Performance of the faecal immunochemical test for the detection of colorectal neoplasms and the role of proton pump inhibitors in their diagnostic accuracy.

AIM: The faecal immunochemical test (FIT) is currently utilized in both symptomatic and screening populations, but little is known about factors that affect its performance. For example, proton pump inhibitor (PPI) therapy has been purported to increase false negative rates. This has significant implications given the extent of PPI prescriptions. The aim of this work was to evaluate the performance of the FIT for the detection of colorectal neoplasms and the impact of PPI therapy on its diagnostic accuracy. METHOD: Symptomatic patients referred on the suspected cancer pathway and those on polyp surveillance between 2015 and 2019 were approached to participate. Estimates of the accuracy of FIT at different cut-off levels in diagnosing colorectal neoplasms were made. Logistic regression was used to assess the effect of PPIs on the FIT results. RESULTS: A total of 667 participants were eligible for the final analysis. At a cut-off of 10 µg/g faeces, the overall sensitivity and specificity of FIT for the detection of colorectal cancer (CRC) was 0.85 (95% CI 0.71-0.94) and 0.81 (95% CI 0.78-0.84), respectively. For the detection of advanced neoplasia, the sensitivity was 0.70 (95% CI 0.58-0.79) and the specificity was 0.83 (95% CI 0.80-0.86). At higher thresholds, the sensitivity steadily declined whilst specificity increased. PPI therapy did not have a significant effect on performance of the FIT. CONCLUSION: FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.

The Paddington International Virtual Chromoendoscopy Score in ulcerative colitis exhibits very good inter-rater agreement after computerized module training: a multicenter study across academic and community practice (with video).

BACKGROUND AND AIMS: Electronic virtual chromoendoscopy (EVC) can demonstrate ongoing disease activity in ulcerative colitis (UC), even when Mayo subscores suggest healing. However, applicability of EVC technology outside the expert setting has yet to be determined. METHODS: Fifteen participants across 5 centers reviewed a computerized training module outlining high-definition and EVC (iScan) colonoscopy modes. Interobserver agreement was then tested (Mayo score, Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and the Paddington International Virtual Chromoendoscopy Score [PICaSSO] for UC), using a colonoscopy video library (30 cases reviewed pretraining and 30 post-training). Knowledge sustainability was retested in a second round (42 cases; 9/15 participants), 6 months after training provision. RESULTS: Pretraining intraclass correlation coefficients (ICC) were good for the Mayo endoscopic subscore (ICC, .775), UCEIS scoring erosions/ulcers (ICC, .770), and UCEIS overall (ICC, .786) and for mucosal (ICC, .754) and vascular components of PICaSSO (ICC, .622). For the vascular components of UCEIS, agreement was only moderate (ICC, .429) and did not enhance post-training (ICC, .417); conversely, use of PICaSSO improved post-training (mucosal ICC, .848; vascular, .746). Histologic correlation using the New York Mt. Sinai System was strong for both PICaSSO components (Spearman's ρ for mucosal: .925; vascular, .873; P < .001 for both). Moreover, accuracy in specifically discriminating quiescent from mild histologic strata was strongest for PICaSSO (area under the receiver operating characteristic curve [AUROC] for mucosal, .781; vascular, .715) compared with Mayo (AUROC, .708) and UCEIS (AUROC for UCEIS overall, .705; vascular, .562; bleeding, .645; erosions/ulcers, .696). Inter-rater reliability for PICaSSO was sustained by round 2 participants (round 1 and 2 ICC for mucosal, .873 and .869, respectively; vascular, .715 and .783, respectively), together with histologic correlation (ρ mucosal, .934; vascular, .938; P < .001 for both). CONCLUSIONS: PICaSSO demonstrates good interobserver agreement across all levels of experience, providing excellent correlation with histology. Given the ability to discriminate subtle endoscopic features, PICaSSO may be applied to refine stratified treatment paradigms for UC patients.

Stopping antithrombotic therapy after acute upper gastrointestinal bleeding is associated with reduced survival.

