What gastroenterologists should know about direct oral anticoagulants.

Direct oral anticoagulants are being increasingly used in patients with non-valvular atrial fibrillation and venous thromboembolism, due to their improved efficacy/ safety ratio, a predictable anticoagulant effect without need for routine coagulation monitoring, and fewer food and drug interactions compared with vitamin K antagonists. Gastrointestinal bleeding remains a serious complication, whose management is challenging for gastroenterologists due to the lack of a standardized clinical approach. Clinical experience on periendoscopic management of these drugs is still limited and there is a paucity of clinical data supporting guidelines recommendations', and this ultimately turns out in different, unsubstantiated and potentially harmful practices of patient management. Present study will provide a thorough revision on the risk of GI bleeding for DOAC therapy and the identification of patient risk factors to individualize treatment. Moreover, the approach to management of DOACs in case of bleeding complications is discussed, and an algorithm of different strategies in presence or not of plasma level measurement is proposed. Finally the periendoscopic management for elective procedures will be reviewed, at the light of the guideline recommendations and new evidences from observational studies.

Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme.

OBJECTIVE: Although a split regimen of bowel preparation has been associated with higher levels of bowel cleansing, it is still uncertain whether it has a favourable effect on the adenoma detection rate (ADR). The present study was aimed at evaluating whether a split regimen was superior to the traditional 'full-dose, day-before' regimen in terms of ADR. DESIGN: In a multicentre, randomised, endoscopist-blinded study, 50-69-year-old subjects undergoing first colonoscopy after positive-faecal immunochemical test within an organised colorectal cancer organised screening programmes were 1:1 randomised to receive low-volume 2-L polyethylene glycol (PEG)-ascorbate solution in a 'split-dose' (Split-Dose Group, SDG) or 'day-before' regimen (Day-Before Group, DBG). The primary endpoint was the proportion of subjects with at least one adenoma. Secondary endpoints were the detection rates of advanced adenomas and serrated lesions at per-patient analysis and the total number of lesions. RESULTS: 690 subjects were included in the study. At per-patient analysis, the proportion of subjects with at least one adenoma was significantly higher in the SDG than in the DBG (183/345, 53.0% vs 141/345, 40.9%, relative risk (RR) 1.22, 95% CI 1.03 to 1.46); corresponding figures for advanced adenomas were 26.4% (91/345) versus 20.0% (69/345, RR 1.35, 95% CI 1.06 to 1.73). At per-polyp analysis, the total numbers of both adenomas and advanced adenomas per subject were significantly higher in the SDG (1.15 vs 0.8, p <0.001; 0.36 vs 0.22, p<0.001). CONCLUSIONS: In an organised screening setting, the adoption of a split regimen resulted into a higher detection rate of clinically relevant neoplastic lesions, thus improving the effectiveness of colonoscopy. Based on such evidence, the adoption of a split regimen for colonoscopy should be strongly recommended. CLINICAL TRIAL REGISTRATION NUMBER: NCT02178033.

Barriers against split-dose bowel preparation for colonoscopy.

OBJECTIVE: Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients' attitude towards split regimen and patient-related factors associated with its uptake. DESIGN: In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4 L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. RESULTS: Of the 1447 patients (mean age 59.2±13.5 years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p<0.001, χ2 for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service >1 h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). CONCLUSION: Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. TRIAL REGISTRATION NUMBER: NCT02287051; pre-result.

Resect and discard strategy in clinical practice: a prospective cohort study.

BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has shown promising results in discriminating adenomatous from non-adenomatous colonic polyps. In patients with small polyps (< 10  mm), the application of NBI within a "resect and discard" strategy, might allow post-polypectomy surveillance intervals to be determined independently from histopathology. The aim of the present study was to assess the feasibility and safety of this approach in routine clinical practice. PATIENTS AND METHODS: Consecutive colonoscopy outpatients with one or more polyps smaller than 10  mm were prospectively included. Each polyp was categorized by the endoscopist as adenoma or non-adenoma according to simplified NBI criteria, and future post-polypectomy surveillance interval was assigned accordingly. Following histopathology, post-polypectomy surveillance interval was subsequently re-assigned, and the accordance between endoscopy- and histology-directed surveillance strategies was calculated. RESULTS: Among 942 colonoscopy patients, 286 (30.4 %) with only small polyps were included. In total, 511 small polyps were evaluated; 350 (68.5 %) were adenomas and 18 of these (5.1 %) had histologic features of advanced neoplasia. For the in vivo diagnosis of adenoma, NBI sensitivity, specificity, accuracy, and positive and negative likelihood ratios were 94.9 %, 65.8 %, 85.7 %, 2.80, and 0.08, respectively. The endoscopy-directed surveillance strategy was in accordance with the histology-directed strategy in 237 of 286 patients (82.9 %). In 9.8 % and 7.3 % patients, the endoscopy-directed approach would have resulted in early and delayed surveillance, respectively. CONCLUSIONS: The resect and discard strategy seems to be a viable, safe, and cost-effective approach for the management of patients with small polyps. However, caution in the application of the strategy should be advocated for patients with polyps 6 - 9  mm in size and those with right-sided lesions, due to their malignant potential. The study was registered on Clinicaltrials.gov (NCT01462123).

