Enteroscopy in diagnosis and treatment of small bowel bleeding: A Delphi expert consensus.

BACKGROUND: Enteroscopy plays an important role in the management of small bowel bleeding. However, current guidelines are not specifically designed for small bowel bleeding and recommendations from different international societies do not always align. Consequently, there is heterogeneity in the definitions of clinical entities, clinical practice policies, and adherence to guidelines among clinicians. This represents an obstacle to providing the best patient care and to obtain homogeneous data for clinical research. AIMS: The aims of the study were to establish a consensus on the definitions of bleeding entities and on the role of enteroscopy in the management of small bowel bleeding using a Delphi process. METHODS: A core group of eight experts in enteroscopy identified five main topics of small bowel bleeding management and drafted statements on each topic. An expert panel of nine gastroenterologists participated in three rounds of the Delphi process, together with the core group. RESULTS: A total of 33 statements were approved after three rounds of Delphi voting. CONCLUSION: This Delphi consensus proposes clear definitions and a unifying strategy to standardize the management of small bowel bleeding. Furthermore, it provides a useful guide in daily practice for both clinical and technical issues of enteroscopy.

Baveno VII - Renewing consensus in portal hypertension.

To expand on the work of previous meetings, a virtual Baveno VII workshop was organised for October 2021. Among patients with compensated cirrhosis or compensated advanced chronic liver disease (cACLD - defined at the Baveno VI conference), the presence or absence of clinically significant portal hypertension (CSPH) is associated with differing outcomes, including risk of death, and different diagnostic and therapeutic needs. Accordingly, the Baveno VII workshop was entitled "Personalized Care for Portal Hypertension". The main fields of discussion were the relevance and indications for measuring the hepatic venous pressure gradient as a gold standard, the use of non-invasive tools for the diagnosis of cACLD and CSPH, the impact of aetiological and non-aetiological therapies on the course of cirrhosis, the prevention of the first episode of decompensation, the management of an acute bleeding episode, the prevention of further decompensation, as well as the diagnosis and management of splanchnic vein thrombosis and other vascular disorders of the liver. For each of these 9 topics, a thorough review of the medical literature was performed, and a series of consensus statements/recommendations were discussed and agreed upon. A summary of the most important conclusions/recommendations derived from the workshop is reported here. The statements are classified as unchanged, changed, and new in relation to Baveno VI.

Quality performance measures for small capsule endoscopy: Are the ESGE quality standards met?

Background and study aims The European Society of Gastrointestinal Endoscopy (ESGE) recently issued a quality performance measures document for small bowel capsule endoscopy (SBCE). The aim of this nationwide survey was to explore SBCE practice with ESGE quality measures as a benchmark. Patients and methods A dedicated per-center semi-quantitative questionnaire based on ESGE performance measures for SBCE was created by a group of SBCE experts. One-hundred-eighty-one centers were invited to participate and were asked to calculate performance measures for SBCE performed in 2018. Data were compared with 10 ESGE quality standards for both key and minor performance measures. Results Ninety-one centers (50.3 %) participated in the data collection. Overall in the last 5 years (2014-2018), 26,615 SBCEs were performed, 5917 of which were done in 2018. Eighty percent or more of the participating centers reached the minimum standard established by the ESGE Small Bowel Working Group (ESBWG) for four performance measures (indications for SBCE, complete small bowel evaluation, diagnostic yield and retention rate). Conversely, compliance with six minimum standards established by ESBWG concerning adequate bowel preparation, patient selection, timing of SBCE in overt bleeding, appropriate reporting, reading protocols and referral to device-assisted enteroscopy was met by only 15.5 %, 10.9 %, 31.1 %, 67.7 %, 53.4 %, and 32.2 % of centers, respectively. Conclusions The present survey shows significant variability across SBCE centers; only four (4/10: 40 %) SBCE procedural minimum standards were met by a relevant proportion of the centers ( ≥ 80 %). Our data should help in identifying target areas for quality improvement programs in SBCE.

Patient's performance status should dictate transfusion strategy in nonvariceal acute upper gastrointestinal bleeding (NV-AUGIB): A prospective multicenter cohort study: Transfusion strategy in NV-AUGIB.

