Infliximab reintroduction is not associated to a higher rate of immune-related adverse effects in patients with inflammatory bowel disease initially treated with a three-infusion induction regimen.

BACKGROUND: Episodic infliximab (IFX) treatment is associated with a higher risk for acute infusion reactions (AIR) and secondary loss of response (SLR), but this has not been evaluated in patients initially treated with an induction regimen with 3 IFX infusions. AIMS: To evaluate whether IFX reintroduction after > or = 4 months in patients treated with a 3-infusion induction regimen is associated with a higher incidence of AIR or SLR. METHODS: Incidence of immunogenic adverse effects was assessed in patients with inflammatory bowel disease who received > or = 4 consecutive IFX infusions (3 infusions at weeks 0, 2, and 6, plus > or = 1 maintenance infusion) (Continuous, n=47) and patients who were treated with a successful initial 3-infusion induction scheme and in whom IFX was then discontinued because of a complete response but reintroduced > or = 4 months later (Reintro, n=29). RESULTS: AIR rate was 17% in both groups, and SLR rate was 26% in the Continuous group and 15% in the Reintro group (not significant). The lack of concomitant immunomodulators and/or pretreatment with hydrocortisone were associated with AIR development (P=0.002). CONCLUSIONS: In patients who completed a 3-infusion induction regimen, IFX can be safely reintroduced even after a long time from discontinuation.

Endoscopic resection of ampullary tumors: 12-year review of 21 cases.

BACKGROUND: Endoscopic snare papillectomy is increasingly performed with curative intent for benign papillary tumors. This study aimed to evaluate the outcome of endoscopic resection for ampullary tumors at a single center. METHODS: All ampullary tumors without macroscopic features of malignancy identified by the endoscopic retrograde cholangiopancreatography (ERCP) from January 1995 to February 2007 were included in the study. Papillectomy was performed by snare resection using electrocautery. Argon plasma coagulation was effective for fulguration of small tissue remnants not amenable to snare resection. RESULTS: Of the 21 patients (9 men and 12 women; mean age, 67.2 +/- 14.3 years) evaluated, 11 had adenoma (7 had low-grade dysplasia [LGD] and 4 had high-grade dysplasia [HGD]), and 10 had carcinoma. All the patients underwent papillectomy. Of the 21 patients, 18 had extraductal growth or minimal intraductal growth, and 3 had extensive intraductal growth. The endoscopic complications (23.8%) included one case of mild bleeding, two cases of mild pancreatitis, and two cases of moderate pancreatitis. After papillectomy, 15 patients underwent Whipple procedures (endoscopic failure, 74.1%), including 3 patients with extensive intraductal growth (complete removal of the lesion impossible), 9 patients with carcinoma beyond the mucosal layer, and 3 patients with recurrence treated surgically. Endoscopic success (28.5%) was obtained for the remaining six patients (4 with LGD and 2 with HGD). Papillectomy was determined to be curative after a mean follow-up period of 15.9 +/- 14.9 months. CONCLUSIONS: In the hands of an experienced endoscopist, endoscopic papillectomy is a clinically effective treatment for ampullary tumors without invasive neoplasia. Evaluation of a prepapillectomy tumor extension is an important criterion for assessment of endoscopic success.

Steroid-refractory ulcerative colitis: predictive factors of response to cyclosporine and validation in an independent cohort.

BACKGROUND: One-third of patients with steroid-refractory ulcerative colitis (UC) do not respond to cyclosporine and require colectomy. Since alternative pharmacological treatments for this condition are available, it is pertinent to identify factors that predict response. The objective of this study was to determine predictive factors of response prior to cyclosporine administration, with validation in an independent cohort. METHODS: The 2 cohorts of patients were identified from prospectively established databases. All patients had received 1 mg/kg/day prednisolone or equivalent for at least 5 days before cyclosporine. The efficacy measure was need of early surgery (within 3 months). RESULTS: From 1998 to 2005, 34 patients were treated in 1 institution (derivation cohort) and 38 patients in the second institution (validation cohort). Eleven patients in the derivation cohort and 9 patients in the validation cohort underwent early colectomy. Univariate analysis in the derivation cohort demonstrated a significant association of colectomy with C-reactive protein (P = 0.012) and the Ho index before initiation of cyclosporine (P = 0.013). Regression analysis showed that only the Ho index (P = 0.011) had an independent predictive value. The Ho index predicted need of colectomy, with an area under the characteristic receiver operating curve of 0.79 (95% confidence interval [CI], 0.59-0.99) in the derivation cohort and 0.74 (95% CI, 0.53-0.96) in the validation cohort. The cutoff point with the best sensitivity and specificity ratio was > or =5. CONCLUSIONS: The Ho-based predictive score is a good predictor of response to cyclosporine and avoidance of colectomy, and may aid in the indication of this treatment for management of steroid-resistant UC.

