Pathophysiology of idiopathic gastroparesis and implications for therapy

Objectives: Idiopathic gastroparesis is a gastric motility disorder characterized by chronic upper gastrointestinal symptoms and delayed gastric emptying without an identifiable underlying condition. This review summarizes recent understanding of the pathophysiology and treatment of idiopathic gastroparesis. Materials and methods: Structured literature search in the PubMed, Embase and ClinicalTrials.gov databases. Results: Idiopathic gastroparesis involves several alterations in gastric motility and sensation, including delayed gastric emptying, altered myoelectrical activity, impaired fundic accommodation, visceral hypersensitivity and disturbances in antropyloroduodenal motility and coordination. Multiple cellular changes have been identified, including depletion of interstitial cells of Cajal (ICC) and enteric nerves, as well as stromal fibrosis. The underlying cause of these changes is not fully understood but may be an immune imbalance, including loss of anti-inflammatory heme-oxygenase-1 positive (HO-1) macrophages. There is currently no causal therapy for idiopathic gastroparesis. The treatment ladder consists of dietary measures, prokinetic and antiemetic medications, and varying surgical or endoscopic interventions, including promising pyloric therapies. There are ongoing trials with several novel medications, raising hopes for future treatment. Conclusions: Patients with idiopathic gastroparesis present several pathophysiological alterations in the stomach, where depletion of ICC is of special importance. Treatment is currently focused on alleviating symptoms through dietary adjustments, medication or surgical or endoscopic interventions.acceptedVersio

Heat-shock protein 90α in plasma reflects severity of fatigue in patients with Crohn’s disease

Heat-shock proteins (HSPs) are evolutionarily conserved proteins with important cellular homeostasis functions during harmful conditions, including inflammation. Some HSPs are secreted extracellularly and act on distant cells by downregulating inflammation and increasing cellular stress defence mechanisms. HSP90a has been postulated to signal fatigue in chronic inflammation. We investigated whether HSP90a is associated with fatigue in patients with Crohn’s disease. Fifty-three patients with newly diagnosed Crohn’s disease were included in a cross-sectional study. Data on demographics and disease distribution were obtained. Fatigue was measured by the fatigue visual analogue scale (fVAS). Disease activity was assessed by the Simple Endoscopic Score for Crohn’s disease and Harvey Bradshaw Index. C-reactive protein, faecal calprotectin and HSP90a were also measured. The median fVAS score was 52 mm, indicating significant fatigue. HSP90a scores correlated significantly with fVAS (r¼0.31, P¼0.03). In a multivariate regression model, HSP90a was the only significant contributor to fVAS scores (b¼0.31, P¼0.03). When patients were dichotomised into groups with high and low HSP90a concentrations, significantly higher fVAS scores were demonstrated in the group with high HSP90a (M¼62.4, confidence interval 53.0–71.8 vs. 43.3, 31.6–55.0; P¼0.01). Thus, HSP90a may contribute to fatigue generation and/or modulation in patients with Crohn’s disease.publishedVersio

Clinical variables as indicative factors for endoscopy in adolescents with esophageal atresia

Introduction: Gastro-esophageal reflux disease (GERD) occurs frequently in patients operated for esophageal atresia (EA). Longstanding esophagitis may lead to dysphagia, strictures, columnar metaplasia, and dysplasia with an increased risk of adenocarcinoma. Are clinical factors and non-invasive assessments reliable indicators for follow-up with endoscopy? Material and method: A follow-up study with inclusion of EA adolescents in Norway born between 1996 and 2002 was conducted. Clinical assessment with pH monitoring, endoscopy with biopsies, along with interviews and questionnaires regarding gastroesophageal reflux disease (GERD) and dysphagia were performed. Results: We examined 68 EA adolescents. 62% reported GERD by interview, 22% by questionnaire. 85% reported dysphagia by interview, 71% by questionnaire. 24-hour pH monitoring detected pathological reflux index (RI) (&gt;7%) in 7/59 (12%). By endoscopy with biopsy 62 (92%) had histologic esophagitis, of whom 3 (4%) had severe esophagitis. Gastric metaplasia was diagnosed in twelve (18%) adolescents, intestinal metaplasia in only one (1.5%). None had dysplasia or carcinoma. Dysphagia and GERD were statistically correlated to esophagitis and metaplasia, but none of the questionnaires or interviews alone were good screening instruments with high combined sensitivity and specificity. A compound variable made by simply taking the mean of rescaled RI and dysphagia by interview showed to be the best predictor of metaplasia (85% sensitivity, 67% specificity). Conclusion: The questionnaires and interviews used in the present study were not good screening instruments alone. However, combining dysphagia score by interview and RI may be helpful in assessing which patients need endoscopy with biopsy at each individual follow-up examination.</p

