Showing papers in "Best Practice & Research in Clinical Gastroenterology in 2013"

Diabetes, obesity and gut microbiota.

Abstract: The gut microbiota composition has been associated with several hallmarks of metabolic syndrome (e.g., obesity, type 2 diabetes, cardiovascular diseases, and non-alcoholic steatohepatitis). Growing evidence suggests that gut microbes contribute to the onset of the low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. Recently, enteroendocrine cells and the endocannabinoid system have been shown to control gut permeability and metabolic endotoxaemia. Moreover, targeted nutritional interventions using non-digestible carbohydrates with prebiotic properties have shown promising results in pre-clinical studies in this context, although human intervention studies warrant further investigations. Thus, in this review, we discuss putative mechanisms linking gut microbiota and type 2 diabetes. These data underline the advantage of investigating and changing the gut microbiota as a therapeutic target in the context of obesity and type 2 diabetes.

Glycobiome: bacteria and mucus at the epithelial interface.

Abstract: The human gastrointestinal tract is colonised with a dense and diverse microbial community, that is an important player in human health and physiology. Close to the epithelial cells the mucosal microbiota is separated from the host with a thin lining of host derived glycans, including the cell surface glycocalyx and the extracellular secreted mucus. The mucosa-associated microbial composition differs from the luminal content and could be particularly important for nutrient exchange, communication with the host, development of the immune system, and resistance against invading pathogens. The mucosa-associated microbiota has adapted to the glycan rich environment by the production of mucus-degrading enzymes and mucus-binding extracellular proteins, and include mucus-degrading specialists such as Akkermansia muciniphila and Bacteroides thetaiotaomicron. This review is focussed on the host-microbe interactions within the glycan landscape at the epithelial interface and considers the spatial organisation and composition of the mucosa-associated microbiota in health and disease.

Experimental models of the gut microbiome

Abstract: The human gut contains a diverse microbiota with large potential to influence health. Given the difficulty to access the main sites of the gut, in vitro models have been developed to dynamically monitor microbial processes at the site of metabolic activity. These models range from simple batch fermentations to complex multi-compartmental continuous systems. The latter include different models, focussing on similar but each also on distinct digestive parameters. The most intensively used include the three-stage continuous culture system, SHIME®, EnteroMix, Lacroix model and TIM-2. Especially after inclusion of surface-attached mucosal microbes (M-SHIME), such models have been shown representative of the in vivo situation in terms of microbial composition and activity. They have even been shown to maintain the interpersonal variation among different human fecal inocula. Novel developments, such as the incorporation of host cells, will further broaden the potential of in vitro models to unravel the importance of gut microbes for human health and disease. © 2013 Elsevier Ltd. All rights reserved.

Intestinal microbiota: a source of novel biomarkers in inflammatory bowel diseases?

Abstract: The human intestine harbours a complex microbial ecosystem that performs manifold functions important to the nutrition and health of its host. Extensive study has revealed that the composition of the intestinal microbiota is altered in individuals with inflammatory bowel disease (IBD). The IBD associated intestinal microbiota generally has reduced species richness and diversity, lower temporal stability, and disruption of the secreted mucus layer structure. Multiple studies have identified certain bacterial taxa that are enriched or depleted in IBD including Enterobacteriaceae, Ruminococcus gnavus, and Desulfovibrio (enriched) and Faecalibacterium prausnitzii, Lachnospiraceae, and Akkermansia (depleted). Additionally, the relative abundance of some taxa appears to correlate with established markers of disease activity such as Enterobacteriaceae (enriched) and Lachnospiraceae (depleted). Signature shifts in fecal microbial community composition may therefore prove to be valuable as diagnostic biomarkers, particularly for longitudinal monitoring of disease activity and response to treatments.

Helicobacter pylori and the gastric microbiota

Abstract: The human microbiota along the gastrointestinal tract is currently extensively studied and a number of studies focuses on elucidating the association between a more or less diverse intestinal microbial community and health and disease. The human stomach is considered to be exclusively inhabited by Helicobacter pylori and further lacks a colonizing non-H. pylori bacterial flora due to the acidic environment. However, recently a limited number of studies using molecular-based methods have provided a broader picture of the stomach microbiota. The question is whether changes in gastric pH or antibiotic treatment can lead to significant shifts in the stomach microbiota that may be involved in disease development such as gastric cancer.