INTRODUCTION: Antithrombotic drugs are often stopped following acute upper gastrointestinal bleeding (AUGIB) and frequently not restarted. The practice of antithrombotic discontinuation on discharge and its impact on outcomes are unclear. OBJECTIVE: To assess whether restarting antithrombotic therapy, prior to hospital discharge for AUGIB, affected clinical outcomes. DESIGN: Retrospective cohort study. SETTING: University hospital between May 2013 and November 2014, with median follow-up of 259 days. PATIENTS: Patients who underwent gastroscopy for AUGIB while on antithrombotic therapy. INTERVENTIONS: Continuation or cessation of antithrombotic(s) at discharge. MAIN OUTCOMES MEASURES: Cause-specific mortality, thrombotic events, rebleeding and serious adverse events (any of the above). RESULTS: Of 118 patients analysed, antithrombotic treatment was stopped in 58 (49.2%). Older age, aspirin monotherapy and peptic ulcer disease were significant predictors of antithrombotic discontinuation, whereas dual antiplatelet use predicted antithrombotic maintenance. The 1-year postdischarge mortality rate was 11.3%, with deaths mainly due to thrombotic causes. Stopping antithrombotic therapy at the time of discharge was associated with increased mortality (HR 3.32; 95% CI 1.07 to 10.31, P=0.027), thrombotic events (HR 5.77; 95% CI 1.26 to 26.35, P=0.010) and overall adverse events (HR 2.98; 95% CI 1.32 to 6.74, P=0.006), with effects persisting after multivariable adjustment for age and peptic ulcer disease. On subgroup analysis, the thromboprotective benefit remained significant with continuation of non-aspirin regimens (P=0.016). There were no significant differences in postdischarge bleeding rates between groups (HR 3.43, 0.36 to 33.04, P=0.255). CONCLUSION: In this hospital-based study, discontinuation of antithrombotic therapy is associated with increased thrombotic events and reduced survival.

Twitter debate: controversies in functional gastrointestinal disorders.

The new 'Controversies In…' series for the Frontline Gastroenterology Twitter debates addressed the difficult area of functional gastrointestinal disorders, facilitated by the former editor-in-chief Anton Emmanuel. Key topics discussed included distinguishing functional dyspepsia from genuine gastroparesis, when we should investigate for bile acid malabsorption, the current treatments for constipation-predominant irritable bowel syndrome and, importantly, how to manage consultations with complex patients presenting with functional bowel disease. The debate generated over a million impressions on twitter and this article aims to summarise the key educational points from the event.

Faecal immunochemical testing (FIT) in symptomatic patients: what are we missing?

OBJECTIVE: Faecal immunochemical test (FIT) shows promise as a non-invasive triage test for colorectal cancer (CRC) in the symptomatic population. The aim of this study was to assess the use of FIT within the recent NG12 and DG30 National Institute for Health and Care Excellence (NICE) guidelines. DESIGN: A single-centre prospective study of patients referred to University Hospitals Coventry and Warwickshire NHS Trust via the 2-week wait (TWW) pathway between January 2015 and March 2016 was conducted. 612 patients were reviewed, of which 519 were found to meet the NG12 criteria and 79 met the DG30 criteria. Data included age, sex, symptoms, colonoscopy or CT colonography, histology and FIT results. MAIN OUTCOME MEASURES: FIT was performed in all patients and sensitivity, specificity, positive predictive value and negative predictive value, with 95% CI, for cancers and adenomas within each pathway (TWW, NG12 and DG30) was calculated. RESULTS: CRC sensitivity in TWW pathway patients, NG12 and DG30 group was 86.84% (95% CI 71.91% to 95.59%), 84.85% (95% CI 68.1% to 94.89%) and 100% (95% CI 47.82% to 100%), respectively. Specificity was 82.23% (95% CI 78.85% to 85.27%), 81.28% (95% CI 77.52% to 84.65%) and 91.89% (95% CI 83.18% to 96.97%), respectively. Adenoma sensitivity in the groups was 30.69% (95% CI 29.9% to 40.66%), 30.77% (95% CI 21.51% to 41.32%) and 25% (95% CI 3.19% to 65.09%), respectively. CONCLUSION: Use of FIT within the remit of the NG12 NICE guidelines shows a high sensitivity and specificity and may be an effective triage tool when considering whether to perform investigations. However, there is still a miss rate. FIT within DG30 has excellent sensitivity and improved specificity; however, DG30 targets lower risk groups and accounts for only 13% of the entire referrals for suspected cancer. Therefore, managing the larger, higher risk NG12 group may require the addition of another test or marker to ensure that CRC is not missed.