Fatigue: a frequent and biologically based phenomenon in newly diagnosed celiac disease

Fatigue is increasingly recognized as a major complaint in patients with chronic inflammatory and autoimmune diseases. Although fatigue is assumed to represent a significant problem in celiac disease, existing knowledge is scarce, and opinions are conflicting. This study aimed to investigate the prevalence and severity of fatigue in patients with newly diagnosed celiac disease and compare it with healthy control subjects. Ninety patients with newly diagnosed celiac disease were compared with 90 age- and sex-matched healthy subjects. The primary endpoints were fatigue severity as measured by: the fatigue Visual Analog Scale (fVAS), the Fatigue Severity Scale (FSS), and the inverted Vitality subscale of the MOS36 (SF-36vs). Higher scores indicate more severe fatigue. Clinically relevant fatigue was determined using predefined cut-off values. Secondary endpoints were the associations between fatigue, and sex, age, depression, pain, and selected biochemical variables. The median (IQR) fVAS-scores were 43.0 (18.0–64.5) in patients, and 9.0 (2.0–16.0) in the control group (p < 0.001); and the FSS scores 3.8 (2.0–4.8) in patients, and 1.4 (1.0–1.9) in control subjects (p < 0.001). Inverted SF-36vs scores had a mean (SD) value of 58.8 (23.6) in patients, and 29.7 (14.3) in healthy subjects (p < 0.001). The presence of clinically relevant fatigue ranged from 41 to 50% in patients. Increased fatigue severity was associated with female sex, younger age, and elevated pain and depression scores, but not with levels of selected biochemical variables, including hemoglobin. Fatigue is a severe and frequent phenomenon in patients with untreated celiac disease.publishedVersio

Inter-observer agreement in the assessment of endoscopic findings in ulcerative colitis

BACKGROUND: Endoscopic findings are essential in evaluating the disease activity in ulcerative colitis. The aim of this study was to evaluate how endoscopists assess individual endoscopic features of mucosal inflammation in ulcerative colitis, the inter-observer agreement, and the importance of the observers' experience. METHODS: Five video clips of ulcerative colitis were shown to a group of experienced and a group of inexperienced endoscopists. Both groups were asked to assess eight endoscopic features and the overall mucosal inflammation on a visual analogue scale. The following statistical analyses were used; Contingency tables analysis, kappa analysis, analysis of variance, Pearson linear correlation analysis, general linear models, and agreement analysis. All tests were carried out two-tailed, with a significance level of 5%. RESULTS: The inter-observer agreement ranged from very good to moderate in the experienced group and from very good to fair in the inexperienced group. There was a significantly better inter-observer agreement in the experienced group in the rating of 6 out of 9 features (p < 0.05). The experienced and inexperienced endoscopists scored the "ulcerations" significantly different. (p = 0.05). The inter-observer variation of the mean score of "erosions", "ulcerations" and endoscopic activity index in mild disease, and the scoring of "erythema" and "oedema" in moderate-severe disease was significantly higher in the inexperienced group. A correlation was seen between all the observed endoscopic features in both groups of endoscopists. Among experienced endoscopists, a set of four endoscopic variables ("Vascular pattern", "Erosions", "Ulcerations" and Friability") explained 92% of the variation in EAI. By including "Granularity" in these set 91% of the variation in EAI was explained in the group of inexperienced endoscopists. CONCLUSION: The inter-observer agreement in the rating of endoscopic features characterising ulcerative colitis is satisfactory in both groups of endoscopists but significantly higher in the experienced group. The difference in the mean score between the two groups is only significant for "ulcerations". The endoscopic variables "Vascular pattern", "Erosions", "Ulcerations" and Friability" explained the overall endoscopic activity index. Even though the present result is quite satisfactory, there is a potential of improvement. Improved grading systems might contribute to improve the consistency of endoscopic descriptions

A pilot study of implementation of endoscopic sleeve gastroplasty (ESG) in Norway