Nutrition, the gut microbiome and the metabolic syndrome

Abstract: Metabolic syndrome is a lifestyle disease, determined by the interplay of genetic and environmental factors. Obesity is a significant risk factor for development of the metabolic syndrome, and the prevalence of obesity is increasing due to changes in lifestyle and diet. Recently, the gut microbiota has emerged as an important contributor to the development of obesity and metabolic disorders, through its interactions with environmental (e.g. diet) and genetic factors. Human and animal studies have shown that alterations in intestinal microbiota composition and shifts in the gut microbiome towards increased energy harvest are associated with an obese phenotype. However, the underlying mechanisms by which gut microbiota affects host metabolism still need to be defined. In this review we discuss the complexity surrounding the interactions between diet and the gut microbiota, and their connection to obesity. Furthermore, we review the literature on the effects of probiotics and prebiotics on the gut microbiota and host metabolism, focussing primarily on their anti-obesity potential.

Precancerous lesions in the stomach: From biology to clinical patient management

Abstract: Gastric cancer is the final step in a multi-stage cascade triggered by long-standing inflammatory conditions (particularly Helicobacter pylori infection) resulting in atrophic gastritis and intestinal metaplasia: these lesions represent the cancerization field in which (intestinal-type) gastric cancer develops. Intraepithelial neoplasia is consistently recognized as the phenotypic bridge between atrophic/metaplastic lesions and invasive cancer. This paper addresses the epidemiology, pathology, molecular profiling, and clinical management of advanced precancerous gastric lesions.

Fecal transplant: A safe and sustainable clinical therapy for restoring intestinal microbial balance in human disease?

Abstract: Recent studies have suggested an association between intestinal microbiota composition and human disease, however causality remains to be proven. With hindsight, the application of fecal transplantation (FMT) does indeed suggest a causal relation between interfering with gut microbiota composition and a resultant cure of several disease states. In this review, we aim to show the available evidence regarding the involvement of intestinal microbiota and human (autoimmune) disease. Moreover, we refer to (mostly case report) studies showing beneficial or adverse effects of fecal transplantation on clinical outcomes in some of these disease states. If these findings can be substantiated in larger randomized controlled double blind trials also implementing gut microbiota composition before and after intervention, fecal transplantation might provide us with novel insights into causally related intestinal microbiota, that might be serve as future diagnostic and treatment targets in human disease.

Influence of fermented milk products, prebiotics and probiotics on microbiota composition and health

Abstract: The gut microbiota is a highly diverse and relative stabile ecosystem increasingly recognized for its impact on human health. The homeostasis of microbes and the host is also referred to as eubiosis. In contrast, deviation from the normal composition, defined as dysbiosis, is often associated with localized diseases such as inflammatory bowel disease or colonic cancer, but also with systemic diseases like metabolic syndrome and allergic diseases. Modulating a gut microbiota dysbiosis with nutritional concepts may contribute to improving health status, reducing diseases or disease symptoms or supporting already established treatments. The gut microbiota can be modulated by different nutritional concepts, varying from specific food ingredients to complex diets or by the ingestion of particular live microorganisms. To underpin the importance of bacteria in the gut, we describe molecular mechanisms involved in the crosstalk between gut bacteria and the human host, and review the impact of different nutritional concepts such as pre-, pro- and synbiotics on the gastrointestinal ecosystem and their potential health benefits. The aim of this review is to provide examples of potential nutritional concepts that target the gut microbiota to support human physiology and potentially health outcomes.

Function of the microbiota.

