The Effect of Early vs Delayed Initiation of Adalimumab on Remission Rates in Patients With Crohn's Disease With Poor Prognostic Factors: The MODIFY Study.

Background: Data on the effectiveness of anti-tumor necrosis factor medications in patients with Crohn's disease (CD) with poor prognostic factors (PPFs) are scarce. This study aimed to generate real-world evidence on the effect of early (≤24 months after diagnosis) vs delayed (>24 months) initiation of adalimumab (ADL) on the 26-week remission rate (Harvey-Bradshaw Index ≤4) in these patients. Methods: This multicentre, retrospective, chart review study performed in 10 Greek hospitals enrolled adult patients with moderate to severe CD (Harvey-Bradshaw Index ≥8) with ≥3 PPFs who were initiated on ADL ≥12 months before enrollment. A sample size of 164 patients (early:delayed cohort allocation ratio, 30:70) was required to address the primary endpoint. Results: Eligible patients (n = 171) were consecutively enrolled. In the early vs delayed cohorts, the 26-week remission rates (off-steroids) using the last-observation-carried-forward imputation method were 60.7% (37/61) vs 47.2% (50/106), respectively (Δ = 13.5%, P = .044). The respective remission rates were 61.2% vs 42.4% among anti-tumor necrosis factor-naive patients (P = .023) and 58.3% vs 53.2% among anti-tumor necrosis factor-experienced patients (P = .374). The 52-week remission rates using as-observed data were 78.8% and 60.3%, and the intestinal resection rates were 6.5% and 11.9% in the early vs delayed ADL cohorts, respectively. Conclusions: Patients with CD with PPFs who received early vs delayed treatment with ADL achieved higher clinical response and remission rates. This effect was more pronounced in those patients who were bio-naive and steroid-dependent/refractory with concurrent extraintestinal manifestations than those who were not.

Perioperative Use of Anti-TNFa Biological Agents in Open and Laparoscopic Surgery for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) consists of two disorders: Crohn's disease (CD) and ulcerative colitis (UC). Over the past few decades, a great body of knowledge has accumulated regarding the pathogenesis of IBD, and effective pharmaceutical agents, such as inhibitors of tumor necrosis factor (anti-TNF), have been introduced. Although these agents have dramatically improved the outcome of IBD, up to 70% of patients with CD and 10-30% of those with UC still undergo surgery within 10 years from diagnosis. Because of their young age and high recurrence rates, these patients are appropriate candidates for laparoscopic surgery as an alternative to laparotomy. Recently, considerable attention has been focused on perioperative outcomes of patients who are receiving anti-TNF agents and require surgery. The aim of this narrative review is to discuss the current evidence regarding the impact of perioperative anti-TNF treatment on post-operative complication rates with a special focus on laparoscopic surgery.

Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis.

Both Helicobacter pylori infection and metabolic syndrome present significant global public health burdens. Metabolic syndrome is closely related to insulin resistance, the major underlying mechanism responsible for metabolic abnormalities, and Helicobacter pylori infection has been proposed to be a contributing factor. There is growing evidence for a potential association between Helicobacter pylori infection and insulin resistance, metabolic syndrome and related morbidity, including abdominal obesity, type 2 diabetes mellitus, dyslipidemia, hypertension, all of which increase mortality related to cardio-cerebrovascular disease, neurodegenerative disorders, nonalcoholic fatty liver disease and malignancies. More specifically, insulin resistance, metabolic syndrome and hyperinsulinemia have been associated with upper and lower gastrointestinal tract oncogenesis. Apart from cardio-cerebrovascular, degenerative diseases and nonalcoholic fatty liver disease, a number of studies claim that Helicobacter pylori infection is implicated in metabolic syndrome-related Barrett's esophagus and esophageal adenocarcinoma development, gastric and duodenal ulcers and gastric oncogenesis as well as lower gastrointestinal tract oncogenesis. This review summarizes evidence on the potential impact of Helicobacter pylori-related metabolic syndrome on gastroesophageal reflux disease-Barrett's esophagus-esophageal adenocarcinoma, gastric atrophy-intestinal metaplasia-dysplasia-gastric cancer and colorectal adenoma-dysplasia-colorectal cancer sequences. Helicobacter pylori eradication might inhibit these oncogenic processes, and thus further studies are warranted.

