Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects.

BACKGROUND: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control. OBJECTIVE: In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP. METHODS: Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0). RESULTS: As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025. CONCLUSIONS: This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP. TRIAL REGISTRATION: Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50513.

A Review on Endoscopic Management of Acute Cholecystitis: Endoscopic Ultrasound-Guided Gallbladder Drainage and Endoscopic Transpapillary Gallbladder Drainage.

A percutaneous cholecystostomy tube (PCT) is the conventionally favored nonoperative intervention for treating acute cholecystitis. However, PCT is beset by high adverse event rates, need for scheduled reintervention, and inadvertent dislodgement, as well as patient dissatisfaction with a percutaneous drain. Recent advances in endoscopic therapy involve the implementation of endoscopic transpapillary drainage (ETP-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), which are increasingly preferred over PCT due to their favorable technical and clinical success combined with lower complication rates. In this article, we provide a comprehensive review of the literature on EUS-GBD and ETP-GBD, delineating instances when clinicians should opt for endoscopic management and highlighting potential risks associated with each approach.

Update on endoscopic ultrasound-guided liver biopsy.

Endoscopic ultrasound guided liver biopsy (EUS-LB) has emerged as a minimally-invasive alternative to the traditional (percutaneous or transjugular) liver biopsy techniques for the diagnosis of liver parenchymal diseases. Po-tentially, EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure. Additionally, EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy. Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield, increased acquisition of complete portal tracts, and longer specimen length as compared to the traditional approaches. EUS-LB is associated with lesser post-procedural pain and shorter recovery time, while providing lower risk of complications when compared to traditional liver biopsy. Innovations in needle types, needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique. This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB, and compares EUS-LB with traditional methods of liver biopsy.

Effect of pancreatic endotherapy on quality of life in chronic pancreatitis patients: A systematic review.

BACKGROUND: Pancreatic endotherapy provides treatment options for the management of chronic pancreatitis-related structural complications such as pancreatic duct stones, strictures, and pancreatic fluid collections. Most studies detailing endotherapy, however, have focused on technical success outcomes such as stone clearance or stricture resolution. AIM: To review the effect of pancreatic endotherapy on patient-centered outcomes. METHODS: Systematic review of studies examining pancreatic endotherapy. RESULTS: A total of 13 studies including 3 randomized clinical trials were included. The majority of studies found an improvement in quality of life with pancreatic endotherapy. CONCLUSION: While pancreatic endotherapy does appear to improve quality of life, there are clear gaps in knowledge regarding many pancreatic endotherapy modalities. Furthermore, qualitative analysis is lacking in these studies and further work is needed to elucidate the patient experience with pancreatic endotherapy.