Abstract: The gut microbiota of humans is complex but stable in composition and function. Metabolic conversions performed by the members of the microbiota yield both beneficial and hazardous compounds, and have a systematic impact on human health. Comparative studies have shown that the microbiota of patients, suffering from a number of diseases, is in dysbiosis, which is characterized by a distinct composition. Compositional differences have also been noted between members of geographically distant healthy populations. To be able to identify which compositional changes promote compromised health, it is of interest to identify members of the microbiota that perform essential metabolic transformations. This review provides an insight into the microbial contribution to the metabolism of carbohydrates, proteins and bile acids, and focuses on the link between diversity and function.

Precancerous lesions of the biliary tree

Abstract: The neoplasms of the biliary tree include the carcinomas of the intra- and extrahepatic bile ducts, the gallbladder and the ampulla. Two types of precancerous lesions precede these adenocarcinomas: the flat and non-tumour forming type that is called biliary intraepithelial neoplasia, and the papillary and tumour-forming type that has been named intraductal papillary neoplasm of the bile duct. Rarely also biliary mucinous cystic neoplasm can give rise to invasive biliary adenocarcinomas. This review discusses the pathological, molecular, epidemiological, clinical and prognostic features of the precancerous biliary lesions, separated according to their origin in the bile ducts, the ampulla and the gall bladder.

Safety of long-term PPI therapy

Abstract: Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders Long-term use is becoming increasingly common, in some cases without a proper indication A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment

Liver abnormalities and endocrine diseases

Abstract: The liver and its pleotropic functions play a fundamental role in regulating metabolism, and is also an inevitable target of multiple metabolic disorders. The numerous and constant relationships and feedback mechanisms between the liver and all endocrine organs is reflected by the fact that an alteration of one oftentimes results in the malfunction of the other. Hypo- and hyperthyroidism are frequently associated with hepatic alterations, and thyroid diseases must be excluded in transaminase elevation of unknown cause. Drugs such as propylthiouracil, used in the treatment of hyperthyroidism, may induce liver damage, and other drugs such as amiodarone, carbamazepine, and several chemotherapeutic agents can lead to both thyroid and liver abnormalities. Liver diseases such as hepatitis, hepatocellular carcinoma, and cirrhosis may cause altered levels of thyroid hormones, and alcoholic liver disease, both due to the noxious substance ethanol as well as to the hepatic damage it causes, may be responsible for altered thyroid function. Both excess and insufficiency of adrenal function may result in altered liver function, and adrenocortical dysfunction may be present in patients with cirrhosis, especially during episodes of decompensation. Again an important player which affects both the endocrine system and the liver, alcohol may be associated with pseudo-Cushing syndrome. Sex hormones, both intrinsic as well as extrinsically administered, have an important impact on liver function. While oestrogens are related to cholestatic liver damage, androgens are the culprit of adenomas and hepatocellular carcinoma, among others. Chronic liver disease, on the other hand, has profound repercussions on sex hormone metabolism, inducing feminization in men and infertility and amenorrhoea in women. Lastly, metabolic syndrome, the pandemia of the present and future centuries, links the spectrum of liver damage ranging from steatosis to cirrhosis, to the array of endocrine alterations that are features of the syndrome, including insulin resistance, central obesity, and hyperlipidaemia. Clinical practice must integrally evaluate the effects of the intricate and tight relationship between the liver and the endocrine system, in order to better address all manifestations, complications, and prevent deterioration of one or the other organ-system.

Gastro-Intestinal Vascular Emergencies

Abstract: Gastro-Intestinal Vascular Emergencies include all digestive ischaemic injuries related to acute or chronic vascular and/or haemodynamic diseases. Gastro-intestinal ischaemic injuries can be occlusive or non-occlusive, arterial or venous, localized or generalized, superficial or transmural and share the risks of infarction, organ failure and death. The diagnosis must be suspected, at the initial presentation of any sudden, continuous and unusual abdominal pain, contrasting with normal physical examination. Risk factors are often unknown at presentation and no biomarker is currently available. The diagnosis is confirmed by abdominal computed tomography angiography identifying intestinal ischaemic injury, either with vascular occlusion or in a context of low flow. Recent knowledge in the pathophysiology of acute mesenteric ischaemia, clinical experience and existing recommendations have generated a multimodal and multidisciplinary management strategy. Based on the gastro-intestinal viability around a simple algorithm, and coordinated by gastroenterologists, the dual aim is to avoid large intestinal resections and death.

