Comprehensive overview of novel chemical drugs for ulcerative colitis: focusing on phase 3 and beyond.

INTRODUCTION: Despite the growing number of highly efficacious biologics and chemical drugs for ulcerative colitis (UC), steroid-free disease control is still difficult to achieve in subgroups of patients due to refractoriness, adverse events, primary or secondary failure. New treatments are therefore still required in order to optimize clinical management of patients with UC. AREAS COVERED: The efficacy and safety of both currently available and newly developed small molecules have been summarized. The PubMed database and clinicaltrials.gov were considered in order to search for phase 2b and 3 trials on new chemical drugs for UC. The study drugs reviewed included Janus kinases (JAK) and sphingosine-1-phosphate receptor (S1Pr) inhibitors, α4 integrin antagonist, and micro-RNA-124 upregulators. EXPERT OPINION: Rapidity of onset, low immunogenicity, and safety are the main characteristics of small molecules currently available or under evaluation for treatment patients with UC. Among the currently available chemical drugs, the selective JAK and the S1Pr inhibitors are characterized by a good safety profile combined with the ability to induce clinical remission in UC. A relatively low frequency of endoscopic improvement and healing currently appears associated with their use, being higher in UC patients treated with S1Pr inhibitor Etrasimod. Overall, additional new safe and effective drugs are still required in order to optimize disease control in a larger majority of UC patients.

Endoscopic Gallbladder Drainage: A Comprehensive Review on Indications, Techniques, and Future Perspectives.

In recent years, therapeutic endoscopy has become a fundamental tool in the management of gallbladder diseases in light of its minimal invasiveness, high clinical efficacy, and good safety profile. Both endoscopic transpapillary gallbladder drainage (TGBD) and endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) provide effective internal drainage in patients with acute cholecystitis unfit for cholecystectomy, avoiding the drawbacks of external percutaneous gallbladder drainage (PGBD). The availability of dedicated lumen-apposing metal stents (LAMS) for EUS-guided transluminal interventions contributed to the expansion of endoscopic therapies for acute cholecystitis, making endoscopic gallbladder drainage easier, faster, and hence more widely available. Moreover, EUS-GBD with LAMS opened the possibility of several cholecystoscopy-guided interventions, such as gallstone lithotripsy and clearance. Finally, EUS-GBD has also been proposed as a rescue drainage modality in malignant biliary obstruction after failure of standard techniques, with encouraging results. In this review, we will describe the TBGD and EUS-GBD techniques, and we will discuss the available data on clinical efficacy in different settings in comparison with PGBD. Finally, we will comment on the future perspectives of EUS-GBD, discussing the areas of uncertainty in which new data are more strongly awaited.

Endoscopic submucosal dissection with adaptive traction strategy: first prospective multicenter study.

BACKGROUND AND AIMS: Traction has become the reference strategy for colorectal endoscopic submucosal dissection (ESD). One of its major limitations is that the force of traction decreases as dissection progresses. The ATRACT traction device uses a pulley system to increase traction during the procedure, making it easier and faster. A retrospective study of 54 cases showed interesting results in terms of efficacy and safety throughout the digestive tract. We sought to confirm these initial results with a prospective study of resections of colorectal lesions. METHODS: In this prospective multicenter study, 5 experienced operators from 3 different centers each performed 10 procedures using the ATRACT device consecutively for all conventional colorectal ESDs measuring between 4 and 10 cm in conventional locations (no recurrent lesions, appendicular, of the ileo-cecal valve, in contact with the pectinate line or measuring more than 2/3 of the circumference). RESULTS: Between November 2022 and April 2023, 50 ESDs were performed in 49 patients. On average, the main diameter of the lesions was 66.6 mm, with a surface area of 3066 mm2. The mean operating time was 55.2 minutes, resulting in a mean resection speed of 61.4 mm2/min. En Bloc and R0 resection rates were 100% and 98% respectively. Resections were curative in 94% of cases. 4 perforations (8%) occurred, all of which were closed endoscopically without the need for surgery. 1 case of delayed hemorrhage (2%) was noted. To date, this is the series with the highest resection speeds in the literature for colorectal ESD. For comparison, Yamamoto et al. reported a speed of 23.5 mm2/min using the "pocket" strategy and Bordillon et al. reported a speed of 39.1 mm2/min using the double-clip traction technique. These results need to be confirmed in larger studies, and in non-expert centers. CONCLUSIONS: This prospective evaluation confirms the efficacy and safety of the adaptive traction strategy with the ATRACT device for colorectal ESD with high resection speed.

Indications, Techniques and Future Perspectives of Walled-off Necrosis Management.

Necrotizing pancreatitis is a complex clinical condition burdened with significant morbidity and mortality. In recent years, the huge progress of interventional endoscopic ultrasound (EUS) has allowed a shift in the management of pancreatic necrotic collections from surgical/percutaneous approaches to mini-invasive endoscopic internal drainage and debridement procedures. The development of lumen-apposing metal stents (LAMSs), devices specifically dedicated to transmural EUS interventions, further prompted the diffusion of such techniques. Several studies have reported excellent outcomes of endoscopic interventions, in terms of technical success, clinical efficacy and safety compared to surgical interventions, and thus endoscopic drainage of walled-off necrosis (WON) has become a fundamental tool for the management of such conditions. Despite these advancements, some critical unresolved issues remain. Endoscopic therapeutic approaches to WON are still heterogeneous among different centers and experts. A standardized protocol on indication, timing and technique of endoscopic necrosectomy is still lacking, and experts often adopt a strategy based on personal experience more than robust data from well-conducted studies. In this review, we will summarize the available evidence on endoscopic management of WON and will discuss some unanswered questions in this rapidly evolving field.