Crohnology: a tale of time and times and inflammatory bowel diseases.

Time, times and timing are key words in inflammatory bowel diseases (IBD). The leitmotif of this issue of World Journal of Gastroenterology is time. We have asked experts to review on the epidemiology of these diseases over time, the changes in innate immunity that could be present in the first time, and then the timing of key treatments. The correct time of using azathioprine, mercaptopurine, infliximab, cyclosporine and surgery are reviewed. We have chosen experts with not only great clinical expertise but also personal interest in clinical and basic investigation. Our goal in this monograph is to get an idea not only of the present but of the immediate future in some of the key management issues in IBD. To this end, we think that the authors are the most adequate.

Identification of significant difficulty of selective deep cannulation by a simple predictive model: an endoscopic scale for teaching ERCP.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure associated with a risk of serious complications. This cohort study was designed to assess the accuracy of an endoscopic method aimed at discriminating procedures eligible to teach ERCP: patients with and without significant difficulty of selective deep cannulation (DSDC). METHODS: Clinically relevant variables were analyzed in a cohort of 400 consecutive patients (estimation group = 250 patients; validation group = 150 patients) who underwent an ERCP procedure. RESULTS: Multivariate analysis identified fixated duodenum, inflamed duodenum, soft major papilla, previous biliary surgery, and papilla with ectopion as independent predictors of DSDC. We constructed a model and a score system combining these five variables. The area under the ROC curve was 0.81 for the estimation group and 0.80 for the validation group. Using the best cutoff score (> 1.63), absence of significant DSDC could be excluded with high accuracy (negative predictive value = 89.2%) in 111 (44.4%) of 250 patients. Similarly, it could be excluded with the same certainty in 77 (51.3%) of the 150 patients in the validation group. CONCLUSIONS: A combination of easily accessible variables accurately predicts the absence of significant DSDC in half the patients who underwent the ERCP procedure. This score system discriminates procedures eligible to teach ERCP.

[Infectious mononucleosis in patients with inflammatory bowel disease under treatment with azathioprine]. / Mononucleosis infecciosa en pacientes con enfermedad inflamatoria intestinal en tratamiento con azatioprina.

The use of immunomodulators for the treatment of inflammatory bowel disease is increasing. One of the most common adverse effects associated with this kind of drugs are infectious complications. In recent years, special attention has been paid to certain latent infections which, in patients under immunomodulatory therapy, can be reactivated and prove lethal. Consequently, preventive actions have been adopted, such as screening for hepatitis B virus and tuberculosis infection before starting these treatments. Primary infection with the Epstein-Barr herpesvirus is usually asymptomatic. However, this virus can have an aggressive course and even lead to the development of lymphoma. We report two cases of atypical infectious mononucleosis in patients with inflammatory bowel disease under azathioprine therapy and review the available evidence on the most appropriate therapeutic approach in this subset of patients.

[Intravenous cyclosporine A in the treatment of refractory Crohn's disease]. / Ciclosporina A intravenosa en el tratamiento de la enfermedad de Crohn activa refractaria al tratamiento convencional.

BACKGROUND: Intravenous cyclosporine (iv CyA) is efficient in ulcerative colitis, but data are scarce in Crohn's disease (CD). PATIENTS AND METHOD: Patients with CD refractory to standard therapy who were treated with iv CyA. RESULTS: All patients with steroid-refractory disease achieved a complete response. In perianal disease, a complete response was attained in 3 out of 16 patients, while 9 showed a partial response. Only 1 out of 8 patients with enteric fistulae showed a complete response and a further one had a partial response. CONCLUSIONS: Intravenous CyA seems to be useful in steroid-refractory CD but not in fistulizing CD.

Decision tree for early introduction of rescue therapy in active ulcerative colitis treated with steroids.