Management of the Patient with Incomplete Response to PPI Therapy

Abstract: Proton pump inhibitors (PPIs) remove most of the acid from the gastroesophageal refluxate. However, PPIs do not eliminate reflux and the response of specific GERD symptoms to PPI therapy depends on the degree to which acid drives those symptoms. PPIs are progressively less effective for heartburn, regurgitation, chest pain and extra-oesophageal symptoms. Hence, with an incomplete PPI response, obtaining an accurate history, detailing which symptoms are ‘refractory’ and exactly what evidence exists linking these symptoms to GERD is paramount. Reflux can continue to cause symptoms despite PPI therapy because of persistent acid reflux or weakly acidic reflux. Given these possibilities, diagnostic testing (pH or pH-impedance monitoring) becomes essential. Antireflux surgery is an alternative in patients if a clear relationship is established between persistent symptoms, particularly regurgitation, and reflux. Treating visceral hypersensitivity may also benefit the subset of GERD patients whose symptoms are driven by this mechanism.

Cost-effectiveness of screening and treating Helicobacter pylori for gastric cancer prevention

Abstract: Gastric cancer is the second leading cause of cancer-related death worldwide. A meta-analysis of seven randomized controlled trials concluded that Helicobacter pylori eradication reduces gastric cancer incidence by 35%. Current consensus is that H. pylori screening and treatment is cost-effective only in high-risk populations. This paper provides an up-to-date overview of the evidence for cost-effectiveness of H. pylori screening and treatment in different population settings and risk levels for H. pylori infection. Ten unique cost-effectiveness or cost-utility analyses were identified. All found that screening for H. pylori to prevent gastric cancer in the general population costs less than $50,000 per LYG. This finding was robust for differences in H. pylori prevalence, gender and ethnicity. Based on limited evidence, re-treatment (for treatment failure), repeated screening, limiting screening and treatment to those with the CagA phenotype, or universal treatment, does not appear to be cost-effective. However, most included studies failed to consider both the broader benefits as well as the adverse effects of widespread use of antibiotics for H. pylori.

Variceal and other portal hypertension related bleeding.

Abstract: Variceal bleeding is one of the commonest and most severe complications of liver cirrhosis. Even with the current best medical care, mortality from variceal bleeding is still around 20%. When cirrhosis is diagnosed, varices are present in about 30–40% of compensated patients and in 60% of those who present with ascites. Once varices have been diagnosed, the overall incidence of variceal bleeding is in the order of 25% at two years. Variceal size is the most useful predictor for variceal bleeding, other predictors are severity of liver dysfunction (Child–Pugh classification) and the presence of red wale marks on the variceal wall. The current consensus is that every cirrhotic patient should be endoscopically screened for varices at the time of diagnosis to detect those requiring prophylactic treatment. Non-selective beta-adrenergic blockers (NSBB) and endoscopic band ligation (EBL) have been shown effective in the prevention of first variceal bleeding. The current recommendation for treating acute variceal bleeding is to start vasoactive drug therapy early (ideally during the transferral or to arrival to hospital, even if active bleeding is only suspected) and performing EBL. Once bleeding is controlled, combination therapy with NSBB + EBL should be used to prevent rebleeding. In patients at high risk of treatment failure despite of using this approach, an early covered-TIPS within 72 h (ideally 24 h) should be considered. Data on management of gastric variceal bleeding is limited. No clear recommendation for primary prophylaxis can be done. In acute cardiofundal variceal bleeding, vasoactive agents together with cyanoacrylate (CA) injection seem to be the treatment of choice. Further CA injections and/or NSBB may be used to prevent rebleeding. TIPS or Balloon-occluded retrograde transvenous obliteration when TIPS is contraindicated may be used as a rescue therapy.

Precancerous lesions of the pancreas

Abstract: Pancreatic cancer has a very poor prognosis, with a five year survival of only 5%. New studies have shown that it takes over 11 years for cells to develop invasive capability. This provides an opportunity to intervene if precursor lesions can be detected. This paper reviews the molecular, pathological, clinical findings and management of pancreatic intraepithelial neoplasia (PanIN), intraductal pancreatic mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN), three precursor lesions which can give rise to invasive carcinoma of the pancreas.

