RSS 1.0Gastroenterology and Hepatology Services
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Retrospective study on pain management pathway for patients with suspected renal/ ureteric colic in a U.K. accidents and emergency department: A quality improvement project.Competing Interests: No competing interests were disclosed. Background: In acute settings around the globe, renal/ureteric colic remains one of the most common diagnoses for patients presenting with loin-to-groin pain. Even though management spans from medical expulsive therapies to surgical options, pain as a significant component of a patient's presentation must be dealt with quickly, decisively, and safely, as it can be excruciating and its effects on overall health are dire. This study aimed to explore compliance with the National Institute for Health and Care Excellence (NICE) guidelines for pain management in patients with suspected renal/ureteric colic. It includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs), intravenous paracetamol, and opioids as first-, second-, and third-line analgesics, respectively, and does not offer antispasmodics. In the event of deviations from the standard, the aim was to put in corrective measures, followed by re-exploration of compliance with patient care. Methods: This study involved a single healthcare facility with the study type being retrospective before interventions and prospective after interventions. In the first cycle, we retrieved and analysed 78 patients records whom had been suspected to have renal/ureteric colic between July and September 2022. The inclusion criteria were documented complaints of "flank/loin-to-groin pain" and diagnosis prior to performing diagnostic tests. We surveyed the first-, second-, and third-line painkillers issued, and whether an antispasmodic was given. We collected and entered data into a Microsoft Excel file and correlated it with NICE standards. Having found deviations from the standard, we conducted interventions, allowed time for clinicians to adapt, and re-explored compliance using patient case records [n=58] between February and May 2023. Results: In the 1 st cycle, 78 patients were suspected of having renal/ureteric colic. M: F = 1.2:1. Non-contrast computerized tomography of the kidney ureters and bladder (NC-CTKUB) confirmed 87% of patients with stones and 3% had no stones. NC-CTKUB was not performed in 9% of patients because they were young, and urinalysis showed no microscopic hematuria. One patient had discharged against medical advise before the NC-CTKUB was performed. Compliance with the NICE pain management guidelines for suspected renal/ureteric colic was full in 23% of cases but unsatisfactory in 78% of cases. In the 2 nd cycle, M: F = 1.5:1, NC-CTKUB was not re-audited, as the first cycle study yielded excellent results, and our action plan resulted in an NICE pain management compliance rate of 56%. Although our interventions resulted in improvements of more than twice the initial results, work still needs to be performed. Conclusion: Clinicians' ability to correctly diagnose renal/ureteric colic is remarkable. However, the pain management compliance rate indicates room for improvement. This may be due to the limited awareness of the NICE guideline or the fact that the clinical team has an affinity for certain analgesics compared to others. We propose the need to consider select variables to existing standard guidelines to enhance compliance for improved patient care. (Copyright: © 2024 Ojo C et al.)
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Spontaneous Jejunal perforation in coeliac disease: diagnostic dilemma and navigating treatment beyond gluten-free diet in the absence of refractory diseaseCoeliac disease (CD) is relatively common in the West, affecting up to 1% undergoing serological screening and 0.6% histologically confirmed diagnosis of the population [1]. The pathophysiology involves a complex interplay between genetic susceptibility, environmental, and immunologic factors, resulting in chronic inflammation. 95% of people with CD exhibits the HLA-DQ2 and HLA-DQ8 genes which are crucial for presenting gluten-derived peptides to immune cells. The end result is activation of CD4+ T-helper cells in the lamina propria. These cells release inflammatory cytokines such as interferon-gamma that drive chronic inflammation and ultimately villous atrophy [2]. While treatment is mainly conservative and mandatory avoidance of gluten-containing diet, a small proportion fails to response to this measure, leading to progressive disease and refractory malabsorption. This is called the refractory CD (RCD). Diagnosis of this requires absolute proof that Gluten-Free Diet (GFD) has been adopted for at least 12 months, apart from exclusion of other potential causes that may mimic CD [3]. RCD is categorised into type 1 and type 2, based on the presence of aberrant intraepithelial lymphocytes, with the latter carrying a worse prognosis. Most cases of CD associated Ulcerative Jejunitis (UJ), a chronic immune-mediated deep ulceration within the jejunum is found coexisting with type 2 RCD. Very few presents with UJ alone with no RCD association.