BACKGROUND: Corticosteroids are the treatment of choice for moderate-to-severe active ulcerative colitis (UC) but up to 30%-40% of patients fail to respond. It has been reported that early clinical-biological parameters may identify those patients at high risk of colectomy. The aim was to identify predictors of rapid response to systemic steroids in moderate-to-severe attacks of UC. METHODS: Consecutive patients treated with prednisone 1 mg/kg/day for moderate-to-severe attacks of UC were prospectively included. Clinical and biological parameters at 3 and 7 days after starting steroids were recorded. Response was defined as mild or inactive UC activity at day 7 (as assessed by the Montreal Classification of severity) together with no need for rescue therapies (cyclosporin, infliximab, or colectomy). A logistic regression analysis was performed to identify those independent predictors of response. In addition, a decision-tree analysis was also performed. RESULTS: Sixty-eight percent of patients (64 out of 94) responded to steroids. In the univariate analysis the number of bowel movements, rectal bleeding, platelet count, and C-reactive protein (CRP) levels at day 3 were associated with response at day 7, but only rectal bleeding was found to be an independent predictor in the logistic regression analysis. Conversely, the classification and regression tree (CART) model included these four variables. The decision-tree model showed a higher sensitivity in predicting a rapid response to steroids than the logistic regression one. CONCLUSIONS: Rapid response to steroids in active UC attacks can be predicted after 3 days of treatment by simple clinical and biological parameters. A decision-tree model for early introduction of rescue therapies is provided.

Predictors of clinical response to systemic steroids in active ulcerative colitis.

Although systemic steroids remain as the gold standard for the treatment of acute moderate to severe active ulcerative colitis (UC), 15-57% of patients do not achieve clinical remission. We sought to identify clinical, biological, or radiologic predictive factors of response to steroid treatment in acute UC attacks. The medical records of 39 consecutive patients admitted for an acute attack of UC and treated with systemic steroids, were reviewed. Epidemiologic, demographic, and clinical data at baseline and clinical data 3 days after starting steroid treatment were registered. Treatment failure was defined as the need of IV cyclosporine or colectomy before hospital discharge. Twenty-four patients (62%) responded to systemic steroids. Thirteen out of the 15 nonresponders, were treated with IV cyclosporine, avoiding colectomy in 7 cases (54%). More than six bowel movements per day at the third day of treatment, blood in stools in the third day of therapy, extensive UC, and the presence of malnutrition were associated with steroid treatment failure, but only blood in stools (P=.04), and more than six movements per day (P=.012) after 3 days of treatment, were found to be independent predictive factors of steroid refractoriness. In conclusion, clinical evaluation 3 days after starting systemic steroids seems to be the best tool to assess short-term prognosis.

Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety.

BACKGROUND/AIMS: The most rational treatment of moderate ascites is spironolactone alone or in combination with furosemide. However, it is unknown which of these two treatment schedules is preferable. METHODS: One hundred nonazotemic cirrhotic patients with moderate ascites were randomly assigned to be treated with spironolactone and furosemide (Group 1: 50 patients) or with spironolactone alone (Group 2: 50 patients). If no response was obtained, the doses of diuretics were increased up to 400 mg/day of spironolactone and 160 mg/day of furosemide. In patients of group 2 not responding to 400 mg/day of spironolactone, furosemide was added. In cases with an excessive response, the dosage of diuretics was reduced. RESULTS: The response rate (98% in Group 1 vs. 94% in Group 2), the rapidity of ascites mobilization and the incidence of complications induced by diuretic therapy was similar in both groups. The need to reduce the diuretic dosage was significantly higher in Group 1 than Group 2 (68% vs. 34%; P=0.002). CONCLUSIONS: In the treatment of moderate ascites, spironolactone alone seems to be as safe and effective as spironolactone associated with furosemide. Since spironolactone alone requires less dose adjustment, it would be more suitable for treating ascites on an outpatient basis.

Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats.

Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation-dehydroxylation resistant and cholylglycine, a deconjugation-dehydroxylation susceptible bile acid were used. Rats with CCl(4)-induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks. Healthy rats, as controls, were treated similarly. In cirrhotic rats receiving placebo, bile secretion from an acute biliary fistula was lower than in healthy rats (27.2 +/- 6.5 vs. 53.0 +/- 3.1 microL/kg/min; mean +/- SE, P<.05). The administration of conjugated bile acids to cirrhotic rats normalized bile secretion (cholylsarcosine, 51.8 +/- 6.29; cholylglycine, 52.72 +/- 8.9 microL/kg/min). Total ileal bacterial content was 6-fold higher in ascitic cirrhotic rats than in healthy rats. Conjugated bile acid administration reduced bacterial content to normal levels. Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%). Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 +/- 0.002; cholylglycine 0.101 +/- 0.007 EU/mL) compared with placebo (0.282 +/- 0.124, P <.001). Survival was greater in animals receiving conjugated bile acids (cholylsarcosine, 10/15; cholylglycine, 11/15; placebo, 5/15). In conclusion, the administration of conjugated bile acids to ascitic cirrhotic rats increased bile acid secretion, eliminated intestinal bacterial overgrowth, decreased bacterial translocation, decreased endotoxemia, and increased survival. Oral conjugated bile acids may be useful in preventing bacterial translocation, endotoxemia, and spontaneous bacterial perotonitis in cirrhotic patients.