Vermeire S.,Catholic University of Leuven |
Sandborn W.J.,University of California at San Diego |
Danese S.,University of Milan |
Hebuterne X.,University of Nice Sophia Antipolis |
And 17 more authors.
The Lancet | Year: 2017
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. © 2017 Elsevier Ltd.
PubMed | Pontifical Catholic University of Parana and Gastroenterology Center
Type: Journal Article | Journal: Endoscopy international open | Year: 2016
Celiac disease (CD) is a chronic systemic autoimmune disorder affecting genetically predisposed individuals, triggered and maintained by the ingestion of gluten. Triggered and maintained by the ingestion of gluten, celiac disease is a chronic systemic autoimmune disorder affecting genetically predisposed individuals. Persistent related inflammation of the duodenal mucosa causes atrophy architecture detectable on esophagogastroduodenoscopy (EGD) and histopathology. We investigated the association between endoscopic features and histopathological findings (Marsh) for duodenal mucosa in celiac disease patients and propose an endoscopic classification of severity.Between January 2000 and March 2010, an electronic database containing 34,540 EDGs of patients aged >14 years was searched for cases of CD. Out of 109 cases, 85 met the inclusion criteria: conventional EGD combined with chromoendoscopy, zoom and biopsy. EGD types 0, I and II corresponds to Marsh grades 0, 1 and 2, respectively, while EGD type III corresponds to Marsh grade 3 and 4.Five patients (5.8%) were EGD I but not Marsh grade 1; 25 patients (29.4%) were EGD II, 4 of whom (16%) were classified as Marsh grade2; and 55 patients (64.7%) were EGD III, 51 (92.7%) of whom were classified as Marsh grades 3 and 4. The Spearman correlation coefficient (r=0.33) revealed a significant association between the methods (P=0.002).Changes in the duodenal mucosa detected on EGD were significantly and positively associated with histopathologic findings. The use of chromoendoscopy in addition to conventional EGD enhances changes in the duodenal mucosa and permits diagnosis of CD, even in routine examinations. The proposed endoscopic classification is practical and easily reproducible and provides valuable information regarding disease extension.
Hlavaty T.,University Hospital Bratislava Ruzinov |
Batovsky M.,University Hospital Bratislava |
Balakova D.,Comenius University |
Pav I.,University Hospital Bratislava |
And 12 more authors.
Bratislava Medical Journal | Year: 2013
Background and aims: The thiopurine drugs, azathioprine (AZA) and 6-mercaptopurine, are established in the treatment of inflammatory bowel diseases (IBD). Polymorphisms in thiopurine S-methyltransferase (TPMT) gene have been associated with adverse drug reactions (ADRs) to AZA. Methods: The aim of this study was to evaluate TPMT polymorphisms and AZA-related toxicity in a Slovak cohort of 220 IBD patients treated with AZA. In every patient, the dose and duration of AZA therapy, concomitant 5-aminosalicylate (5-ASA) medication, frequency, type, time to onset, dose of ADR and concomitant 5-ASA at the onset of ADR were recorded. Each patient was also genotyped for the presence of variant TPMT alleles (*2,*3A,*3B,*3C). Frequency, type and circumstances of ADRs were compared according to TPMT status. Results: Of the 220 patients, 205 (93.2 %) were wild-type (TPMT*1/*1), one (0.5%) carried a TPMT*1/*3C allele, 13 (5.9 %) carried TPMT *1/*3A allele and one was homozygous for TMPT *3A allele. No TPMT *2 mutation was found. The incidence of adverse drug reactions was 62/205 (30.2 %) in the wild-type group as compared to 13/15 (86.7 %) in the TPMT mutation group, p=2.10-5. Leukopenia (WBC< 3.0*10^9/L) occurred in 21/205 (10.2 %) patients with wild type TPMT versus 11/15 (73.3 %) patients with TPMT mutations, p=0.000001. There was no significant difference between TMPT groups in gastrointestinal or other ADRs. No impact of 5-ASA on the incidence and severity of AZA adverse drug reactions was observed. Conclusion: The incidence of leukopenia in TPMT mutant patients was significantly higher and more severe as compared to TPMT wild type patients. We observed no impact of concomitant 5-ASA therapy on AZA induced toxicity.
Gotoda T.,National Cancer Center Hospital |
Iwasaki M.,Research Center for Cancer Prevention and Screening |
Kusano C.,National Cancer Center Hospital |
Seewald S.,Gastroenterology Center |
Oda I.,National Cancer Center Hospital
British Journal of Surgery | Year: 2010
Background: Criteria for endoscopic resection in patients with early gastric cancer (EGC) have been expanded recently by the National Cancer Centre (NCC). This study compared long-term outcomes in patients with EGC who underwent endoscopic treatment according to guideline criteria with those treated according to expanded criteria. Methods: Baseline and outcome data from patients undergoing curative endoscopic resection for EGC between January 1999 and December 2005 were collected from electronic medical records. Survival time hazard ratios and 95 per cent confidence intervals were calculated using the Cox proportional hazards model. Results: Of 1485 patients who had a curative resection, 635 (42.8 per cent) underwent resection according to traditional criteria and 625 (42.1 percent) according to expanded criteria. There was no significant difference in overall survival between the groups. Conclusion: Patients who have treatment following the expanded criteria have similar long-term survival and outcomes to those treated according to guideline criteria. Copyright © 2010 British Journal of Surgery Society Ltd.
