The COLO-COHORT (Colorectal Cancer Cohort) study: Protocol for a multi-centre, observational research study and development of a consent-for-contact research platform.

AIM: The COLO-COHORT study aims to produce a multi-factorial risk prediction model for colorectal neoplasia that can be used to target colonoscopy to those at greatest risk of colorectal neoplasia, ensuring that people are not investigated unnecessarily and maximizing the use of limited endoscopy resources. The study will also explore the link between neoplasia and the human gut microbiome. Additionally, the study aims to generate a cohort of colonoscopy patients who are 'research ready' through the development of a consent-for-contact (C4C) platform, to facilitate a range of colorectal cancer prevention studies to be conducted at scale and speed. METHODS AND ANALYSIS: This is a multi-centre observational study involving sites across the UK. Recruitment is over a 6-year period (2019-2025). Patients recruited to the study are those attending for colonoscopy. Patients are recruited into two groups, namely observational group A (10 000 patients) and C4C group B (10 000 patients), known as COLO-SPEED (Colorectal Cancer Screening Prevention Endoscopy and Early Diagnosis; https://colospeed.uk). Patients complete a health questionnaire, provide anthropometric measurements and submit biosamples (blood and stool-depending on the part of the study they are recruited into). Patients' colonoscopy and histology findings are also recorded. Models of factors associated with the presence of neoplasia at colonoscopy will be developed using logistic or multinomial regression. For internal validation, model discrimination and calibration will be assessed and bootstrapping and cross-validation approaches used. To enable long-term follow-up for outcomes related to colorectal cancer and polyps, patients are asked to consent to follow-up through data linkage with national databases. DISSEMINATION: In keeping with good research practice, following analysis by the study team the study investigators will make the anonymized dataset available to other researchers. The C4C platform will also be accessible to other researchers. The study findings will be submitted for publication in peer-reviewed journals and lay summaries will be disseminated to participants and the wider public.

Systematic review and meta-analysis: Associations between metabolic syndrome and colorectal neoplasia outcomes.

AIM: Metabolic syndrome (MetS) is a cluster of factors including obesity, hypertension, diabetes, hypercholesterolemia and hyperlipidaemia. It has been associated with an increased risk of colorectal neoplasia. This systematic review and meta-analysis assessed the association between MetS and (i) recurrence of adenomas or occurrence of CRC in patients with prior adenomas, and (ii) survival in patients with CRC. METHOD: MEDLINE, Embase, Scopus and Web of Science were searched up to 22 November 2019. Two authors independently conducted title and abstract screening; full text of eligible studies was evaluated. Where ≥3 studies reported effect measures for a specific outcome, meta-analysis using random effects model was conducted. I2 was used to assess between-study heterogeneity. Quality appraisal was undertaken with the Newcastle-Ottawa Score. RESULTS: The search identified 1,764 articles, 55 underwent full text screening, resulting in a total of 15 eligible studies. Five studies reported on metachronous neoplasia, with differing outcomes precluded a meta-analysis. No consistent relationship between MetS and metachronous neoplasia was found. Ten studies reported on survival outcomes. MetS was associated with poorer CRC-specific survival (HR = 1.8, 95% CI: 1.04-3.12, I2  = 92.7%, n = 3). Progression-free survival was also worse but this did not reach statistical significance (HR = 1.12, 95% CI: 0.89-1.42, I2  = 85.6%, n = 3). There was no association with overall survival (HR = 1.04, 95% CI: 0.94-1.15, I2  = 43.7%, n = 7). Significant heterogeneity was present but subgroup analysis did not account for this. CONCLUSION: MetS is associated with poorer CRC-specific survival, but evidence is inconsistent on metachronous neoplasia. Further research is warranted to better understand the impact of MetS on the adenoma-carcinoma pathway.

Uncovering undiagnosed liver disease: prevalence and opportunity for intervention in a population attending colonoscopy.

OBJECTIVE: Due to high rates of obesity and alcohol consumption, the prevalence of fatty liver disease is increasing. There is no widely adopted approach to proactively screen for liver disease in the community. We aimed to assess the burden of potentially undiagnosed liver disease in individuals attending for colonoscopy to develop a pathway to identify and manage individuals with undiagnosed liver disease. DESIGN: The OSCAR Study was a cross-sectional study recruiting patients attending for colonoscopy. Patients' metabolic and liver risk factors were measured. The prevalence of undiagnosed significant fatty liver disease was measured using the Fatty Liver Index (FLI) and Fibrosis-4 score (FIB-4). RESULTS: 1429 patients (mean age 59±14 years; 48.8% men) were recruited. 73.3% were overweight/obese, 12.7% had diabetes and 17.9% had metabolic syndrome. 19% were consuming more than recommenced alcohol levels (<14 units/week) and 41% had an AUDIT-C score ≥5. After excluding those with known liver disease, 43.2% of the cohort had a high FLI (high likelihood of fatty liver). 5.3% of these had a high FIB-4 score (>2.67, high probability of advanced fibrosis) and 90% of these were previously undiagnosed. 818 patients had a predicted 10-year cardiovascular event risk of ≥10%, however only 377 (46.1%) were on statin therapy. CONCLUSION: High levels of obesity, metabolic dysfunction and undiagnosed fatty liver disease were found in individuals attending for colonoscopy. Clinical encounters in the endoscopy unit may represent an opportunity to risk assess for liver and metabolic disease and provide an environment to develop targeted interventions.