Epidemiology of reflux symptoms and GORD

Abstract: Gastro-oesophageal reflux disease (GORD) occurs when reflux of gastric contents causes troublesome symptoms and/or complications (the Montreal definition). GORD is a common condition with a substantial economical burden to the community and it has a significant negative effect on health-related quality of life (HRQoL) while endoscopic findings like erosive oesophagitis per se seem to correlate badly with the experienced HRQoL. The prevalence of GORD varies over the world for unknown reasons, but genetic differences, difference in the Helicobacter pylori prevalence and life style factors like obesity might influence. The prevalence is lowest in East Asia (2.5–9.4%) and higher in Mid (7.6–19.4%) and Western Asia (12.5–27.6%). The highest population-based prevalence is reported from Europe (23.7%) and the US (28.8%). GORD seems to be fairly stable over time both in terms of symptoms and erosive oesophagitis, but the prevalence seems to be increasing both in Asia and in the West.

Precancerous lesions in inflammatory bowel disease.

Abstract: Reduction of mortality from colorectal cancer is a prime goal in the clinical management of patients with extensive, longstanding ulcerative colitis and colonic Crohn's disease. The cornerstone of current cancer prevention efforts is endoscopic surveillance for colorectal dysplasia, or intraepithelial neoplasia, the direct histological precursor of cancer. A diagnosis of dysplasia provides a reliable indicator of heightened cancer risk and an end-point for colonoscopic surveillance allowing most patients to undergo prophylactic colectomy before the development of incurable cancer. This article reviews the classification, pathological criteria and clinical implications of colorectal dysplasia, current recommendations for the performance of surveillance colonoscopy, recent technical advances in colonoscopic imaging to enhance the detection of dysplasia, and a summary of the molecular genetic events implicated in its development.

Acute upper gastrointestinal bleeding (UGIB) – Initial evaluation and management

Abstract: Acute upper gastrointestinal bleeding (UGIB) is the most common reason that the 'on-call' gastroenterologist is consulted. Despite the diagnostic and therapeutic capabilities of upper endoscopy, there is still significant associated morbidity and mortality in patients experiencing acute UGIB, thus this is a true GI emergency. Acute UGIB is divided into non-variceal and variceal causes. The most common type of acute UGIB is 'non-variceal' and includes diagnoses such as peptic ulcer (gastric and duodenal), gastroduodenal erosions, Mallory-Weiss tears, erosive oesophagitis, arterio-venous malformations, Dieulafoy's lesion, and upper GI tract tumours and malignancies. This article focuses exclusively on initial management strategies for acute upper GI bleeding. We discuss up to date and evidence-based strategies for patient risk stratification, initial patient management prior to endoscopy, potential causes of UGIB, role of proton pump inhibitors, prokinetic agents, prophylactic antibiotics, vasoactive pharmacotherapies, and timing of endoscopy.

Liver disease and malnutrition.

Abstract: Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

Foreign bodies and caustic lesions

Abstract: Foreign body ingestions, food bolus impactions, and caustic agent injuries are frequent but specific situations. Although most foreign bodies will naturally pass through the digestive tract, practitioners should recognize specific situations were endoscopic management is required. In such cases, timing and adequate equipment are critical. Endoscopic treatment is successful in about 95% of patients. Severe complications (including oesophageal perforations) are rare. Underlying diseases (including eosinophilic oesophagitis) must be investigated after food bolus impaction. Accidental or suicidal ingestion of corrosive agents may result in severe upper gastrointestinal tract injuries requiring a multidisciplinary approach including gastroenterologists, surgeons, otorhynolaryngologists, anaesthesiologists and psychiatrists. Treatment includes conservative management of patients with mild injuries, while patients with severe injuries undergo emergency surgical exploration. At distance of the ingestion episode, oesophageal reconstruction is required in patients who underwent oesophageal resection and in patients who developed oesophageal strictures that failed dilatation.