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Cost-effectiveness of a novel, non-active implantable device as a treatment for refractory gastro-esophageal reflux disease.Aims: Gastro-esophageal reflux disease (GERD) is a common, chronic gastrointestinal condition characterized by heartburn, chest pain, regurgitation, and bloating. The current standard of care includes chronic treatment with proton pump inhibitors (PPIs) or, in selected patients, laparoscopic anti-reflux surgery. RefluxStop is a novel implantable device indicated for GERD patients eligible for laparoscopic surgical treatment. The aim of this analysis was to assess the cost-effectiveness of RefluxStop against available treatment options for GERD. Material and methods: A Markov model was developed to assess the cost-effectiveness of RefluxStop compared with PPI-based medical management (MM) and two surgical management options, LNF and magnetic sphincter augmentation (MSA, LINX system), in people with GERD. Clinical outcomes and costs were estimated over a lifetime horizon from the UK National Health Service perspective and an annual discount rate of 3.5% was applied. Results: RefluxStop showed favorable surgical outcomes compared with both LNF and MSA. The base case incremental cost-effectiveness ratios compared with MM, LNF, and MSA were £4,156, £6,517, and £249 per QALY gained, respectively. At the UK cost-effectiveness threshold of £20,000 per QALY gained, the probability that RefluxStop was cost-effective against MM, LNF, and MSA was 100%, 93%, and 100%, respectively. Limitations: The model presented the results of a comparison, with evidence for RefluxStop derived from its single-arm CE mark trial and that for comparators from the literature. The varied clinical care pathway of individual GERD patients was necessarily simplified for modeling purposes, and necessary assumptions were made; however, the model results proved robust to sensitivity analyses. Conclusions: Introduction of RefluxStop was estimated to extend life expectancy and improve quality-of-life of GERD patients when compared with MM, LNF, and MSA. The results of the cost-effectiveness analysis demonstrated that RefluxStop is highly likely to be a cost-effective treatment option within NHS England.
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Attitudes to radiation safety and cholangiogram interpretation in endoscopic retrograde cholangiopancreatography (ERCP): A UK surveyBackground Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) exposes staff and patients to potentially harmful ionizing radiation. We performed a UK survey to explore trainee and trainer attitudes to radiation protection and cholangiogram interpretation in ERCP. Methods An electronic 10-point survey was prospectively distributed to endoscopy unit leads, training programme directors between October and November 2019. Only UK-based ERCP trainees and trainers with hands-on procedural exposure were eligible for the survey. Results The survey was completed by 107 respondents (58 trainees and 49 trainers), with an estimated overall response rate of 46%. Overall, 49% of respondents were up to date with their radiation protection course, 38% were aware of European Basic safety standards directive (BSSD), 38% wore radiation protection goggles, and 40% were aware of the average radiation screening dose per ERCP procedure. Compared with trainers, trainees were less likely to routinely wear thyroid protection shields (76% vs 92%; p=0.028), have awareness of the BSSD (20% vs 49%; p=0.037) or know their average procedural radiation dosages (21% vs 63%; p<0.001). With regard to cholangiogram interpretation, only 26% had received formal training, with 97% of trainees expressing a desire for further training. Conclusion This survey highlights a relative complacency in safety attitudes to radiation protection during ERCP. These data provide impetus to improve training and quality assurance in radiation protection, which should be regarded as a mandatory safety aspect prior to commencing hands-on ERCP training.
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Symptomatic vitamin A deficiency in a patient on long-term colesevelam.Introduction Bile acid sequestrants including colesevelam are increasingly used by gastroenterologists. The risk of fat-soluble vitamin deficiency when sequestrants are used is recognised. Vitamin A deficiency is uncommon in the UK, but delayed diagnosis can cause irreversible blindness. There are no guidelines for the monitoring of fat-soluble vitamin levels. Case discussion We describe a 63-year-old man who had a neuroendocrine tumour, treated with ileal resection and lanreotide and complicated by the development of severe bile acid malabsorption, pancreatic exocrine insufficiency and intermittent episodes of small intestinal bacterial overgrowth. Three and a half years after starting colesevelam, he developed progressive visual symptoms due to severe vitamin A deficiency. After diagnosis and parenteral vitamin A replacement, his visual symptoms improved but have not resolved. Conclusions Clinicians prescribing bile acid sequestrants should be aware that vitamin A deficiency may arise and should consider regular monitoring of serum levels.
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Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionalsRamadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients' risk as low or moderate, high, or very high. We advise all patients at very high risk and most patients at high risk to not observe fasting due to potential harm. For others, we offer nuanced recommendations on medication rescheduling, lifestyle changes, and tailored fasting advice to minimise adverse effects. Shared decision making that respects patients' religious motivations is essential, with risks and benefits carefully weighed on an individual basis.
