Introduction

Multi-drug resistant organism (MDRO) infections have become a significant concern associated with the use of reusable duodenoscopes, even with stringent sterilization protocols. As a result, various modalities have been developed to reduce the risk of cross-contamination. However, limited data exist that directly compare these different approaches. The aim of this study was to compare the efficacy and operator usability of two different modalities: single-use disposable duodenoscopes (SDDs) and reusable duodenoscopes with disposable end caps, in performing ERCP procedures. The use of disposable duodenoscopes has gained interest as an alternative to standard reusable duodenoscopes due to their potential to reduce the risk of MDRO infections. Nevertheless, the efficacy and operator usability of these devices in comparison to reusable duodenoscopes with disposable end caps have not been fully evaluated.

Aims & Methods

A multi-center retrospective study was conducted to evaluate the efficacy and usability of a single-use disposable duodenoscopes (SDD) and reusable duodenoscopes with disposable end caps in performing ERCP procedures. The study included patients who underwent ERCP using either the SDD or the reusable duodenoscope with disposable end cap, with each procedure performed by an expert endoscopist from one of four academic centers.The primary outcome measures included technical success rate, procedural complexity, completion of ERCP with the device, and adverse events. In addition, the endoscopists rated the devices on a scale of 1 (easy) to 5 (severely difficult) for location and visualization quality, maneuverability based on papillary orientation, suction/air control, and elevator efficiency.

Results

The study included 158 patients, with 56 undergoing ERCP using a SDD (mean age 60, 54% male) and 102 using the standard reusable duodenoscope with a disposable end cap (mean age 59, 41% male) (Figure 1 & 2). The technical success rate was 98% for both groups, and the procedural complexity of the ERCP cases performed was graded as follows: Grade 1 (15%), Grade 2 (36%), Grade 3 (32%), and Grade 4 (17%). Two patients (4%) in the SDD group required conversion to a reusable duodenoscope, while none in the disposable end cap group did. Endoscopists rated the SDD and disposable end cap on a scale of 1 (easy) to 5 (severely difficult) for location and visualization quality (2.08 vs 1.12), maneuverability based on papillary orientation (1.29 vs 1.01), suction/air control (1.47 vs 1.00), and elevator efficiency (1.92 vs 1.08). Overall, most endoscopists considered both options comparable to their reusable counterparts.

Conclusion

In conclusion, the study showed that the single use duodenoscope and the reusable duodenoscope with a disposable end cap had comparable efficacy in performing ERCPs of varying complexity. Although operator usability was slightly better with the reusable duodenoscope and disposable end cap combination compared to the SDD, both were considered comparable to standard reusable duodenoscopes. With ongoing technological advancements, these alternative modalities can further improve in functionality, reduce the risk of multi-drug resistant organism (MDRO) cross-contamination, and serve as viable alternatives to standard reusable duodenoscopes.

Introduction

Third-space endoscopy (TSE) is standard for treating neoplastic and motility disorders but is limited by intra-procedural bleeding. Vessel pre-sealing using electrocautery in an underwater setting may mitigate this, improving procedural safety and efficiency.

Aims & Methods

We conducted a randomized controlled trial (NCT05804266) comparing underwater (saline immersion) vs conventional CO₂-based coagulation during TSE procedures (ESD and POEM). Patients were randomized 1:1. The same electrosurgical settings (SWIFT COAG E3, 89 W for POEM and SWIFT COAG E4, 124 W for ESD) and instruments (VIO 3 and HybridKnife T-type, Erbe Elektromedizin GmbH, Tübingen, Germany) were used across arms. In the underwater group, vessels ≥1.2 mm were coagulated under saline immersion to enable pre-sealing; smaller vessels were treated conventionally. In the control group, all vessels were treated under CO₂, with vessel isolation when needed. Primary endpoint was the rate of intra-procedural bleeding requiring further hemostatic treatment (knife tip, coagulation forceps) of pre-sealed vessels. Secondary outcomes included other adverse events (ie delayed bleeding).

Results

Among 70 patients (37 underwater, 33 CO₂, no significant demographic difference including history of antiplatelet/anticoagulant therapy, discontinued in all patients on therapy), intra-procedural bleeding requiring hemostasis of pre-sealed vessels occurred in 12/37 (32.4%) underwater group vs 25/33 (75.8%) control (RR 0.43(0.26-0.71); NNT 2.3; P<0.01). In the underwater group, no patient required coagulation forceps; all bleedings were managed with the knife. In contrast, 9/33 (27.3%) control patients required forceps (RR: 0.05 (0.00-0.78); NNT 3.76 P<0.01). One intra-procedural perforation and two post-procedural adverse events (delayed bleeding and fever) occurred in the control group; none in the underwater arm (n.s). No mortality occurred.

Conclusion

Underwater (saline immersion) vessel pre-sealing significantly reduces the risk of intraprocedural bleeding and consequently the need of hemostatic devices, suggesting a safer, cost-effective alternative to conventional coagulation in TSE.

Introduction

Patients with recurrent acute pancreatitis (RAP) are at significant risk of developing early chronic pancreatitis (CP), which progresses into irreversible, end-stage CP with severe symptoms. There is no specific therapy in RAP or in early CP that may hinder disease progression. The pathogenesis of CP is complex and involves interactions among multiple cell types, including pancreatic acinar, ductal, and stellate cells (PSC). Therefore, it is pivotal to identify common pathogenic pathways in these cells that could be targeted pharmacologically. The Orai1-mediated store-operated Ca²⁺ entry (SOCE) is a ubiquitous signaling mechanism, which may become overactivated in pathological states resulting intracellular Ca²⁺overload.

Aims & Methods

In this study, we used ex vivo and in vivo preclinical disease models to demonstrate that Orai1 inhibition prevents progression of RAP and early CP. CP was induced in wild type FVB/N mice by repeated administration of cerulein (50 µg/kg) for two weeks, followed by administration of a selective Orai1 inhibitor (CM5480; 20 mg/kg) on the last five days, and histological parameters, fibrosis, pancreas weight/body weight ratio, and hydroxyproline (HyP) content were quantified. Functional and morphological assays were used to evaluate acinar and ductal functions. In vitro experiments were performed on PSCs.

Results

Our findings show that SARAF, an endoplasmic reticulum resident protein that inhibits Orai1 activity, is significantly reduced in pancreatic acinar cells from mouse and human CP tissue, leading to an increase in Orai1-mediated extracellular Ca²⁺ influx. In contrast, inhibiting Orai1 significantly reduced tissue damage during experimental CP in mice, as well as the extent of fibrosis and immune cell infiltration. Furthermore, CM5480-treated mice had significantly improved pancreatic acinar and ductal functions. Finally, Orai1 inhibition reduced PSC activation in vitro and in vivo, as well as migration and proliferation, while causing a cell cycle arrest and accumulation of PSCs in the S phase.

Conclusion

We suggest that the overactivation of Orai1 is a crucial pathogenetic event in the progression of early CP, and inhibition of Orai1 could prevent the development of end-stage CP.

Disclosure

The selective Orai1 inhibitor CM5480 was provided by CalciMedica.