Resection margin involvement after endoscopic excision of malignant colorectal polyps: definition of margin involvement and its impact upon tumour recurrence.

AIMS: Malignant polyps are examined to assess histological features which predict residual tumour in the unresected bowel and guide surgical decision-making. One of the most important of these features is resection margin involvement, although the best definition of margin involvement is unknown. In this study we aimed to investigate three different definitions and determine their impact on clinical outcomes. METHODS AND RESULTS: One hundred and sixty-five malignant polyps removed endoscopically were identified and histological features correlated with either residual tumour in subsequent surgical resections or tumour recurrence following a period of clinical follow-up. Involvement of the polyp margin by cancer was defined in three different ways and outcomes compared. Tumour recurrence was associated with tumour grade, mucinous histology and resection margin involvement. All three definitions of margin involvement separated polyps into clinically significant categories; however, a margin ≤ 1 mm identified 73% of polyps as 'high-risk' compared with 59.1% when involvement was defined as tumour within the zone of coagulation artefact at the polyp base or 50% when tumour was present at the margin. All three 'low-risk' groups had a locoregional recurrence rate < 6.5%. CONCLUSIONS: Definitions of margin involvement for endoscopically removed malignant polyps in the colon and rectum vary between health-care systems, but a 1-mm clearance is widely used in Europe and North America. Our results suggest that a 1-mm margin is unnecessary and should be replaced by a definition based on tumour at the margin or within coagulation artefact at the polyp base.

Derivation and validation of a novel method to subgroup patients with functional dyspepsia: beyond upper gastrointestinal symptoms.

BACKGROUND: Conventionally, patients with functional dyspepsia are subgrouped based on upper gastrointestinal symptoms, according to the Rome criteria. However, psychological co-morbidity and extraintestinal symptoms are also relevant to functional gastrointestinal disorders. AIM: To investigate whether it is possible to subgroup people with functional dyspepsia using factors beyond upper gastrointestinal symptoms. METHODS: We collected demographic, symptom and psychological health data from adult subjects meeting the Rome III criteria for functional dyspepsia in two secondary care cross-sectional surveys in Canada and the UK. We performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot, and compared these by visual inspection, describing cluster characteristics. RESULTS: In total, 400 individuals met Rome III criteria for functional dyspepsia in the Canadian cohort, and 262 the UK cohort. A four-cluster model was the optimum solution and the characteristics of the clusters were almost identical between the two cohorts. The clusters were defined by a pattern of gastrointestinal symptoms and were further differentiated by the extent of extraintestinal and psychological co-morbidity. Cluster 1 (mean age 46.7 years, 66.7% female) consisted of epigastric pain and nausea with high psychological burden, cluster 2 (mean age 41.5 years, 77.7% female) high overall gastrointestinal symptom severity with high psychological burden, cluster 3 (45.8 years, 67.2% female) oesophageal symptoms and early satiety with low psychological burden, and cluster 4 (mean age 40.4 years, 71.5% female) postprandial fullness with low psychological burden. We validated the model derived using the Canadian study population externally by applying it to the UK dataset. We demonstrated reproducibility; it would perform similarly when applied to a different dataset. CONCLUSIONS: Latent class analysis identified four distinct functional dyspepsia subgroups characterised by varying degrees of gastrointestinal symptoms, extraintestinal symptoms and psychological co-morbidity. Further research is needed to assess whether they might be used to direct treatment.

First UK experience of endoscopic vacuum therapy for the management of oesophageal perforations and postoperative leaks.

Oesophageal perforations and anastomotic leaks are associated with high morbidity and mortality. Endoscopic vacuum therapy (EVT) is a promising novel treatment that promotes healing and avoids sepsis. There are no data reporting its use in the UK. We report the first British experience of EVT in two elderly frail patients. Two patients were treated in our institution with EVT using Eso-SPONGE®. One patient had spontaneous oesophageal perforation and the other had anastomotic leakage post-Merendino oesophageal reconstruction (oesophagogastric continuity with jejunal interposition anastomosis). Both patients were over 65 years of age. One patient had 13 endoscopic Eso-SPONGE® exchanges over 8 weeks, while the other one had 6 exchanges over 4 weeks. Complete resolution of oesophageal leakage was achieved in both cases. EVT should be considered in the management of patients with oesophageal perforations and postoperative leaks. This novel therapeutic intervention has the potential to significantly reduce morbidity and mortality in these patients.

Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin.

OBJECTIVES: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. METHODS: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn's disease (CD). Disease activity was assessed using clinical indices, self-reported flare or faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. RESULTS: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84-17.0] and UC (OR 10.8; 95% CI 1.8-64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49-5.39; and OR 0.21; 95% CI 0.21-1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84-34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46-6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47-43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28-14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. CONCLUSIONS: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.

Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis.

BACKGROUND: Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. METHODS: For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). FINDINGS: We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]). INTERPRETATION: Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants. FUNDING: Leeds Teaching Hospitals Charitable Foundation.

Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease is associated with psychological comorbidity and impaired quality of life. Psychological comorbidity could affect the natural history of inflammatory bowel disease. Psychological therapies might therefore have beneficial effects on disease activity, mood, and quality of life in patients with inflammatory bowel disease. We did a systematic review and meta-analysis examining these issues. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for articles published between 1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients with inflammatory bowel disease aged at least 16 years that compared psychological therapy with a control intervention or usual treatment were eligible. We pooled dichotomous data to obtain relative risks of induction of remission in active disease or prevention of relapse of quiescent disease, with 95% CIs. We pooled continuous data to estimate standardised mean differences in disease activity indices, anxiety, depression, perceived stress, and quality-of-life scores in patients dichotomised into those with clinically active or quiescent disease, with 95% CIs. We extracted data from published reports and contacted the original investigators of studies for which the required data were not available. We pooled all data using a random-effects model. FINDINGS: The search identified 1824 studies, with 14 RCTs of 1196 patients eligible for inclusion. The relative risk of relapse of quiescent inflammatory bowel disease with psychological therapy versus control was 0·98 (95% CI 0·77-1·24; p=0·87; I2=50%; six trials; 518 patients). We observed a significant difference in depression scores (standardised mean difference -0·17 [-0·33 to -0·01]; p=0·04; I2=0%; seven trials; 605 patients) and quality of life (0·30 [0·07-0·52]; p=0·01; I2=42%; nine trials; 578 patients) with psychological therapy versus control at the end of therapy for patients with quiescent disease. However, these beneficial effects were lost at final point of follow-up (depression scores -0·11 [-0·27 to 0·05], p=0·17, I2=0%, eight trials, 593 patients; quality of life 0·15 [-0·05 to 0·34], p=0·14, I2=22%, ten trials, 577 patients). When we assessed the effect of individual physiological therapies on quality of life, only cognitive behavioural therapy had any significant beneficial effect (0·37 [0·02-0·72]). We noted no effect on disease activity indices or other psychological wellbeing scores when compared with control in patients with quiescent disease. Dichotomous data for induction of remission and continuous data for change in clinical disease activity indices, depression, anxiety, and perceived stress scores were only reported in one RCT of patients with active disease. Quality of life was assessed in two RCTs of patients with active disease, but was not significantly different between intervention and control groups (0·27 [-0·05 to 0·59]). INTERPRETATION: Psychological therapies, and cognitive behavioural therapy in particular, might have small short-term beneficial effects on depression scores and quality of life in patients with inflammatory bowel disease. Further RCTs of these interventions in patients with coexistent psychological distress are required. FUNDING: None.