Removal of infused water predominantly during insertion (water exchange) is consistently associated with a greater reduction of pain score - review of randomized controlled trials (RCTs) of water method colonoscopy.

INTRODUCTION: Variation in the outcomes in RcTs comparing water-related methods and air insufflation during the insertion phase of colonoscopy raises challenging questions regarding the approach. This report reviews the impact of water exchange on the variation in attenuation of pain during colonoscopy by water-related methods. METHODS: Medline (2008 to 2011) searches, abstracts of the 2011 Digestive Disease Week (DDW) and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of the colonoscope. Results: Since 2008 nine published and one submitted RcTs and five abstracts of RcTs presented at the 2011 DDW have been identified. Thirteen RcTs (nine published, one submitted and one abstract, n=1850) described reduction of pain score during or after colonoscopy (eleven reported statistical significance); the remaining reports described lower doses of medication used, or lower proportion of patients experiencing severe pain in colonoscopy performed with water-related methods compared with air insufflation (Tables 1 and 2). The water-related methods notably differ in the timing of removal of the infused water - predominantly during insertion (water exchange) versus predominantly during withdrawal (water immersion). Use of water exchange was consistently associated with a greater attenuation of pain score in patients who did not receive full sedation (Table 3). CONCLUSION: The comparative data reveal that a greater attenuation of pain was associated with water exchange than water immersion during insertion. The intriguing results should be subjected to further evaluation by additional RcTs to elucidate the mechanism of the pain-alleviating impact of the water method.

Removal of infused water predominantly during insertion (water exchange) is consistently associated with an increase in adenoma detection rate - review of data in randomized controlled trials (RCTs) of water-related methods.

INTRODUCTION: Variation in outcomes in RcTs comparing water-related methods and air insufflation raises challenging questions regarding the new approach. This report reviews impact of water exchange - simultaneous infusion and removal of infused water during insertion on adenoma detection rate (ADR) defined as proportion of patients with a least one adenoma of any size. METHODS: Medline (2008-2011) searches, abstract of 2011 Digestive Disease Week (DDW) meeting and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of colonoscope. RESULTS: Since 2008, eleven reports of RcTs (6 published, 1 submitted and 4 abstracts, n=1728) described ADR in patients randomized to be examined by air and water-related methods. The water-related methods differed in timing of removal of the infused water -predominantly during insertion (water exchange) (n=825) or predominantly during withdrawal (water immersion) (n=903). Water immersion was associated with both increases and decreases in ADR compared to respective air method patients and the net overall change (-7%) was significant. On the other hand water exchange was associated with increases in ADR consistently and the net changes (overall, 8%; proximal overall, 11%; and proximal <10 mm, 12%) were all significant. CONCLUSION: Comparative data generated the hypothesis that significantly larger increases in overall and proximal colon ADRs were associated with water exchange than water immersion or air insufflation during insertion. The hypothesis should be evaluated by RCTs to elucidate the mechanism of water exchange on adenoma detection.

Dual cut-off transient elastography to assess liver fibrosis in chronic hepatitis B: a cohort study with internal validation.

BACKGROUND: Transient elastography has gained popularity to stage liver fibrosis in chronic viral hepatitis, however, diagnostic cut-offs for severe fibrosis in chronic hepatitis B are poorly defined. AIM: To evaluate an algorithm with two distinct cut-offs for positive and negative prediction of significant fibrosis and cirrhosis in chronic hepatitis B patients. METHODS: Two cohorts of treatment-naïve patients with chronic hepatitis B (125 training and 92 validations) were consecutively and concurrently examined by percutaneous liver biopsy and transient elastography. Fibrosis was staged by Metavir (significant fibrosis = F ≥ 2; cirrhosis = F4) in ≥ 2 cm long liver tissue cores. RESULTS: A >13.1 kPa positive and a ≤ 9.4 kPa negative cut-off for cirrhosis had a >90% sensitivity and specificity, with an accuracy of 94%. The corresponding cut-offs for F ≥ 2 were >9.4 and ≤ 6.2 kPa, thus classifying 56% of patients with an overall accuracy of 90%. In the validation cohort, F4 and F ≥ 2 were predicted by the above transient elastography cut-offs with an overall accuracy >90%. In 165 patients with higher than upper limit of normal transaminase activity the dual cut-off algorithm of transient elastography was as accurate as in the 52 patients with normal alanine aminotransferase values in the prediction and exclusion of cirrhosis, only. CONCLUSIONS: A dual cut-off algorithm allowed for correctly classifying both significant fibrosis and cirrhosis in the majority of the patients with chronic hepatitis B, independent of alanine aminotransferase values, thus reducing the need for liver biopsy investigations.

