Gastro Update Europe 2020.

This narrative review summarizes a selection of clinically important novel gastrointestinal developments, presented and discussed at the virtual Gastro Update Europe. The selected topics, fully referenced, reflect what the distinguished faculty considered of vital importance to be communicated to the astute busy gastro-hep clinician who is eager to stay abreast of important novel developments. Whenever appropriate, a personal comment or addition was added to further raise the educational value of this review. Given its narrative character, statements and conclusions are largely expert opinion based. A full reference list of the lectures is included.

The value of esophageal histology in the diagnosis of gastroesophageal reflux disease in patients with heartburn and normal endoscopy.

Histologic markers of reflux-induced mucosal injury are demonstrable in patients with nonerosive gastroesophageal reflux disease (neGERD). They include papillary elongation, basal cell hyperplasia, and dilation of intercellular spaces, especially of the prickle layer. These abnormalities are responsive to acid-suppressive therapy. Unfortunately, the longitudinal and circumferential distributions of these anomalies are nonuniform. They are presumably focalized on top of the esophageal folds, where the brunt of acid exposure and injury occurs. Therefore, based on current evidence, routine, random, nontargeted biopsies of the distal esophagus cannot be recommended in patients with neGERD. This may change if future studies reveal a high sensitivity and specificity of biopsies obtained from the squamocolumnar junction and the tops of the mucosal folds at 2 cm and 4 to 5 cm in patients with neGERD.

Non-erosive reflux disease--defining the entity and delineating the management.

In the developed world, most patients with gastroesophageal reflux disease (GERD) do not exhibit erosions when examined by standard white light endoscopy. Despite the high prevalence of such non-erosive reflux disease (NERD), relatively little is known of its underlying pathophysiology, hence there is no clear guide to clinical management. To establish areas of agreement or uncertainty in NERD, an international meeting was held in Vevey, Switzerland, in late 2007. The goal was to document current thinking in the areas of clinical presentation, assessment of clinical outcome, pathobiological mechanisms, and define optimal clinical strategies to diagnose and manage NERD. After extensive debates, the modified Delphi technique was utilized to reach a consensus on 85 specific statements. In addition, it was proposed that NERD be defined as 'a subcategory of GERD characterised by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions/breaks at conventional endoscopy and without recent acid suppressive therapy'. Evidence in support of this diagnosis may include responsiveness to acid suppression therapy, abnormal reflux monitoring or the identification of specific novel endoscopic findings. Defining the current state of knowledge in NERD should help improve the elucidation and management of this condition in the future.

Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain.

Abdominal cramping and pain is a frequent problem in the adult population of Western countries, with an estimated prevalence of < or =30%. Hyoscine butylbromide (scopolamine butylbromide) [Buscopan/Buscapina] is an antispasmodic drug indicated for the treatment of abdominal pain associated with cramps induced by gastrointestinal (GI) spasms. It was first registered in Germany in 1951 and marketed in 1952, and has since become available worldwide both as a prescription drug and as an over-the-counter medicine in many countries. This article reviews the pharmacology and pharmacokinetic profile of hyoscine butylbromide, and summarises efficacy and safety data from clinical trials of this drug for abdominal cramping and pain. Pharmacological studies have revealed that hyoscine butylbromide is an anticholinergic drug with high affinity for muscarinic receptors located on the smooth-muscle cells of the GI tract. Its anticholinergic action exerts a smooth-muscle relaxing/spasmolytic effect. Blockade of the muscarinic receptors in the GI tract is the basis for its use in the treatment of abdominal pain secondary to cramping. Hyoscine butylbromide also binds to nicotinic receptors, which induces a ganglion-blocking effect. Several pharmacokinetic studies in humans have consistently demonstrated the low systemic availability of hyoscine butylbromide after oral administration, with plasma concentrations of the drug generally being below the limit of quantitation. The bioavailability of hyoscine butylbromide, estimated from renal excretion, was generally <1%. However, because of its high tissue affinity for muscarinic receptors, hyoscine butylbromide remains available at the site of action in the intestine and exerts a local spasmolytic effect.Ten placebo-controlled studies have evaluated the efficacy and safety of oral or rectal hyoscine butylbromide. Hyoscine butylbromide was considered beneficial in all of these trials, which supports its use in the treatment of abdominal pain caused by cramping. Hyoscine butylbromide is barely absorbed and detectable in the blood and does not penetrate the blood-brain barrier, and is, therefore, generally well tolerated. Few adverse events have been reported; in particular, no significant increases in the incidence of anticholinergic-related adverse effects have been observed. In summary, hyoscine butylbromide appears to be a valuable treatment option for patients with symptoms of abdominal pain or discomfort associated with cramping.

Influence of corticotropin-releasing hormone on gastric sensitivity and motor function in healthy volunteers.

