Nathan S. S. Atkinson

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis

Objective Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. Design In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. Results In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). Conclusion The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.

Helicobacter Pylori Infection: Diagnostic Strategies in Primary Diagnosis and After Therapy.

Accurate diagnosis of Helicobacter pylori infection pre- and post-treatment is mandatory in the current era of decreasing prevalence and increasing antibiotic resistance. The diagnostic performance of most tests is poorer in clinical situations with low bacterial density which is seen in conditions such as atrophic gastritis or intake of antisecretory and antibiotic medications. Noninvasive tests require less cost and resource but provide excellent accuracy; however, endoscopy with testing of gastric biopsy specimens is indicated where alarming symptoms are present or antibiotic susceptibility testing by culture is desired. Newer modalities such as polymerase chain reaction testing provide additional virulence and antibiotic sensitivity profiling. This article outlines new developments and the key parameters of each test, as careful selection of test modality within the clinical context is required for adequate management of infected symptomatic patients.

Lung B-line artefacts and their use

BACKGROUND The analysis of lung artefacts has gained increasing importance as markers of lung pathology. B-line artefact (BLA), caused by a reverberation phenomenon, is the most important lung artefact. In this review, we discuss the current role of BLA in pneumology and explore open questions of the published consensus. METHODS We summarized current literature about BLA. Also, we presented observations on healthy subjects and patients with interstitial syndrome (pulmonary fibrosis and edema), to investigate technical factors influencing BLA visualization. RESULTS BLA imaging is influenced by more factors than recently assumed. When multiple BLA is visualized in the lung, they represent a sign of increased density due to the loss of aeration in the lung periphery. This condition may indicate different diseases including cardiogenic pulmonary edema, diffuse or focal interstitial lung diseases (ILD), infections and acute respiratory distress syndrome (ARDS). Correct interpretation of BLA in lung ultrasound is strongly influenced by associated sonographic signs and careful integration of all relevant clinical information. CONCLUSIONS BLA is useful to monitor clinical response, and may become crucial in directing the diagnostic process. Further research is warranted to clarify technical adjustments, different probe and machine factors that influence the visualization of BLA.

Systematic Review and Meta-analysis: Placebo Rates in Induction and Maintenance Trials of Ulcerative Colitis

BACKGROUND AND AIMS Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool. RESULTS In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits. CONCLUSIONS Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials.

Ultrasound contrast agents

Endoscopic ultrasound (EUS) plays an important role in imaging of the mediastinum and abdominal organs. Since the introduction of US contrast agents (UCA) for transabdominal US, attempts have been made to apply contrast-enhanced US techniques also to EUS. Since 2003, specific contrast-enhanced imaging was possible using EUS. Important studies have been published regarding contrast-enhanced EUS and the characterization of focal pancreatic lesions, lymph nodes, and subepithelial tumors. In this manuscript, we describe the relevant UCA, their application, and specific image acquisition as well as the principles of image tissue characterization using contrast-enhanced EUS. Safety issues, potential future developments, and EUS-specific issues are reviewed.

'Lemonade Legs': Why do Some Patients Get Profound Hypomagnesaemia on Proton-Pump Inhibitors?

Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis.

Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease

Minimising placebo response is essential for drug development.

Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application

Evolution of treatment targets in IBD has increased the need for objective monitoring of disease activity to guide therapeutic strategy. Although mucosal healing is the current target of therapy in IBD, endoscopy is invasive, expensive and unappealing to patients. GI ultrasound (GIUS) represents a non-invasive modality to assess disease activity in IBD. It is accurate, cost-effective and reproducible. GIUS can be performed at the point of care without specific patient preparation so as to facilitate clinical decision-making. As compared with ileocolonoscopy and other imaging modalities (CT and MRI), GIUS is accurate in diagnosing IBD, detecting complications of disease including fistulae, strictures and abscesses, monitoring disease activity and detecting postoperative disease recurrence. International groups increasingly recognise GIUS as a valuable tool with paradigm-changing application in the management of IBD; however, uptake outside parts of continental Europe has been slow and GIUS is underused in many countries. The aim of this review is to present a pragmatic guide to the positioning of GIUS in IBD clinical practice, providing evidence for use, algorithms for integration into practice, training pathways and a strategic implementation framework.

Autoimmune pancreatitis: Imaging features

Background and Objectives: Autoimmune pancreatitis (AIP) remains a difficult disease to diagnose before treatment, particularly if presenting as a focal mass lesion. The purpose of this multicenter retrospective study is to analyze imaging features of histologically confirmed AIP to determine the additional diagnostic value of contrast-enhanced ultrasound (CEUS), contrast-enhanced endoscopic ultrasound (CE-EUS), and elastography to B-mode features. Patients and Methods: We report on a retrospective data collection of 60 histologically confirmed cases of AIP in comparison to 16 patients with pancreatic adenocarcinomas (PDAC). All CE (-E) US examinations were assessed by two independent readers in consensus. The role of CEUS and CE-EUS for pancreatic evaluation was defined according to the 2011 European Federation of Societies for Ultrasound in Medicine and Biology guidelines. Results: After injection of ultrasound (US) contrast agents, most AIP lesions displayed focal or diffuse isoenhancement (86.6%) in the arterial phase, while most of the PDAC lesions (93.7%) were hypoenhancing (P < 0.01). During the late phase, most AIP lesions were hyper-(65%) or iso-enhancing (35%), while most PDAC lesions were hypoenhancing (93.7%). CE-EUS was performed in a subset of ten patients and showed hyperenhancement in all AIP cases. Most focal AIP lesions (n = 27, 79.4%) were stiffer than the surrounding pancreatic parenchyma. Conclusions: In this study, percutaneous and endoscopic contrast enhanced harmonic US techniques consistently revealed diffuse and focal types of AIP to have features consistent with vascularized lesions. Differentiation from the typically hypovascularized pancreatic adenocarcinoma was possible with CE (-E) US evaluation.

Serous pancreatic neoplasia, data and review

AIM To describe the imaging features of serous neoplasms of the pancreas using ultrasound, endoscopic ultrasound, computed tomography and magnetic resonance imaging. METHODS This multicenter international collaboration enhances a literature review to date, reporting features of 287 histologically confirmed cases of serous pancreatic cystic neoplasms (SPNs). RESULTS Female predominance is seen with most SPNs presenting asymptomatically in the 5th through 7th decade. Mean lesion size was 38.7 mm, 98% were single, 44.2% cystic, 46% mixed cystic and solid, and 94% hypoechoic on B-mode ultrasound. Vascular patterns and contrast-enhancement profiles are described as hypervascular and hyperenhancing. CONCLUSION The described ultrasound features can aid differentiation of SPN from other neoplastic lesions under most circumstances.