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Impact of introducing transnasal endoscopy on expanding diagnostic endoscopy servicesIntroduction: Demand for endoscopic services is outstripping capacity in the UK. Transnasal endoscopy (TNE) utilises a narrow calibre endoscope to pass through the nasal passages, thereby reducing retching and discomfort. It is better tolerated compared with standard transoral endoscopy (TOE) but is still rarely used as a diagnostic modality. There is still uncertainty about how well it performs against TOE in diagnostic ability, cost and efficiency. Methods: We explored utilising TNE to deal with the growing demand for endoscopy. We compared findings to TOE procedures undertaken during the same time period. We evaluated cost differences, duration/time in the department for procedures as well as quality of procedures (both in terms of performance indicators as well as image quality using the validated POLPREP score). Results: A total of 241 upper gastrointestinal endoscopy procedures were evaluated (100 TNE and 141 matched TOE) between December 2021 and February 2022. TNE outperformed TOE in obtaining >95% success rate in nationally approved key performance indicators (retroflexion and duodenal intubation, both p=0.026). It also was associated with better image quality in the oesophagus with a POLPREP A3 Score (excellent image quality) in 36/98 available images compared with 26/136 TOE (p=0.028) and was equivalent to TOE in the stomach and duodenum. TNE was identified as having a key role in facilitating complex cases, previously failed via the TOE route with a success rate in 11/12 (91.7%) of such cases. TNE also shows promise in correcting misdiagnoses of short-segment Barrett's oesophagus (39%) compared with TOE (14.8%) (p=0.087). Conclusion: TNE is an emerging endoscopic modality, which shows great promise in replacing TOE in most diagnostic circumstances. In a modern healthcare service, TNE is cheaper, better tolerated and outperforms TOE in multiple domains.
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The risk of Venous Thromboembolism in children with Inflammatory Bowel DiseaseBackground: Recent studies of children with inflammatory bowel disease (IBD) demonstrate an increased venous thromboembolism (VTE) risk. However, estimates of risk are variable and case numbers are limited. The aim of this study was to provide national estimates of the risk of VTE in children with IBD. Methods: Hospital Episode Statistics was used to identify patients diagnosed with either IBD or VTE before reaching 18 years of age between 2001 and 2019. Populations and subgroups are described, and the risks of developing VTE in the general and IBD populations were calculated. Results: Children with VTE following a diagnosis of IBD or in the previous 6 months (n = 85) and with VTE without IBD (n = 4160) were studied. The absolute risk in children with IBD was 9.42 (95% confidence interval [CI], 7.4-11.4) per 10 000 patient-years, compared with 0.18 (95% CI, 18-0.19) in children without IBD. Between 6 months prior to and 1 year following IBD diagnosis was the highest absolute risk period for VTE (18.0; 95% CI, 13.7-22.4). The relative risk of VTE in children with IBD vs children without IBD was greatest in younger patient groups: the relative risk for the age band 0 to 8 years was 96.5 (95% CI, 51.8-179.9) and for 9 to 11 years was 153.1 (95% CI, 81.2-288.8) vs 14.3 (95% CI, 10.3-20.0) for 15 to 17 years. Cerebral venous sinus thrombosis represented 17.6% of pediatric VTE events in IBD patients compared with 4.2% in children without IBD (P = .001). Conclusions: This study confirms the increased risk of VTE in children with IBD compared with children without IBD. The time of greatest VTE risk was around diagnosis. Cerebral venous sinus thrombosis was significantly more common in children with IBD than other children.
