Over-the-scope clip as first-line treatment of peptic ulcer bleeding: a multicenter randomized controlled trial (TOP Study).

BACKGROUND: First-line over-the-scope (OTS) clip treatment has shown higher efficacy than standard endoscopic therapy in acute nonvariceal upper gastrointestinal bleeding (NVUGIB) from different causes. We compared OTS clips with through-the-scope (TTS) clips as first-line mechanical treatment in the specific setting of peptic ulcer bleeding. METHODS: We conducted an international, multicenter randomized controlled trial on consecutive patients with suspected NVUGIB. Patients with Forrest Ia-IIb gastroduodenal peptic ulcer were randomized 1:1 to OTS clip or TTS clip treatment. The primary outcome was the rate of 30-day rebleeding after successful initial hemostasis. Secondary outcomes included the rates of successful initial hemostasis and overall clinical success, defined as the composite of successful initial hemostasis and no evidence of 30-day rebleeding. RESULTS: 251 patients were screened and 112 patients were randomized to OTS (n = 61) or TTS (n = 51) clip treatment. The 30-day rebleeding rates were 1.6% (1/61) and 3.9% (2/51) in patients treated with OTS clips and TTS clips, respectively (Kaplan-Meier log-rank, P = 0.46). Successful initial hemostasis rates were 98.4% (60/61) in the OTS clip group and 78.4% (40/51) in the TTS clip group (P = 0.001). Overall clinical success rates were 96.7% (59/61) with OTS clips and 74.5% (38/51) with TTS clips (P = 0.001). CONCLUSIONS: Low rates of 30-day rebleeding were observed after first-line endoscopic treatment of acute peptic ulcer bleeding with either OTS or TTS clips. However, OTS clips showed higher efficacy than TTS clips in achieving successful initial hemostasis and overall clinical success.

Implementation of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) sedation training course in a regular endoscopy unit.

BACKGROUND: Several scientific societies have endorsed non-anesthesiologist sedation (NAS) during gastrointestinal endoscopy, considering it a safe procedure when administered by adequately trained personnel. This study aimed to evaluate the occurrence of adverse events after implementation of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) sedation training program. METHODS: From January 2017 to August 2018, data from all consecutive endoscopic procedures in adults (≥ 18 years) performed at our endoscopy unit were collected using an electronic reporting system. RESULTS: All staff (physicians and nurses) completed the ESGE-ESGENA sedation course. In total, 12 132 patients underwent endoscopic procedures, 10 755 (88.6 %) of which were performed in a non-anesthesiological setting. Of these, about 20 % used moderate sedation with midazolam + fentanyl and 80 % used deep sedation with additional propofol. No sentinel, 5 (0.05 %) moderate risk, and 18 (0.17 %) minor risk adverse events occurred, all during moderate or deep sedation, and all managed by endoscopy staff without the need for anesthesiologist assistance. CONCLUSIONS: After completing the ESGE-ESGENA sedation training program, the rate of adverse events was very low in our institution. The findings support implementation of the program in all digestive endoscopy units and inclusion in the curriculum for physicians and nurses to ensure safe endoscopic procedures.

Bowel Preparation With Polyethylene Glycol 3350 or Fasting Only Before Peroral Single-balloon Enteroscopy: A Randomized European Multicenter Trial.

BACKGROUND: Although bowel preparation before colonoscopy and capsule endoscopy is widely evaluated and usually follows established guidelines, a standard preparation regime for peroral small bowel enteroscopy is yet to be defined.The aim of the present study was to compare small bowel preparation with polyethylene glycol (PEG) and "fasting only" (FO) before peroral single-balloon enteroscopy (SBE). STUDY: We compared small bowel preparation with PEG versus "FO" for peroral SBE in a randomized European multicenter trial. Patients' and procedural characteristics were documented and carefully analyzed. Primary endpoint was the oral intubation depth of the small bowel. A modified Boston preparation scale was used to assess bowel cleansing as a secondary endpoint. RESULTS: In total, 43 patients were enrolled in this study (FO group: n=25; PEG group: n=18). In both groups, patients' characteristics were comparable. The indications for oral enteroscopy were equally distributed in both groups (P=0.894). The oral intubation depth was significantly higher in the PEG versus the FO group (261±87 vs. 203±66 cm; P=0.019; mean±SD), while the quality of bowel preparation was equally sufficient in both groups [complete visualization of the mucosa (Boston preparation scale) 83% versus 76% (P=1.000)]. CONCLUSIONS: Small bowel preparation with PEG for SBE yields significantly deeper intubation as compared with "FO" preparation. As patient comfort and safety was similar in both groups, PEG preparation might be favored, especially if deep intubation of the small bowel is desired. For patients requiring visualization of the proximal jejunum, a FO preparation seems to be sufficient.

Computed tomography or contrast-enhanced ultrasonography for follow-up of liver metastases after Cyberknife therapy?: A prospective pilot study.

OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) allows the study of vascularization of secondary liver lesions. The Cyberknife (Accuray, Inc, Sunnyvale, CA) is a therapeutic method that allows a tumor target to be subjected to a high radiant dose gradient. This prospective pilot study aimed to demonstrate the concordance of CEUS versus contrast-enhanced computed tomography (CECT) in determining the stability or disease progression of secondary liver lesions after treatment with the Cyberknife. METHODS: Twenty-four patients were consecutively enrolled, and 3 different operators evaluated the CEUS images and the intermodality concordance with CECT. All patients received CEUS at 1 and 2 months after the Cyberknife therapy. The intermodality agreement was evaluated by the Cohen κ coefficient and a multivariate analysis according to the method of Janson and Olsson (Educ Psychol Meas 2001; 61:277-289). RESULTS: Forty secondary liver lesions were detected and treated. Forty-one CECT and 51 CEUS examinations were performed without any adverse events in the 24 patients. The intermodality agreement rates, calculated for the operators as Cohen κ values, were κ = 1.00, 0.881, and 0.767, respectively. The multivariate analysis of intermodality agreement showed an almost perfect value (ι = 0.841). CONCLUSIONS: This pilot study found excellent diagnostic correspondence between CEUS and CECT in the evaluation of local disease stability or progression after Cyberknife therapy in liver metastases. These findings suggest that CEUS could play an important role in the surveillance of these patients because of its high accuracy and reproducibility, thus reducing the need for CECT.

Emerging drug for diarrhea predominant irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders with a 9 - 23% prevalence estimated in the general population. Patients can be subdivided into those who tend to have predominant diarrhea (IBS-D) or predominant constipation (IBS-C). Total annual productivity loss related to IBS in US is estimated at $205 million, with a significant impairment of health-related quality of life. A gold standard for the treatment of IBS is not established. Symptoms might improve with the use of few drugs and behavioral therapy, however, data concerning efficacy, safety and tolerability are limited. Therefore, development and validation of new therapies targeting at the molecular level are widely awaited. AREAS COVERED: We will specifically describe in this review Phase II and Phase III trials, with specific focus on treatment of IBS-D patients. Unfortunately, it is difficult to draw definite conclusions from Phase II and Phase III trials, because of the known high placebo effect. EXPERT OPINION: Drugs active on opioid receptor subtypes and neurokinin (NK) receptors seem to be the most promising, but substantial progress of information in this field is still needed. The achievement of more insights on the pathogenesis of IBS could surely better drive and target the therapy, but still strong efforts are awaited.

Associations between liver enzymes, psychopathological and clinical features in eating disorders.

Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) and in subjects who are overweight or with hyperlipidemia, which can be found to be associated with binge eating disorder (BED) and bulimia nervosa (BN). Liver functioning and psychopathological features have been evaluated in 43 patients with AN, 33 with BN, and 32 with BED. Body mass index was found to be inversely associated with AST and ALT in AN, and directly associated with AST and ALT in BED. A positive association between ALT and AST and body shape concern in AN was observed. Liver enzymes could be considered as an index of severity in AN and BED patients.

Endoscopic lithotripsy of a gallstone impacted in lumen-apposing metal stent positioned for cholecysto-gastrostomy.

Video 1Endoscopic lithotripsy of a gallstone impacted in the lumen-apposing metal stent positioned for cholecysto-gastrostomy.

Linear EUS Accuracy in Preoperative Staging of Gastric Cancer: A Retrospective Multicenter Study.

INTRODUCTION: Preoperative gastric cancer (GC) staging is the most reliable prognostic factor that affects therapeutic strategies. Contrast-enhanced computed tomography (CECT) and radial endoscopic ultrasound (R-EUS) scans are the most commonly used staging tools for GC. The accuracy of linear EUS (L-EUS) in this setting is still controversial. The aim of this retrospective multicenter study was to evaluate the accuracy of L-EUS and CECT in preoperative GC staging, with regards to depth of tumor invasion (T staging) and nodal involvement (N staging). MATERIALS AND METHODS: 191 consecutive patients who underwent surgical resection for GC were retrospectively enrolled. Preoperative staging had been performed using both L-EUS and CECT, and the results were compared to postoperative staging by histopathologic analysis of surgical specimens. RESULTS: L-EUS diagnostic accuracy for depth of invasion of the GC was 100%, 60%, 74%, and 80% for T1, T2, T3, and T4, respectively. CECT accuracy for T staging was 78%, 55%, 45%, and 10% for T1, T2, T3, and T4, respectively. L-EUS diagnostic accuracy for N staging of GC was 85%, significantly higher than CECT accuracy (61%). CONCLUSIONS: Our data suggest that L-EUS has a higher accuracy than CECT in preoperative T and N staging of GC.

Safety of a novel 1L-polyethylene glycol-ascorbate solution for colonoscopy cleansing (REAL Study).

BACKGROUND AND AIM: Very low-volume bowel preparation (BP) for colonoscopy with 1-liter polyethylene glycol plus ascorbate (1L-PEG-Asc) has displayed high tolerability and quality of bowel cleansing. Concerns have been raised regarding its safety. We aimed to evaluate the incidence of adverse events (AEs) following BP with 1L-PEG-Asc or 2L-PEG-Asc. PATIENTS AND METHODS: From January 2019 to September 2020, data from all consecutive adult outpatients who underwent colonoscopy in Our Unit were collected. AEs were assessed by reviewing the clinical and laboratory data of patients who attended the Emergency Department (ED) of Modena District Hospitals in the 7 days following the colonoscopy, and were classified as "BP-related" or "BP-unrelated". RESULTS: During the study, 4069 (68.03%) and 1912 (31.97%) patients underwent colonoscopy after taking 2L-PEG-Asc or 1L-PEG-Asc, respectively. Regarding AEs, 77 (1.29%) patients attended ED, 53 (53/4069, 1.30%) and 24 (24/1912, 1.25%) after taking 2L-PEG-Asc and 1L-PEG-Asc. BP-related AEs were observed in 5 (5/4069, 0.12%) and 4 (4/1912, 0.21%) patients, respectively. The most frequent BP-related AEs were tachyarrhythmias (6/5981, 0.10%). CONCLUSION: The incidence rate of clinically relevant BP-related AEs is extremely low. This strongly suggests that 1L-PEG-Asc colonoscopy BP is as safe as 2L-PEG-Asc BP in a real-life clinical setting of unselected patients.

Successful repair of wide traumatic rectal perforation using over-the-scope clip.

Background and study aims We report on a case of a traumatic rectal perforation that occurred in a 16-year-old girl, which was successfully treated using an over-the-scope clip, avoiding major surgery and stoma.

Biosimilars in inflammatory bowel disease: A review of post-marketing experience.

Biologic compounds are obtained from living organisms or cell cultures by means of biotechnology methods. A similar biologic drug, commonly called biosimilar, is a product copied by a native approved biologic drug whose license has expired. Biosimilar drugs usually are marketed at a lower price and provide important financial savings for public healthcare systems. Some differences between biosimilars and original biologic drugs might exist but they are acceptable if they fall within defined "boundaries of tolerance": differences in some features between the two molecules are considered important only if clinical relevant. Considering that the efficacy of the innovator biologic drug has already been established, the clinical studies required for approval of a biosimilar could be reduced compared with those required for the approval of the originator. In this review, real life data available in inflammatory bowel disease patients treated with biosimilars are reported, documenting in general satisfactory outcomes, sustained efficacy and no sign of increased immunogenicity, although, further controlled data are awaited.

CT-P13: design, development, and place in therapy.

The introduction of biological agents has revolutionized the management of many life-threatening and debilitating immune-mediated diseases. Because of the high cost of biological drugs and their patent expiration, the market has opened to biosimilar agents, copy versions of the originators, which can lead to reduced health care expenditure and increase treatment access worldwide. CT-P13 is the first biosimilar of infliximab (IFX) and has been approved for the same indications as its originator drug. It obtained regulatory approval by the European Medicines Agency in September 2013 and by the US Food and Drug Administration in April 2016. The Phase I and Phase III clinical trials conducted in ankylosing spondylitis and rheumatoid arthritis have demonstrated pharmacokinetic and efficacy equivalence with comparable safety and immunogenicity to IFX. For these reasons, the use of CT-P13 has been extrapolated also to inflammatory bowel disease. There have been some initial concerns regarding the use of CT-P13 in inflammatory bowel disease patients, because of the lack of randomized controlled trials. However, emerging real-world data have further confirmed the comparability between CT-P13 and its reference product in terms of efficacy, safety, and immunogenicity, in patients naïve to the anti-tumor necrosis factor alpha agents and after switching from IFX, and will be summarized in this review.

Genetic risk variants as therapeutic targets for Crohn's disease.

INTRODUCTION: The pathogenesis of Inflammatory bowel diseases (IBD) is multifactorial, with interactions between genetic and environmental factors. Despite the existence of genetic factors being largely demonstrated by epidemiological data and several genetic studies, only a few findings have been useful in term of disease prediction, disease progression and targeting therapy. Areas covered: This review summarizes the results of genome-wide association studies in Crohn's disease, the role of epigenetics and the recent discovery by genetic studies of new pathogenetic pathways. Furthermore, it focuses on the importance of applying genetic data to clinical practice, and more specifically how to better target therapy and predict potential drug-related toxicity. Expert opinion: Some genetic markers identified in Crohn`s disease have allowed investigators to hypothesize about, and in some cases, prove the usefulness of new specific therapeutic agents. However, the heterogeneity and complexity of this disease has so far limited the daily clinical use of genetic information. Finally, the study of the implications of genetics on therapy, either to predict efficacy or avoid toxicity, is considered still to be in its infancy.