compared to the controls. The risk of PI was related to three or more bowel movements per day (OR = 25.0), the passage of loose stools (OR = 7.7), and previous surgery (OR = 3.7). At the 6-month follow-up, FE-1 values became normal in 24 patients and showed persistently low concentrations in 12. These patients had a larger number of bowel movements per day (OR = 5.4), previous surgery (OR = 5.7), and a longer duration of the disease (OR = 4.2). PI is frequently found in IBD patients, particularly in those with loose stools, a larger number of bowel movements/day and previous surgery. PI is reversible in most patients, and persistent PI is not associated with clinically active disease.

Transperineal ultrasound in the detection of perianal and rectovaginal fistulae in Crohn's disease.

OBJECTIVES: Perianal and rectovaginal fistulae are common complications in Crohn's disease. Magnetic resonance imaging (MRI) and endoanal ultrasound are used for imaging perianal fistulae and abscesses, but both methods require expensive equipment and experienced investigators. Transperineal ultrasound may represent another method of detecting perianal complications in Crohn's disease. We investigated Crohn's disease perianal and rectovaginal fistulae using transperineal ultrasound and compared the findings with results of endoanal ultrasound as reference standard. METHODS: A total of 46 patients with Crohn's disease and perianal and/or rectovaginal or anovulvar fistulae underwent, transperineal and endoanal ultrasound, on the same day. Transperineal ultrasound was performed using regular convex and high-resolution linear probes. Endoanal ultrasound was performed using an ultrasound system with a 7 MHz rotating endoanal probe. Fistulae were classified according to Parks' classification in intrasphincteric, transsphincteric, suprasphincteric, and extrasphincteric. Rectovaginal or anovulvar fistulae were described separately. Presence of abscesses was also reported. RESULTS: Fifty-two fistulae (3 intra-sphincteric, 28 transsphincteric, 8 suprasphincteric, 2 extrasphincteric, 9 rectovaginal, and 2 anovulvar) were detected by transperineal ultrasound. Endoanal ultrasound confirmed the correct classification of 45 fistulae (predictive positive value: 86.5%). Of the 53 fistulae detected by endoanal ultrasound, 45 were correctly classified by transperineal ultrasound (sensitivity 84.9%). Transperineal ultrasound showed 10 perianal abscesses: 2 horseshoe, 4 deep, and 4 superficial. Endoanal ultrasound confirmed all horseshoe, 3 deep, and 2 superficial abscesses and did not find further abscesses. CONCLUSIONS: Transperineal ultrasound is a simple, painless, real-time method to detect and classify perianal and rectovaginal fistulae and/or abscesses in Crohn's disease.

New onset of atrial fibrillation after introduction of azathioprine in ulcerative colitis: case report and review of the literature.

CASE REPORT: We present the case of a 52-year-old man with steroid-dependent ulcerative colitis, needing immunosuppressive therapy with azathioprine. The drug had been started 3 years earlier, but stopped after a few months because the patient reported palpitations, lipothymia, nausea and vomiting. Given the continued steroid-dependent ulcerative colitis and the lack of clinical documentation about a reaction with a dubious relationship to azathioprine, we decided to rechallenge the patient with the drug under clinical monitoring and after informed consent. After starting 50 mg of azathioprine, the patient showed general malaise, nausea and vomiting. An ECG showed atrial fibrillation, and the patient reported that the symptoms were similar to those previously experienced. DISCUSSION: We have found two other cases of similar onset of atrial fibrillation after azathioprine use, although some confounding elements in these episodes make the possible causal relationship between the drug and this adverse event uncertain.

Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study.

BACKGROUND: Triple therapy is recommended for Helicobacter pylori eradication, yet consensus on the duration of treatment is lacking. AIM: To compare the efficacy and safety of 1- and 2-week regimens of omeprazole, amoxicillin and clarithromycin in a large, multicentre, double-blind and randomised study. METHODS: A total of 909 H pylori-positive patients with duodenal ulcer, enrolled in 81 endoscopy units in Italy, were randomised to receive omeprazole, amoxicillin and clarithromycin for either 1 week (OAC1W) or 2 weeks (OAC2W) or omeprazole and amoxicillin for 2 weeks. H pylori eradication was assessed by histological examination and carbon-13 urea breath test 4 weeks after treatment. RESULTS: Both the intention-to-treat (ITT; n = 907) and per protocol (PP; n = 661) analyses showed no significant differences between the eradication rates of OAC1W (ITT 79.7%; PP 83.6%) and OAC2W (ITT 81.7%; PP 84.9%; ITT p = 0.53; PP p = 0.71). Both triple omeprazole, amoxicillin and clarithromycin regimens gave significantly higher eradication rates compared with omeprazole and amoxicillin treatment (ITT 44.6%; PP 42.8%; p<0.001). Poor compliance was reported in 18.6%, 17.3% and 15.1% (p = 0.51) of patients for OAC2W, OAC1W and omeprazole and amoxicillin, respectively. Adverse events occurred in 9.9% and 9.6% (p = 0.88) of patients for OAC2W and OAC1W, respectively, and in 5.9% for omeprazole and amoxicillin (p = 0.11). CONCLUSIONS: 1-week and 2-week triple treatments for H pylori eradication are similar in terms of efficacy, safety and patient compliance.