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Update from 2010 (standard operating procedure) : protocol for the 2024 British Society of Gastroenterology Guidelines on colorectal surveillance in inflammatory bowel diseaseIntroduction: The evolving landscape of inflammatory bowel disease (IBD) necessitates refining colonoscopic surveillance guidelines. This study outlines methodology adopted by the British Society of Gastroenterology (BSG) Guideline Development Group (GDG) for updating IBD colorectal surveillance guidelines. Methods and analysis: The 'Grading of Recommendations, Assessment, Development and Evaluation' (GRADE) approach, as outlined in the GRADE handbook, was employed. Thematic questions were formulated using either the 'patient, intervention, comparison and outcome' format or the 'current state of knowledge, area of interest, potential impact and suggestions from experts in the field' format. The evidence review process included systematic reviews assessed using appropriate appraisal tools. An extensive list of potential outcomes was compiled from literature and expert consultations and then ranked by GDG members. The top outcomes were identified for evidence synthesis in three key areas: utility of surveillance in IBD, quality of bowel preparation and use of advanced imaging techniques in colonoscopy for IBD. Risk thresholding exercises determined specific risk levels for different surveillance strategies and intervals. This approach enabled the GDG to establish precise thresholds for interventions based on relative and absolute risk assessments, directly informing the stratification of surveillance recommendations. Significance of effect sizes (small, moderate, large) will guide the final GRADE assessment of the evidence. Ethics and dissemination: Ethics approval is not applicable. By integrating clinical expertise, patient experiences and innovative methodologies like risk thresholding, we aim to deliver actionable recommendations for IBD colorectal surveillance. This protocol, complementing the main guidelines, offers GDGs, clinical trialists and practitioners a framework to inform future research and enhance patient care and outcomes.
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Automated decision making in Barrett's oesophagus : development and deployment of a natural language processing toolManual decisions regarding the timing of surveillance endoscopy for premalignant Barrett's oesophagus (BO) is error-prone. This leads to inefficient resource usage and safety risks. To automate decision-making, we fine-tuned Bidirectional Encoder Representations from Transformers (BERT) models to categorize BO length (EndoBERT) and worst histopathological grade (PathBERT) on 4,831 endoscopy and 4,581 pathology reports from Guy's and St Thomas' Hospital (GSTT). The accuracies for EndoBERT test sets from GSTT, King's College Hospital (KCH), and Sandwell and West Birmingham Hospitals (SWB) were 0.95, 0.86, and 0.99, respectively. Average accuracies for PathBERT were 0.93, 0.91, and 0.92, respectively. A retrospective analysis of 1640 GSTT reports revealed a 27% discrepancy between endoscopists' decisions and model recommendations. This study underscores the development and deployment of NLP-based software in BO surveillance, demonstrating high performance at multiple sites. The analysis emphasizes the potential efficiency of automation in enhancing precision and guideline adherence in clinical decision-making.
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The diagnostic accuracy of colon capsule endoscopy in Inflammatory bowel disease - a systematic review and meta-analysisColon capsule endoscopy (CCE) has regained popularity for lower gastrointestinal investigations since the COVID-19 pandemic. While there have been systematic reviews and meta-analyses on colonic polyp detection using CCE, there is a lack of comprehensive evidence concerning colonic inflammation. Therefore, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of CCE for colonic inflammation, predominantly ulcerative colitis (UC) and Crohn's disease (CD). Methods: We systematically searched electronic databases (EMBASE, MEDLINE, PubMed Central, and Cochrane Library) for studies comparing the diagnostic accuracy between CCE and optical endoscopy as the standard reference. A bivariate random effect model was used for the meta-analysis. Results: From 3797 publications, 23 studies involving 1353 patients were included. Nine studies focused on UC, and ten focused on CD. For UC, CCE showed a pooled sensitivity of 92% (95% CI, 88-95%), a specificity of 71% (95% CI, 35-92%), and an AUC of 0.93 (95% CI, 0.89-0.97). For CD, the pooled sensitivity was 92% (95% CI, 89-95%), and the specificity was 88% (95% CI, 84-92%), with an AUC of 0.87 (95% CI, 0.76-0.98). Overall, for inflammatory bowel disease, the pooled sensitivity, specificity, and AUC were 90% (95% CI, 85-93%), 76% (95% CI, 56-90%), and 0.92 (95% CI, 0.94-0.97), respectively. Conclusions: Despite the challenges around standardised disease scoring and the lack of histological confirmation, CCE performs well in diagnosing inflammatory bowel disease. It demonstrates high sensitivity in both UC and Crohn's terminal ileitis and colitis and high specificity in Crohn's disease. Further studies are needed to evaluate the diagnostic accuracy of other colonic inflammatory conditions.
