Associations between patient factors and successful colon capsule endoscopy - A prospective cohort study.

AIM: To establish patient factors associated with a successful colon capsule endoscopy (CCE) test. METHOD: This prospective cohort study used data collected from patients who underwent CCE as part of the ScotCap evaluation prior to April 2020. A CCE was defined as successful if the capsule visualized the whole colon and rectum (complete test) with sufficient bowel cleansing to permit assessment of the colonic mucosa (adequate bowel preparation). Factors from patients in symptomatic and surveillance groups were analysed for associations with a successful test, complete test, adequate bowel preparation and requirement for further procedure using univariate, multivariate logistic, least absolute shrinkage and selection operator regression. RESULTS: Data from 263 symptomatic and 137 surveillance patients were analysed. There was an association between a symptomatic patient's age and a successful test (OR = 0.97, 95% CI: 0.95-0.99), adequate bowel preparation (OR = 0.97, 95% CI: 0.94-1.00) and further procedure requirement (OR = 1.04, 95% CI: 1.02-1.06). An association was found, for symptomatic patients, between a faecal immunochemical test result in the range 10-399 µg/g and a further procedure (OR = 2.32, 95% CI: 1.23-4.48). In patients undergoing surveillance for previous colorectal cancer (OR = 0.42, 95% CI: 0.18-0.97), had previous bowel resection surgery (OR = 0.43, 95% CI: 0.19-0.98) or took a beta blocker medication (OR = 0.32, 95% CI: 0.11-0.88), an association was found with further procedure requirement. CONCLUSIONS: Among symptomatic patients, younger age was associated with obtaining a successful CCE test. Clinicians could consider patient selection based on these results to improve the rate of successful testing in clinical practice.

The incidence of malignancy in the residual rectum of IBD patients after colectomy: a systematic review and meta-analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) who have had a total colectomy remain with their rectum in situ, and are therefore at risk of rectal carcinoma. It is not clear how high the incidence of rectal cancer is in this cohort. The primary objective of this meta-analysis was to estimate the incidence of rectal cancer in patients with ulcerative colitis or Crohn's disease who have undergone colectomy but have a residual rectum, and to identify the risk factors for its development. In doing so, we explore the current recommendations for screening processes for these patients. METHODS: A systematic review of the literature was performed. Five databases (Medline, Embase, Pubmed, Cochrane Library and Scopus) were searched from inception to 29 October 2021, to identify studies adhering to the population, intervention, control and outcomes (PICO) criteria. The included studies were critically appraised, and the relevant data was extracted. Cancer incidence was estimated from the reported information. Risk stratification was analysed using RevMan. A narrative approach was undertaken for the exploration of the existing screening guidelines. RESULTS: Data from 23 of the 24 identified studies was suitable for analysis. The pooled incidence of rectal carcinoma was calculated to be 1.3%. Subgroup analysis showed an incidence of 0.7% and 3.2% for patients with a de-functioned rectal stump and ileorectal anastomosis, respectively. Patients with a history of a colorectal carcinoma were more likely to have a subsequent diagnosis of rectal carcinoma (RR 7.2, 95% CI 2.4-21.1). Patients with previous colorectal dysplasia were also at higher risk (RR 5.1, 95% CI 3.1-8.2). No universal standardised guidance regarding screening for this cohort could be identified in the available literature. CONCLUSIONS: The overall risk of malignancy was estimated to be 1.3%, which is lower than previously reported. There is a need for clear and standardised screening guidance for this group of patients.

An evaluation of a novel bowel preparation regimen and its effect on the utility of colon capsule endoscopy: a prospective cohort study with historical controls.

BACKGROUND: The aim of this study was to evaluate the efficacy of a novel bowel preparation and booster regimen for colon capsule endoscopy (CCE) using macrogol, phospho-soda and gastrografin, compared with a control regimen consisting of polyethylene glycol and sodium picosulfate. METHODS: This was a prospective cohort study using historical controls. Symptomatic patients undergoing CCE between 11/07/2021 and 21/12/2021 using the novel regimen were included. Symptomatic patients who underwent CCE in the ScotCap evaluation using the control regimen were used as historical controls. We measured the rate of complete test (visualisation of the whole colon and rectum), adequate bowel preparation, successful test (complete and adequate bowel preparation) and need for further test following CCE. The rate of adverse events was also collected. RESULTS: Patients undergoing CCE using the new and control regimen were 200 and 316, respectively. The median age, age range and proportion of female patients in the new and control regimen cohorts was 61 vs 60 years, 16-86 vs 20-83 years, and 60.5% vs 56.6%. The rate of complete test, adequate bowel reparation and successful test for the new and control regimen was 69% vs 72.2%, 86.6% vs 80.7% and 60.5% vs 65.8%. Comparing the new and control regimen, 39.5% vs 37.3% of patients required no test following CCE, 26% vs 32.6% required a colonoscopy, 31.5% vs 21.5% required a flexible sigmoidoscopy and 3% vs 2.9% required a computed tomography colonogram. No adverse events were reported using the new regimen compared to 2 (0.6%) in the control group. CONCLUSIONS: The rate of adequate bowel preparation has improved following the introduction of a new regimen. However, further work is needed to increase the complete test rate. A significant proportion of patients continue to avoid colonoscopy following CCE.