Behlul B.,Tekden Hospital |
Ayfer S.,Ege University |
Sezgin V.,Izmir Kâtip Celebi University |
Altay K.,Izmir Kâtip Celebi University |
And 8 more authors.
Przeglad Gastroenterologiczny | Year: 2014
Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is used in the diagnosis and therapy of biliary tract diseases. The ERCP is an invasive procedure that does not increase complications in the elderly. Few studies have assessed the safety of ERCP in the elderly. Life expectancy is rising, which causes an increasing demand for ERCP in the elderly. Aim: To show that therapeutic ERCP is safe and we compared the level of complications among the elderly (> 80 years of age) and the level among a younger group (< 65 years of age). Material and methods: The study was designed retrospectively. The details of all patients 80 years of age and older undergoing ERCP were analysed. One hundred and fifty patients were included in each of the groups: > 80 years of age, older group A; and < 65 years of age, younger group B. Results: In group A, 4 cases (2.7%) of bleeding (all mild) was observed, and perforation was not observed. The ERCP-related mild pancreatitis was observed in 7 patients (4.6%). There were no cases of mortality during procedures of ERCP in group A. In group B 6 bleeding cases (4%) (all mild) were observed. Perforation was not observed in group B. ERCP-related mild pancreatitis occurred in 11 patients (7.3%). There were no cases of mortality during procedures of ERCP in group B. Our study showed that ERCP is a safe and effective procedure in elderly patients. Conclusions: Outcomes of ERCP for diagnostic and therapeutic success, and complication rates, are similar to those in younger patients. The ERCP is effective and safe in the elderly. © 2014 Termedia Sp. z o.o. All rights reserved.
PubMed | Izmir University, Tekden Hospital, Ege University, Ataturk Government Hospital and 2 more.
Type: Journal Article | Journal: Przeglad gastroenterologiczny | Year: 2014
Endoscopic retrograde cholangiopancreatography (ERCP) is used in the diagnosis and therapy of biliary tract diseases. The ERCP is an invasive procedure that does not increase complications in the elderly. Few studies have assessed the safety of ERCP in the elderly. Life expectancy is rising, which causes an increasing demand for ERCP in the elderly.To show that therapeutic ERCP is safe and we compared the level of complications among the elderly (> 80 years of age) and the level among a younger group (< 65 years of age).The study was designed retrospectively. The details of all patients 80 years of age and older undergoing ERCP were analysed. One hundred and fifty patients were included in each of the groups: > 80 years of age, older group A; and < 65 years of age, younger group B.In group A, 4 cases (2.7%) of bleeding (all mild) was observed, and perforation was not observed. The ERCP-related mild pancreatitis was observed in 7 patients (4.6%). There were no cases of mortality during procedures of ERCP in group A. In group B 6 bleeding cases (4%) (all mild) were observed. Perforation was not observed in group B. ERCP-related mild pancreatitis occurred in 11 patients (7.3%). There were no cases of mortality during procedures of ERCP in group B. Our study showed that ERCP is a safe and effective procedure in elderly patients.Outcomes of ERCP for diagnostic and therapeutic success, and complication rates, are similar to those in younger patients. The ERCP is effective and safe in the elderly.
Kreisel W.,University Hospital Freiburg |
Deibert P.,University Hospital Freiburg |
Kupcinskas L.,Lithuanian University of Health Sciences |
Sumskiene J.,Lithuanian University of Health Sciences |
And 11 more authors.
Digestive and Liver Disease | Year: 2015
Background: Phosphodiesterase-5-inhibitors may lower portal pressure. Aims: To investigate the effect of the phosphodiesterase-5-inhibitor udenafil on hepatic and systemic haemodynamics in liver cirrhosis. Methods: In an open-label phase-II-study, patients with liver cirrhosis Child A/B and hepatic venous pressure-gradient ≥12. mmHg received 12.5 mg/day, 25 mg/day, 50 mg/day, 75. mg/day (n= 5, each), or 100. mg/day (n= 10) udenafil p.o. for one week. On days 0 and 6, hepatic venous pressure-gradient was measured prior to and one hour after drug ingestion. Endpoints were reduction of hepatic venous pressure-gradient from day 0 pre to day 6 post intake and reduction in the acute setting. Pharmacokinetics were measured in the two lowest dosage groups. Results: Combining the 75 and 100mg/day groups hepatic venous pressure-gradient reduction after drug intake was 19.9% (p=0.0006) on day 0. From day 0 pre-dose to day 6 post-dose hepatic venous pressure-gradient decreased by 15.7% (p=0.040) and in 5/15 patients by ≥20% or to <12 mmHg. In the 100 mg/day group, mean arterial pressure decreased from 98.9mmHg by 6.2mmHg (p=0.037) from day 0 pre-dose to day 6 post-dose. Heart rates or electrocardiograms were unchanged. Udenafil was eliminated with t1/2=25 h. Conclusions: Oral application of 75-100. mg of the phosphodiesterase-5-inhibitor udenafil lowers portal pressure in the acute setting by about 20% without relevant systemic cardiovascular side effects. © 2014 Editrice Gastroenterologica Italiana S.r.l.