Chromogranin A levels in chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success. AIM: We evaluated plasma chromogranin A (CgA) as a marker of HCC. PATIENTS: CgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls. METHODS: CgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy). RESULTS: CgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21-145.9)U/L vs. 15.3 (10.9-29.25)U/L, p<0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p<0.005). CgA values significantly correlated with AFP levels (r(s)=0.42, p<0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66-82), with a sensitivity of 70% (CI 50.6-85.2) and a specificity of 67% (CI 55.9-76.3). CONCLUSIONS: Despite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.

Elective surgery for benign liver tumours.

BACKGROUND: Benign liver tumours (haemangioma, focal nodular hyperplasia, and hepatic adenoma) have different prevalence and prognosis. Spontaneous rupture and malignant transformation can complicate hepatic adenoma. Elective surgery is controversial, and indications are represented by uncertain diagnosis, presence of symptoms, and prevention of major complications. OBJECTIVES: To assess the beneficial and harmful effects of elective surgery of benign liver tumours. We identified 31 cases series. These were small (with less than 60 participants) and the types of tumours mixed. These studies reported no significant mortality, but in the six studies with mortality it ranged from 1% to 17%. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (searches in Issue 1, 2006), MEDLINE, EMBASE, CancerLit, and Science Citation Index Expanded (SCI-EXPANDED) (searched December 2005). A further search included the proceedings of major hepatological and surgical congresses (Annual Meetings of the American Association for the Study of the Liver (AASLD) and European Association for the Study of the Liver (EASL)), and examination of the references of relevant papers and reference lists of the identified studies. SELECTION CRITERIA: Randomised clinical trials in adult patients with benign liver tumours without indications for emergency surgery in which elective surgery (resection) versus no intervention or sham operation are compared. DATA COLLECTION AND ANALYSIS: All trials identified through searches were evaluated for eligibility for inclusion. We intended to extract relevant data in order to analyse the outcomes as per our published protocol using intention-to-treat analysis. MAIN RESULTS: We could not identify any randomised clinical trials. AUTHORS' CONCLUSIONS: We were unable to find evidence supporting or refuting elective surgery for patients with benign liver tumours. We need large, long-term randomised clinical trials with adequate methodology to assess the benefits and harms of elective surgery.

Gallbladder motility in obesity, diabetes mellitus and coeliac disease.

We reviewed data on gallbladder motility in obesity, diabetes and coeliac disease. In obesity, a condition characterised by increased risk of gallstone(s), decreased gallbladder motility has heterogeneously been reported as a consequence of the different type of meals used to induce gallbladder contraction, characteristics of the population studied, technique used, and proportion of patients with hyperinsulinaemia. Moreover, recent studies have evaluated the effect of dietary restriction on gallbladder motility in obese patients. A two- to three-fold increase in the risk of cholesterol gallstone(s) has been reported in diabetic patients, mainly in relation to obesity and hypertriglyceridaemia. Furthermore, decreased gallbladder motility has been described and attributed to other factors, including underlying autonomic neuropathy, reduced gallbladder sensitivity to cholecystokinin and/or reduced number of cholecystokinin receptors on the gallbladder wall. Impaired gallbladder motility has been reported also in patients with coeliac disease in relation to reduced secretion of enteric hormones and/or decreased gallbladder sensitivity to them. In particular, untreated coeliacs, when compared to controls, showed low postprandial cholecystokinin and increased fasting somatostatin levels. Interestingly, the correlation between fasting somatostatin levels and gallbladder size has clearly been confirmed in patients affected by somatostatinoma or treated with somatostatin or its analogues. Gallbladder motility can be affected by various clinical conditions, such as obesity, diabetes mellitus and coeliac disease.

On-line estimation of myoelectric signal spectral parameters and nonstationarities detection.

In this communication, we present a method for detecting nonstationarities of random time series with an approximately Gaussian distribution of amplitudes. This method is suitable for real time implementation. Here we report some results obtained by applying them to a time series of spectral parameters of surface myoelectric signals, collected during voluntary isometric contractions of human muscles. Moreover, we describe the computerized system that we used to implement our detector of nonstationarity. This system is based on the TMS 320C25 DSP chip and realizes on-line estimation and display of spectral parameters, as well as detection of their nonstationarities, featuring a sampling frequency up to 20 k samples/s. A friendly user interface, fully menu driven, allows the user to select different options during the system's operation by means of hot keys. The accuracy of the system was tested by comparing its estimates with those of an off-line system, previously characterized, which we took as a reference. The estimates of spectral parameters obtained by means of the two systems were always consistent. The on-line stationarity detector was able to recognize rates of variation of the spectral parameters as small as 1%/s during contractions lasting 10-15 s. This sensitivity makes it suitable for clinical application. The set of results herein presented has been selected to highlight the main characteristics of the system.