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Duty of Candour legislation in post-colonoscopy colorectal cancer : a prospective cohort studyBackground: This study investigated the application of Duty of Candour (DoC) legislation in the context of post-colonoscopy colorectal cancers (PCCRCs). DoC mandates transparent disclosure of notifiable safety incidents to patients in the English National Health Service, including incidences leading to severe or moderate harm. This study aimed to analyze the application of DoC in PCCRCs, improve understanding of the legislation, and identify challenges in DoC implementation. Methods: A national audit of PCCRCs was conducted between September 2021 and May 2022. PCCRCs were identified using linked administrative datasets, and root-cause analyses were performed using structured templates. "Avoidability" and harm were categorized into specific levels, and guidance was provided on improving consistency in judgments. Results: 16% of 1724 PCCRCs resulted in major harm or death, of which 27% (75) were probably or definitely avoidable. Hospitals deemed DoC discharge necessary in only 53% of these cases. When including moderate harm, 11% of all PCCRCs would trigger DoC discharge, yet this was deemed necessary in only 45% of such cases. Conclusions: There is inconsistent application of DoC in PCCRC cases. Challenges include determining "avoidability" and harm, particularly when diagnosis is delayed. Clearer guidance and definitions of harm are needed to improve adherence to regulations.
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Pain and Operative Technologies Used in Office Hysteroscopy: A Systematic Review of Randomized Controlled Trials.Objective: To identify technologies associated with the least operative pain in women undergoing operative office hysteroscopic procedures. Data sources: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials were searched until January 2021 using a combination of keywords "hysteroscop*," "endometrial ablation," "outpatient," "ambulatory," "office," and associated Medical Subject Headings. Methods of study selection: Randomized controlled trials evaluating the effect of hysteroscopic devices on pain experienced by women undergoing operative office hysteroscopy were included. Data were also collected regarding efficacy, procedural time, adverse events, and patient/clinician acceptability and/or satisfaction. Tabulation, integration, and results: The search returned 5347 records. Ten studies provided data for review. Two trials compared endometrial ablation using bipolar radiofrequency with thermal balloon energy, with no significant difference in pain observed (p <.05). Seven trials evaluated technologies for endometrial polypectomy, of which, 4 compared energy modalities: miniature bipolar electrode resection against resectoscopy (N = 1), morcellation (N = 2), and diode laser resection (N = 1). Two studies compared hysteroscope diameter, and one study compared methods of polyp retrieval. A significant reduction in pain was found using morcellators rather than miniature bipolar electrosurgical devices (p <.001), 22Fr rather than 26Fr resectoscopes (p <.001), and 3.5-mm fiber-optic hysteroscopes with 7Fr forceps rather than 5-mm lens-based hysteroscopes with 5Fr forceps (p <.05). One study investigating septoplasty showed significant reduction in pain when cold mini-scissors, rather than a miniature bipolar electrode, were used (p = .013). Average procedural times ranged from 5 minutes 28 seconds to 22 minutes. The incidence of adverse events was low, and data regarding efficacy and acceptability/satisfaction were limited. Conclusion: Pain is reduced when mechanical technologies such as morcellators and scissors are used compared with electrical devices for removing structural lesions in the office. For hysteroscopic and ablative procedures, smaller and quicker devices are less painful. Large-scale RCTs investigating patient pain and experience with modern operative devices in the office setting are urgently needed.
