Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn's disease.

BACKGROUND: Autologous haematopoietic stem cells transplantation (HSCT) has been shown to be effective in refractory Crohn's disease. AIM: We analysed the effects of HSCT on the immune response of patients treated for moderate-severe Crohn's disease, refractory or intolerant to multiple drugs. METHODS: Unselected peripheral blood stem cells were collected after mobilisation with cyclophosphamide (CTX) and G-CSF. The conditioning regimen included CTX and rabbit antithymocyte globulin. Blood samples for immunological analyses were collected at baseline, after mobilisation, and 3, 6 and 12 months after transplantation. Immunological analyses evaluated: (1) CD4(+)/CD25(high+)/FoxP3(+) regulatory T cells (T-regs); (2) Toll-like receptor 2-(TLR2) and TRL4-expressing monocytes (CD14(+) cells); (3) IL-12, IL-10, TNF-alpha-production by mitogen-stimulated CD14(+) cells and IFN-gamma production by CD4(+) T cells. Immunological results were compared with healthy donors and associated with clinical and endoscopic response during 12 months of follow-up. RESULTS: Overall, T-regs increased, whilst TLR4-expressing cells, as well as TNF-alpha and IL-10, all higher than healthy donors at baseline, significantly decreased after transplantation. Full responders at T(3) had higher T-regs and lower IFN-gamma and IL12. T-regs decreased and IL12 and TLR2 increased in the only relapsed patient. CONCLUSIONS: HSCT can induce and maintain clinical and endoscopic remission in refractory Crohn's disease, which is associated with immunomodulation.

Vitamin D and inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are the main forms of inflammatory bowel disease (IBD), chronic relapsing-remitting inflammatory conditions of uncertain origin affecting the gastrointestinal tract. Much effort has recently been made both in defining the mechanisms underlying the development of IBD, and in broadening the spectrum of effective treatment. Substantial progress has been made in characterising immune-cell populations and inflammatory mediators in IBD. 1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the bioactive form of Vitamin D(3), besides having well-known control findings of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune- omeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases, including IBD. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Future studies now need to focus on the potential of vitamin D and its derivatives as therapeutic adjuncts in the treatment of IBD.

Validation of the Italian translation of the Inflammatory Bowel Disease Questionnaire.

BACKGROUND: Health-related quality of life is an important measure of treatment outcome; its evaluation requires the use of internationally validated ad hoc questionnaires. The McMaster Inflammatory Bowel Disease Questionnaire (IBDQ) is the most used specific instrument. AIM: To assess the validity and reliability of the Italian translation of the IBDQ. METHODS: The IBDQ underwent forward and backward translation; 13 patients were enrolled for cognitive testing of the Italian version to increase clarity. For field testing, 113 patients (65 with Crohn's disease and 48 with ulcerative colitis) completed both the IBDQ and the generic instrument 36-item Short Form Health Survey scale (SF-36). RESULTS: Data quality was optimal with high completeness and low floor and ceiling effect. Item internal consistency was satisfied for 100% of patients, while discriminant validity showed a few items with higher correlations with other scales. Cronbach's alpha coefficient was 0.96. Test-retest correlations indicated good reliability (Pearson R 0.81). Exploratory factor analysis indicated that the original grouping of the item was suboptimal. The score proved sensitive to disease activity, gender and quality of life as measured by the SF-36. CONCLUSIONS: The Italian translation of the McMaster Inflammatory Bowel Disease Questionnaire sounds natural and is easy to understand. A field test gave results comparable to other international validations, supporting its use in cross-national surveys.

Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis.