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Real-world clinical effectiveness of ustekinumab in the treatment of Crohn's disease in the East Midlands UK.Objectives To evaluate the effectiveness of ustekinumab in treating Crohn’s disease (CD) in a UK real-world setting. Design This was a multicentre, retrospective observational study of patients (aged ≥18 years) with CD or inflammatory bowel disease of unclassified type (IBDU) starting ustekinumab between 11 November 2016 and 1 August 2020 across eight English hospitals. The primary objective was to determine the proportion of patients achieving corticosteroid-free remission at week 52 for patients with CD/IBDU following initiation with ustekinumab. Corticosteroid-free remission was defined as achieving a clinical Harvey-Bradshaw Index (HBI) score of ≤4 and corticosteroid-free status. Results The analysis included 422 patients with CD/IBDU. Corticosteroid-free remission was 41% (68/166) at week 16, 41% (47/115) at week 30 and 48% (38/80) at week 52. Clinical remission was 51% (85/166) at week 16 and 50% (40/80) at week 52. Clinical response was 34% (43/125) at week 16 and 32% (17/53) at week 52. Objective remission was 40% (4/10) at week 16 and 70% (7/10) at week 52. Corticosteroid-free remission at week 52 was achieved in patients with previous exposure to 1–2 biologics and/or small oral molecules (56%; 35/63), those without surgical history (64%; 16/25), and those without penetrating disease (54%; 29/54). Patients who achieved clinical remission at week 16 were more likely to achieve corticosteroid-free remission at week 52 (70%; 14/20) versus those who did not (20%; 4/20). In total, 37 adverse events occurred in 21 patients. Conclusion This multicentre study provides real-world experience of ustekinumab in patients with CD/IBDU in England.
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Advance care planning in end-stage cirrhosis in a UK district general hospital.Advance care planning (ACP) has been shown to improve health-related quality of life (QoL) for patients with advanced liver disease and their caretakers.1,2 It is increasingly recognised that ACP alongside palliative input should be initiated in these patients early to help to address their needs as their disease progresses and facilitate completion of advance directives via discussion between healthcare professionals, patients and their carers.2 This study assessed the local practice of implementing ACP in patients with end-stage cirrhosis against international recommendations. We also explored quality of life (QoL), depression score, religious belief and spiritual needs in these patients using questionnaires. The findings of the study provide a better insight of our local patient cohort with advanced cirrhosis and allow us to improve our approach in delivering ACP to these patients.
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Can an educational video improve the adequacy of bowel preparation for patients undergoing their first colonoscopy? Results of the EBOPS RCT.Background and study aims The aim of this study was to assess the effect of an educational video on the quality of bowel preparation of patients from a UK population attending for their first colonoscopy. Patients and methods A prospective, endoscopist-blinded trial with 1:1 allocation was performed. Patients referred for their first colonoscopy were recruited between February 2019 and December 2019. All participants were prescribed Moviprep and received the trial site’s standard written bowel preparation instructions, with the intervention group also receiving a bespoke educational video. Adequacy of bowel preparation (defined as a Boston Bowel Preparation Scale of ≥2 in each segment of the bowel) and polyp detection rates (PDRs) were compared. Fisher’s chi squared test was utilized with P <0.05 as the threshold for significance. Results A total of 509 participants completed the trial from six centers; 251 were randomized to the intervention group. The mean age was 57 years and 52.3% were female. The primary endpoint was met with an adequacy rate of 216 of 251 (86.1%) in the intervention group, compared with 205 of 259 (79.1%) in the control group ( P <0.05, odds ratio [OR] 1.626, 95% CI 1.017–2.614). The PDR was significantly higher in the intervention group (39% vs 30%, OR 1.51, 95% CI 1.04–2.19, P <0.05). Conclusions An educational video leads to improved bowel preparation for patients attending for their first colonoscopy, and is also associated with greater detection of polyps. Widespread adoption of an educational video incurs minimal investment, but would reduce the number of inadequate procedures, missed pathology, and the cost that both these incur.