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Prediction of long-term survival after gastrectomy using random survival forests.Background: No well validated and contemporaneous tools for personalized prognostication of gastric adenocarcinoma exist. This study aimed to derive and validate a prognostic model for overall survival after surgery for gastric adenocarcinoma using a large national dataset. Methods: National audit data from England and Wales were used to identify patients who underwent a potentially curative gastrectomy for adenocarcinoma of the stomach. A total of 2931 patients were included and 29 clinical and pathological variables were considered for their impact on survival. A non-linear random survival forest methodology was then trained and validated internally using bootstrapping with calibration and discrimination (time-dependent area under the receiver operator curve (tAUC)) assessed. Results: The median survival of the cohort was 69 months, with a 5-year survival of 53.2 per cent. Ten variables were found to influence survival significantly and were included in the final model, with the most important being lymph node positivity, pT stage and achieving an R0 resection. Patient characteristics including ASA grade and age were also influential. On validation the model achieved excellent performance with a 5-year tAUC of 0.80 (95 per cent c.i. 0.78 to 0.82) and good agreement between observed and predicted survival probabilities. A wide spread of predictions for 3-year (14.8-98.3 (i.q.r. 43.2-84.4) per cent) and 5-year (9.4-96.1 (i.q.r. 31.7-73.8) per cent) survival were seen. Conclusions: A prognostic model for survival after a potentially curative resection for gastric adenocarcinoma was derived and exhibited excellent discrimination and calibration of predictions.
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Recurrent pyroglutamic acidosis in the context of undiagnosed liver cirrhosis - a case reportMetabolic associated fatty liver disease, previously known as nonalcoholic fatty liver disease, is the most common cause of chronic liver disease across all ethnic groups; however, it remains enormously underestimated.1 , 2 Sepsis, hepatotoxic medications and malnutrition in the acute settings on top of unknown cirrhosis can lead to decompensation and various metabolic complications. Pyroglutamic acidosis is a rarely recognised cause for unexplained high anion gap metabolic acidosis that is felt to be frequently underdiagnosed. Particular patients at risk include women, the elderly, those on regular paracetamol and those suffering with malnourishment or sepsis. Other risk factors include alcohol abuse and chronic liver disease (3). We present the case of a patient with recurrent episodes of pyroglutamic acidosis and encephalopathy in the context of undiagnosed nonalcoholic fatty liver disease with cirrhosis.
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The outcomes of emergency hospital admissions with non-malignant upper gastrointestinal bleeding in England between 2003 and 2015Background: Upper gastrointestinal bleeding (UGIB) is a common medical emergency with significant mortality. Despite developments in endoscopic and clinical management, only minor improvements in outcomes have been reported. Methods: This was a retrospective cohort study of patients with non-malignant UGIB emergency admissions in England between 2003 and 2015, using Hospital Episode Statistics. Multilevel logistic regression analysis examined the associations with mortality. Results: 242 796 patients with an UGIB admission were identified (58.8 % men; median age 70 [interquartile range (IQR) 53 - 81]). Between 2003 and 2015, falls occurred in both 30-day mortality (7.5 % to 7.0 %; P < 0.001) and age-standardized mortality (odds ratio (OR) 0.74, 95 % confidence interval [CI] 0.69 - 0.80; P < 0.001), including from variceal bleeding (OR 0.63, 95 %CI 0.45 - 0.87; P < 0.005). Increasing co-morbidity (Charlson score > 5, OR 2.94, 95 %CI 2.85 - 3.04; P < 0.001), older age (> 83 years, OR 6.50, 95 %CI 6.09 - 6.94; P < 0.001), variceal bleeding (OR 2.03, 95 %CI 1.89 - 2.18; P < 0.001), and a weekend admission (Sunday, OR 1.18, 95 %CI 1.12 - 1.23; P < 0.001) were associated with 30-day mortality. Of deaths at 30 days, 8.9 % were from ischemic heart disease (IHD) and the cardiovascular age-standardized mortality rate following UGIB was high (IHD deaths within 1 year, 1188.4 [95 %CI 1036.8 - 1353.8] per 100 000 men in 2003). Conclusions: Between 2003 and 2015, 30-day mortality among emergency admissions with non-malignant UGIB fell by 0.5 % to 7.0 %. Mortality was higher among UGIB admissions at the weekend, with important implications for service provision. Patients with UGIB had a much greater risk of subsequently dying from cardiovascular disease and addressing this risk is a key management step in UGIB.