The value of physical examination in the era of telemedicine.

Telemedicine use has expanded rapidly to cope with increasing demand on services by delivering remote clinical review and monitoring of long-term conditions. Triaging individual patients to determine their suitability for telephone, video or face-to-face consultations is necessary. This is crucial in the context of COVID-19 to ensure doctor-patient safety. Telemedicine was shown to be safe and feasible in managing certain chronic diseases and providing patient education. When reviewing newly referred or long-term patients, different specialty clinics have different requirements for physical examination. Clinicians prefer face-to-face consultations at the initial visit to establish a doctor-patient relationship; telephone or video consultations are reasonable options for long-term patients where physical examination may not be needed. Video consultations, often aided by sophisticated devices and apps or medical assistants, are useful to facilitate remote physical examination. Most patients prefer telemedicine as it saves time and travel cost and provides better access to appointments.

Panenteric capsule endoscopy identifies proximal small bowel disease guiding upstaging and treatment intensification in Crohn's disease: A European multicentre observational cohort study.

BACKGROUND: Endoscopically defined mucosal healing in Crohn's disease is associated with improved outcomes. Panenteric capsule endoscopy enables a single non-invasive assessment of small and large bowel mucosal inflammation. AIMS AND METHODS: This multicentre observational study of patients with suspected and established Crohn's disease examined the feasibility, safety and impact on patient outcomes of panenteric capsule endoscopy in routine clinical practice. The potential role in assessment of disease severity and extent by a comparison with existing clinical and biochemical markers is examined. RESULTS: Panenteric capsule endoscopy was performed on 93 patients (71 with established and 22 with suspected Crohn's disease). A complete examination occurred in 85% (79/93). Two cases (2.8%) of capsule retention occurred in patients with established Crohn's disease. Panenteric capsule resulted in management change in 38.7% (36/93) patients, including 64.6% (32/48) of those with an established diagnosis whose disease was active, and all three patients with newly diagnosed Crohn's disease. Montreal classification was upstaged in 33.8% of patients with established Crohn's disease and mucosal healing was demonstrated in 15.5%. Proximal small bowel disease upstaged disease in 12.7% and predicted escalation of therapy (odds ratio 40.3, 95% confidence interval 3.6-450.2). Raised C-reactive protein and faecal calprotectin were poorly sensitive in detecting active disease (0.48 and 0.59 respectively). CONCLUSIONS: Panenteric capsule endoscopy was feasible in routine practice and the ability to detect proximal small bowel disease may allow better estimation of prognosis and guide treatment intensification. Panenteric capsule endoscopy may be a suitable non-invasive endoscopic investigation in determining disease activity and supporting management decisions.

A risk-stratified approach to colorectal cancer prevention and diagnosis.

Population screening and endoscopic surveillance are used widely to prevent the development of and death from colorectal cancer (CRC). However, CRC remains a major cause of cancer mortality and the increasing burden of endoscopic investigations threatens to overwhelm some health services. This Perspective describes the rationale for and approach to improved risk stratification and decision-making for CRC prevention and diagnosis. Limitations of current approaches will be discussed using the UK as an example of the challenges faced by a particular health-care system, followed by discussion of novel risk biomarker utilization. We explore how risk stratification will be advantageous to current health-care providers and users, enabling more efficient use of limited colonoscopy resources. We discuss risk stratification in the setting of population screening as well as the surveillance of high-risk groups and investigation of symptomatic patients. We also address challenges in the development and validation of risk stratification tools and identify key research priorities.

British society of gastroenterology Endoscopy Quality Improvement Programme (EQIP): overview and progress.