The treatment of Helicobacter pylori infection: the changing picture of a still unresolved problem.

More than 20 years from the discovery of Helicobacter pylori there is still a need to eradicate the bacterium. The efficacy of the current preferred first-line therapy--the triple regimen--has progressively decreased over the last 5 - 6 years, paralleling the progressive increase in the prevalence of resistant bacterial strains. Similarly, the quadruple therapy has progressively lost its importance as rescue therapy in some countries where bismuth is no longer available. A large number of studies investigating new combinations of drugs, new antibiotics and new regimens have been published in recent years. The most promising regimens--sequential therapy and triple therapy with lovofloxacin--have progressively gained importance but still need further confirmation of their efficacy before they can replace the old protocols in the everyday treatment of H. pylori infection.

Bowel ultrasound in Crohn's disease.

Most published studies have found bowel ultrasound to be a useful tool in the management of Crohn's disease. Indeed, it has been successfully used as the imaging technique of choice in screening patients with clinically suspected Crohn's disease. In these patients, bowel ultrasound, which is well accepted by patients, non-invasive and of low cost, may be the first diagnostic tool employed for young patients and can be used in the preliminary diagnostic work-up prior to further invasive tests. The most important application of bowel ultrasound is, however, in the follow-up of patients already diagnosed with Crohn's disease, in whom it may be useful to assess the site and extent of the lesions and to ensure the early detection of intra-abdominal complications, particularly abscesses and strictures. In this regard, improving the ultrasound assessment of intramural blood flow by means of colour power-Doppler ultrasonography and intravenous contrast agents may help to differentiate fibrotic and inflammatory strictures, and to discriminate inflammatory masses from intra-abdominal abscesses. Despite several attempts to correlate ultrasound findings with clinical and biochemical activity, there are as yet no convincing data on the usefulness of ultrasound in assessing the activity of Crohn's disease. In contrast, preliminary results are in agreement regarding the usefulness of ultrasound in the assessment of postoperative recurrence and in monitoring the outcome of the disease following surgery. In fact, the persistence of a thickened bowel wall or increased high bowel wall thickening at ultrasound following surgery has been identified as an index of early surgical recurrence. How these data may be usefully employed in the management of individuals with Crohn's disease needs to be investigated in further studies.

Sympathetic overactivity in active ulcerative colitis: effects of clonidine.

Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile. We tested the hypotheses that 1) an exaggerated sympathetic activity characterizes active ulcerative colitis (UC) and 2) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC. In 23 patients with UC and 20 controls, muscle sympathetic nerve activity (MSNA), ECG, blood pressure, and respiration were continuously recorded, and plasma catecholamine was evaluated both at rest and during a 75 degrees head-up tilt. Autonomic profile was assessed by MSNA, norepinephrine, epinephrine, spectral markers of low-frequency (LF) cardiac sympathetic (LF(RR); normalized units) and high-frequency (HF) parasympathetic (HF(RR); normalized units) modulation and sympathetic vasomotor control (LF systolic arterial pressure; LF(SAP)), obtained by spectrum analysis of the R-R interval and systolic pressure variability. Among UC patients, 16 agreed to be randomly assigned to 8-wk transdermal clonidine (15 mg/wk, 9 subjects), or placebo (7 patients). An autonomic profile, Disease Activity Index (DAI), and endoscopic pattern were compared before and after clonidine/placebo. At rest, MSNA, heart rate (HR), LF(RR), LF/HF, and LF(SAP) were higher and HF(RR) was lower in patients than in controls. Tilt decreased HF(RR) and increased MSNA and LF(RR) less in patients than in controls. Clonidine decreased HR, MSNA, epinephrine, LF(RR), and increased HF(RR), whereas placebo had no effects. Changes of the autonomic profile after clonidine were associated with reduction of DAI score. An overall increase of sympathetic activity characterized active UC. Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease.

