Tight control for Crohn's disease with adalimumab-based treatment is cost-effective: an economic assessment of the CALM trial.

OBJECTIVE: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective. DESIGN: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI <150, moderate: CDAI ≥150 to <300, severe: CDAI ≥300 to <450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Over 48 weeks, TC was associated with a higher clinical remission (CDAI <150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included. CONCLUSION: A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems. TRIAL REGISTRATION NUMBER: NCT01235689; Results.

Chronic cholestatic liver diseases - Primary biliary cholangitis and Primary sclerosing cholangitis.

Cholestasis is defined as hepatocyte and cholangiocyte bile excretion failure or failure of bile transport to the duodenum. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis as chronic progressive cholestatic diseases are the common reasons of chronic cholestasis. Altogether with cholestatic laboratory picture the pruritus, liver osteodystrophy and fatigue are associated symptoms in both diseases. All associated symptoms and complications are needed to be diagnosed and treated early. In case of liver cirrhosis complicatons of accompanied portal hypertension should be treated and liver transplantation must be considered in all those patients. Diagnosis of PBC is based on cholestatic laboratory features, animitochondrial antibody positivity or typical histological patern. Most patients are asymptomatic in time of diagnosis. First line therapy is ursodeoxycholic acid. In case of first line therapy failure, the prognosis is unfavourable. In this case, second line therapy must be considered. In case of PSC the diagnosis is based on MRCP finding mainly, laboratory test and liver biopsy in some cases. Progressive inflamatory and fibrosing impairment affecting intrahepatic and extrahepatict biliary ducts and strong association with inflamatory bowel disease, especially ulcerative colitis is typical for PSC. Endoscopic therapy with dilatation of dominant structure is crucial. The effect of pharmacotherapy is still being discussed and ursodeoxycholic acid could be used. During follow up patients are in the risk of bacterial cholangitis and malignant tumor development (cholangiogenic and colorectal carcinoma mainly). In PSC patients the severe pruritus and reccurent bacterial cholangitis could be an indication for the liver transplantation.

Bleeding in portal hypertension.

Liver cirrhosis is the most common reason of clinically significant portal hypertension in the western countries. Portal vein or hepatic veins thrombosis is less common. Variceal bleeding is the most severe life threatening complication of portal hypertension. Appropriate treatment includes initial general management, fluid replacement and hemosubstitution, antibiotic prophylaxis, vasoactive medication and endoscopic treatment. Transjugular intrahepatic portosystemic shunt (TIPS) is standard option in case of first line treatment failure. Dedicated esophageal metal stent or balloon tamponade could be used as a bridge to the TIPS or in case of TIPS contraindication. Non selective beta-blockers and endoscopic therapy are used in primary and secondary prophylaxis.

Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. METHODS: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNFα treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7·5 mg, 22·5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks. Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score ≤2 with no individual subscore >1 and rectal bleeding subscore ≤1) at week 12. The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted. This study is registered with ClinicalTrials.gov, number NCT01620255. FINDINGS: Between Nov 2, 2012, and Feb 4, 2016, we screened 587 patients; 357 were eligible and randomly assigned to receive placebo (n=73) or PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70). Remission rates at week 12 were significantly greater in three of four active-treatment groups than in the placebo group (2·7% [two of 73]): 7·5 mg (11·3% [eight of 71]), 22·5 mg (16·7% [12 of 72]), 75 mg (15·5% [11 of 71]), and 225 mg (5·7% [four of 70]). These rates corresponded to a stratum-adjusted (anti-TNFα-naive and anti-TNFα-experienced) risk difference versus placebo of 8·0% for 7·5 mg (90% CI 1·9 to 14, p=0·0425), 12·8% for 22·5 mg (5·6 to 19·9, p=0·0099), 11·8% for 75 mg (4·8 to 18·8, p=0·0119), and 2·6% for 225 mg (-1·2 to 6·4, p=0·1803). Four of 73 (5·5%) patients had a serious adverse event in the placebo group, ten of 71 (14·1%) in the 7·5 mg group, one of 70 (1·4%) in the 22·5 mg group, three of 73 (4·1%) in the 75 mg group, and three of 70 (4·3%) in the 225 mg group. No safety signal was observed for the study drug. INTERPRETATION: PF-00547659 was safe and well tolerated in this patient population, and better than placebo for induction of remission in patients with moderate to severe ulcerative colitis. The greatest clinical effects were observed with the 22·5 mg and 75 mg doses. FUNDING: Pfizer.

Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

BACKGROUND: Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. METHODS: CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 µg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week). De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met. The primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers 48 weeks after randomisation. Primary and safety analyses were done in the intention-to-treat population. This trial has been completed, and is registered with ClinicalTrials.gov, number NCT01235689. FINDINGS: Between Feb 11, 2011, and Nov 3, 2016, 244 patients (mean disease duration: clinical management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group). 29 (24%) patients in the clinical management group and 32 (26%) patients in the tight control group discontinued the study, mostly because of adverse events. A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 (56 [46%] of 122 patients) than in the clinical management group (37 [30%] of 122 patients), with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1% (95% CI 3·9-28·3; p=0·010). 105 (86%) of 122 patients in the tight control group and 100 (82%) of 122 patients in the clinical management group reported treatment-emergent adverse events; no treatment-related deaths occurred. The most common adverse events were nausea (21 [17%] of 122 patients), nasopharyngitis (18 [15%]), and headache (18 [15%]) in the tight control group, and worsening Crohn's disease (35 [29%] of 122 patients), arthralgia (19 [16%]), and nasopharyngitis (18 [15%]) in the clinical management group. INTERPRETATION: CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone. Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability. FUNDING: AbbVie.

Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn's disease and ulcerative colitis.

OBJECTIVE: The infliximab biosimilar CT-P13 (Remsima(®), Inflectra(®)) was approved in Europe for the treatment of inflammatory bowel disease (IBD) based on extrapolation of data from patients with rheumatic disease. Because there are limited published reports on clinical outcomes for IBD patients treated with CT-P13, we monitored responses to induction treatment with this biosimilar in patients with Crohn's disease (CD) or ulcerative colitis (UC) in centres across the Czech Republic. MATERIAL AND METHODS: Fifty-two patients with CD (n = 30) or UC (n = 22) were treated with 5 mg/kg CT-P13 for up to 14 weeks. Effectiveness of therapy was evaluated with the Crohn's Disease Activity Index (CDAI) or the Mayo Scoring System (MSS) in patients with CD or UC, respectively, before and after 14 weeks. Additional goals were to evaluate weight changes, serum C-reactive protein (CRP) levels, and complications/adverse events. RESULTS: In patients with CD, remission (CDAI <150) was achieved in 50.0% of cases, and partial response (≥70-point decrease in CDAI score from baseline) in the remaining 50.0%. In patients with UC, remission (total score on partial Mayo index ≤2 points) was achieved in 40.9% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 54.5%, and no response in 4.5%. There were statistically significant improvements in CDAI, MSS and CRP serum levels after 14 weeks of therapy, and body weight increased. Four adverse events were identified (n = 1 each): lower-extremity phlebothrombosis, herpes labialis, pneumonia and allergic reaction. CONCLUSIONS: This prospective observational study provides evidence of the effectiveness of CT-P13 in IBD.

Clinical Trial: A Pragmatic Randomised Controlled Study to Assess the Effectiveness of Two Patient Management Strategies in Mild to Moderate Ulcerative Colitis-The OPTIMISE Study.

Background: Current management of mild-to-moderate ulcerative colitis (UC) involves monitoring clinical markers of disease activity, such as stool frequency (SF) and rectal bleeding (RB), and adjusting treatment accordingly. Our aim was to assess whether targeting treatment based on faecal calprotectin (FC) levels (treat-to-target; T2T) provides greater UC disease control versus a symptom-based approach. Methods: This was a pragmatic, randomised (1:1) controlled study of patients with mild-to-moderate UC (global Mayo score 2-6) treated with ≤2.4 g/day 5-aminosalicylic acid that compared the effectiveness of two management strategies with (interventional arm) and without (reference arm) FC home monitoring over 12 months of follow-up. Treatment was optimised in the interventional arm using FC values and clinical symptoms (PRO-2), while the reference arm used only PRO-2. Results: 193 patients completed the study. No significant difference was found for the primary endpoint (Mayo Endoscopic Subscore [MES] = 0 at 12 months). A numerical advantage for the interventional arm over the reference arm for the primary endpoint (37.0% vs. 33.4%, respectively) and for MES ≤ 1, RB = 0, and SF ≤ 1 at 12 months was found following imputation for missing data. The composite endpoint of MES = 0, RB = 0, and SF ≤ 1 at 12 months was achieved at a significantly higher rate in the interventional arm than the reference arm (effect size [ES]: 0.17, 95% CI 0.02-0.32; p < 0.05). A similar result was obtained for MES ≤ 1, RB = 0 and SF ≤ 1 (ES: 0.22; 95% CI 0.07-0.37; p < 0.05). Conclusions: T2T using FC monitoring was effective in patients with mild-to-moderate UC at 12 months. Further longer-term studies are required to confirm the results.