High quality gastrointestinal (GI) endoscopy improves patient care. Raising standards in endoscopy improves diagnostic accuracy, management of pathology and ultimately improves outcomes. Historical identification of significant variation in colonoscopy quality led to the development of the Joint Advisory Group (JAG) on GI Endoscopy, the Global Rating Scale (GRS), JAG Endoscopy Training System (JETS) training and certification. These measures led to major improvements in UK endoscopy but significant variation in practice still exists. To improve quality further the British Society of Gastroenterology Endoscopy Quality Improvement (EQIP) has been established with the aim of raising quality and reducing variation in the quality of UK endoscopy. A multifaceted approach to quality improvement (QI) will be undertaken and is described in this manuscript. Upper GI EQIP will support adoption of standards alongside regional upskilling courses. Lower GI EQIP will focus on supporting endoscopists to achieve current standards alongside approaches to reducing postcolonoscopy colorectal cancer rates. Endoscopic retrograde cholangiopancreatography EQIP will adopt a regional approach of using local data to support network-based QI. Newer areas of endoscopy practice such as small bowel endoscopy and endoscopic ultrasound will focus on identifying key performance indicators as well as standardising training and accreditation pathways. EQIP will also support QI in management of GI bleeding as well as standardising the approach to new techniques and technologies. Where evidence is lacking, approaches to gather new evidence and support the translation into clinical practice will be supported.

The NHS Bowel Cancer Screening Program: current perspectives on strategies for improvement.

Colorectal cancer (CRC) is the third most common cancer in the UK. The English National Health Service (NHS) Bowel Cancer Screening Program (BCSP) was introduced in 2006 to improve CRC mortality by earlier detection of CRC. It is now offered to patients aged 60-74 years and involves a home-based guaiac fecal occult blood test (gFOBt) biennially, and if positive, patients are offered a colonoscopy. This has been associated with a 15% reduction in mortality. In 2013, an additional arm to BCSP was introduced, Bowelscope. This offers patients aged 55 years a one-off flexible sigmoidoscopy, and if several adenomas are found, the patients are offered a completion colonoscopy. BCSP has been associated with a significant stage shift in CRC diagnosis; however, the uptake of bowel cancer screening remains lower than that for other screening programs. Further work is required to understand the reasons for nonparticipation of patients to ensure optimal uptake. A change of gFOBt kit to the fecal immunochemical tests (FIT) in the English BCSP may further increase patient participation. This, in addition to increased yield of neoplasia and cancers with the FIT kit, is likely to further improve CRC outcomes in the screened population.

The National Oesophagogastric Cancer Awareness Campaign: a locality outcome analysis from County Durham.

INTRODUCTION: Oesophageal and gastric cancer is common. Despite advances in investigation and treatment, the outcomes from these cancers remain poor. As part of the Be Clear On Cancer Campaign, the Department of Health runs the National Oesophagogastric Cancer Campaign each year, with key messages of (1) 'Having heartburn most days, for 3 weeks or more could be a sign of cancer' and (2) 'if food is sticking when you swallow, tell your doctor'. METHODS: We evaluated the effect of the National Oesophagogastric Cancer Campaign in our locality. RESULTS: Reviewing new referrals from primary care for upper gastrointestinal symptoms during the campaign period, and a period thereafter, we found that there was no significant impact of the campaign in the diagnosis of oesophagogastric cancers. Furthermore, it increased routine waiting times for elective gastroscopies in our endoscopy units. CONCLUSION: We believe that alternative strategies need to be considered for earlier detection of oesophagogastric cancer.

Oesophageal candidiasis and squamous cell cancer in patients with gain-of-function STAT1 gene mutation.

BACKGROUND: Oesophageal candidiasis is a common, usually self-limiting opportunistic infection, but long-term infection with Candida is known to predispose to oral and oesophageal squamous cell cancer (SCC). Permissive factors that lead to immune deficiencies can underlie persistent or recurring candidiasis, called chronic mucocutaneous candidiasis (CMC). Secondary immune deficiencies are most often due to human immunodeficiency virus (HIV) infection, antibiotic use and immunosuppressive treatment (steroids, chemotherapy). Inborn errors of the immune system (primary immune deficiencies) can present with isolated CMC known as CMC disease (CMCD), which is most often found in patients with autoimmune polyendocrinopathy syndrome type 1 (APS1)/APECED or in patients with an underlying gain-of-function STAT1 mutation (GOF-STAT1). OBJECTIVE: To describe a new form of inherited/familial CMC with a high risk for developing squamous cell carcinoma of the oesophagus, due to a gain-of-function mutation in the STAT1 gene. METHODS AND RESULTS: This report describes a family of patients with CMC with confirmed GOF-STAT1 mutation. These patients usually present with CMCD in childhood, have severe oral and oesophageal candidiasis accompanied by severe difficulty swallowing, chest pain, heartburn, and are at risk of developing oral and/or oesophageal SCC. This case series describes six patients in three generations of the same family, two of whom developed and died of SCC. We recommend regular endoscopic surveillance to detect early oesophageal neoplasia in patients with CMCD as well as urgent endoscopy in symptomatic patients. CONCLUSION: CMC is not a well-recognised condition in gastroenterology practice and clinicians need to be aware of the genetics of the condition as well as the risk for oesophageal cancer so that they can counsel their patients and arrange surveillance appropriately.