Systematic review with meta-analysis of over 90 000 patients. Does fast-track review diagnose colorectal cancer earlier?

BACKGROUND: National UK data on colorectal cancer (CRC) stage at diagnosis is incomplete. Site-specific fast-track (2-week wait) cancer data are not collected directly by NHS England. Policy making based on these data alone can lead to inaccuracy. AIMS: To review available data on key outcomes (cancer conversion rate and stage at diagnosis) for the UK's lower gastrointestinal 2-week wait pathway. METHODS: A comprehensive literature search was conducted between 2000 and 2017. Primary outcomes were cancer conversion rate and cancer stage at diagnosis. Results were expressed as proportions with 95% CIs. A random effects model was used for meta-analysis; heterogeneity was assessed by I2 . RESULTS: Of 95 papers reviewed, 49 were included in analysis with a total study population of 93,655. Cancer conversion rate was 7.7% (95% CI: 6.9-8.5). The proportion presenting at Dukes A = 11.2% (95% CI 7.4-15.6), B = 36.7% (95% CI 30.8-42.8), C = 35.7% (95% CI: 30.8-40.8) and D = 11.1% (95% CI 7.3-15.5). No colonic pathology was diagnosed in 54.6% (95% CI: 46.2-62.8). CONCLUSIONS: Only 7.7% of patients referred by the 2-week wait pathway were found to have CRC. No beneficial effect on stage at diagnosis was found compared to non-2-week wait referral pathways. Over half of patients had no colonic pathology and detection of adenomas was very low. These results should prompt a reconsideration of the benefits of the 2-week wait pathway in CRC diagnosis and outcomes, with more focus on strategies to improve patient selection.

Time to endoscopy for acute upper gastrointestinal bleeding: Results from a prospective multicentre trainee-led audit.

Background: Endoscopy within 24 h of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24 h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups. Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p = 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p = 0.004), but not 30-d mortality (p = 0.344). Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

Influence of parathyroidectomy on blood pressure and function of the transplanted kidney in patients with tertiary hyperparathyroidism.

BACKGROUND: Tertiary hyperparathyroidism is one of the causes of bone demineralisation, nephrolithiasis and a potential risk factor influencing blood pressure and excretory graft function in patients after kidney transplantation (Tx). The aim of the study is to analyse the influence of parathyroidectomy (PTx) on graft function and blood pressure control in these patients. METHODS: 392 subsequent patients after kidney Tx were included into this analysis. Records of 84 patients (21.4%) with elevated plasma calcium concentration (> 2.6 mmol/l) during observation were reviewed. In 39 patients (9.9%) calcaemia remained elevated for over 1 year after kidney Tx. Eleven patients (2.81%) were referred for PTx. In 2 cases PTx were performed within the first 6 months, while the 9 others undergone surgery between 16 and 36 months after Tx. We have evaluated the influence of PTx on renal allograft excretory function, blood pressure and the number of antihypertensive drugs in kidney transplant patients. RESULTS: In 7 out of 11 patients the indication for PTx was renal osteodystrophy, while in other cases the indication was the asymptomatic hypercalcaemia. Shortly after surgery normalisation of calcaemia was observed in all cases. However the creatinine clearance did not changed shortly after PTx (64 +/- 12 vs. 63 +/- 16 ml/min), and a slight deterioration of transplanted kidney excretory function was observed in 2 patients. 12 months after PTx deterioration of GFR (5320 ml/min) of borderline significance was found. All patients before PTx suffered from arterial hypertension, ten of them were receiving antihypertensive drugs (average 1.6 medicine per patient). Two weeks after PTx a transient decline of both systolic and diastolic blood pressures (-13 +/- 14 mmHg; p = 0.02 and -46 mmHg; p = 0.06, respectively) was observed. However there was a negative correlation between initial plasma calcium concentration and decline of diastolic blood pressure (R = -0.884; p = 0.0003). Six and twelve months after PTx blood pressure values were at the same magnitude as before PTx. CONCLUSIONS: (1) Parathyroidectomy and normalisation of calcaemia did not influence significantly the excretory allograft kidney function. (2) Patients benefit from PTx only with the transient improvement of their blood pressure control.