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Budget Impact of RefluxStopTM as a Treatment for Patients with Refractory Gastro-oesophageal Reflux Disease in the United KingdomBackground: Gastro-oesophageal reflux disease (GORD) is a common condition associated with heartburn and regurgitation. Standard of care for GORD patients in the UK involves initial treatment with proton pump inhibitors (PPIs) and laparoscopic antireflux surgery in patients unwilling to continue or intolerant of long-term PPI treatment. Recently, RefluxStop™, a novel, implantable medical device, has proven to be an efficacious and cost-effective treatment for patients with GORD. The current analysis aimed to describe the budget impact of introducing RefluxStop™ within National Health Service (NHS) England and Wales. Objectives: To estimate the more immediate, short-term clinical and economic effects of introducing RefluxStop™ as a therapeutic option for patients with GORD treated within NHS England and Wales. Methods: A model adherent to international best practice guidelines was developed to estimate the budget impact of introducing RefluxStop™ over a 5-year time horizon, from an NHS perspective. Two hypothetical scenarios were considered, one without RefluxStop™ (comprising PPI treatment, laparoscopic Nissen fundoplication, and magnetic sphincter augmentation using the LINX® system) and one with RefluxStop™ (adding RefluxStop™ to the aforementioned treatment options). Clinical benefits and costs associated with each intervention were included in the analysis. Results: Over 5 years, introducing RefluxStop™ allowed the avoidance of 347 surgical failures, 39 reoperations, and 239 endoscopic esophageal dilations. The financial impact of introducing RefluxStop™ was £3 029 702 in year 5, corresponding to a 1.68% increase in annual NHS spending on GORD treatment in England and Wales. Discussion: While the time horizon was too short to capture some of the adverse events of PPIs and complications of GORD, such as the development of Barrett’s esophagus or esophageal cancer, the use of RefluxStop™ was associated with a substantial reduction in surgical complications, including surgical failures, reoperations, and endoscopic esophageal dilations. This favorable clinical profile resulted in cost offsets for the NHS and contributed to the marginal budget impact of RefluxStop™ estimated in the current analysis. Conclusions: Introducing RefluxStop™ as a treatment option for patients with GORD in England and Wales may be associated with clinical benefits at the expense of a marginal budget impact on the NHS.
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Cost-effectiveness of a novel, non-active implantable device as a treatment for refractory gastro-esophageal reflux disease.Aims: Gastro-esophageal reflux disease (GERD) is a common, chronic gastrointestinal condition characterized by heartburn, chest pain, regurgitation, and bloating. The current standard of care includes chronic treatment with proton pump inhibitors (PPIs) or, in selected patients, laparoscopic anti-reflux surgery. RefluxStop is a novel implantable device indicated for GERD patients eligible for laparoscopic surgical treatment. The aim of this analysis was to assess the cost-effectiveness of RefluxStop against available treatment options for GERD. Material and methods: A Markov model was developed to assess the cost-effectiveness of RefluxStop compared with PPI-based medical management (MM) and two surgical management options, LNF and magnetic sphincter augmentation (MSA, LINX system), in people with GERD. Clinical outcomes and costs were estimated over a lifetime horizon from the UK National Health Service perspective and an annual discount rate of 3.5% was applied. Results: RefluxStop showed favorable surgical outcomes compared with both LNF and MSA. The base case incremental cost-effectiveness ratios compared with MM, LNF, and MSA were £4,156, £6,517, and £249 per QALY gained, respectively. At the UK cost-effectiveness threshold of £20,000 per QALY gained, the probability that RefluxStop was cost-effective against MM, LNF, and MSA was 100%, 93%, and 100%, respectively. Limitations: The model presented the results of a comparison, with evidence for RefluxStop derived from its single-arm CE mark trial and that for comparators from the literature. The varied clinical care pathway of individual GERD patients was necessarily simplified for modeling purposes, and necessary assumptions were made; however, the model results proved robust to sensitivity analyses. Conclusions: Introduction of RefluxStop was estimated to extend life expectancy and improve quality-of-life of GERD patients when compared with MM, LNF, and MSA. The results of the cost-effectiveness analysis demonstrated that RefluxStop is highly likely to be a cost-effective treatment option within NHS England.
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Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study.Background: Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods: This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results: Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions: After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.