BACKGROUND: As stress may be involved in the generation of functional dyspeptic symptoms, we evaluated the effect of the stress hormone, corticotropin-releasing hormone, on proximal stomach function. Twelve healthy volunteers [six women; 23 years (20-26 years)] underwent a barostat study on 2 days. During the infusion of corticotropin-releasing hormone (2.3 microg/kg/h) or saline, a stepwise distension protocol was performed followed by ingestion of a liquid meal (Nutridrink, 200 ml, 300 kcal). RESULTS: Corticotropin-releasing hormone infusion induced a significant increase in cortisol levels and basal volumes compared with placebo. The threshold for discomfort, meal-induced accommodation, dyspeptic symptoms, heart rate and blood pressure were all not significantly altered by corticotropin-releasing hormone infusion. CONCLUSION: In healthy volunteers, peripheral infusion of corticotropin-releasing hormone reduces basal fundic tone, but has no effect on meal-induced accommodation or visceral sensitivity to gastric distension. Our findings suggest that in healthy volunteers, peripheral corticotropin-releasing hormone seems not to be involved in the onset of dyspeptic symptoms.

Agreement between endoscopic and histological gastric atrophy scores.

BACKGROUND: This study was conducted to investigate the strength of agreement between the endoscopic atrophic border (EAB) and the histological score for atrophy. METHODS: A series of 298 dyspeptic Japanese patients underwent upper endoscopy. The grade of gastric atrophy was estimated according to the EAB. Antral and corpus biopsy specimens were taken and were evaluated semiquantitatively according to the updated Sydney classification system, including the score for atrophy. The StatExact software package was used to calculate the weighted kappa statistics. RESULTS: The strength of agreement between the endoscopic atrophy score (EAB) and the histological atrophy score was good, with a weighted kappa value of 0.51 (95% confidence interval, 0.44-0.59). CONCLUSIONS: The strength of agreement between the endoscopic and histological atrophy scores is not worse than the interobserver histological agreement between two pathologists. It is worthwhile to carry out further research on the use of the EAB to identify and score gastric atrophy.

The stool antigen test for detection of Helicobacter pylori after eradication therapy.

BACKGROUND: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed. OBJECTIVE: To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection. DESIGN: Prospective blinded study. SETTING: Six clinical centers in the United States and Europe. PATIENTS: 84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms. MEASUREMENTS: At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy. RESULTS: Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%]). CONCLUSION: A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.

Reflections on esophageal columnar metaplasia (Barrett)-ANNO 2015.

Esophageal columnar metaplasia (ECM) (Barrett's esophogus) continues to generate clinical and basic attention. Yet many questions remain unanswered and global consensus on important issues is often still lacking. This article discusses a selection of certain recent findings and reflects on some remaining uncertainties of this intriguing disease.

Gene therapy for esophageal carcinoma: the use of an explant model to test adenoviral vectors ex vivo.

Adenoviral gene therapy might be a promising therapeutic strategy for esophageal carcinoma. However, adenoviral transduction efficacy in vivo is still limited. This efficacy can be improved by the insertion of an Arg-Gly-Asp (RGD) peptide in the HI-loop of the viral fiber knob. Indeed in established esophageal cell lines, we observed an up to six-fold improved transduction using the RGD-targeted adenovirus. Established cell lines, however, are easily transformed and do not represent the more complex in vivo histology and anatomy. Therefore, we set up an esophageal explant model using esophageal biopsies from patients. Viability is a limiting factor for this system. Cultured squamous epithelium, intestinal metaplasia and squamous cell carcinoma had a sufficient viability to study adenoviral transduction. Viability of the cultured adenocarcinoma biopsies was poor. Adenoviral transduction in the explant model was poor and was localized in particular cells. The transduction of the nontargeted and RGD-targeted adenovirus was similar in localization and efficacy. In conclusion, we established an esophageal explant system to test the transduction of adenoviral vectors ex vivo. The transduction was limited and localized in specific cells. RGD-targeted adenovirus did not show an improved transduction in this system.

The pathogenicity of cytomegalovirus in inflammatory bowel disease: a systematic review and evidence-based recommendations for future research.

During recent years, a clear association between complicated courses of ulcerative colitis and the presence of cytomegalovirus (CMV) has been established. The exact pathogenic role of CMV in these patients remains unclear despite a great number of published reports. Therefore, we undertook a systematic review to appraise critically all available evidence in the literature on the role of CMV during inflammatory bowel disease. We identified and analyzed more than 30 case reports and 9 case series. Based on these results, we propose a model for viral replication during inflammation and provide recommendations for future research.

Intestinal metaplasia of the esophagus or esophagogastric junction: evidence of distinct clinical, pathologic, and histochemical staining features.

Our purpose was to evaluate the clinical, histologic, and histochemical staining characteristics of intestinal metaplasia (IM) at an endoscopically normal-appearing esophagogastric junction (IM-EGJ) compared with IM in a columnar-lined esophagus (IM-CLE). A prospective study included 253 patients referred for elective upper gastrointestinal endoscopy. Biopsy specimens were obtained from 2 cm above and immediately distal to the squamocolumnar junction, the gastric corpus, and the antrum. Any red mucosa above the EGJ was sampled. IM-CLE (prevalence, 5.5%) typically occurred in white male smokers with a long history of reflux symptoms. IM-EGJ (prevalence, 9.1%) was associated with corpus and antrum gastritis and with IM at these sites. IM-CLE usually (13/14 [93%]) was the incomplete type IM, whereas only 12 (52%) of 23 patients in the IM-EGJ group had incomplete IM. IM-EGJ and IM-CLE should be considered as separate entities. Further research is needed to evaluate whether neoplastic progression of IM-EGJ is related to its mucin profile.

