Aromatase inhibitors and the risk of colorectal cancer in postmenopausal women with breast cancer.

Background: A large trial of postmenopausal women with breast cancer reported an imbalance in colorectal cancer events with aromatase inhibitors (AIs), compared with tamoxifen in the adjuvant setting. This unexpected signal was observed within 3 years of randomization. To date, no observational studies have examined this important safety question in the natural setting of clinical practice. Thus, the objective of this study was to determine whether AIs, when compared with tamoxifen, are associated with increased risk of colorectal cancer in postmenopausal women with breast cancer. Patients and methods: Using the UK Clinical Practice Research Datalink, we identified women, at least 55 years of age, with breast cancer newly treated with either AIs or tamoxifen between 1 January 1996 and 30 September 2015, with follow-up until 30 September 2016. High-dimensional propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident colorectal cancer associated with AIs when compared with tamoxifen overall, by cumulative duration of use, and time since initiation. All exposures were lagged by 1 year for latency considerations. Results: A total of 9701 and 8893 patients initiated AIs and tamoxifen as first-line hormonal therapy (median follow-up of 2.4 and 2.9 years, respectively). Compared with tamoxifen, AIs were not associated with an increased risk of colorectal cancer (incidence rates of 150 per 100 000 person-years in both groups; adjusted HR: 0.90, 95% CI: 0.53-1.52). Similarly, there was no evidence of an association with cumulative duration of use (P-heterogeneity = 0.54), and time since initiation (P-heterogeneity = 0.66). Conclusions: In this first population-based study, the use of AIs was not associated with an increased risk of colorectal cancer. These findings should provide reassurance to the concerned stakeholders.

The risk of gastric cancer in patients with gastric intestinal metaplasia in 5-year follow-up.

BACKGROUND: Gastric intestinal metaplasia (GIM) is the premalignant stage of gastric cancer; however, consensus on its management has not been established. AIM: To determine the risk factors for gastric cancer in a population of patients with GIM to guide the appropriate clinical recommendations in a low prevalence area for gastric cancer. METHODS: This was a retrospective cohort study. Ninety-one patients with GIM diagnosed between 2004 and 2014 were recruited for surveillance EGD every 6-12 months until a diagnosis of gastric cancer or completion of the planned 5-year follow-up duration. Possible risk factors for gastric cancer were assessed. RESULTS: At initial presentation, 81 of the 91 patients (89%) had complete GIM, whereas the remaining 11% had a study entry diagnosis of incomplete GIM. No cancer developed amongst patients with complete GIM. In contrast, five of the 10 patients exhibiting incomplete GIM (50%) progressed to high-grade dysplasia (n=2) or cancer (n=3). Male gender (P=.027), and incomplete GIM (P=.001) were associated with high-risk histology (dysplasia or cancer) by study end. A trend suggested a possible association with smoking (P=.08). CONCLUSION: Male patients and those with incomplete GIM are at greatest risk of developing dysplasia or early gastric cancer. Further studies in determining optimal surveillance intervals and impact on cancer incidence and mortality are still required.

Measures of trainee performance in advanced endoscopy: A systematic review.

INTRODUCTION: The diversity, technical skills required, and risk inherent to advanced endoscopy techniques all contribute to complex training curricula and steep learning curves. Since trainees develop endoscopy skills at different rates, there has been a shift towards competency-based training and certification. Validated endoscopy performance measures for trainees are, therefore, necessary. The aim of this systematic review was to describe and critically assess the existing evidence regarding measures of performance for trainees in advanced endoscopy. METHODS: A systematic review of the literature from January 1980 to January 2016 was carried out using the MEDLINE, EMBASE, CENTRAL, and ISI Web of knowledge databases. MeSH terms related to 'advanced endoscopy' and 'performance' were applied to a highly sensitive search strategy. The main outcomes were face, content, and construct validity, as well as reliability. RESULTS: The literature search yielded 1,662 studies and 77 met the inclusion criteria after abstract and full-text review (endoscopic retrograde cholangiopancreatography (ERCP)=23, endoscopic ultrasound (EUS)=30, colonoscopic polypectomy (CP)=11, balloon-assisted enteroscopy (BAE)=7, luminal stenting=3, radiofrequency ablation (RFA)=2, and endoscopic muscosal resection (EMR)=1). Good validity and reliability were found for measurement tools of overall performance in ERCP, EUS and CP, with applications for both patient-based and simulator training models. A number of specific technical skills were also shown to be valid measures of performance. These include: selective biliary cannulation, sphincterotomy, biliary stent placement, stone extraction and procedure time for ERCP; pancreatic solid mass T-staging, EUS-guided fine needle aspiration (EUS-FNA) procedure time, number of EUS-FNA passes and puncture precision for EUS; procedure time and en bloc resection rate for CP; retrograde fluoroscopy time for BAE; and mean number of endoscopy sessions required to achieve complete eradication of intestinal metaplasia (CIEM) for RFA. The evidence for EMR and luminal stenting is of insufficient quality to make recommendations. CONCLUSIONS: We have identified multiple valid and readily available performance measures for advanced endoscopy trainees for ERCP, EUS, CP, BAE and RFA procedures. These tools should be considered in advanced endoscopy training programs wishing to move away from apprenticeship-based training and towards competency-based learning with the help of patient-based and simulator tools.

