Mistakes in mouse models of IBD and how to avoid them 

Learn how to get the most from experimental colitis models!

In general, mouse models of colitis are used to study its pathophysiology and for the development of new treatment modalities for inflammatory bowel disease (IBD). For the latter it is essential to select a mouse model that has many overlapping features with human IBD.

More than 50 experimental colitis models have been developed and they have provided us with very useful insights into IBD physiology, as reviewed by Bouma and Strober1 and others,2–4 but they have limited use in predicting the clinical relevance of therapeutic targets in IBD.5 Experimental colitis models broadly fit into four different groups. First is spontaneous colitis, resulting from a naturally occurring genetic abnormality. Second is induced colitis occurring as a consequence of a targeted mutation or the introduction of a transgene. Third is induced colitis resulting from administration of different exogenous causative agents. Fourth is induction of colitis by manipulation of the immune system. We have learned a great deal from these models about the involvement of genetics, the microbiota and the role of different cells and the mucus layer in the development of IBD. Here we discuss the major mistakes that are made using experimental colitis models, based on our own experience and the scientific literature. Recently increased awareness has developed for the necessity to improve the methodological quality of animal studies. 

Mistakes in colorectal cancer and how to avoid them

Specialist tips on diagnosis, prevention and treatment!

Colorectal cancer (CRC) is one of the most common malignancies and the second leading cause of cancer death in both sexes in developed countries. Over the past 30 years, a great advance in the understanding of this disease has occurred, from colorectal carcinogenesis to diagnosis, prevention and treatment.

Although the majority of CRCs are related to environmental factors, up to 25% of cases have a familial component and potential genetic basis, and highly penetrant monogenic germline mutations account for up to 5% of all CRC cases1. Identification and characterization of these hereditary disorders have allowed modification of their natural history, with a substantial decrease in morbidity and mortality among high-risk patients1. Nonetheless, the majority of patients who are at high risk of CRC remain undiagnosed due to lack of suspicion. On the other hand, studies from the past two decades have suggested that besides adenomas, serrated polyps are also precursors of CRC, responsible for up to 15–30% of all malignancies.2 Several studies have demonstrated that serrated polyps are common precursors of colonoscopy interval cancers (cancers diagnosed within the surveillance interval after a complete colonoscopy), mainly due to their challenging clinical management.Finally, strategies for CRC prevention have shown efficacy in reducing CRC incidence and mortality, and colonoscopy is an integral part of CRC screening strategies. The main objective of screening colonoscopy is the detection and removal of premalignant lesions or early CRC.3 However, colonoscopy is not perfect, and some lesions may be missed. Colonoscopy quality is an emerging concept, and some quality indicators have been demonstrated to be directly related to the development of interval CRC.3 Here we discuss the major mistakes that are made when gastroenterologists deal with CRC diagnosis, prevention and treatment, and how to avoid them. The list of mistakes and the discussion that follows is evidence based and integrated with our longstanding clinical experience. 

Mistakes in dyspepsia and how to avoid them

Expert knowledge at your fingertips!

Dyspepsia refers to upper abdominal discomfort that is thought to arise from the upper gastrointestinal tract. Symptoms include epigastric pain or discomfort, bloating, early satiety and/or fullness after meals, repeated belching or regurgitation (often rumination), nausea and heartburn.1 The symptoms of dyspepsia are nonspecific, but most commonly result from one of four underlying disorders: functional (nonulcer) dyspepsia, gastro-oesophageal reflux disease (GORD; 10–20% erosive esophagitis), peptic ulcer disease (5–15%) and malignancy (~1%).2 Dyspeptic symptoms may also result from other problems, such as medication intolerance, pancreatitis, biliary tract disease or motility disorders (e.g. gastroparesis or gastric dumping).

Clinical guidelines recommend that endoscopy is not always required for diagnosis; a positive diagnosis of GORD and functional dyspepsia can be based on clinical presentation in the absence of alarm symptoms or features (see below).3,4 In many cases symptoms are increased after meal ingestion (postprandial distress syndrome), being triggered by impaired gastric accommodation and visceral hypersensitivity to gastric distension.5 Other patients have an epigastric pain syndrome in which discomfort is independent of food intake and gastrointestinal function.6 There is an important overlap between functional dyspepsia and other functional gastrointestinal diseases (e.g. irritable bowel syndrome [IBS]) and chronic pain syndromes (e.g. fibromyalgia).7 Psychological disease (e.g. anxiety or somatization disorder) and/or psychosocial stress are also present in a significant proportion of patients who seek medical attention.8,9 Notwithstanding the constructive advice provided by published reviews and guidelines, the broad definition of dyspepsia, lack of diagnostic investigations, uncertain cause of disease, psychosocial issues and paucity of specific treatments make the management of dyspepsia challenging. Here, I discuss 10 common and/or high-impact mistakes that are made in the diagnosis and treatment of patients with dyspeptic symptoms: five related to diagnosis, five related to treatment.

Mistakes in coeliac disease diagnosis and how to avoid them

Learn from leaders in the field!

Coeliac disease is regarded as an autoimmune disorder triggered by gluten, which activates an immune reaction against the autoantigen tissue transglutaminase (transglutaminase 2; TG2) in genetically predisposed subjects. Genetic susceptibility to coeliac disease has been proven by its close linkage with major histocompatibility complex (MHC) class II human leukocyte antigen (HLA) DQ2 and DQ8 haplotypes. The identification of biomarkers for coeliac disease (e.g. endomysial antibodies [EmA] and antibodies to TG2 [anti-TG2]) has changed the epidemiology of coeliac disease from being a rare to a frequent condition, with an expected prevalence of 1% in the worldwide population.1 Nonetheless, the majority of patients who have coeliac disease remain undiagnosed, leaving the coeliac ‘iceberg’ mostly submerged. Coeliac disease can be difficult to diagnose because symptoms vary from patient to patient. Indeed, the heterogeneity among the clinical signs and the lack of specificity of many of the presenting symptoms means that the diagnosis of coeliac disease can be a challenge even for experts.

Despite substantial differences in the mode of presentation and the availability of new diagnostic tools, small intestinal biopsy, which shows different grades of mucosal damage, remains the gold standard for coeliac disease diagnosis. A delayed diagnosis of coeliac disease in the elderly can be considered a risk factor for complications including refractory coeliac disease, ulcerative jejunoileitis, collagenous sprue, small bowel carcinoma and enteropathy-associated T-cell lymphoma (EATL). Complicated coeliac disease is not so frequent, being found only in about 1–2% of the total number of coeliac disease patients, but for those who have it the prognosis is very poor, with a low rate of survival after 5 years.2 Here we discuss the major mistakes that are made when diagnosing coeliac disease and how to avoid them. The list of mistakes and the discussion that follows is evidence based and integrated with our clinical experience of more than 30 years in this field.
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