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The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel DiseaseBackground: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet's syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM. Methods: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis. Results: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn's disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86). Conclusions: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN. Keywords: Crohn’s disease; Sweet’s syndrome; aphthous stomatitis; dermatological; erythema nodosum; extra intestinal manifestations; inflammatory bowel disease; psoriasis; pyoderma gangrenosum; ulcerative colitis.
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Impact of postoperative chemotherapy on survival for oesophagogastric adenocarcinoma after preoperative chemotherapy and surgery.Background: Perioperative chemotherapy is widely used in the treatment of oesophagogastric adenocarcinoma (OGAC) with a substantial survival benefit over surgery alone. However, the postoperative part of these regimens is given in less than half of patients, reflecting uncertainty among clinicians about its benefit and poor postoperative patient fitness. This study estimated the effect of postoperative chemotherapy after surgery for OGAC using a large population-based data set. Methods: Patients with adenocarcinoma of the oesophagus, gastro-oesophageal junction or stomach diagnosed between 2012 and 2018, who underwent preoperative chemotherapy followed by surgery, were identified from a national-level audit in England and Wales. Postoperative therapy was defined as the receipt of systemic chemotherapy within 90 days of surgery. The effectiveness of postoperative chemotherapy compared with observation was estimated using inverse propensity treatment weighting. Results: Postoperative chemotherapy was given to 1593 of 4139 patients (38.5 per cent) included in the study. Almost all patients received platinum-based triplet regimens (4004 patients, 96.7 per cent), with FLOT used in 3.3 per cent. Patients who received postoperative chemotherapy were younger, with a lower ASA grade, and were less likely to have surgical complications, with similar tumour characteristics. After weighting, the median survival time after postoperative chemotherapy was 62.7 months compared with 50.4 months without chemotherapy (hazard ratio 0.84, 95 per cent c.i. 0.77 to 0.94; P = 0.001). Conclusion: This study has shown that postoperative chemotherapy improves overall survival in patients with OGAC treated with preoperative chemotherapy and surgery.
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Diagnostic yield from symptomatic gastroscopy in the UK : British Society of Gastroenterology analysis using data from the National Endoscopy DatabaseObjective: This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation. Design: A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett's oesophagus (BO) diagnosis). Adjusted positive predictive values (aPPVs) were calculated. Results: 382 370 diagnostic gastroscopies were analysed; 30.4% were performed in patients aged <50 and 57.7% on female patients. The overall unadjusted PPV for cancer was 1.0% (males 1.7%; females 0.6%, p<0.01). Other major pathology was found in 9.1% of procedures, whereas 89.9% reported only normal findings or minor pathology (92.5% in females; 94.6% in patients <50).Highest cancer aPPVs were reached in the over 50s (1.3%), in those with dysphagia (3.0%) or weight loss plus another symptom (1.4%). Cancer aPPVs for all other symptoms were below 1%, and for those under 50, remained below 1% regardless of symptom. Overall, 73.7% of gastroscopies were carried out in patient groups where aPPV cancer was <1%.The overall unadjusted PPV for BO was 4.1% (males 6.1%; females 2.7%, p<0.01). The aPPV for BO for reflux was 5.8% and ranged from 3.2% to 4.0% for other symptoms. Conclusions: Cancer yield was highest in elderly male patients, and those over 50 with dysphagia. Three-quarters of all gastroscopies were performed on patients whose cancer risk was <1%, suggesting inefficient resource utilisation.
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X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.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).