[Cystic polyposis of the stomach (fundic gland polyps)--relationship to the absence of Helicobacter pylori infection and a therapy with drugs suppressing gastric acidity]. / Cystická polypóza zaludku (polypy ze zlázek fundu)--vztah k neprítomnosti infekce Helicobacter pylori a k uzívání léku snizujících zaludecní aciditu.

BACKGROUND: Cystic gastric polyps (fundic gland polyps) have been diagnosed relatively frequently in recent years. The aim of the study was to assess their incidence and relation to possible etiological factors reported in the literature. MATERIAL AND METHODS: Over a 5 year period, we have endoscopically and histologically proved cystic polyps in 32 patients. All were examined for Helicobacter pylori infection using either the invasive rapid test, histological examination or 13C urea breath test. RESULTS: Cystic gastric polyps were found significantly more frequently in women (27) than in men (5). All patients were treated with long-term medication suppressing gastric acidity (26 patients with proton pump inhibitors, and 6 with H2 receptor blockers). Helicobacter pylori infection was not detected in either of the patients with proven cystic gastric polyps. Cystic gastric polyps have not the typical clinical picture and they are largely found incidentally during gastroscopic examination, especially in patients with reflux esophagitis or functional dyspepsia. CONCLUSION: The results confirm evidence in the literature of a close relation between cystic gastric polyps and intensive suppressive treatment of gastric acidity, particularly in combination with the current absence of Helicobacter pylori infection. Precise explanation of this relation and the etiology of cystic gastric polyps is still missing. Important is the fact that the literature reports do not indicate a risk of malignant transformation.

Influence of the secondary deployment of expanded polytetrafluoroethylene-covered stent grafts on maintenance of transjugular intrahepatic portosystemic shunt patency.

PURPOSE: To evaluate the effects of secondary deployment of expanded polytetrafluoroethylene (ePTFE)-covered stent grafts in the treatment of dysfunctional transjugular intrahepatic portosystemic shunts (TIPSs) in comparison with other common approaches (conventional angioplasty or implantation of bare metal stents). MATERIALS AND METHODS: A retrospective review of 121 dysfunctional bare metal TIPS presenting between 2000 and 2004 was conducted. The group was divided into four subgroups according to the type of intervention: conventional angioplasty (52 cases; 43%), bare metal stent deployment (35 cases; 28.9%), nondedicated ePTFE-covered stent-graft deployment (15 cases; 12.4%), and dedicated ePTFE-covered stent-graft deployment (19 cases; 15.7%). In all four groups, the primary patency after the specific intervention was calculated and mutually compared. RESULTS: Primary patency rates after 12 and 24 months were 49.7% and 25.3%, respectively, in conventional angioplasty; 74.9% and 64.9%, respectively, with bare metal stents; 75.2% and 64.5%, respectively, with nondedicated ePTFE-covered stent grafts; and 88.1% and 80.8%, respectively, with dedicated ePTFE-covered stent grafts. CONCLUSIONS: In the treatment of dysfunctional TIPS, better patency after the intervention was obtained by deploying dedicated ePTFE-covered stent grafts in comparison with conventional angioplasty, bare metal stents, and nondedicated ePTFE-covered stents.

Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding.

Administration of nonselective beta-blockers in prophylaxis of first variceal bleeding is not suitable for all patients. Thus, we evaluated endoscopic variceal band ligation (EVBL) in primary prevention of bleeding in patients with cirrhosis and large esophageal varices. A total of 73 consecutive patients with liver cirrhosis and large esophageal varices without a history of gastrointestinal bleeding were randomized to receive either EVBL or propranolol and were followed for up to 18 months. Forty patients underwent EVBL and 33 patients received propranolol. Variceal bleeding occurred in 2 patients in the EVBL (5%) and in 2 patients in the propranolol group (6%, NS). The 18 month actuarial risk for first variceal bleed was 5% in the EVBL (95% CI, 0-12%) and 20% in the propranolol group (95% CI, 0-49%, NS). The actuarial probability of death at 18 months of follow-up was 5% (95% CI, 0-11%) in the EVBL group and 7% (95% CI, 0-17%, NS) in the propranolol arm. In conclusion, EVBL was an effective and safe alternative to propranolol in primary prophylaxis of bleeding in patients with large esophageal varices.