A colorectal cancer missed by colon capsule endoscopy: a case report.

BACKGROUND: Colon capsule endoscopy (CCE) is a non-invasive alternative to colonoscopy. The reported sensitivity and specificity of CCE for the detection of clinically significant colonic neoplasia is high. To date, there have been no reported cases of colorectal cancer (CRC) missed by CCE which were located in segments adequately visualised by the capsule. CASE PRESENTATION: We present the case of a 71-year-old female, who underwent CCE for new lower gastrointestinal symptoms. The CCE reported 17 polyps (largest size 10 mm) and angiodysplasia. A 40 mm caecal pole tumour, not detected by the CCE, was identified at follow up colonoscopy. Surgical resection was performed, and the pathology sample was reported as moderately differentiated adenocarcinoma, pT2 pN0 (0/19) M0, with no evidence of EMVI. The patient made an uneventful recovery. The caecal pole tumour was not definitively identified on retrospective review of the CCE images. CONCLUSION: To date, this is the first published case of a CRC missed entirely by CCE. Further research is required to allow calculation of the post CCE interval CRC rate to allow comparison with colonoscopy and CT colonogram.

Causes of death after emergency general surgical admission: population cohort study of mortality.

BACKGROUND: A substantial number of patients treated in emergency general surgery (EGS) services die within a year of discharge. The aim of this study was to analyse causes of death and their relationship to discharge diagnoses, in patients who died within 1 year of discharge from an EGS service in Scotland. METHODS: This was a population cohort study of all patients with an EGS admission in Scotland, UK, in the year before death. Patients admitted to EGS services between January 2008 and December 2017 were included. Data regarding patient admissions were obtained from the Information Services Division in Scotland, and cross-referenced to death certificate data, obtained from the National Records of Scotland. RESULTS: Of 507 308 patients admitted to EGS services, 7917 died while in hospital, and 52 094 within 1 year of discharge. For the latter, the median survival time was 67 (i.q.r. 21-168) days after EGS discharge. Malignancy accounted for 48 per cent of deaths and was the predominant cause of death in patients aged over 35 years. The cause of death was directly related to the discharge diagnosis in 56.5 per cent of patients. Symptom-based discharge diagnoses were often associated with a malignancy not diagnosed on admission. CONCLUSION: When analysed by subsequent cause of death, EGS is a cancer-based specialty. Adequate follow-up and close links with oncology and palliative care services merit development.

Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study.

BACKGROUND: The use of biologic therapy for Crohn's disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. METHODS: We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. RESULTS: The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000-2004],18.3% in cohort 2 [2005-2008], 14.7% in cohort 3 [2009-2013], and 13.0% in cohort 4 [2014-2017] p <0.001. The 5-year cumulative risk of biologic prescription was 5.7% in cohort 1, 12.2% in cohort 2, 22.0% in cohort 3, and 44.9% in cohort 4 p <0.001. CONCLUSIONS: The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.

Video consultation for new colorectal patients.

AIM: For patients, an outpatient review can lead to a stressful journey to hospital with the resultant risks associated with breaching social distancing. Despite this, video consultations (VCs) have not been frequently used in colorectal practice. We assessed outcomes, including the economic and environmental impact, of a VC clinic for new colorectal referrals. METHOD: This was a prospective observational study. Fifty consecutive patients attending a VC colorectal appointment were reviewed between March 2019 and February 2020. Face-to-face appointments during the same time period were also assessed. The distance, time, cost and carbon emissions of journeys were estimated using web-based resources. Estimated loss of earnings used data from the Office for National Statistics. The subsequent management plans were also recorded. RESULTS: Of 50 patients using VC, 40 used home devices and 10 used equipment in their local medical facility. Three patients had difficulties with the technology and converted to telephone review. Failure to attend VC appointments was less than for face-to-face appointments (4% vs 6.1%). VC appointments saved 6685 miles of travel (range 2-364 miles), 148 h travelling time and £1767 costs. Additional savings for loss of earnings were approximately £33.56 per patient. The carbon emissions saved was 4659 lb CO2 equivalent, corresponding to over 250 000 charges of a smartphone. CONCLUSION: The use of VC resulted in significant savings related to travel and reduced time and costs for patients who chose to use the service, in addition to the environmental benefits. In this current climate VC clinics have a central role in outpatient care for both new patients and follow-ups.