BACKGROUND: Non-variceal acute UGI bleeding (NV-AUGIB) is a frequent indication for transfusion, but the best hemoglobin threshold and target values for transfusion in relation to the patients' performance status are unknown. OBJECTIVE: To identify threshold and target hemoglobin levels for transfusion favoring survival of patients with NV-AUGIB stratified by ASA score. DESIGN: Prospective cohort study. SETTING: 50 hospitals of the Italian National Health Service. PARTICIPANTS: 2758 consecutive patients with NV-AUGIB admitted to 50 Italian hospitals from January 1st, 2014 to December 31st, 2015. Five hemoglobin cut-off values were evaluated. RESULTS: 30-days mortality: overall: 5.4%; ASA 1-2 patients: 2.5%; ASA 3-4 patients: 10.8%. Mortality was higher when hemoglobin at admission was ≤ 7 g/dL in ASA 1-2 patients, and when it was ≤ 8 g/dL in ASA 3-4 patients. The hemoglobin levels after transfusion favouring survival were ≥ 8 g/dL in ASA 1-2, p <0.0001 and 9-10 g/dL in ASA 3-4 patients; p = 0.0002. CONCLUSIONS: In patients with NV-AUGIB the physical performance status should dictate the transfusion strategy. In ASA 1-2 patients, admission hemoglobin values ≤ 7 g/dL should prompt transfusion, aiming at a target value of 8-9 g/dL; the corresponding figures for ASA 3-4 patients are: admission hemoglobin level ≤ 8 g/dL and target value of 9-10 g/dL.

Adherence to European Society of Gastrointestinal Endoscopy recommendations of endoscopists performing small bowel capsule endoscopy in Italy.

BACKGROUND: The European Society of Gastrointestinal Endoscopy (ESGE) has recently issued a technical review focused on small bowel capsule endoscopy (SBCE). AIM: To compare SBCE current practice in Italy to ESGE technical recommendations. MATERIAL AND METHODS: A dedicated per-centre semi-quantitative questionnaire was prepared by a group of SBCE experts. One-hundred-fifty Centres were invited to participate in the data collection concerning SBCEs performed between June 2016 and June 2017. Data were compared with ESGE recommendations. RESULTS: 120 Centres participated in the data collection. Current practices agreed with ESGE recommendations in 56.3% (9/16) of the issues evaluated. Differences between ESGE recommendations and current practice concerned the management of patients with pacemakers or cardiac implantable defibrillators (which was in agreement with ESGE recommendations in 31.7% and 15.8% of Centres, respectively), the SBCE setting (only 51% of SBCEs were performed as outpatients procedures), the assessment of capsule excretion (timing and modality were in agreement with ESGE recommendation in 20.0% of Centres), and in the involvement of trained nurses or fellows in training as pre-readers (7/120; 5.8%). CONCLUSIONS: Although SBCE is widely used and largely available in Italy, there are still some technical, practical and organizational issues that can be modified to bridge the gap between current practice and ESGE guideline recommendations.

Virtual Chromoendoscopy With FICE for the Classification of Polypoid and Nonpolypoid Raised Lesions in Ulcerative Colitis.

GOALS: The aim of this study was to analyze the performance of Fuji Intelligent Color Enhancement (FICE) using the classification of Kudo in the differentiation of neoplastic and non-neoplastic raised lesions in ulcerative colitis (UC). BACKGROUND: The Kudo classification of mucosal pit patterns is an aid for the differential diagnosis of colorectal polyps in the general population, but no systematic studies are available for all forms of raised lesions in UC. STUDY: All raised, polypoid and nonpolypoid, lesions found during consecutive surveillance colonoscopies with FICE for long-standing UC were included. In the primary prospective analysis, the Kudo classification was used to predict the histology by FICE. In a post hoc analysis, further endoscopic markers were also explored. RESULTS: Two hundred and five lesions (mean size, 8 mm; range, 2 to 30 mm) from 59 patients (mean age, 56 y; range, 21 to 79 y) were analyzed. Twenty-three neoplastic (11%), 18 hyperplastic (9%), and 164 inflammatory (80%) lesions were found. Thirty-one lesions (15%), none of which were neoplastic, were unclassifiable according to Kudo. After logistic regression, a strong negative association resulted between endoscopic activity and neoplasia, whereas the presence of a fibrin cap was significantly associated with endoscopic activity. Using FICE, the sensitivity, specificity, and positive and negative likelihood ratios of the Kudo classification were 91%, 76%, 3.8, and 0.12, respectively. The corresponding values by adding the fibrin cap as a marker of inflammation were 91%, 93%, 13, and 0.10, respectively. CONCLUSIONS: FICE can help to predict the histology of raised lesions in UC. A new classification of pit patterns, based on inflammatory markers, should be developed in the setting of UC to improve the diagnostic performance.

Small-Bowel Capsule Endoscopy in Clinical Practice: Has Anything Changed Over 13 Years?