BACKGROUND & AIMS: It is uncertain whether mucosal healing after the first course of corticosteroids therapy predicts outcome in patients with ulcerative colitis (UC). We evaluated whether early clinical and endoscopic responses to this therapy are associated with late outcomes in UC. METHODS: Patients with newly diagnosed UC who were prescribed corticosteroid therapy (n = 157) were followed up for 5 years. They were evaluated using clinical (Powel-Tuck [PT]) and endoscopic (Baron) indexes after 3 and 6 months, then every 6 months. Outcomes at month 3 (early response) were used to identify patients with complete (group A: PT, 0-1; Baron, 0), partial (group B: PT, 0-1; Baron, 1-3), or no response (group C: persistence of clinical and endoscopic activity). The association between early and late outcomes was assessed. RESULTS: After 5 years, there were significant differences between complete and partial responders in the rates of hospitalization (25% in group A vs 48.7% in group B; P = .0152; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.21-6.72), immunosuppression therapy (5% in group A vs 25.6% in group B; P = .0030; OR, 6.55; 95% CI, 1.67-25.67), colectomy (3.3% in group A vs 18.0% in group B; P = .0265; OR, 6.34; 95% CI, 1.24-32.37), and their combination (26.7% in group A vs 48.7% in group B; P = .0249; OR, 2.61; 95% CI, 1.12-6.11). After multivariate analysis, lack of mucosal healing was the only factor associated with negative outcomes at 5 years (immunosuppressors: hazard risk [HR], 10.581; 95% CI, 2.193-51.039; P = .0033; hospitalization: HR, 3.634; 95% CI, 1.556-8.485; P = .0029; colectomy: HR, 8.397; 95% CI, 1.278-55.186; P = .0268). CONCLUSIONS: No mucosal healing after corticosteroid therapy is associated with a more aggressive disease course.

Immunomodulators for all patients with inflammatory bowel disease?

Recent insight into the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) have led to the development of new treatment options, with a progressive shift to more evidence-based strategies based on sound pathophysiological rationales. A better understanding of inflammatory bowel disease (IBD) pathophysiology has progressively resulted in a more frequent use of immunomodulators. We review the recommended or suggested use of conventional immunomodulators such as azathioprine, 6-mercaptopurine, methotrexate in the treatment of IBD. Moreover, an effort is made to explore some critical areas in which early and more diffuse use of these agents may be advocated.

Peripheral regulatory T cells and serum transforming growth factor-ß: relationship with clinical response to infliximab in Crohn's disease.

BACKGROUND: CD4(+)Foxp3(+) regulatory T cells (Treg) inhibit T-cell proliferation in vitro and are effective in suppressing colitis in mouse models. Tumor necrosis factor (TNF)-α, which is centrally involved in Crohn's disease (CD) pathogenesis, also impairs Treg function. Here we investigated the influence of anti-TNF therapy on Treg frequency and function in CD. METHODS: Twenty CD patients were treated with infliximab administered at weeks 0, 2, and 6. Blood was collected immediately before the first infusion and after 10 weeks. Treg frequency was quantified by flow cytometry. Treg function was measured using a standard coculture assay. Serum levels of transforming growth factor (TGF)-ß1 and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Pretreatment Treg frequency and serum TGF-ß1 levels were significantly higher in nonresponder than responder patients. Clinical improvement in 12 CD patients was associated with a significant increase of Treg frequency after 10 weeks. Treg were functionally active before and after treatment with infliximab, both in responder and nonresponder CD patients. In responder patients the restoration of Treg pool was accompanied by a parallel significant increase of serum TGF-ß1 and IL-10. No significant change in the elevated Treg or serum TGF-ß1 was seen in nonresponder patients. CONCLUSIONS: This study suggests that there may be a relationship between numbers of Treg in the blood, serum TGF-ß1, and response to infliximab; however, further prospective studies are needed.

Prevalence and pathogenesis of anemia in inflammatory bowel disease. Influence of anti-tumor necrosis factor-alpha treatment.

BACKGROUND: Anemia is a common complication of inflammatory bowel disease, but its epidemiology may be changing due to earlier diagnosis and improved treatments. We investigated the prevalence and pathogenesis of anemia in patients with inflammatory bowel disease. DESIGN AND METHODS: In a cross-sectional study 263 out-patients with inflammatory bowel disease (165 with Crohn's disease, 98 with ulcerative colitis) were investigated. The influence of time from diagnosis, disease activity, inflammation and the status of iron and hematinic vitamins on the level of hemoglobin and prevalence of anemia were evaluated. In a second group of 27 patients with Crohn's disease, undergoing anti-tumor necrosis factor-alpha treatment with infliximab because of refractory or fistulizing disease, we determined the effects of infliximab on disease activity, hemoglobin, serum erythropoietin levels, iron status and inflammation. RESULTS: In all, 104 of the 263 patients with inflammatory bowel disease were anemic. Age, gender and azathioprine treatment had no influence on anemia. The prevalence of anemia was highest at diagnosis (65%), decreased during the first 4 years after disease onset, and was stable thereafter. Active disease was associated with higher rates of anemia. At diagnosis most anemic patients had anemia of chronic disease; during follow-up iron deficiency and multifactorial forms of anemia became more prevalent. Eighteen of 27 patients undergoing treatment with infliximab were anemic; most of them had anemia of chronic disease. Infliximab reduced disease activity and improved anemia in 12 patients. This was mediated by an increased production of erythropoietin for the degree of anemia. In vitro infliximab increased the growth of erythroid progenitors from the peripheral blood of patients with active disease. Conclusions Anemia is a common problem in out-patients with inflammatory bowel disease; the prevalence and severity of anemia are related to the activity of the bowel disorder. The pathogenesis of anemia changes during the course of the disease, with anemia of chronic disease having a major role at diagnosis and iron deficiency and multifactorial forms of anemia during follow-up. In patients requiring anti-tumor necrosis factor-alpha treatment, response to therapy improves erythropoiesis.

Hydrosonography of the gastrointestinal tract.

OBJECTIVE: Bowel sonography has become accepted as a useful tool in several gastrointestinal disorders. Filling of the gut with echo-poor liquids has been proposed to achieve a detailed evaluation of the bowel. This article refers to a review made concerning the benefits and limits of hydrosonography of the gastrointestinal tract. CONCLUSION: The use of a luminal contrast agent in bowel sonography may improve results but should be adopted on a case-by-case basis, according to the clinical context and the experience of the sonologist.

Biologic targeting in the treatment of inflammatory bowel diseases.

The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Under normal situations, the intestinal mucosa is in a state of "controlled" inflammation regulated by a delicate balance of proinflammatory (tumor necrosis factor [TNF-alpha], interferon-gamma [IFN-gamma], interleukin-1 [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 inflammatory bowel disease therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-kappaB), and other miscellaneous therapies are being evaluated as potential therapies for the treatment of inflammatory bowel disease. In this context, infliximab and adalimumab are currently the only biologic agents approved in Europe for the treatment of inflammatory Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP571, certolizumab pegol, etanercept, onercept. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanism 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. Therapeutics agents to inhibit leukocyte trafficking include natalizumab (approved for use in Crohn's disease in USA), MLN-02, and ISIS 2302. Other agents being investigated for the treatment of Crohn's disease include inhibitors of T cell activation, proinflammatory cytokine receptors, Th1 polarization, growth hormone, and growth factors. Agents being investigated for treatment of ulcerative colitis include many of those mentioned above. 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 perspective on the development of therapies for inflammatory bowel disease. A review is made of the main areas of research exploring the mechanisms associated with the pathogenesis of IBD, providing advances in the agents currently in use, and identifying a host of new therapeutic biologic targets.

Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal.

OBJECTIVES: Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC. METHODS: In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables. RESULTS: After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434-3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064-3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103-3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3-6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267-6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005). CONCLUSIONS: Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.

CARD15 gene variants and risk of reoperation in Crohn's disease patients.

OBJECTIVES: Several studies have investigated, with conflicting results, the risk factors for reoperation in Crohn's disease (CD) patients. CARD15 gene variants have been identified as a major genetic risk factor for CD patients and associated with ileal disease, stenosis, and risk of surgery. However, data regarding the association between these variants and the need for reoperation are very few and conflicting. This study evaluated the risk factors of reoperation, including CARD15 gene variants. METHODS: A total of 253 consecutive CD patients, recruited in four Italian tertiary-care inflammatory bowel disease (IBD) referral centers, who had submitted to surgery for CD, were included in the study. Clinical characteristics of CD patients, time and main indications for surgery, type of operation, postoperative therapy, and time to second surgery were recorded. CARD15 gene variants were determined by DNA sequencing analysis in each center. Factors related to surgical recurrence, including CARD15 variants, were estimated by Cox proportional hazard regression. RESULTS: In all, 89 patients (35.1%) showed at least one surgical recurrence. Reoperation was significantly correlated with stenosis as indications at initial surgery only. CARD15 variants were found in 36.0% of patients, but did not correlate significantly with the demographic and clinical characteristics of the patients, rate of first surgical recurrence, and time to second operation. CARD15 variants did not significantly affect the reoperation rate, irrespective of indications for surgery. CONCLUSIONS: Reoperation for CD is correlated with stenosis at initial surgery, but not with CARD15 gene variants. This finding does not justify more aggressive prophylactic therapy on the basis of CARD15 genotype.

An analysis of the factors associated with the development of complications in patients undergoing precut sphincterotomy: a prospective, controlled, randomized, multicenter study.

OBJECTIVES: Precut is performed when biliary access at endoscopic retrograde cholangiopancreatography (ERCP) fails. Precut may have adjunctive risks, but some authors have suggested that the attempts to cannulate the papilla that precede precutting cause complications. We evaluated the role of the timing of precut in determining the development of complications and with respect to the other factors involved. METHODS: During ERCP, after 10 min of attempts to cannulate, patients were randomized to an early-precut group (n=77) undergoing precut immediately or a late-access group (n=74) in which cannulation was attempted for 10 further minutes before the endoscopist was free to perform precut or to persist in cannulation. Occurrence of complications and the associated risk factors were recorded. RESULTS: The two groups were similar for general characteristics. The number of attempts to cannulate, the number of pancreas injections, and the incidence of acinarization were higher in the late-access group. The cannulation rate was 94%. The incidence of overall complications was similar, but the pancreatitis rate was higher in the late-access group (14.9 vs. 2.6%, P=0.008). Amylase levels increased by 398.9+/-879.4 in the early-precut group and 833.6+/-1478.4 in the late-access group (P=0.029). Nondilated bile duct and pancreatic injection were related to the development of pancreatitis, whereas the performance of precut was related to other complications. CONCLUSIONS: Early precut is associated with lower pancreatitis rate, suggesting that pancreatitis develops as a consequence of the attempts to cannulate the papilla and pancreatic injection, and not precutting.

Use of double-balloon enteroscopy in the management of patients with Crohn's disease: feasibility and diagnostic yield in a high-volume centre for inflammatory bowel disease.

BACKGROUND: Double-balloon enteroscopy (DBE) is theoretically useful in Crohn's disease (CD) since it is potentially able to investigate the whole small intestine, but sparse data are available. AIM: To assess the feasibility, safety, and diagnostic yield of DBE in CD. METHODS: The study was conducted in a tertiary care centre for inflammatory bowel disease. Thirty-seven patients with CD (18/19 male/female, mean age 42 years, range 13-77 years) were considered. Thirty-two DBEs from the oral approach and 18 from the anal (in 6 patients from both ways with a complete exploration in 4, 10.8%) were performed. Indications were: first diagnosis/staging in 16 cases, diagnosis of stenosis in 7, obscure bleeding in 10, suspected neoplasia in 2, and postsurgical evaluation in 2. One hundred and thirty-three other procedures (3.7 per patient) were performed with the same indication. RESULTS: Insertion depth from the oral route was 266.5 ± 100 cm and from the anal route 72.5 ± 60 cm. Ileocecal valve was passed in 8/13 patients, but in 4 DBE explored less than 50 cm of ileum. Diagnostic yield was 59.4% but changed according to indication (40% in obscure bleeding, 100% in case of strictures) and was higher when DBE was conducted on the basis of previous investigations (77.8% versus 40%, p = 0.037). CONCLUSION: DBE is a feasible, useful, but technically demanding method in CD. Definition of the proper introduction route by means of previous investigations is associated with a higher efficacy of DBE.

Predictors of long-term outcome of functional dyspepsia and duodenal ulcer after successful Helicobacter pylori eradication--a 7-year follow-up study.

AIMS: To investigate the course of dyspeptic symptoms, predictors of symptom relief and use of antidyspeptic drugs in patients with duodenal ulcer disease and functional dyspepsia 6-7 years after successful Helicobacter pylori eradication. PATIENTS AND METHODS: Patients with H. pylori-positive duodenal ulcer or functional dyspepsia, included in a prospective, randomized study from January 1996 to June 1997, and successfully treated with standard triple therapy, were eligible. After 6-7 years, case histories of 142 patients were retrieved and patients were interviewed by telephone. They were asked about the presence of dyspeptic symptoms and health care needs during the last week and over the last 6-7 years. Predictive factors of complete long-term relief of symptoms have been evaluated. RESULTS: Of the 114 eligible patients, 104 (49 with duodenal ulcer and 55 with functional dyspepsia) were included in the study. The mean duration of follow up was 6.6+/-0.5 years. Complete relief of dyspeptic symptoms was reported, in this period, by 49.0% of duodenal ulcer patients and 36.4% of patients with functional dyspepsia (P=0.271). Persistence of symptoms within 3 months of H. pylori eradication and female sex were predictive of persistence of symptoms in the following 6-7 years, in patients with functional dyspepsia. In turn, approximately 50% of the patients with complete symptom remission, within 6 months of H. pylori eradication, later became symptomatic. Since the end of the H. pylori eradication trial, 26.9% of patients were still using or had used antidyspeptic drugs; patients with functional dyspepsia having used them more frequently than duodenal ulcer patients (36.4 vs. 16.3%; P=0.037). CONCLUSION: In clinical practice, long-term symptomatic benefit, in duodenal ulcer patients, after H. pylori eradication, is similar to that in patients with functional dyspepsia. Early evaluation of symptoms after successful H. pylori eradication may be predictive of outcome in dyspeptic patients. Most symptomatic patients did not seek antidyspeptic drugs. Use of antisecretory medications was, however, greater in patients with functional dyspepsia than in duodenal ulcer patients.

Management of NSAID-induced gastrointestinal toxicity: focus on proton pump inhibitors.

The association between NSAIDs and the presence of upper gastrointestinal (GI) complications is well established. Evidence that acid aggravates NSAID-induced injury provides a rationale for minimizing such damage by acid suppression. Proton pump inhibitors (PPIs) appear to be very effective in treating NSAID-related dyspepsia, and also in healing gastric and duodenal ulcers in patients continuing to receive the NSAID. An analysis of data from comparative studies of PPIs versus ranitidine, misoprostol and sucralfate shows a therapeutic advantage in favour of the PPI. Several studies now confirm the efficacy of co-therapy with PPIs in the short- and long-term prevention of NSAID-induced upper GI injury. PPIs are more effective than histamine H(2)-receptor antagonists at standard dosages in reducing the risk of gastric and duodenal ulcer, and are superior to misoprostol in preventing duodenal but not gastric lesions. However, when balancing effectiveness and tolerance, PPIs may be considered the treatment of choice in the short- and long-term prevention of NSAID-related mucosal lesions. To date, there are only a few published articles dealing with the role of PPIs in the prevention of upper GI complications. Recent epidemiological and interventional studies provide some evidence that PPIs are of benefit. However, more controlled studies using clinical outcomes are needed to establish the best management strategy (PPIs combined with traditional NSAIDs or with cyclo-oxygenase-2 selective inhibitors) especially in patients with multiple risk factors, in patients using concomitant low-dose aspirin, corticosteroids or anticoagulants (high risk group), or in patients with a history of ulcer complications (very high risk group). Furthermore, it should be underlined that Helicobacter pylori infection positively interacts with the gastroprotective effect of PPIs; therefore, the true efficacy of these drugs in preventing NSAID-related ulcer complications should be reassessed without the confounding influence of this microorganism.

Prospective study of long-term results and prognostic factors after conservative surgery for small bowel Crohn's disease.

BACKGROUND & AIMS: Several bowel-sparing techniques have been proposed for treating patients with CD, but there have been no prospective studies analyzing risk factors and long-term outcome. We prospectively evaluated safety and long-term efficacy of conservative surgery for patients with complicated CD. METHODS: From 1993-2007, 393 of 502 consecutive patients underwent surgery for complicated CD of the small bowel. Those with colonic involvement were excluded. The Student t test, chi(2) test, Kaplan-Meier estimates, and Cox proportional hazard model were used to analyze postoperative complications and long-term outcome. RESULTS: A total of 865 jejunoileal segments underwent 318 small bowel resections and 367 strictureplasties (either classic or nonconventional). There were no deaths; the complication rate was 5.6%, and the cumulative 10-year recurrence rate was 35%. None of the prognostic factors were correlated with postoperative complications. Younger age, an upper jejunoileal location, stricturing behavior, and small-bowel wall thickening 12 months after surgery showed hazard ratios of 2.4 (95% confidence interval [CI], 1-5.4; P = .03), 2.5 (95% CI, 1.3-4.7; P = .004), 2.2 (95% CI, 1.1-4.1; P = .01), and 4.5 (95% CI, 2.3-8.6; P = .000), respectively. Immunomodulator therapy failed to reduce long-term surgical recurrence. CONCLUSIONS: Young patients with extended and stricturing disease are at high risk for disease recurrence after surgery. Bowel wall thickening was a reliable prognostic factor for these patients. Conservative surgery is safe and effective in treating patients with jejunoileal CD and should be considered as the first-line surgical treatment, preventing the risk of short bowel syndrome caused by repeated resections.

Combining two imaging techniques is best to diagnose small-bowel Crohn's disease.

In most patients with Crohn's disease, diagnostic gastrointestinal lesions are located in the small bowel, which is not easily accessible to direct investigation. This commentary focuses on an article by Solem et al., which compared the utility of four primary small-bowel imaging modalities (CT enterography, ileocolonoscopy, capsule endoscopy, and small-bowel follow-through) in diagnosis of active small-bowel Crohn's disease. Capsule endoscopy had lower diagnostic specificity than the other techniques. This result, in conjunction with the need to perform preliminary small-bowel radiography to detect asymptomatic, partial, small-bowel obstructions, makes capsule endoscopy a poor choice as a first-line test for Crohn's disease. We concur with Solem et al.'s opinion that a combination of two of the other available imaging methods is the best diagnostic option for small-bowel Crohn's disease, although the choice of which two to use should be based on the facilities and expertise that are available locally.

HLA and autoimmune digestive disease: a clinically oriented review for gastroenterologists.

OBJECTIVES: The human leukocyte antigen (HLA) system includes genes involved in graft-vs-host rejection and in immune response. The discovery that HLAs are associated with several diseases led to appealing developments both in basic biomedical research and in clinical medicine, and offered the opportunity to improve the understanding of pathogenesis and classification of diseases, as well as to provide diagnostic and prognostic indicators. The aim of this article is to review the association between HLA alleles and autoimmune digestive disease and its current relationship with modern HLA nomenclature and clinical practice. METHODS: Articles dealing with the association between HLAs and autoimmune digestive disease (including celiac disease, inflammatory bowel disease, autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis) were searched for using Pubmed and SCOPUS databases from earliest records to January 2008. RESULTS: The review has provided two sections. In the first, we explain the basic principles of HLA structure, function, and nomenclature, as an introduction to the second section, which describes current associations between HLA alleles and digestive diseases. The clinical implications of each HLA association are critically discussed. Actually, a clinical role for HLA typing is suggested for only a few conditions, e.g., celiac disease. CONCLUSIONS: The knowledge of current HLA nomenclature and of its association with some digestive diseases such as celiac disease can be useful in clinical practice for diagnostic and prognostic purposes. This can avoid improper HLA typing as well as stressing the need for further studies on other possible clinical applications.