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A colitis bundle initiative to improve the outcome of acute IBD colitis patientsIntroduction Early detection and assessment of the severity are crucial in the management of an IBD flare-ups. This is so steroid therapy, the initial remission-inducing treatment can be administered at that right time. However, in those with severe colitis where steroid therapy is inadequate, often rescue therapy, either in the form of biologics or surgery is required. Simple measures during flare-ups would help to achieve this and potentially be life-saving. Methods This project aims to review the current performance against the IBD management NICE guideline and to introduce a trust-wide Colitis bundle to ensure junior doctors and consultants can make important decisions regarding colitis patient care. A retrospective audit was carried out on 40 In-patients with a diagnosis of an acute flare of ulcerative and Crohn’s colitis over the year 2021. A proforma was created based on the latest colitis management guidelines. This reviewed step-by-step management plans over the first 3 days period – which, if perfectly followed, will ensure deliverance of rescue therapy safely by day 3 or day 4. Results The results showed a delay in managing acute IBD flare-ups, in which the initial steroid therapy was given to only 82.8% and the VTE prophylaxis was commenced only on 65.7% of the cases. Recognition of colitis severity as defined by Truelove and Witt’s score was also poor as it happened in only 20% of the cases. This downplayed the urgency of acknowledging the need for an escalated treatment strategy, which subsequently resulted in a delay in pre-biologics screening test – this happened in 25.7% of cases only within the first 2 days of diagnosis. As this test was essential in those requiring rescue biologic therapies, this resulted in an overall delay in its initiation as demonstrated in Figure 1. Abstract P21 Figure 1 Time between the biologic therapy decision and its first dose administration Conclusions The quality improvement project has demonstrated poor recognition and assessment of acute IBD flare-ups as recommended by the NICE guideline. This subsequently led to a delay in initiation of the steroid therapy, pre-biologic screening test, and initiation of rescue biologic therapies in those with severe colitis. This is due to the lack of exposure among junior and senior doctors towards the guideline. As a response, a mass education at a Trust level for the doctors was recommended and a colitis bundle was constructed, which comprised of evidence-based action plans checklist divided into Day 1 to Day 3 to make sure that all the aspects are not missed.
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Increased ERCP Volume Improves Cholangiogram Interpretation - A New Performance Measure for ERCP Training?Background/aims: Cholangiogram interpretation is not used as a key performance indicator (KPI) of endoscopic retrograde cholangiopancreatography (ERCP) training, and national societies recommend different minimum numbers per annum to maintain competence. This study aimed to determine the relationship between correct ERCP cholangiogram interpretation and experience. Methods: One hundred fifty ERCPists were surveyed to appropriately interpret ERCP cholangiographic findings. There were three groups of 50 participants each: "Trainees," "Consultants Group 1" (performed >75 ERCPs per year), and "Consultants Group 2" (performed >100 ERCPs per year). Results: Trainees was inferior to Consultants Groups 1 and 2 in identifying all findings except choledocholithiasis outside the intrahepatic duct on the initial or completion/occlusion cholangiogram. Consultants Group 1 was inferior to Consultants Group 2 in identifying Strasberg type A bile leaks (odd ratio [OR] 0.86, 95% confidence interval [CI] 0.77-0.96), Strasberg type B (OR 0.84, 95% CI 0.74-0.95), and Bismuth type 2 hilar strictures (OR 0.81, 95% CI 0.69-0.95). Conclusions: This investigation supports the notion that cholangiogram interpretation improves with increased annual ERCP case volumes. Thus, a higher annual volume of procedures performed may improve the ability to correctly interpret particularly difficult findings. Cholangiogram interpretation, in addition to bile duct cannulation, could be considered as another KPI of ERCP training.
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An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.Backgrounds & aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. Methods: We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts. Results: We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders. Conclusions: This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. Lay summary: Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.
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Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study.Objectives: This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. Methods: This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. Results: A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. Conclusion: The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.
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X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.Background & Aims Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Results Single-marker association analyses found approximately 100 loci displaying P < 5 × 10–4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10–6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028–1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09–1.26; P = 9.93 × 10–8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10–9; OR, 1.33; 95% CI, 1.21–1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.
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Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinomaGenome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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The impact of reader fatigue on the accuracy of capsule endoscopy interpretationBackground and aims: Capsule endoscopy (CE) interpretation requires the review of many thousands of images, with lesions often limited to just a few frames. In this study we aim to determine whether lesion detection declines according to the number of capsule videos read. Methods: 32 participants, 16 of which were novices (NR) and 16 experienced (ER) capsule readers took part in this prospective evaluation study. Participants read six capsule cases with a variety of lesions, in a randomly assigned order during a single sitting. Psychomotor Vigilance Tests and Fatigue Scores were recorded prior to commencing and then after every two capsules read. Changes in lesion detection and measures of fatigue were assessed across the duration of the study. Results: Mean agreement with the predefined lesions was 48.3% (SD:16.1), and 21.3% (SD:15.1) for the experienced and novice readers respectively. Lesion detection declined amongst experienced reader after the first study (p = 0.01), but remained stable after subsequent capsules read, while NR accuracy was unaffected by capsule numbers read. Objective measures of fatigue did not correlate with reading accuracy. Conclusion: This study demonstrates that reader accuracy declines after reading just one capsule study. Subjective and objective measures of fatigue were not sufficient to predict the onset of the effects of fatigue.