Negative Effects on Psychological Health and Quality of Life of Genuine Irritable Bowel Syndrome-type Symptoms in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with inflammatory bowel disease (IBD), but it is unclear whether this relates to occult IBD activity. We attempted to resolve this issue in a secondary care population by using a cross-sectional study design. METHODS: We analyzed Rome III IBS symptoms, disease activity indices, and psychological, somatization, and quality of life data from 378 consecutive, unselected adult patients with IBD seen in clinics at St James's University Hospital in Leeds, United Kingdom from November 2012 through June 2015. Participants provided a stool sample for fecal calprotectin (FC) analysis; levels ≥250 µg/g were used to define mucosal inflammation. By using symptom data and FC levels we identified 4 distinct groups of patients: those with true IBS-type symptoms (IBS-type symptoms with FC levels <250 µg/g, regardless of disease activity indices), quiescent IBD (no IBS-type symptoms with FC levels <250 µg/g, regardless of disease activity indices), occult inflammation (normal disease activity indices and FC levels ≥250 µg/g, regardless of IBS symptom status), or active IBD (abnormal disease activity indices with FC levels ≥250 µg/g, regardless of IBS symptom status). We compared characteristics between these groups. RESULTS: Fifty-seven of 206 patients with Crohn's disease (27.7%) and 34 of 172 patients with ulcerative colitis (19.8%) had true IBS-type symptoms. Levels of psychological comorbidity and somatization were significantly higher among patients with true IBS-type symptoms than patients with quiescent IBD or occult inflammation. Quality of life levels were also significantly reduced compared with patients with quiescent disease or occult inflammation and were similar to those of patients with active IBD. By using FC levels ≥100 µg/g to define mucosal inflammation, we found a similar effect of IBS-type symptoms on psychological health and quality of life. CONCLUSIONS: In a cross-sectional study, we identified a distinct group of patients with IBD and genuine IBS-type symptoms in the absence of mucosal inflammation. These symptoms had negative effects on psychological well-being and quality of life to the same degree as active IBD. New management strategies are required for this patient group.

Enhancing Diagnostic Performance of Symptom-Based Criteria for Irritable Bowel Syndrome by Additional History and Limited Diagnostic Evaluation.

OBJECTIVES: Symptom-based criteria to diagnose irritable bowel syndrome (IBS) positively perform only modestly. Our aim was to assess whether including other items from the clinical history and limited diagnostic evaluation improves their performance. METHODS: We collected complete symptom, colonoscopy, and histology data from 318 consecutive, unselected adult patients with lower gastrointestinal (GI) symptoms in secondary care. All participants underwent colonoscopy, with relevant organic findings recorded. The reference standard used to define the presence of true IBS was patient-reported lower abdominal pain or discomfort associated with a change in bowel habit, in the absence of organic GI disease. Sensitivity, specificity, and positive and negative likelihood ratios (LRs), with 95% confidence intervals, were calculated for Rome III criteria, as well as for modifications, incorporating nocturnal stools, results of simple blood tests (hemoglobin and C-reactive protein (CRP)), measures of somatization, and/or affective disorders (hospital anxiety or depression scale (HADS) score). RESULTS: The sensitivity and specificity of the Rome III criteria for identifying IBS was 69.6%, and 82.0%, respectively, with positive and negative LRs of 3.87 and 0.37, respectively. Clinically useful enhancements in positive LRs were provided by combining Rome III criteria with: (a) high level of somatization (7.27); (b) normal hemoglobin and CRP with HADS score of ≥8 (5.04); (c) normal hemoglobin and CRP with a high level of somatization (7.56); or (d) no nocturnal passage of stool with a high level of somatization (17.3). Specificity was ≥95% with each of these modifications. CONCLUSIONS: Incorporating nocturnal stools, somatization, and affective disorders from the clinical history, and hemoglobin and CRP measurements, enhances the positive LR and specificity of symptom-based Rome III criteria for IBS.

Validation and modification of a diagnostic scoring system to predict microscopic colitis.

OBJECTIVE: Many patients with diarrhoea undergo colonoscopy. If this is macroscopically normal, random biopsies are obtained to rule out microscopic colitis (MC), but most patients have functional disease. Accurate predictors of MC could avoid the need to take biopsies in a substantial proportion of patients, saving money for the health service. We validated a previously described diagnostic scoring system for MC, and incorporated further variables to assess whether this improved performance. MATERIAL AND METHODS: Consecutive adults with loose stools undergoing colonoscopy in Leeds, UK were included. Demographic and symptom data were collected prospectively. The diagnostic scoring system described previously was applied. In addition, the incorporation of further variables, including drugs associated with MC, number of stools, nocturnal passage of stools, and duration of loose stools, into the scoring system was assessed. Sensitivities, specificities, and positive and negative predictive values were calculated. RESULTS: Among 242 patients (mean age 51.0 years, 163 (67.4%) female), 26 (10.7%) of whom had MC, a cut off of ≥4 on the original scoring system had a sensitivity of 92.3% and specificity of 35.2%. Nocturnal passage of stools and duration of loose stools <6 months were significant predictors of MC. Incorporating these variables in a new scoring system with a cut off of ≥6 identified MC with 95.7% sensitivity and 46.0% specificity. CONCLUSIONS: Incorporating nocturnal passage of stools and duration of loose stools into the scoring system may improve ability to predict MC, and avoid random colonic biopsies in a greater proportion of patients with loose stools.