Multidisciplinary management strategies for acute non-variceal upper gastrointestinal bleeding.

BACKGROUND: The modern management of acute non-variceal upper gastrointestinal bleeding is centred on endoscopy, with recourse to interventional radiology and surgery in refractory cases. The appropriate use of intervention to optimize outcomes is reviewed. METHODS: A literature search was undertaken of PubMed and the Cochrane Central Register of Controlled Trials between January 1990 and April 2013 using validated search terms (with restrictions) relevant to upper gastrointestinal bleeding. RESULTS: Appropriate and adequate resuscitation, and risk stratification using validated scores should be initiated at diagnosis. Coagulopathy should be corrected along with blood transfusions, aiming for an international normalized ratio of less than 2·5 to proceed with possible endoscopic haemostasis and a haemoglobin level of 70 g/l (excluding patients with severe bleeding or ischaemia). Prokinetics and proton pump inhibitors (PPIs) can be administered while awaiting endoscopy, although they do not affect rebleeding, surgery or mortality rates. Endoscopic haemostasis using thermal or mechanical therapies alone or in combination with injection should be used in all patients with high-risk stigmata (Forrest I-IIb) within 24 h of presentation (possibly within 12 h if there is severe bleeding), followed by a 72-h intravenous infusion of PPI that has been shown to decrease further rebleeding, surgery and mortality. A second attempt at endoscopic haemostasis is generally made in patients with rebleeding. Uncontrolled bleeding should be treated with targeted or empirical transcatheter arterial embolization. Surgical intervention is required in the event of failure of endoscopic and radiological measures. Secondary PPI prophylaxis when indicated and Helicobacter pylori eradication are necessary to decrease recurrent bleeding, keeping in mind the increased false-negative testing rates in the setting of acute bleeding. CONCLUSION: An evidence-based approach with multidisciplinary collaboration is required to optimize outcomes of patients presenting with acute non-variceal upper gastrointestinal bleeding.

Guía práctica para el manejo de la hemorragia digestiva alta no varicosa / Clinical practice guidelines for managing nonvariceal upper gastrointestinal bleeding

La hemorragia digestiva alta no varicosa (HDANV) es una emergencia médica frecuente que se asocia a una considerable morbilidad y mortalidad. En los últimos años se han producido importantes avances en el manejo de la HDANV, que han permitido disminuirla recidiva hemorrágica y la mortalidad en estos pacientes. El objetivo del presente documento es ofrecer una guía de manejo de la HDANV eminentemente práctica basada en la evidencia científica y en las recomendaciones de los recientes consensos. Lostres puntos clave del manejo de la HDANV son: a) la reanimación hemodinámica precozy la prevención de las complicaciones de la patología cardiovascular de base, quees frecuente en pacientes con HDANV; b) el tratamiento endoscópico de las lesiones con alto riesgo de recidiva; y c) el uso de inhibidores de la bomba de protones a dosis altas pre y postendoscopia. La combinación de estas medidas permite reducir la recidiva y la mortalidad de la HDANV (AU)

Nonvariceal upper gastrointestinal (GI) bleeding is a common medical emergency associated with appreciable morbidity and mortality. The significant advances made in managing this condition in recent years have reduced the rates of rebleeding and mortality. These clinical guidelines for managing this emergency are intended to be highly practical, evidence-based, and take recent consensus statements into account. The 3 keys to managing nonvariceal upper GIbleeding are a) early restoration of fluids and blood pressure and the prevention of underlying cardiovascular disease, which is common in these patients; b) endoscopy to treat lesions at high risk of rebleeding; and c) medical therapy with high doses of proton pump inhibitors before and after endoscopy. These 3 measures, used in combination, reduce upperGI rebleeding and mortality rates (AU)

Meta-analysis: rectal indomethacin for the prevention of post-ERCP pancreatitis.