Helicobacter pylori infection and esophageal adenocarcinoma: a review and a personal view.

Esophageal adenocarcinoma (EAC) is etiologically associated with gastroesophageal reflux disease (GERD). There is evidence to support the sequence GERD, Barrett's esophagus (BE), dysplasia, and finally EAC, with Helicobacter pylori (H. pylori) being implicated in each step to EAC. On the other side of this relation stands the hypothesis of the protective role of H. pylori against EAC. Based on this controversy, our aim was to review the literature, specifically original clinical studies and meta-analyses linking H. pylori infection with EAC, but also to provide our personal and others' relative views on this topic. From a total of 827 articles retrieved, 10 original clinical studies and 6 meta-analyses met the inclusion criteria. Original studies provided inconclusive data on an inverse or a neutral association between H. pylori infection and EAC, whereas meta-analyses of observational studies favor an inverse association. Despite these data, we consider that the positive association between H. pylori infection and GERD or BE, but not EAC, is seemingly a paradox. Likewise, the oncogenic effect of H. pylori infection on gastric and colon cancer, but not on EAC, also seems to be a paradox. In this regard, well-designed prospective cohort studies with a powered sample size are required, in which potential confounders should be taken into consideration since their design.

Impact of reactive oxygen species generation on Helicobacter pylori-related extragastric diseases: a hypothesis.

Helicobacter pylori (H. pylori) induces reactive oxygen species (ROS) production that contribute to pathogenesis of a variety of H. pylori-related gastric diseases, as shown in animal and human studies. Helicobacter pylori infection is also associated with variety of systemic extragastric diseases in which H. pylori-related ROS production might also be involved in the pathogenesis of these systemic conditions. We proposed that Hp-related ROS may play a crucial role in the pathophysiology of Hp-related systemic diseases including Alzheimer's disease, multiple sclerosis, glaucoma and other relative neurodegenerative diseases, thereby suggesting introduction of relative ROS scavengers as therapeutic strategies against these diseases which are among the leading causes of disability and are associated with a large public health global burden. Moreover, we postulated that H. pylori-related ROS might also be involved in the pathogenesis of extragastric common malignancies, thereby suggesting that H. pylori eradication might inhibit the development or delay the progression of aforementioned diseases. However, large-scale future studies are warranted to elucidate the proposed pathophysiological mechanisms, including H. pylori-related ROS, involved in H. pylori-associated systemic and malignant conditions.

Impact of nitroglycerin and glucagon administration on selective common bile duct cannulation and prevention of post-ERCP pancreatitis.

OBJECTIVE: Easy common bile duct (CBD) cannulation is associated with low complication rate. This study aimed to investigate the potential impact of nitroglycerin and glucagon administration on selective CBD cannulation and prevention of post-ERCP pancreatitis. METHODS: A prospective single center, double-blind randomized study in which a total of 455 patients were randomly assigned to CBD cannulation by receiving 6 puffs (2.4 mg) sublingual nitroglycerin and glucagon 1 mg intravenously (n = 227, group A) or 6 puffs sterile water and 20 mg hyoscine-n-butyl bromide intravenously (n = 228, group B). After ERCP, patients were followed for the development of drugs' side-effects and post-ERCP complications. RESULTS: There were no statistically significant differences between the two groups regarding demographic data and ERCP findings. Success rate of selective CΒD cannulation was 95.15% in group A versus 82.29% in group B (p < .001). Time required for CBD cannulation was 2.82 ± 2.31 min in group A versus 4.27 ± 3.84 min in group B (p = .021). Needle-knife papillotomy was used in 11 (4.85%) patients of group A and 39 (17.11%) patients of group B (p = .001). The frequency of post-ERCP pancreatitis was significantly lower in group A than in group B (3.08% versus 7.46%, p = .037). No difference was observed between the two groups with regard to the occurrence of post-procedure hemorrhage. There was no procedure-related mortality; no adverse event related to the combination regimen was observed. CONCLUSIONS: Combined nitroglycerin and glucagon administration achieves a high selective CBC cannulation rates with concomitant reduction of post-ERCP pancreatitis incidence. However, further relative large-scale studies are needed to confirm our findings before definite conclusions can be drawn (Clinical trial registration number: NT: 4321).

Prevalence and Characteristics of Extra-intestinal Manifestations in a Large Cohort of Greek Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Extraintestinal manifestations [EIMs] are common in inflammatory bowel disease [IBD]. Data on epidemiology and risk factors of EIMs in IBD patients are limited. The aim of this study was to investigate the prevalence of EIMs in a large cohort of Greek IBD patients and identify risk factors for their development. METHODS: The study population consisted of IBD patients, who were followed in eight tertiary Greek hospitals. Demographic and clinical characteristics of patients were analysed. The diagnosis of EIMs was based on standard criteria and on specialist consultation. RESULTS: In total, 1860 IBD patients (1001 with Crohn's disease [CD], 859 with ulcerative colitis [UC]) were registered. Among them 615 [33.1%] exhibited at least one EIM; 238 patients [38.6%] developed an EIM before IBD diagnosis. An association between active IBD and presence of an EIM was established in 61.1% of the patients. Arthritic [peripheral arthritis], mucocutaneous [erythema nodosum], and ocular [episcleritis] were the most common manifestations. EIMs were more prevalent in females, patients with CD, smokers [for all p <0.0001], patients with extensive UC [p = 0.007], and patients with a previous appendectomy [p < 0.0001] or a major IBD-related surgery [p = 0.012]. CONCLUSIONS: About one-third of Greek IBD patients developed at least one EIM. Of those, more than one-third had their EIM diagnosed before IBD, and in about two-thirds it was related to disease activity. EIMs were more frequently present in females and patients with extensive UC in multivariate analysis.

Effect of infliximab on the healing of intestinal anastomosis. An experimental study in rats.

BACKGROUND AND AIM: Infliximab is effective in the induction and maintenance of remission in Crohn's disease. Whether, the perioperative administration of anti-TNF-a compromises intestinal healing leading to anastomotic failure and increased risk of postoperative complications, remains controversial. The aim of the study was to evaluate the effect of Infliximab on intestinal anastomosis healing. METHODS: Fifty six wistar rats were divided into 4 groups: (a) 20 rats were subjected to excision of part of the terminal ileum followed by anastomosis which was evaluated on the 3rd or 7th postoperative day; (b) 20 rats received Infliximab and thereafter, the same surgical protocol as group (a) was followed; (c) 8 rats received Infliximab and served as relative control group; and (d) 8 served as absolute control group. Bursting pressure was used for testing intestinal healing. Additionally, the anastomoses were examined macroscopically, histologically and immunohistochemically for TGFb1, MMP1, MMP2 and Collagen V. The results were confirmed by Western blot analysis. RESULTS: There were no significant differences in bursting pressures and septic intra-abdominal events among non-Infliximab (a) and Infliximab-treated (b) groups. Infliximab-treated (b) group showed mild to moderate inflammation, whereas the non-Infliximab (a) group exhibited severe inflammation. Expression of TGFb1, MMP2 and collagen V was significantly higher in the Infliximab-treated (b) group. CONCLUSION: Infliximab seems to influence intestinal healing in terms of less inflammatory activity and higher tissue remodeling activity.

Isotretinoin and ulcerative colitis: A case report and review of the literature.

This case report describes a case of ulcerative colitis the onset of which occurred after the use of isotretinoin for acne treatment. Our patient, a healthy male young adult, after several months of isotretinoin use, developed gastrointestinal disorders and after thorough medical workup was diagnosed with ulcerative colitis. The literature regarding a possible correlation between isotretinoin use and ulcerative colitis is scarce. Nevertheless, recent epidemiological studies have shed more light on this possible association.