Colon capsule endoscopy: an innovative method for detecting colorectal pathology during the COVID-19 pandemic?

AIM: The coronavirus pandemic has led to significant challenges for healthcare delivery across the globe. Non-emergency endoscopic activity in the UK has been postponed, raising concerns of increased delays in the diagnosis of colorectal cancer and a surge in demand once services resume. Measures to mitigate this risk must be considered. METHOD: This paper reviews various investigative modalities for colorectal disease which could be deployed during cessation of colonoscopy services. We focus on colon capsule endoscopy (CCE) due to its relevance during the COVID-19 pandemic and its ability to triage patients effectively to further endoscopic investigations. RESULTS: CT of the abdomen and pelvis has been suggested as a triage tool while access to colonoscopy is limited. However, CT may lead to the spread of COVID-19 as patients attend the hospital, and it exposes them to the risks of radiation. Faecal immunochemistry tests have been demonstrated as a good predictor of colonic pathology and could be safely used to risk stratify patients when prioritizing colonoscopy. CCE is a safe and innovative technology for investigating the colon. Procedures can be carried out in the community and can be conducted safely during the coronavirus pandemic. It has been shown to be an accurate detector of colonic neoplasia and can reduce demand for colonoscopy. CONCLUSION: As colonoscopy services resume, they will probably experience high demand leading to further delays for patients. CCE could be used to reduce the number of patients requiring colonoscopy and triage those requiring further endoscopic investigations appropriately.

Colon capsule endoscopy.

There are multiple indications for luminal imaging of the colon. From assessment of known disease, to diagnosing new pathology; intra-luminal visualisation is the mainstay of gastrointestinal diagnosis. Colonoscopy and radiological imaging are currently the most frequently deployed diagnostic methods. However, both have an associated risk profile, have significant resource pressures and are not universally tolerated. Colon capsule endoscopy (CCE) offers an adjunct to these diagnostic options. In this narrative review the utility of CCE is described. Its current uses, potential benefits and future developments are also discussed.

European Society of ColoProctology: guideline for haemorrhoidal disease.

AIM: The goal of this European Society of ColoProctology project was to establish a multidisciplinary, international guideline for haemorrhoidal disease (HD) and to provide guidance on the most effective (surgical) treatment for patients with HD. METHODS: The development process consisted of six phases. In phase one we defined the scope of the guideline. The patient population included patients with all stages of haemorrhoids. The target group for the guideline was all practitioners treating patients with haemorrhoids and, in addition, healthcare workers and patients who desired information regarding the treatment management of HD. The guideline needed to address both the diagnosis of and the therapeutic modalities for HD. Phase two consisted of the compilation of the guideline development group (GDG). All clinical members needed to have affinity with the diagnosis and treatment of haemorrhoids. Further, attention was paid to the geographical distribution of the clinicians. Each GDG member identified at least one patient in their country who could read English to comment on the draft guideline. In phase three review questions were formulated, using a reversed process, starting with possible recommendations based on the GDG's knowledge. In phase four a literature search was performed in MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews. The search was focused on existing systematic reviews addressing each review question, supplemented by other studies published after the time frame covered by the systematic reviews. In phase five data of the included papers were extracted by the surgical resident (RT) and checked by the methodologist (JK) and the GDG. If needed, meta-analysis of the systematic reviews was updated by the surgical resident and the methodologist using Review Manager. During phase six the GDG members decided what recommendations could be made based on the evidence found in the literature using GRADE. RESULTS: There were six sections: (i) symptoms, diagnosis and classification; (ii) basic treatment; (iii) outpatient procedures; (iv) surgical interventions; (v) special situations; (vi) other surgical techniques. Thirty-four recommendations were formulated. CONCLUSION: This international, multidisciplinary guideline provides an up to date and evidence based summary of the current knowledge of the management of HD and may serve as a useful guide for patients and clinicians.

Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

A validated severity score for haemorrhoids as an essential prerequisite for future haemorrhoid trials.