BACKGROUND: In Lombardia, one of the 20 Italian administrative Regions, small-bowel capsule endoscopy (SBCE) was introduced in 2001. In January 2011, the Regional Health Authorities established a reimbursement for outpatient SBCE. AIM: To prospectively record data on SBCE between 2011-2013 and compare them to similar data retrospectively collected from the same geographical area (covering the period 2001-2008) and published in 2008. METHODS: Consecutive SBCEs performed between January 2011 and December 2013 in Lombardia were prospectively collected. RESULTS: In 3 years, 3142 SBCEs were collected; the diagnostic yield (DY) and the overall complication rate were 48.4 and 0.9%, respectively. The main indication was suspected small-bowel bleeding (76.6% of patients); complete small-bowel inspection was achieved in 2796 (89.0%) patients. SBCE was performed as an outpatient procedure in 1945 patients (61.9%). A significant increase in the rate of patients undergoing SBCE for suspected small-bowel bleeding was observed from 2001-2008 to 2011-2013 (67.3 vs. 76.1%; p < 0.001). There was an increase in the number of complete small-bowel examinations (81.2 vs. 89.0%; p < 0.001) and of outpatient SBCEs (6.7 vs. 61.9%; p < 0.001). Conversely, both the retention rate (2.1 vs. 0.8%; p < 0.001) and the rate of patients undergoing SBCE for Crohn's disease (11.5 vs. 5.5%; p < 0.001) decreased significantly. The overall DY remained stable (50.6 vs. 48.4%; p = 0.089). CONCLUSION: Our study shows that, over 13 years, the SBCE safety profile and completion rate significantly improved over time; a change in the spectrum of clinical indications was also observed.

Short article: Negative small-bowel cross-sectional imaging does not exclude capsule retention in high-risk patients.

BACKGROUND AND AIMS: Both Agile patency capsule (PC) and small-bowel cross-sectional imaging (SBCSI) techniques have been used to assess small-bowel patency in patients at high risk of capsule retention. The present study aimed to compare capsule retention rates in high-risk patients with negative PC or SBCSI. MATERIALS AND METHODS: Between January 2011 and December 2013, consecutive patients undergoing small-bowel capsule endoscopy (SBCE) in the Lombardia region were prospectively entered into a dedicated registry. They were classified as being at high or low risk of capsule retention by the local investigator according to predefined clinical criteria. High-risk patients underwent either PC or SBCSI depending on local expertise and availability; those who tested negative underwent SBCE. RESULTS: Out of 3117 patients (male/female: 1667/1450, mean age: 63.1±17.7), 2942 (94.4%) were classified as being at low risk and 175 (5.6%) were classified as being at high risk for capsule retention. Among 175 high-risk patients, 151 (86.3%) had negative PC and 24 (13.7%) had negative SBCSI: capsule retention occurred in two patients with negative SBCSI (8.3%) and in one patient (0.7%) with negative PC (P=0.049). The capsule retention rates in high-risk patients with negative PC and in low-risk patients (20/2942; 0.7%) were comparable (P=1.0). CONCLUSION: The capsule retention rate is similar in low-risk and negative PC high-risk patients. Conversely, high-risk patients with negative SBCSI have a significantly higher capsule retention rate. Our data suggest that in high-risk patients, negative SBCSI examination is not reassuring and, when SBCE is indicated, PC should be performed.

Primary prophylaxis of variceal bleeding in children and the role of MesoRex Bypass: Summary of the Baveno VI Pediatric Satellite Symposium.

UNLABELLED: Approaches to the management of portal hypertension and variceal hemorrhage in pediatrics remain controversial, in large part because they are not well informed by rigorous clinical studies. Fundamental biological and clinical differences preclude automatic application of approaches used for adults to children. On April 11-12, 2015, experts in the field convened at the first Baveno Pediatric Satellite Meeting to discuss and explore current available evidence regarding indications for MesoRex bypass (MRB) in extrahepatic portal vein obstruction and the role of primary prophylaxis of variceal hemorrhage in children. Consensus was reached regarding MRB. The vast majority of children with extrahepatic portal vein obstruction will experience complications that can be prevented by successful MRB surgery. Therefore, children with extrahepatic portal vein obstruction should be offered MRB for primary and secondary prophylaxis of variceal bleeding and other complications, if appropriate surgical expertise is available, if preoperative and intraoperative evaluation demonstrates favorable anatomy, and if appropriate multidisciplinary care is available for postoperative evaluation and management of shunt thrombosis or stenosis. In contrast, consensus was not achieved regarding primary prophylaxis of varices. Although variceal hemorrhage is a concerning complication of portal hypertension in children, the first bleed appears to be only rarely fatal and the associated morbidity has not been well characterized. CONCLUSION: There are few pediatric data to indicate the efficacy and safety of pharmacologic or endoscopic therapies as primary prophylaxis or that prevention of a sentinel variceal bleed will ultimately improve survival; therefore, no recommendation for primary prophylaxis with endoscopic variceal ligation, sclerotherapy, or nonspecific beta-blockade in children was proposed.

Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 - 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 - 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence). MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).

Overview of biological therapy in ulcerative colitis: current and future directions.

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly. To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies. The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study.

BACKGROUND & AIMS: Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known. METHODS: A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months. RESULTS: Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52-92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5-20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24-42%) and 76% (95% CI: 67-83%), respectively. CONCLUSIONS: Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV.