Systematic review with meta-analysis: endoscopic balloon dilatation for Crohn's disease strictures.

BACKGROUND: Endoscopic balloon dilatation (EBD) is recognised treatment for symptomatic Crohn's strictures. Several case series report its efficacy. A systematic analysis for overall efficacy can inform the design of future studies. AIM: To examine symptomatic (SR) and technical response (TR) and adverse events (AE) of EBD. Stricture characteristics were also explored. METHODS: A systematic search strategy of COCHRANE, MEDLINE and EMBASE was performed. All original studies reporting outcomes of EBD for Crohn's strictures were included. SR was defined as obstructive symptom-free outcome at the end of follow-up, TR as post-dilatation passage of the endoscope through a stricture, and adverse event as the presence of complication (perforation and/or bleeding). Pooled event rates across studies were expressed with summative statistics. RESULTS: Twenty-five studies included 1089 patients and 2664 dilatations. Pooled event rates for SR, TR, complications and perforations were 70.2% (95% CI: 60-78.8%), 90.6% (95% CI: 87.8-92.8%), 6.4% (95% CI: 5.0-8.2) and 3% (95% CI: 2.2-4.0%) respectively. Cumulative surgery rate at 5 year follow-up was 75%. Pooled unweighted TR, SR, complication, perforation and surgery rates were 84%, 45%, 15%, 9% and 21% for de novo and 84%, 58%, 22%, 5% and 32% for anastomotic strictures. Outcomes between two stricture types were no different on subgroup meta-analysis. CONCLUSIONS: Efficacy and complication rates for endoscopic balloon dilatation were higher than previously reported. From the few studies with 5 year follow-up the majority required surgery. Future studies are needed to determine whether endoscopic balloon dilatation has significant long-term benefits.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease.

Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory adipokine, functions via leptin receptors, signaling via the long isoform of receptor, LepRb. Leptin promotes DC maturation and increases CCR7 expression on blood DC. Increased mesenteric fat and leptin occur early in Crohn's disease (CD), suggesting leptin-mediated change in intestinal CCR7 expression on DC as a pro-inflammatory mechanism. We have demonstrated CCR7 expression and capacity to migrate to its ligand macrophage inflammatory protein 3ß in normal human ileal DC but not colonic or blood DC. In CD, functional CCR7 was expressed on DC from all sites. Only DC populations containing CCR7-expressing cells produced LepRb; in vitro exposure to leptin also increased expression of functional CCR7 in intestinal DC in a dose-dependent manner. In conclusion, leptin may regulate DC migration from gut, in homeostatic and inflammatory conditions, providing a link between mesenteric obesity and inflammation.

Systematic review of abdominal surgery for chronic idiopathic constipation.

AIM: Constipation is a common problem which increases in prevalence with age. Chronic constipation is complex and difficult to treat. Some patients will not respond to pharmacological therapy and therefore surgery may be considered. A systematic review of the literature was performed to determine the outcome of surgery. METHOD: Published papers were identified by a search of The Cochrane Library, MEDLINE, CINAHL and EMBASE. They were reviewed and the data were extracted. RESULTS: Forty-eight papers were identified, including 1443 patients. Eleven different procedures were described. There was inconsistency in reporting. In 65% of patients the mean frequency of defaecation increased from 1.1 to 19.7 evacuations per week. Where laxative usage was reported (971 patients), it was found that 88% of patients did not need them postoperatively. Early complications included ileus (0-16%), infection (0-13%) and anastomotic leakage (0-22%). Patient satisfaction and quality of life scores were high. Only 30% of studies included data on preoperative psychological assessment. CONCLUSION: Surgery improves constipation and is associated with a higher degree of patient satisfaction, but the quality of studies was very variable. Future controlled trials should examine the ideal therapeutic approach for different patient groups.

Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England.

BACKGROUND: Infliximab is used for treatment of Crohn's disease and, following the Active Ulcerative Colitis Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerative colitis (UC). AIM: To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC. METHODS: A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroenterologists from six English centres. RESULTS: Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing response (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4-59), with 21 (55.3%) being in remission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an average of 10 months (range 8-13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurred in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-severe adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media. CONCLUSION: Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC.

Review article: the psychoneuroimmunology of irritable bowel syndrome--an exploration of interactions between psychological, neurological and immunological observations.

BACKGROUND: The pathogenesis of irritable bowel syndrome (IBS) is founded on interactive mechanisms. Disentangling these processes is a prerequisite for the development of effective drug therapy. AIM: To identify the interaction between the various factors implicated in IBS. METHODS: Articles pertaining to IBS pathogenesis focusing on psychoneuroimmunology were identified using following search terms: IBS, animal models, microbiota, probiotics, immunology, visceral hypersensitivity, imaging, psychology and visceral pain. RESULTS: Cerebral imaging using MRI and proton emission tomography scanning has revealed differential regional cerebral activation, whereas stimuli induced activation has been captured by both MRI and cortical evoked potentials. At the peripheral neurological level, the concept of visceral hypersensitivity has been challenged as perhaps representing psychological traits with symptom over-reporting or hyper-vigilance. Gut mucosal immunology is thought to be relevant with immunological changes reflected as peripheral blood cytokine level changes. Molecular technology advances suggest a role for microbiota by activating the gut immunological system. These interactions have been examined in IBS animal models. CONCLUSIONS: Translation of animal model findings to humans is needed to link the various psychological, neurological and immunological changes noted in IBS. This analysis may identify patient sub-groups, which will ultimately be critical for drug testing to be focused accordingly.

IgA multiple myeloma presenting as non-obstructive jaundice.

Multiple myeloma can occasionally present with jaundice. The underlying process may be pancreatic head myeloma infiltration causing obstructive jaundice or hepatic amyloid deposition resulting in cholestatic jaundice. A rare case of myeloma presenting as jaundice due to hepatic myeloma infiltration is reported.

Helicobacter pylori infection in the cat: evaluation of gastric colonization, inflammation and function.

BACKGROUND: Further elucidation of the consequences of Helicobacter pylori infection on gastric mucosal inflammation and gastric secretory function would be facilitated by an animal model that is susceptible to infection with H. pylori, is broadly similar in gastric physiology and pathology to people, and is amenable to repeated non-invasive evaluation. The goal of this study was to examine the interrelationship of bacterial colonization, mucosal inflammation and gastric secretory function in cats with naturally acquired H. pylori infection. MATERIALS AND METHODS: Twenty clinically healthy cats with naturally acquired H. pylori infection (cagA-, picB) and 19 Helicobacter-free cats were evaluated. Gastric colonization was determined by tissue urease activity, light microscopy, culture and PCR. The mucosal inflammatory response was evaluated by light microscopy, and by RT-PCR of the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-8 and TNF-alpha in gastric mucosa. Gastric secretory function was assessed by measuring pentagastrin-stimulated acid secretion, fasting plasma gastrin, and antral mucosal gastrin and somatostatin immunoreactivity. RESULTS: H. pylori colonized the pylorus, fundus and cardia in similar density. Bacteria were observed free in the lumen of gastric glands and were also tightly adherent to epithelial cells where they were associated with microvillus effacement. Mononuclear inflammation, lymphoid follicle hyperplasia, atrophy and fibrosis were observed primarily in H. pylori-infected cats, with the pylorus most severely affected. Neutrophilic and eosinophilic infiltrates, epithelial dysplasia, and up-regulation of mucosal IL-1beta and IL-8 were observed solely in infected cats. Fasting plasma gastrin concentrations and pentagastrin-stimulated acid output were similar in both infected and uninfected cats. There was no relationship of bacterial colonization density or gastric inflammation to plasma gastrin concentrations or gastric acid output. CONCLUSIONS: The pattern of colonization and the mucosal inflammatory response in cats with naturally acquired H. pylori are broadly similar to those in infected people, particularly children, and non-human primates. The upregulation of IL-8 in infected cats was independent of cagA and picB. Our findings argue against a direct acid-suppressing effect of H. pylori on the gastric secretory-axis in chronically infected cats.

Helicobacter felis infection is associated with lymphoid follicular hyperplasia and mild gastritis but normal gastric secretory function in cats.

The relationship of Helicobacter felis, a bacterium observed in the stomachs of cats, to gastric disease is unclear. The objective of this study was to determine if H. felis infection alters gastric histopathology, proinflammatory cytokine expression, and secretory function and evokes a humoral immune response in cats. Five specific-pathogen-free (SPF) Helicobacter-free cats were studied before and for 1 year after oral inoculation with H. felis (ATCC 49179). Four SPF H. felis-uninfected cats served as controls. The stomachs of all five H. felis-inoculated cats became colonized, as determined by urease activity, histopathology, PCR, culture, and transmission electron microscopy of serial gastric biopsies at 0, 3, 5, 8, and 12 months. Uninoculated cats remained Helicobacter free. Lymphoid follicular hyperplasia, atrophy, and fibrosis were observed primarily in the pylorus of infected cats. Mild mononuclear inflammation was detected in both infected and uninfected cats, but was more extensive in infected cats, with pangastric inflammation, eosinophilic infiltrates, and cardia gastritis observed only in infected cats. No upregulation of antral mucosal interleukin 1alpha (IL-1alpha), IL-1beta, or tumor necrosis factor alpha was detected by reverse transcription-PCR in any cat. The gastric secretory axes, assessed by fasting plasma gastrin, antral mucosal gastrin and somatostatin immunoreactivity, and pentagastrin-stimulated gastric acid secretion, were similar in both infected and uninfected cats. Gradual seroconversion (immunoglobulin G) was observed in four of five infected cats, with enzyme-linked immunosorbent assay values reaching 4x to 12x baseline 12 months postinfection. These findings indicate that H. felis infection in cats induces lymphoid follicular hyperplasia, mild gastritis, and seroconversion, but is associated with normal gastric secretory function.

Nalpha-methyl histamine and histamine stimulate gastrin release from rabbit G-cells via histamine H2-receptors.

BACKGROUND: Gastrin release by Helicobacter pylori may be an important step in the pathway leading to duodenal ulceration. A histamine H3-receptor agonist was found to release gastrin from antral mucosal fragments; this was interpreted as being due to suppression of somatostatin release. H. pylori is reported to produce Nalpha-methyl histamine (NalphaMH), which is an agonist of H3 as well as other histamine receptors. H. pylori infection also recruits mast cells, which release histamine. AIM: To determine the direct effects of histamine receptor agonists on isolated gastrin cells. METHODS: Rabbit G-cells were prepared by countercurrent elutriation and cultured on 24-well plates. RESULTS: NalphaMH (10-6-10-4 M) caused a dose-dependent increase in gastrin release from a basal level of 2.3 +/- 0.2% total cell content (TCC; mean +/- S.E.M.) to a maximum of 5.1 +/- 0.7%, an increase of 117% (P < 0. 005) above basal. This was abolished by the H2-antagonist ranitidine (10-5 M), but not by immunoblockade with anti-somatostatin antibody, the H1-antagonist chlorpheniramine (10-5 M) or the H3-antagonist thioperamide (10-4 M). The histamine H2-receptor agonist dimaprit (10-6-10-4 M) increased gastrin release from 2.4 +/- 0.2% to 3.6 +/- 0.2% TCC (P < 0.001). Gastrin release was also stimulated by histamine (10-7-10-4 M) from a basal value of 3.0 +/- 0.3% to 5.4 +/- 0.5% TCC (P < 0.001). This also was inhibited by ranitidine (10-5 M) (P < 0.01). CONCLUSION: NalphaMH and histamine release gastrin from G-cells via H2-receptors; this might contribute to H. pylori-associated hypergastrinaemia.

Effect of PACAP-27 on 14C-aminopyrine accumulation in isolated rabbit parietal cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in gastric mucosa, but its direct effect on parietal cells is unknown. We examined this using 14C-aminopyrine uptake in elutriated rabbit cells. PACAP-27 had no effect on basal cells but significantly increased the response to histamine (10(-4) M) at 10(-9) M and to carbachol (10(-4) M) in the presence of ranitidine (10(-4) M) at 10(-7) M and 10(-8) M. PACAP (6-38), an antagonist of PACAP, inhibited the effect of PACAP-27 on carbachol-stimulated cells. Vasoactive intestinal peptide had no significant effect. In conclusion, PACAP-27 has a direct additive effect on stimulated rabbit parietal cells in vitro.

How does Helicobacter pylori cause mucosal damage? Its effect on acid and gastrin physiology.

Helicobacter pylori infection increases gastric acid secretion in patients with duodenal ulcers but diminishes acid output in patients with gastric cancer and their relatives. Investigation of the basic mechanisms may show how H. pylori causes different diseases in different persons. Infection of the gastric antrum increases gastrin release. Certain cytokines released in H. pylori gastritis, such as tumor necrosis factor alpha and specific products of H. pylori, such as ammonia, release gastrin from G cells and might be responsible. The infection also diminishes mucosal expression of somatostatin. Exposure of canine D cells to tumor necrosis factor alpha in vitro reproduces this effect. These changes in gastrin and somatostatin increase acid secretion and lead to duodenal ulceration. But the acid response depends on the state of the gastric corpus mucosa. The net effect of corpus gastritis is to decrease acid secretion. Specific products of H. pylori inhibit parietal cells. Also, interleukin 1 beta, which is overexpressed in H. pylori gastritis, inhibits both parietal cells and histamine release from enterochromaffin-like cells. H. pylori also promotes gastric atrophy, leading to loss of parietal cells. Factors such as a high-salt diet and a lack of dietary antioxidants, which also increase corpus gastritis and atrophy, may protect against duodenal ulcers by decreasing acid output. However, the resulting increase of intragastric pH may predispose to gastric cancer by allowing other bacteria to persist and produce carcinogens in the stomach.