Introduction

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has emerged as a viable alternative for biliary drainage in patients with obstructive pancreatobiliary pathology in whom endoscopic retrograde cholangiography (ERCP) is not feasible. Despite its effectiveness, however, this procedure is associated with a significant risk of complications. To carry out this procedure, the initial step is the puncture of the intrahepatic bile duct and the positioning of a guide wire; subsequently, the fistulous tract is dilated, and finally, a stent is placed, creating a bridge between the bile duct and the stomach. Although this sequence is followed in most reported procedures, its technique has not yet been standardized. Therefore, this technique should be homogenized using dedicated devices with the aim of simplifying it as much as possible to reduce the risk of complications.

Aims & Methods

This study aimed to evaluate the feasibility and safety of a newly developed, dedicated, cautery-enhanced tubular stent for EUS-HGS created to simplify this procedure. This multicenter, prospective study included 20 consecutive patients with malignant biliary obstruction who had failed ERCP due to tumor infiltration or altered anatomy. A novel dedicated nitinol stent designed for EUS-HGS was used, featuring a cautery tip for tract creation, a 3 cm uncovered distal portion to prevent migration and a 7 cm silicone covered proximal portion with an anti-migratory distal cup to prevent bile leakage. (video 1 Hot Giobor v3.mp4) The technical and clinical success rates, procedure times, and adverse events were evaluated.

Results

Twenty patients underwent EUS-HGS using the dedicated stent, achieving 100% technical and clinical success rates. The mean procedure time was 16 min. Significant reductions in bilirubin levels were observed in all patients, with no reported severe adverse events or mortality.

Conclusion

Dedicated cautery-enhanced tubular stents for EUS-HGS could simplify the procedure and enhance its safety and efficacy, although further studies are required to validate these findings across broader patient populations and settings.

References

1. Yamazaki H, Yamashita Y, Shimokawa T, Minaga K, Ogura T, Kitano M. Endoscopic ultrasound‐guided hepaticogastrostomy versus choledochoduodenostomy for malignant biliary obstruction: A meta‐analysis. DEN Open. 2024 Apr;4(1):e274.
2. Miyano A, Ogura T, Yamamoto K, Okuda A, Nishioka N, Higuchi K. Clinical Impact of the Intra-scope Channel Stent Release Technique in Preventing Stent Migration During EUS-Guided Hepaticogastrostomy. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2018 Jul;22(7):1312–8.
3. Khashab MA, Messallam AA, Penas I, Nakai Y, Modayil RJ, De la Serna C, et al. International multicenter comparative trial of transluminal EUS-guided biliary drainage via hepatogastrostomy vs. choledochoduodenostomy approaches. Endosc Int Open. 2016 Feb;04(02):E175–81.
4. Park DH, Jang JW, Lee SS, Seo DW, Lee SK, Kim MH. EUS-guided biliary drainage with transluminal stenting after failed ERCP: predictors of adverse events and long-term results. Gastrointest Endosc. 2011 Dec;74(6):1276–84.
5. Honjo M, Itoi T, Tsuchiya T, Tanaka R, Tonozuka R, Mukai S, et al. Safety and efficacy of ultra-tapered mechanical dilator for EUS-guided hepaticogastrostomy and pancreatic duct drainage compared with electrocautery dilator (with video). Endosc Ultrasound. 2018 Dec;7(6):376–82.

Introduction

Chronic pancreatitis (CP) is a multifactorial, inflammatory disease characterized by progressive destruction of the pancreas, with fibrotic transformation of the tissue as a major morphological feature. The incidence of the disease is steadily increasing, but no specific therapy is currently available, making the identification of new therapeutic targets a priority. Plasminogen activator inhibitor-1 (PAI-1, encoded by SERPINE1) has been implicated in various pathological processes, including fibrosis and inflammation. However, its specific involvement in the pathogenesis of CP is not yet fully understood.

Aims & Methods

We therefore aimed to explore the role of PAI-1 in the development of CP and assess the therapeutic potential of PAI-1 inhibitors as antifibrotic agents to prevent the progression of CP.
​The PAI-1 expression was measured in human pancreatic tissue samples with immunohistochemistry, and human blood serum with ELISA. CP was induced in FVB/N mice with intraperitoneal cerulein injections given every hour, every 3 days for a total of 5 times. PAI-1 activity was inhibited with a specific inhibitor, which was administered per os at a dose of 10 mg/kgbw for 6 consecutive days after the 3rd cerulein treatment. Inflammation and fibrosis were assessed using hematoxylin-eosin and Crossman’s trichrome staining, while biochemical assays measured amylase activity and hydroxyproline concentration. SERPINE1 gene expression was quantified using RT-qPCR, and PAI-1 protein levels and localization were assessed via immunohistochemistry and immunofluorescence co-staining. In vitro, pancreatic fibroblast cells isolated from CP mice were treated with a 10 μM PAI-1 inhibitor.

Results

PAI-1 levels were significantly elevated in both pancreatic tissue and blood samples obtained from CP patients. In CP-induced mice, the body weight and the pancreatic weight/body weight ratio significantly reduced, while histopathology showed significant pancreatic atrophy and fibrosis. This was also confirmed by the increased hydroxyproline concentration and decreased amylase activity of the pancreatic tissue. SERPINE1 gene expression was upregulated in pancreatic tissue and fibroblast cultures in the CP group, while PAI-1 protein levels were elevated in pancreatic tissue. The elevated PAI-1 signal localization and the high overlap with vimentin suggests a possible expression role for activated pancreatic stellate cells (PSC). Administration of a PAI-1 inhibitor reduced body weight and pancreatic weight loss rates, along with significant decreases in pancreatic atrophy, fibrosis, hydroxyproline concentrations, and SERPINE1 gene expression compared to the CP group. In vitro, PAI-1 inhibition reduced cell migration rate and SERPINE1 gene expression in PSC derived from CP mice.

Conclusion

Our results indicate an elevation in PAI-1 expression in CP, with the potential for fibrosis and tissue atrophy reduction by the inhibition of PAI-1. These findings propose PAI-1 as a promising therapeutic target for the treatment of chronic pancreatitis.

Introduction

Literature suggests that computer-aided polyp detection (CADe) systems increase adenoma detection rate (ADR) compared to traditional colonoscopy (TC). Multiple systems with comparable efficacy on benchmark datasets have been introduced, including the for research purposes freely available system EndoMind. Although intended for colorectal cancer screening, many studies have been performed in a hospital setting recruiting mostly non-screening patients. Additionally, more recent studies present conflicting data suggesting a less pronounced effect of CADe on ADR.

Aims & Methods

In this randomized clinical trial we aimed to analyze the impact of the CADe system EndoMind on ADR for screening colonoscopy in a multicenter fashion. Adult patients with an indication for colorectal cancer screening, post-polypectomy surveillance or with a positive fecal immunochemical test were eligible for participation in 5 outpatient treating centers in Germany. Exclusion criteria were inflammatory bowel disease, familial polyposis syndrome, previous radiation, or colorectal surgery. Participants were randomized prior to the intervention to the CADe or the TC group. In the first group, the EndoMind CADe system framed detected polyps with a blue box on the main examination monitor during the whole procedure. Colonoscopies were performed by examiners with over 10 years of experience. Primary outcome was ADR. Secondary outcomes included polyp detection rate and withdrawal time. ClinicalTrials.gov trial register number: NCT05006092.

Results

From November 2021 to November 2022, 928 subjects were randomized to the CADe (n = 457) and TC (n = 471) group. Baseline characteristics of patients and bowel preparation quality between both groups were similar. The rate of screening examinations was over 80% in both groups. The mean ADR was 36.8% and 33.8% for the CADe and TC group respectively (p=0.34). Polyp detection rate was 50.8% in the CADe group and 50.5% in the TC group (p=0.94). Mean withdrawal time in total and without time spent on resection was 7.5 min, 6.9 min vs 7.4 min, 6.9 min for the CADe and TC group respectively.

Conclusion

In our multicenter randomized clinical trial the usage of CADe did not improve ADR or polyp detection rate of expert endoscopists in an outpatient setting involving mainly colorectal cancer screening candidates. The evaluation of other systems in this setting is needed in order to estimate the value of CADe.