Mucosal healing is not associated with better outcome during 7 years of follow-up in pediatric patients with Crohn's disease.

BACKGROUND: Mucosal healing (MH) has become a perspective treatment target in patients with Crohn's disease (CD). Data about the impact of MH on long-term outcome in pediatric patients are still scarce. METHODS: 76 pediatric patients with CD were evaluated retrospectively (2000-2015) in a tertiary care center. Based on MH achievement, they were divided into two groups (MH, n= 17; and No MH, n=59). The primary endpoint was to assess the association of MH and the need for CD-related hospitalizations or surgery in pediatric patients with CD. RESULTS: The number of hospitalized patients was 24% in the MH group and 42% in the No MH group, P = 0.26. The total number of CD-related hospitalizations was not significant between the MH group and the No MH group (5 vs. 41, P = 0.15). The time to the first hospitalization was 24 months in MH and 21 months in No MH, P>0.99. 24% patients in the MH group and 39% patients in the No MH group underwent CD-related operation, P = 0.39. Time to the first operation was 43 months for MH and 19 months for the No MH group, P = 0.13. The follow-up period was 91 months in the MH group and 80 months in the No MH group, P = 0.74. The use of infliximab was positively associated with MH, P = 0.002. CONCLUSIONS: MH was not associated with fewer CD-related hospitalizations or operations in pediatric patients with CD during seven years of follow-up.

Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II.

BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.

A Global, Prospective, Observational Study Measuring Disease Burden and Suffering in Patients with Ulcerative Colitis Using the Pictorial Representation of Illness and Self-Measure Tool.

BACKGROUND: The understanding the Impact of ulcerative COlitis aNd Its assoCiated disease burden on patients study [ICONIC] was a 2-year, global, prospective, observational study evaluating the cumulative burden of ulcerative colitis [UC] using the Pictorial Representation of Illness and Self-Measure [PRISM] tool that is validated to measure suffering, but not previously used in UC. METHODS: ICONIC enrolled unselected outpatient clinic attenders with recent-onset UC. Patient- and physician-reported outcomes including PRISM, the Short Inflammatory Bowel Disease Questionnaire [SIBDQ], the Patient Health Questionnaire [PHQ-9], and the Simple Clinical Colitis Activity Indexes [patient: P-SCCAI; physician: SCCAI] were collected at baseline and follow-up visits every 6 months. Correlations between these measures were assessed using Spearman's rank correlation coefficient. RESULTS: Overall, 1804 evaluable patients had ≥1 follow-up visit. Over 24 months, mean [SD] disease severity measured by P-SCCAI/SCCAI reduced significantly from 4.2 [3.6]/3.0 [3.0] to 2.4 [2.7]/1.3 [2.1] [p<0.0001]. Patient-/physician-assessed suffering, quantified by PRISM, reduced significantly over 24 months [p<0.0001]. SCCAI/P-SCCAI, and patient-/physician-assessed PRISM, showed strong pairwise correlations [rho ≥0.60, p<0.0001], although physicians consistently underestimated these disease severity and suffering measures compared with patients. Patient-assessed PRISM moderately correlated with other outcome measures, including SIBDQ, PHQ-9, P-SCCAI, and SCCAI (rho = ≤-0.38 [negative correlations] or ≥0.50 [positive correlations], p<0.0001). CONCLUSION: Over 2 years, disease burden and suffering, quantified by PRISM, improved in patients with relatively early UC. Physicians underestimated burden and suffering compared with patients. PRISM correlated with other measures of illness perception in patients with UC, supporting its use as an endpoint reflecting patient suffering.

Spontaneous bacterial peritonitis in the Czech Republic: prevalence and aetiology.