Gockel I.,Johannes Gutenberg University Mainz |
Muller M.,Gastroenterology Center |
Schumacher J.,University of Bonn
Deutsches Arzteblatt International | Year: 2012
Introduction: Many physicians are inadequately familiar with the clinical features of achalasia. Often, it is not diagnosed until years after the symptoms arise. This is unfortunate, because a delay in diagnosis worsens the prognosis. Methods: Selective review of the literature. Results: Achalasia has a lifetime prevalence of 1:10 000. It is a neurodegenerative disorder in which the neurons of the myenteric plexus are lost, leading to dysfunction of the lower esophageal sphincter and to a derangement of esophageal peristalsis. In the final stage of achalasia, esophageal motility is irreversibly impaired, and complications ensue because of the retention of food that is no longer transported into the stomach. Aspiration causes pulmonary disturbances in up to half of all patients with achalasia. There may also be inflammation of the esophageal mucosa (retention esophagitis); this, in turn, is a risk factor for esophageal cancer, which arises in 4% to 6% of patients. The cause of achalasia is not fully known, but autoimmune processes appear to be involved in patients with a genetic susceptibility to the disease. Conclusion: Achalasia should be diagnosed as early as possible, so that complications can be prevented. In addition, guidelines should be established for cancer prevention in achalasia patients. Currently ongoing studies of the molecular causes of achalasia will probably help us understand its pathophysiology.
Lender N.,Princess Alexandra Hospital |
Lender N.,University of Queensland |
Talley N.J.,University of Newcastle |
Enck P.,University of Tübingen |
And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2014
Background There is emerging debate over the effect of Helicobacter pylori infection on body mass index (BMI). A recent study demonstrated that individuals who underwent H. pylori eradication developed significant weight gain as compared to subjects with untreated H. pylori colonisation. Aim To elucidate the association between H. pylori colonisation and the prevalence of overweight and obesity in developed countries. Methods The literature was searched for publications reporting data on H. pylori prevalence rates and obesity prevalence rates. Studies selected reported H. pylori prevalence in random population samples with sample sizes of more than 100 subjects in developed countries (GDP >25 000 US$/person/year). Corresponding BMI distributions for corresponding countries and regions were identified. Nonparametric tests were used to compare the association between H. pylori and overweight and obesity rates. Results Forty-nine studies with data from 10 European countries, Japan, the US and Australia were identified. The mean H. pylori rate was 44.1% (range 17-75%), the mean rates for obesity and overweight were 46.6 (±16)% and 14.2 (±8.9)%. The rate of obesity and overweight were inversely and significantly (r = 0.29, P < 0.001) correlated with the prevalence of H. pylori infection. Conclusions There is an inverse correlation between H. pylori prevalence and rate of overweight/obesity in countries of the developed world. Thus, the gradual decrease of the H. pylori colonisation that has been observed in recent decades (or factors associated with decrease of) could be causally related to the obesity endemic observed in the Western world. © 2014 John Wiley & Sons Ltd.
Wahab M.A.,Gastroenterology Center |
Fathy O.,Gastroenterology Center |
Elhanafy E.,Gastroenterology Center |
Atif E.,Gastroenterology Center |
And 5 more authors.
Hepato-Gastroenterology | Year: 2011
Background/Aims: Hepatocellular carcinoma (HCC) originating in the caudate lobe is rare, and the treatment for this type of carcinoma is a complex surgical procedure. We aimed to evaluate the surgical outcomes after isolated caudate lobe resection for HCC. Methodology: We retrospectively analyzed 30 consecutive patients with HCC originating in the caudate lobe who underwent isolated caudate lobe resection. Results: Thirty patients underwent caudate lobe resection for HCC. The main sites of the tumors were located in the Spiegel lobe, the paracaval portion and caudate process. The surgical margin was tumor negative in all of the patients. The median tumor size was 4.3cm. The mean operative time was 230±50min and the intraoperative blood loss was 1200±200mL. The hospital morbidity rate was 33%. There was no postoperative mortality. The mean survival rate was 25.3+11.7 months. The overall survival rates were 62%, 34% and 11% at 1, 3 and 5 years, respectively. The disease free survival rate after isolated caudate lobectomy was 31% at 3 years. Recurrence was noted in 12 patients (40%). Eleven patients were identified as having intrahepatic recurrences and 1 patient as having peritoneal dissemination. Conclusions: Isolated caudate lobe resection is a feasible procedure and can be undertaken with low morbidity and nil mortality. Careful technique and detailed anatomic knowledge of the caudate lobe are essential for this procedure. © H.G.E. Update Medical Publishing S.A.