A survey of infectious agents as risk factors for primary sclerosing cholangitis: are Chlamydia species involved?

OBJECTIVES: The aetiology of primary sclerosing cholangitis (PSC) is unknown, and the role of micro-organisms has been studied only to a limited extent. We tested the hypothesis that past or persisting infection with common viruses or atypical bacteria might play a role in genetically susceptible hosts. DESIGN: Case-control study. METHODS: Serological screening for antibodies against 22 viruses as well as Chlamydia spp. and Mycoplasma pneumoniae was carried out in 41 well-established PSC patients. All 5110 sera tested in 1997 for these micro-organisms at our laboratory served as a background reference group. Subsequently, Chlamydia anti-lipopolysaccharide (LPS) antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in the PSC group and in three race-matched control groups (inflammatory bowel disease (IBD) group, n = 35; non-IBD patients group, n = 39; healthy blood donor group, n = 40). Subtyping in Chlamydia trachomatis and C. pneumoniae serotypes by specific anti-major outer membrane protein (MOMP) assays was carried out in the four groups. Immunohistochemical staining using specific markers for chlamydiae was carried out on liver biopsies of 14 PSC patients. RESULTS: There was a markedly elevated seroprevalence of Chlamydia-LPS antibodies compared with the 1997 reference group. The odds ratios (ORs) for the presence of immunoglobulin G, immunoglobulin M and immunoglobulin A antibodies for the PSC patients versus the control group were 2.4 (95% confidence interval (CI) 1.1 to 5.4), 1.9 (95% CI 0.9 to 4.0) and 6.7 (95% CI 3.0 to 17.0), respectively. All other micro-organisms tested showed normal antibody profiles that did not differ from the 1997 reference group. The seroprevalence of Chlamydia-anti-LPS antibodies was elevated markedly in the PSC patients compared with the IBD, non-IBD and blood donor groups. The outcomes in the C. trachomatis and C. pneumoniae anti-MOMP assays did not correlate with the anti-LPS-positive PSC sera. The actual presence of Chlamydia bodies in liver tissue could not be demonstrated. CONCLUSION: Our findings suggest an association between PSC and (previous) infection with Chlamydia.

A physician with a positive hepatitis C virus RNA test after a needlestick injury.

Needlestick accidents continue to be a hazard for healthcare workers. We report the development of acute hepatitis C infection in a physician after needlestick injury. Hepatitis C virus (HCV)-RNA, seroconversion and a raised plasma alanine aminotransferase (ALAT) level were found in plasma three months after the accident. Treatment with interferon alfa and ribavirin was started. While the physician was on treatment, HCV-RNA test results from plasma taken the day treatment was started became available. HCV-RNA was undetectable by quantitative bDNA assay, undetectable by qualitative polymerase chain reaction (PCR) and undetectable by transcription mediated amplification (TMA). A dilemma arose at this point: should the patient stop the treatment or continue the planned therapy? The physician decided to continue a 24-week course of treatment. Six months after the end of treatment, the physician was still HCV-RNA-negative and with a normal plasma ALAT level. The rationale of the decision to continue therapy is discussed. This information may be useful for clinicians confronted with a similar dilemma.

Follow-up for high-grade dysplasia in Barrett's esophagus.

This article will focus on the value of endoscopic follow-up for patients with high-grade dysplasia (HGD). Because the diagnosis of HGD in Barrett's esophagus is not a simple straightforward task, the article first will discuss the controversies regarding the histological diagnosis, followed by a discussion of the importance of endoscopic imaging for making the clinical diagnosis of HGD, and a systematic review of the literature relating to the presence of synchronous cancers in patients with HGD and the occurrence of cancer during endoscopic follow-up in these patients (metachronous cancers). Furthermore, the article will also discuss endoscopic techniques currently available for surveillance of these patients and make recommendations regarding surveillance intervals and the optimal biopsy protocol.

Magnetic resonance cholangiopancreatography.

The current imaging technique and clinical application of MR cholangiopancreatography (MRCP) is reviewed. MRCP has evolved into a feasible method of non-invasively evaluating the pancreaticobiliary system and has considerable clinical utility. If endoscopic retrograde cholangiopancreatography (ERCP) is incomplete or has failed, or in patients with biliary and gastrointestinal surgical procedures, MRCP is a useful alternative modality. In the near future, MRCP may supplant diagnostic ERCP such that ERCP is reserved primarily for therapeutic interventions. Furthermore, when MRCP is performed in conjunction with abdominal MR and MR angiography, the 'all-in-one' examination can evaluate the solid organs and vessels of the abdomen as well as the ductal systems.