BACKGROUND: There is a lack of standardised outcomes for haemorrhoidal disease making comparison between trials difficult. A need for a very well validated severity score is essential to facilitate meta-analysis of comparative studies, enabling evidence-based clinical practice. METHODS: The Hubble trial provides a large cohort of patients with haemorrhoidal disease randomised to rubber band ligation (RBL) or haemorrhoidal artery ligation. The haemorrhoid severity score (HSS) was collected on each patient at baseline, 6 weeks and 1 year after intervention. This allows for the responsiveness of the HSS instrument to be examined and compared with a more specific instrument, the Vaizey incontinence score (also collected). Responsiveness was tested using four methods (effect size, standardised response means (SRM), significance of change, and responsiveness statistic). RESULTS: The four tests of responsiveness demonstrated that the HSS was more responsive to changes in the patient's health status following both of the interventions compared to the Vaizey questionnaire. For example, between baseline and 6 weeks, the RBL intervention effect size scores and SRM calculations indicated a non-significant small amount of change (0.20 and 0.16 respectively). However, using the HSS, the effect size and SRM demonstrated a large magnitude of change (1.12 and 1.01, respectively) which was significant. Similar results were observed at 1 year. Significance of change scores and the index of responsiveness were also higher for the HSS questionnaire than the Vaizey across both treatment modalities. CONCLUSIONS: The HSS is a highly responsive tool for the detection of changes in haemorrhoid symptoms. It should form an essential patient-reported outcome tool for future studies on haemorrhoidal disease.

Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.

Certain members of the microbiota genus Bifidobacterium are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with inflammatory bowel disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells (IECs) from villi-a process termed 'cell shedding'. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly inflammatory conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes.

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip.

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed.

Colorectal complications of end-stage renal failure and renal transplantation: a review.

AIM: End-stage renal failure (ESRF) and renal transplant recipients are thought to be associated with an increased risk of colorectal complications. METHOD: A review of the literature was performed to assess the prevalence and outcome in both benign and malignant colorectal disease. RESULTS: No prospective randomized studies assessing colorectal complications in ESRF or renal transplant were identified. Case series and case reports have described the incidence and management of benign colorectal complications. Complications included diverticulitis,infective colitis, colonic bleeding and colonic perforation. There was insufficient evidence to associated iverticular disease with adult polycystic kidney disease.Three population-based studies have shown up to a twofold increased incidence of colonic cancer but not rectal cancer for renal transplant recipients. Bowel cancer screening (as per the general population) by faecal occult blood testing appears justified for renal transplant patients; however, evidence suggests that consideration of starting screening at a younger age may be worthwhile because of an increased risk of developing colonic cancer.Two population-based studies have shown a threefold and 10-fold increased incidence of anal cancer for renal transplant recipients. A single case­control study demonstrated significant increased prevalence of anal human papilloma virus (HPV) and intraepithelial neoplasia (AIN)in patients with established renal transplants. CONCLUSIONS: Despite the lack of high-level evidence,ESRF and renal transplantation were associated with colorectal complications that could result in major morbidity and mortality. Bowel cancer screening in this patient group appears justified. The effectiveness of screening for HPV, AIN and anal cancer in renal transplant recipients remains unclear.

Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease.

OBJECTIVES: Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD. METHODS: Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease. RESULTS: Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively. CONCLUSIONS: Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.

Pulmonary staging in colorectal cancer: a review.

AIM: Assessment of the chest in colorectal cancer (CRC) staging is variable. The aim of this review was to look at different chest staging strategies and determine which has the greatest efficacy. METHOD: A review of studies assessing chest staging modalities for patients with CRC was performed. Modalities included chest X-ray (CXR), CT and positron emission tomography (PET). RESULTS: The majority of data consisted of case series. Two studies identified a low pick-up rate for CXR as a staging tool. Five studies showed increased detection rates of pulmonary metastases for chest CT vs CXR and abdominal CT. The clinical benefit of the increased detection rates was not clear. The incidence of indeterminate lung lesions (ILL) on staging chest CT varied from 4 to 42%. The majority (≥ 70%) of ILLs did not have any clinical significance. On CT scans, the incidence of pulmonary metastases in patients with rectal cancer ranged from 10 to 18% and in patients with colon cancer the incidence of pulmonary metastases ranged from 5-6%. The incidence of synchronous liver and pulmonary metastases compared with the overall incidence of pulmonary metastases ranged from 45 to 70%. There was no evidence reporting the superiority of PET/CT vs CT for the detection of pulmonary metastases or characterization of ILL. CONCLUSION: Studies show that chest CT scanning increases the detection rates for ILL and pulmonary metastases. The clinical benefit of the increased detection rates is not clear. There is a paucity of data assessing the optimal chest staging strategy for patients presenting with CRC.