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The time to Inflammatory Bowel Disease diagnosis for patients presenting with abdominal symptoms in primary care and its association with emergency hospital admissions and surgery : a retrospective cohort studyBackground: Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed to evaluate this and assess whether time to diagnosis is associated with clinical outcomes. Methods: A retrospective cohort study using English primary care data from January 1, 2010, to December 31, 2019, linked to hospital admission data was undertaken. Patients were followed from the first IBD-related presentation in primary care to IBD diagnosis. Associations of time to diagnosis exceeding a year were assessed using a Robust Poisson regression model. Associations between time to diagnosis and IBD-related emergency hospital admissions and surgery were assessed using Poisson and Cox proportional hazards models, respectively. Results: Of 28 092 IBD patients, 60% had ulcerative colitis (UC) and 40% had Crohn's disease (CD). The median age was 43 (interquartile range, 30-58) years and 51.9% were female. Median time to diagnosis was 15.6 (interquartile range, 4.3-28.1) months. Factors associated with more than a year to diagnosis included female sex (adjusted risk ratio [aRR], 1.23; 95% CI, 1.21-1.26), older age (aRR, 1.05; 95% CI, 1.01-1.10; comparing >70 years of age with 18-30 years of age), obesity (aRR, 1.03; 95% CI, 1.00-1.06), smoking (aRR, 1.05; 95% CI, 1.02-1.08), CD compared with UC (aRR, 1.13; 95% CI, 1.11-1.16), and a fecal calprotectin over 500 μg/g (aRR, 0.89; 95% CI, 0.82-0.95). The highest quartile of time to diagnosis compared with the lowest was associated with IBD-related emergency admissions (incidence rate ratio, 1.06; 95% CI, 1.01-1.11). Conclusion: Longer times to IBD diagnoses were associated with being female, advanced age, obesity, smoking, and Crohn's disease. More IBD-related emergency admissions were observed in patients with a prolonged time to diagnosis.
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National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett's oesophagus and stage I oesophageal adenocarcinomaBarrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment.
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An international genome-wide meta-analysis of primary biliary cholangitis: novel risk loci and candidate drugsBackgrounds & 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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Gut microbiota in celiac diseaseCeliac disease (CD) is an autoimmune gastrointestinal disease triggered by dietary gluten, occurring in genetically predisposed individuals. Currently, a gluten-free diet is the only current evidenced-based treatment for CD. With the growing prevalence of this condition worldwide, adjuvant therapies are needed. We understand that there are several factors that influence the pathogenesis of the condition. There is a complex interplay between genetics, environmental triggers, the immune system and gut microbiota. Recently, there has been a growing focus on the significance of gut microbiota in several autoimmune-based conditions. In particular, there has been much research involving the role of microbial flora and CD. Here, in this mini-review, we highlight the importance of gut microbiota and the symbiotic relationship with the host, introduce key factors that influence the development of the intestinal flora in early colonization, and ultimately explore its role in the pathogenesis of CD.
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Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagusBackground: Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ). Methods: BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined. Results: 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma. Conclusion: Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.
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A Basic Intervention to Improve Compliance With Thromboprophylaxis in Patients With Neck of Femur Fracture.Background: Venous thromboembolism (VTE) is a significant complication following orthopedic intervention for neck of femur fracture. Our aim was to evaluate compliance with The National Institute for Health and Care Excellence guidance surrounding VTE prophylaxis before and after a brief intervention in an orthopedic department at a district general hospital. Methods: A 2-cycle quality improvement project was conducted. The primary outcome measure was whether adequate thromboprophylaxis was appropriately prescribed. For the intervention between the 2 cycles, posters were placed in key prescribing areas of all orthopedic wards. Results: In cycle 1, 63 (76.8%) patients were correctly prescribed enoxaparin, and 14 (17.1%) were prescribed other anticoagulants, leaving 5 patients (6.1%) who did not receive thromboprophylaxis for no apparent reason. In cycle 2, 56 (87.5%) patients were correctly prescribed enoxaparin, and the remaining patients were covered with alternative therapies. Conclusion: Small but basic interventions can lead to improvements in VTE prophylaxis prescribing. Future focus should be on implementing similar interventions across hospitals.