Liver abnormalities in connective tissue diseases

Abstract: The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjogren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.

Advanced precancerous lesions in the liver.

Abstract: We will focus on precursors of the most common liver cancer, i.e. hepatocellular carcinoma (HCC), which takes place in 90% of cases in a hepatitis/cirrhotic setting. High grade dysplastic nodules (HG-DN) are small sizable nodules and the most advanced precancerous lesions of the liver, with a risk of malignant transformation of about 30-40% at 24 months. We will survey the diagnostic distinction between them and early HCC from a clinical, radiological and pathological point of view. The use of a diagnostic algorithm supported by international guidelines is the best practice to manage HG-DN and early HCC. There is no typical imaging for HG-DN, needing all of them to be biopsied for characterization. The natural history of HG-DN is not predictable in individual cases and additional markers should be validated to increase the diagnostic accuracy and predict the behaviour. The treatment of HG-DN is under investigation.

Liver abnormalities in drug and substance abusers.

Abstract: Drug and substance abuse remains a major medical problem Alcohol use, abuse and dependence are highly prevalent conditions Alcohol related liver disease can present as simple steatosis, steatohepatitis, alcoholic hepatitis or liver cirrhosis Paracetamol hepatotoxicity secondary to accidental or deliberate overdose is another common problem While the adverse cardiovascular, neurological, renal and psychiatric consequences of various illicit substance abuses are widely studied and publicized, less attention has been directed towards possible hepatotoxic effects Illicit drug abuse can cause a range of liver abnormalities ranging from asymptomatic derangement of liver function tests to fulminant hepatic failure This article reviews the epidemiology, risk factors, clinical manifestations, pathogenesis, investigations, management and prognostic factors of alcohol related liver disease and paracetamol hepatotoxicity as well as the current knowledge pertaining to hepatotoxicity of the more commonly used illicit substances including cannabis, amphetamine type stimulants, cocaine, khat chewing and complementary and alternate medicine

Early management of acute pancreatitis

Abstract: Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.

Advanced precancerous lesions within the GI tract: The molecular background

Abstract: The mainstream carcinogenic processes involved within the gastrointestinal tract are characterized by phenotypic multistep progression cascades that eventually result in full-blown cancers. In this scenario, the understanding of the molecular dysregulations underlying the precancerous lesions is increasing but still remains incomplete. However, in recent years, the enthusiastic rise of innovative technologies (i.e., next-generation sequencing, high-throughput microarray analysis, mass spectrometry based proteomics) and the unexpected discovery of new classes of biomarkers (i.e., miRNA, long-noncoding RNAs) prompted new strength in the exploration of the accurate and comprehensive molecular characterization of premalignant and malignant neoplastic lesions. The challenge ahead lies in the reliable identification of disease progression-specific targets to enable molecular testing in the clinical management of the secondary prevention of gastrointestinal cancers.

Liver abnormalities in pregnancy

Abstract: Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication.

Pathophysiology of gastroesophageal reflux disease.

Abstract: The gastroesophageal junction is structurally complex and functionally designed to ensure the acid secreted by the most proximal gastric mucosa flows towards the stomach and not up onto the oesophageal squamous mucosa. The pattern and mechanism of reflux vary with the severity of reflux disease and this probably represents different ends of a spectrum rather than distinct pathophysiological mechanisms. Nearly all patients with severe reflux disease have hiatus hernia, however, a substantial proportion of patients with mild reflux disease do not, and this may be a result of intermittent or partial hiatus hernia undetectable by current available tools. The acid pocket is an area of post-prandial unbuffered gastric acidity immediately distal to the gastroesophageal junction and which is enlarged in patients with hiatus hernia. The acid pocket provides a reservoir of acid available to reflux when the intrinsic sphincter fails. Central obesity is an important factor in the aetiology of reflux and does this by the increased abdomino-thoracic pressure gradient inducing hiatus hernia and increasing the rate of flow of reflux when sphincter opens. Central obesity also induces short segment intrasphincteric reflux and thereby columnar metaplasia of the most distal oesophagus.