Biologic therapy for inflammatory bowel disease.

Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn's disease. Therapeutic agents that inhibit leukocyte trafficking include natalizumab, MLN-02 and alicaforsen (ISIS 2302). Other agents being investigated for the treatment of Crohn's disease include inhibitors of T-cell activation, peroxisome proliferator-activated receptors, proinflammatory cytokine receptors and T(h)1 polarisation, and growth hormone and growth factors. Agents being investigated for treatment of ulcerative colitis include many of those mentioned for Crohn's disease. More controlled clinical trials are currently being conducted, exploring the safety and efficacy of old and new biologic agents, and the search certainly will open new and exciting perspectives on the development of therapies for IBD.

Prevalence and clinical significance of sonographic detection of enlarged regional lymph nodes in Crohn's disease.

OBJECTIVE: Reactive regional lymph node enlargement is a frequent ultrasonographic finding in patients with Crohn's disease. However, the prevalence of this condition and its clinical significance are unknown. This study assesses the prevalence of enlarged regional mesenteric lymph nodes and its clinical significance in Crohn's disease, and in particular whether there is a correlation between the sonographic detection of enlarged regional lymph nodes and the degree of clinical or biochemical activity of the disease. MATERIAL AND METHODS: A total of 240 in- and outpatients with Crohn's disease underwent intestinal ultrasound to assess the presence of enlarged regional lymph nodes as well as the thickness and echopattern of the bowel wall, the site and extent of Crohn's disease and the presence of stenosis, fistulas and abscesses. Demographic, clinical and biochemical parameters were also collected for each patient. A multivariate model by means of multiple regression analysis was used to identify independent variables linked to regional lymph node enlargement. RESULTS: Enlarged regional lymph nodes were detected ultrasonographically in 25.4% of Crohn's disease patients. The presence of regional lymph nodes showed a weak correlation with both clinical and biochemical Crohn's disease activity. Regional lymph nodes were found more frequently in young patients (50% of patients < 30 years, 18% of patients between 30 and 50 yrs, and 7% of patients > 50 yrs; p<0.0001) and in patients with a shorter disease duration. Enlarged regional lymph nodes were strongly correlated with internal fistulas and intra-abdominal abscesses. The multiple regression analysis showed that age, duration of disease and presence of internal fistulas were the best independent predictive factors linked to the presence of enlarged mesenteric lymph nodes. CONCLUSIONS: The sonographic detection of enlarged regional lymph nodes is more frequent in young patients, which suggests an earlier phase of Crohn's disease and the presence of septic complications such as fistulas and abscesses, but this is of limited valued in assessing disease activity.

Artificial neural networks are able to recognize gastro-oesophageal reflux disease patients solely on the basis of clinical data.

BACKGROUND: Artificial neural networks (ANN) are modelling mechanisms that are highly flexible and adaptive to solve the non-linearity inherent in the relationship between symptoms and underlying pathology. OBJECTIVES: To assess the efficacy of ANN in achieving a diagnosis of gastro-oesophageal reflux disease (GORD) using oesophagoscopy or pH-metry as a diagnostic gold standard and discriminant analysis as a statistical comparator technique in a group of patients with typical GORD symptoms and with or without GORD objective findings (e.g. a positive oesophagoscopy or a pathological oesophageal pH-metry). METHODS: The sample of 159 cases (88 men, 71 women) presenting with typical symptoms of GORD, were subdivided on the basis of endoscopy and pH-metry results into two groups: GORD patients with or without oesophagitis, group 1 (N=103), and pH and endoscopy-negative patients in whom both examinations were negative, group 2 (N=56). A total of 101 different independent variables were collected: demographic information, medical history, generic health state and lifestyle, intensity and frequency of typical and atypical symptoms based on the Italian version of the Gastroesophageal Reflux Questionnaire (Mayo Clinic). The diagnosis was used as a dependent variable. Different ANN models were assessed. RESULTS: Specific evolutionary algorithms selected 45 independent variables, concerning clinical and demographic features, as predictors of the diagnosis. The highest predictive performance was achieved by a 'back propagation' ANN, which was consistently 100% accurate in identifying the correct diagnosis compared with 78% obtained by traditional discriminant analysis. CONCLUSION: On the basis of this preliminary work, the use of ANN seems to be a promising approach for predicting diagnosis without the need for invasive diagnostic methods in patients suffering from GORD symptoms.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease.

BACKGROUND & AIMS: Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. METHODS: In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. RESULTS: Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. CONCLUSIONS: Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.