BACKGROUND: Despite initial evidence in the literature, nonsteroidal anti-inflammatory drugs (NSAIDs) have not been widely used to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). AIM: To complete a meta-analysis of high-quality RCTs that included the latest available literature published after past meta-analytical efforts METHODS: A comprehensive electronic literature search was carried out for RCTs comparing peri-procedural rectal indomethacin and placebo in preventing PEP. Methodological quality was assessed by the Cochrane risk of bias tool. Fixed model Mantel-Haenszel meta-analysis, Q test and I(2) index were used. Several subgroup and sensitivity analyses were planned. RESULTS: A total of four of 61 retrieved trials between 2007 and 2012 (n = 1470) were included. No significant publication bias existed. All studies used similar criteria to detect pancreatitis. The pooled proportion estimate of the rate of pancreatitis was 5.1% with indomethacin and 10.3% with placebo. After excluding the high-risk patients, the rates were 3.9% and 7.9% respectively. Fixed model meta-analysis showed that the rate of pancreatitis was significantly lower using indomethacin as compared with placebo [OR = 0.49(0.34-0.71); P = 0.0002]. Number needed to treat was 20. There was no significant statistical or clinical heterogeneity. In subgroup analysis, the difference remained unchanged for average-risk population [OR = 0.49(0.28-0.85); P = 0.01] or in preventing severe PEP [OR = 0.41(0.21-0.78); P = 0.007]. The result of the main outcome remained robust in multiple sensitivity analyses. CONCLUSIONS: Rectal indomethacin used immediately before or after ERCP significantly reduces the risk of PEP to half in both low- and high-risk patients, and with both statistically and clinically significant conclusions. These results suggest that a possible change in routine practice for patients at both low and high risk of developing PEP should be advocated.

Randomised clinical trial: MRCP-first vs. ERCP-first approach in patients with suspected biliary obstruction due to bile duct stones.

BACKGROUND: The preferred initial investigation with either magnetic resonance (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) in patients with suspected biliary obstruction remains controversial in many clinical settings. AIM: To assess the effectiveness of an initial MRCP vs. ERCP in the work-up of patients at moderate likelihood of a suspected biliary obstruction. METHODS: Patients with an unconfirmed benign biliary obstruction, based on laboratory and ultrasound findings, were randomised to an ERCP-first or MRCP-first strategy, stratified by level of obstruction. The primary outcome was the occurrence of a disease or procedure-related bilio-pancreatic adverse events within the next 12 months. Secondary outcomes were the number of subsequent bilio-pancreatic procedures, duration of hospitalisation, days away from activities of daily living (ADL), quality of life (SF-36) and mortality. RESULTS: We randomised 126 patients to ERCP-first and 131 to MRCP-first (age 54 ± 18 years, 62% female, 39% post-cholecystectomy). In follow-up, 18/126 (14.3%) ERCP-first and 25/131 (19.1%) MRCP-first patients experienced a procedure- or disease-related complication (P = 0.30) (disease-related in 13 and 18 patients, and procedure-related in 5 and 7 patients respectively). A cause of biliary obstruction was found in 39.7% vs. 49.6% of patients (P = 0.11). Sixty-six (50%) patients in the MRCP-first group ended up avoiding an ERCP in follow-up. ERCP-first and MRCP-first patients were away from usual activities for 3.4 ± 7.7 days and 2.0 ± 4.8 days respectively (P < 0.001). CONCLUSION: A strategy of MRCP-first decreased the need for subsequent MRCPs, but not complications. Further study is required to define factors influencing the eventual use of MRCP vs. ERCP in appropriately selected patients (ClinicalTrial.gov: NCT01424657).

Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: There exists considerable practice variation and little evidence to guide red blood cell (RBC) transfusion in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). Studies in other critically ill cohorts suggest associations between transfusions and adverse patient outcomes. AIM: To characterise any possible clinically-relevant association between RBC transfusion following NVUGIB with rebleeding and mortality. METHODS: Observational study utilising the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE). Multivariable logistic regression models were used to examine and quantify independent associations between RBC transfusion and clinical outcomes. RESULTS: Overall, 1677 patients were included (66.2 ± 16.8 years, 61.7% male, 2.5 ± 1.7 comorbid conditions, initial haemoglobin, 96.8 ± 27.2 g/L); 53.7% received RBC transfusions (2.9 ± 1.6 units of blood), 31.6% had haemodynamic instability, 5.1% fresh blood on rectal examination and 8.6% in the nasogastric tube aspirate. Endoscopic haemostasis was performed in 35.2%. Overall rebleeding (defined as continuous bleeding, rebleeding or surgery) and mortality rates were 17.9% and 5.4%, respectively. After adjusting for potential confounders, transfusion of RBC within 24 h of presentation was significantly and independently associated with an increased risk of rebleeding (OR: 1.0, 95% CI: 0.6-1.8), but not death (OR: 1.5, 95% CI: 0.94-2.23). CONCLUSIONS: This study suggests an association between RBC transfusion following NVUGIB and subsequent rebleeding, after appropriate and extensive adjustment for confounding. Prospective randomised trial evidence is needed to identify the most efficacious and cost-effective transfusional strategies in these patients.

Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding peptic ulcer.

BACKGROUND: Determining the risk of rebleeding after endoscopic therapy for peptic ulcer bleeding (PUB) may be useful for establishing additional haemostatic measures in very high-risk patients. AIM: To identify predictors of rebleeding after endoscopic therapy. METHODS: Bibliographic database searches were performed to identify studies assessing rebleeding after endoscopic therapy for PUB. All searches and data abstraction were performed in duplicate. A parameter was considered to be an independent predictor of rebleeding when it was detected as prognostic by multivariate analyses in ≥2 studies. Pooled odds ratios (pOR) were calculated for prognostic variables. RESULTS: Fourteen studies met the prespecified inclusion criteria. Pre-endoscopic predictors of rebleeding were: (i) Haemodynamic instability: significant in 9 of 13 studies evaluating the variable (pOR: 3.30, 95% CI: 2.57-4.24); (ii) Haemoglobin value: significant in 2 of 10 (pOR: 1.73, 95% CI: 1.14-2.62) and (iii) Transfusion: significant in two of six (pOR not calculable). Endoscopic predictors of rebleeding were: (i) Active bleeding: significant in 6 of 12 studies (pOR: 1.70, 95% CI: 1.31-2.22); (ii) Large ulcer size: significant in 8 of 12 studies (pOR: 2.81, 95% CI: 1.98-4.00); (iii) Posterior duodenal ulcer location: significant in four of eight studies (pOR: 3.83, 95% CI: 1.38-10.66) and (iv) High lesser gastric curvature ulcer location: significant in three of eight studies (pOR: 2.86; 95% CI: 1.69-4.86). CONCLUSIONS: Major predictors for rebleeding in patients receiving endoscopic therapy are haemodynamic instability, active bleeding at endoscopy, large ulcer size, ulcer location, haemoglobin value and the need for transfusion. These risk factors may be useful for guiding clinical management in patients with PUB.

Systematic review: the presenting international normalised ratio (INR) as a predictor of outcome in patients with upper nonvariceal gastrointestinal bleeding.

BACKGROUND: The prognostic value of an elevated international normalised ratio (INR) as part of initial risk stratification in nonvariceal upper gastrointestinal bleeding (NVUGIB) remains poorly characterised. AIM: To assess the usefulness of the initial INR in patients with NVUGIB. METHOD: After a systematic review, we included the presenting INR and other validated prognosticators in multivariable models predicting rebleeding and mortality. Data are reported as odd ratios and 95% confidence intervals. RESULTS: Only two of 769 candidate studies were useful, but reported disparate, highly selected NVUGIB patients with varying threshold initial INR values, yielding conflicting results on predictive ability. The RUGBE cohort included 1869 patients (mean age 66.3 ± 16.8, 38.1% female) with a mean presenting INR of 1.5 ± 1.7. 462 (24.7%) patients had an elevated INR (INR > 2.5 in 7.6%). INR did not add to the prediction of rebleeding. An INR >1.5, in contradistinction, significantly predicted mortality (OR: 1.96; 95% CI: 1.13-3.41). CONCLUSIONS: An elevated INR at initial presentation does not predict rebleeding in NVUGIB. A value 1.5 or greater, however, is associated with increased patient mortality after adjustment for validated prognosticators. The INR appears most useful as proxy of co-morbid burden at the time of initial assessment in NVUGIB.

Wait times for gastroenterology consultation in Canada: the patients' perspective.

Long wait times for health care have become a significant issue in Canada. As part of the Canadian Association of Gastroenterology's Human Resource initiative, a questionnaire was developed to survey patients regarding wait times for initial gastroenterology consultation and its impact. A total of 916 patients in six cities from across Canada completed the questionnaire at the time of initial consultation. Self-reported wait times varied widely, with 26.8% of respondents reporting waiting less than two weeks, 52.4% less than one month, 77.1% less than three months, 12.5% reported waiting longer than six months and 3.6% longer than one year. One-third of patients believed their wait time was too long, with 9% rating their wait time as 'far too long'; 96.4% believed that maximal wait time should be less than three months, 78.9% believed it should be less than one month and 40.3% believed it should be less than two weeks. Of those working or attending school, 22.6% reported missing at least one day of work or school because of their symptoms in the month before their appointment, and 9.0% reported missing five or more days in the preceding month. A total of 20.2% of respondents reported being very worried about having a serious disease (ie, scored 6 or higher on 7-point Likert scale), and 17.6% and 14.8%, respectively, reported that their symptoms caused major impairment of social functioning and with the activities of daily living. These data suggest that a significant proportion of Canadians with digestive problems are not satisfied with their wait time for gastroenterology consultation. Furthermore, while awaiting consultation, many patients experience an impaired quality of life because of their gastrointestinal symptoms.