The effect of the 2-week wait referral system on the detection of and mortality from colorectal cancer: protocol of a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer represents the fourth most common cancer in England and Wales; survival is high for early stage disease but declines sharply with advanced stage. UK figures suggest that cancer survival rates are lower than those of other Western European countries. Current 5-year survival is around 50 %. A rapid access strategy was introduced through the Department of Health in 2000. This 2-week wait (TWW) referral pathway was devised to streamline referral for suspected cancer, allow diagnosis at an earlier stage, reduce cancer survival inequality and reduce cancer-related mortality. However, only around half of patients with colorectal cancer have symptoms that fit the TWW criteria plus there is a fourfold difference in referral rates across England and Wales. High-quality evidence of TWW outcome measures for colorectal cancer is lacking. This systematic review will collate and evaluate the latest evidence on colorectal cancer detection rate, stage at diagnosis and mortality. METHODS: English-language publications from 2000 reporting outcomes on the TWW referral system for suspected colorectal cancer will be eligible for inclusion. Cochrane, EMBASE, MEDLINE via PubMed, NHS Evidence, Trip and the British Library Catalogue databases will be searched. Two paired reviewers will independently screen all titles/abstracts and full text for eligibility, then extract data and assess for bias using standardised formats. They will hand review reference lists of eligible articles. Disagreement will be resolved via third party adjudication. Summary effect measures for post-referral diagnosis and mortality rates will be calculated and expressed as relative risk, hazard rate ratio or risk difference with corresponding 95 % confidence intervals. Where possible summary effect measures will be pooled, heterogeneity and its extent for pooled estimates will be assessed via visual inspection of forest plots and explored via sub-group analysis. DISCUSSION: In this systematic review, we aim to summarise the relevant evidence on cancer detection rate, cancer stage at diagnosis and disease-related mortality rates for patients with suspected colorectal cancer investigated through the TWW referral system in England and Wales. We will highlight gaps in the evidence and provide a better understanding of whether it is meeting its desired effect. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037368.

Ethnic variation in colorectal cancer risk following a positive faecal occult blood test in an English bowel cancer screening programme centre.

BACKGROUND AND AIMS: The literature on colorectal cancer (CRC) screening and ethnic diversity is dominated by studies from the USA. There are no such published data from the UK bowel cancer screening programme (BCSP) population. The Wolverhampton Bowel Cancer Screening Centre serves a population of 900,000 in the Black Country and South Staffordshire. South Asians (SA) comprise 9% of the population. We aimed to determine the effects of ethnicity and sex on the risk for cancer or adenoma detected by colonoscopy following a positive faecal occult blood test over a 5-year period (2007-2011). METHODS: Data were collected from the prospectively maintained BCSP cohort. South Asian patients were identified and compared with those of non-South Asian ethnicity, and colonoscopy outcomes were determined. RESULTS: A total of 3552 participants underwent BCSP colonoscopy (non-South Asian=3363; SA=189). There were 271 cancers (7.6%) detected within the non-South Asian group and seven cancers (0.2%) in the South Asian population (P<0.05). The probability of colon cancer is higher [odds ratio (OR)=3.84, P<0.05] in non-South Asians compared with South Asians. Patients in the 65-70-year age group have the highest risk (OR=1.60; P<0.05) for CRC. During the study 1313 adenomas were detected. A total of 771 high-risk and intermediate-risk adenomas were detected in the non-South Asian group, and 14 were detected in the South Asian group. The risk of adenoma in non-South Asians is six times higher than in South Asians (OR=5.99, P<0.001) following positive faecal occult blood testing. CONCLUSION: There are fewer colorectal cancers in South Asians compared with the non-South Asian population in this regional study. This is the first such study in the BCSP population.