Background and aim - Bariatric surgery is the most effective treatment for obesity but is invasive and associated with serious complications. Endoscopic sleeve gastroplasty (ESG) is a less invasive weight loss procedure to reduce the stomach volume by full-thickness sutures. ESG has been adopted in many countries, but implementation at Scandinavian centres has not yet been documented. We performed a clinical pilot trial at a Norwegian centre with the primary objective to assess the feasibility of the ESG procedure. Patients and methods - We included the first 10 patients treated with ESG at a Norwegian centre in a single-arm pilot study. The eligibility criteria were either a body mass index (BMI) of 40–49.9 kg/m2, BMI 35–39.9 kg/m2 and at least one obesity-related comorbidity, or BMI 30–34.9 kg/m2 and type 2 diabetes. Patient follow-up resembled the scheme used for bariatric surgery at the center, including dietary plans and outpatient visits. Results - All procedures were technically successful except for one patient who had adhesions between the stomach and anterior abdominal wall, related to a prior hernia repair, resulting in less-than-intended stomach volume reduction. Mean total body weight loss (TBWL) after 26 and 52 weeks was 12.2% (95% CI 8.1–16.2) and 9.1% (95% CI 3.3 − 15.0). One patient experienced a minor suture-induced diaphragmatic injury, which was successfully managed conservatively. Conclusions - This first Scandinavian clinical trial of ESG, documenting the implementation of the procedure at a Norwegian center, demonstrated acceptable feasibility and safety, with large variations in individual weight loss during the 52-week follow-up period

Randomised clinical trial and meta-analysis: mesalazine treatment in irritable bowel syndrome—effects on gastrointestinal symptoms and rectal biomarkers of immune activity

Background Low-grade immune activation in the gut is a potential treatment target in irritable bowel syndrome (IBS). Aims To determine improvement in IBS symptoms after mesalazine treatment, and the utility of measures of immune activity in the rectal mucosa Methods This was a randomised, double-blind, placebo-controlled, parallel-arm, multicentre trial in subjects with IBS (Rome III criteria), with an eight-week treatment period of mesalazine 2400 mg or plcebo once-daily. The primary endpoint was the global assessment of satisfactory relief of IBS symptoms in ≥50% of weeks during intervention. IBS symptoms were also measured with the IBS severity scoring system; immune activity was measured by mucosal patch technology. A post hoc meta-analysis of randomised placebo-controlled trials of mesalazine in IBS was added. Results Of 181 included patients, 91 received mesalazine and 90 received placebo. The primary endpoint was met by 32 (36%) patients after mesalazine and 27 (30%) after placebo (p = 0.40). There were no differences in response rates related to IBS subtype or post-infection symptom onset. More reduction of abdominal bloating was noted in the mesalazine group (p = 0.02). The meta-analysis showed no effect of mesalazine on IBS symptoms. No mucosal patch technology measure could predict response to mesalazine, and found no differences in the effects of intervention on levels of immune markers. Conclusions Mesalazine is ineffective in reducing IBS symptoms. Rectal measures of immune activity by the mucosal patch technology cannot predict a higher chance of response to mesalazine.publishedVersio

Transpancreatic biliary sphincterotomy versus double guidewire in difficult biliary cannulation : a randomized controlled trial

Background Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) increases the risk of post-ERCP pancreatitis (PEP). The purpose of this prospective, randomized, multicenter study was to compare two advanced rescue methods, transpancreatic biliary sphincterotomy (TPBS) and a double-guidewire (DGW) technique, in difficult common bile duct (CBD) cannulation. Methods Patients with native papilla and planned CBD cannulation were recruited at eight Scandinavian hospitals. An experienced endoscopist attempted CBD cannulation with wire-guided cannulation. If the procedure fulfilled the definition of difficult cannulation and a guidewire entered the pancreatic duct, randomization to either TPBS or to DGW was performed. If the randomized method failed, any method available was performed. The primary end point was the frequency of PEP and the secondary end points included successful cannulation with the randomized method. Results In total, 1190 patients were recruited and 203 (17.1%) were randomized according to the study protocol (TPBS 104 and DGW 99). PEP developed in 14/104 patients (13.5%) in the TPBS group and 16/99 patients (16.2%) in the DGW group (P=0.69). No difference existed in PEP severity between the groups. The rate of successful deep biliary cannulation was significantly higher with TPBS (84.6% [88/104]) than with DGW (69.7% [69/99]; P=0.01). Conclusions In difficult biliary cannulation, there was no difference in PEP rate between TPBS and DGW techniques. TPBS is a good alternative in cases of difficult cannulation when the guidewire is in the pancreatic duct.Peer reviewe