The aim of the study was to determine the prevalence and detailed data concerning the incidence of spontaneous bacterial peritonitis in the Czech Republic. Ninety-nine patients with liver cirrhosis and ascites were examined. Spontaneous bacterial peritonitis was diagnosed in 35 patients (35.4%). It was revealed more often in patients with alcoholic aetiology of cirrhosis whose anamnesis involved sub-febrile or febrile states and the deterioration of ascites. Elevated serum leucocyte counts and increased levels of C-reactive protein can contribute to the diagnosis. A low level of total protein and albumin in ascites predisposes to the increase of this infection. The reduction of the platelet count in a set of patients with spontaneous bacterial peritonitis indicates the influence of portal hypertension in the aetiology of the disease.

Transduodenal intraluminal high dose rate brachytherapy in the treatment of carcinomas of the subhepatic region.

BACKGROUND/AIMS: The prognosis of carcinomas of the subhepatic region is poor, and therapeutic efforts are limited mostly to palliation. The aim of this study was to retrospectively evaluate the effectiveness of transduodenal administration of intraluminal high dose rate brachytherapy in the palliative treatment of bile duct and pancreatic head carcinomas. METHODOLOGY: Twelve patients with inoperable bile duct and pancreatic head carcinomas were treated by transduodenal brachytherapy using high dose rate remote afterloading system. Eleven patients were treated by intraluminal brachytherapy inserted via a nasobiliary drain and one patient by intraluminal brachytherapy via a nasopancreatic drain inserted in the duct of Wirsung. RESULTS: After transduodenal intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated with the mean survival of 284 days. CONCLUSIONS: Transduodenal intraluminal brachytherapy is technically feasible. The addition of intraluminal brachytherapy may be beneficial to patients in whom drainage can be established. Transduodenal insertion of brachytherapy is not competitive to the percutaneous approach but spreads the possibilities of the treatment of bile duct carcinoma. Intraluminal brachytherapy of pancreatic head carcinoma is feasible only via transduodenal approach.

A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn's disease.

UNLABELLED: CCX282-B, also called vercirnon, is a specific, orally-administered chemokine receptor CCR9 antagonist that regulates migration and activation of inflammatory cells in the intestine. This randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of CCX282-B in 436 patients with Crohn's disease. Crohn's Disease Activity Index (CDAI) scores were 250-450 and C-reactive protein >7.5 mg/L at study entry. In addition to stable concomitant Crohn's medication (85% of subjects), subjects received placebo or CCX282-B (250 mg once daily, 250 mg twice daily, or 500 mg once daily) for 12 weeks. They then received 250 mg CCX282-B twice daily, open-label, through week 16. Subjects who had a clinical response (a ≥ 70 point drop in CDAI) at week 16 were randomly assigned to groups given placebo or CCX282-B (250 mg, twice daily) for 36 weeks. Primary endpoints were clinical response at Week 8 and sustained clinical response at Week 52. During the 12-week Induction period, the clinical response was highest in the group given 500 mg CCX282-B once daily. Response rates at week 8 were 49% in the placebo group, 52% in the group given CCX282-B 250 mg once daily (odds ratio [OR] = 1.12; p = .667 vs placebo), 48% in the group given CCX282-B 250 mg twice daily (OR = 0.95; p = .833), and 60% in the group given CCX282-B 500 mg once daily (OR = 1.53; p = .111). At week 12, response rates were 47%, 56% (OR = 1.44; p = .168), 49% (OR = 1.07; p = .792), and 61% (OR = 1.74; p = .039), respectively. At the end of the Maintenance period (week 52), 47% of subjects on CCX282-B were in remission, compared to 31% on placebo (OR = 2.01; p = .012); 46% showed sustained clinical responses, compared to 42% on placebo (OR = 1.14; p = .629). CCX282-B was well tolerated. Encouraging results from this clinical trial led to initiation of Phase 3 clinical trials in Crohn's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00306215.

Management of acute variceal bleeding.

Portal hypertension as a consequence of liver cirrhosis is responsible for its most common complications: ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy and the most important one--variceal hemorrhage. Variceal bleeding results in considerable morbidity and mortality. This review covers all areas of importance in the therapy of acute variceal hemorrhage--endoscopic and pharmacological treatment, transjugular intrahepatic portosystemic shunt, surgery and balloon tamponade. Indications and limitations of these therapeutic modalities are widely discussed.

TIPS creation in a patient with situs inversus totalis.

We describe the successful creation of a transjugular intrahepatic portosystemic shunt (TIPS) in a patient with complete situs inversus using a simple modification of the standard TIPS technique.