Poor Correlation Between Clinical Disease Activity and Mucosal Inflammation, and the Role of Psychological Comorbidity, in Inflammatory Bowel Disease.

OBJECTIVES: There is a move toward patient-reported outcome measures as end points in clinical trials of novel therapies for inflammatory bowel disease (IBD). However, the association between patient-reported symptoms and mucosal inflammation, and the influence of psychological factors, remains unclear. We examined this in a secondary care population. METHODS: Validated patient-reported disease activity indices were used to define clinically active disease in a cohort of 356 patients with ulcerative colitis (UC) or Crohn's disease (CD). A fecal calprotectin ≥250 µg/g was used to define active mucosal inflammation. The hospital anxiety and depression scale (HADS) and patient health questionnaire (PHQ)-15 were used to assess for anxiety, depression, or somatization, respectively. Logistic regression analysis was performed to determine the association between symptoms, mucosal inflammation, and psychological comorbidity. RESULTS: Clinical disease activity was associated with mucosal inflammation in UC (odds ratio (OR) 3.36; 95% confidence interval (CI) 1.34-8.47) but not in CD (OR 1.69; 95% CI 0.74-3.83). Depression in UC (OR 1.21 per 1-point increase in HADS; 95% CI 1.02-1.44) and somatization in UC (OR 1.17 per 1-point increase in PHQ-15; 95% CI 1.03-1.33) and CD (OR 1.31 per 1-point increase in PHQ-15; 95% CI 1.13-1.52) were associated with clinical disease activity. Overall, patient-reported symptoms yielded poor positive predictive values for mucosal inflammation in both CD and UC. CONCLUSIONS: Patient-reported symptoms and the Harvey-Bradshaw index were poor predictors of mucosal inflammation in CD. Psychological comorbidity was associated with gastrointestinal symptom-reporting. A shift in the focus of IBD management toward one addressing both psychological and physical well-being is required.

Evaluation of a faecal calprotectin care pathway for use in primary care.

BACKGROUND: National Institute for Health and Care Excellence have recommended faecal calprotectin (FC) testing as an option in adults with lower gastrointestinal symptoms for whom specialist investigations are being considered, if cancer is not suspected and it is used to support a diagnosis of inflammatory bowel disease (IBD) or irritable bowel syndrome. York Hospital and Vale of York Clinical Commissioning Group have developed an evidence-based care pathway to support this recommendation for use in primary care. It incorporates a higher FC cut-off value, a 'traffic light' system for risk and a clinical management pathway. OBJECTIVES: To evaluate this care pathway. METHODS: The care pathway was introduced into five primary care practices for a period of six months and the clinical outcomes of patients were evaluated. Negative and positive predictive values (NPV and PPV) were calculated. GP feedback of the care pathway was obtained by means of a web-based survey. Comparator gastroenterology activity in a neighbouring trust was obtained. RESULTS: The care pathway for FC in primary care had a 97% NPV and a 40% PPV. This was better than GP clinical judgement alone and doubled the PPV compared with the standard FC cut-off (250 mcg/g and were diagnosed by 'straight to test' colonoscopy within three weeks. The care pathway was considered helpful by GPs and delivered a higher diagnostic yield after secondary care referral (21%) than the conventional comparator pathway (5%). CONCLUSIONS: A care pathway for the use of FC that incorporates a higher cut-off value, a 'traffic light' system for risk and supports clinical decision making can be achieved safely and effectively. It maintains the balance between a high NPV and an acceptable PPV. A modified care pathway for the use of FC in primary care is proposed.