Introduction

Tertiary lymphoid structure (TLS) is a pathological structure existing in chronic inflammation or autoimmune diseases by promoting the immunotherapy response. However TLS neogenesis has not been evaluated in primary biliary cholangitis (PBC).

Aims & Methods

To determine the characteristics of liver TLSs neogenesis in patients with PBC and investigate the effect of inhibition of TLSs in a murine model of PBC. We performed a retrospective study of patients with PBC who underwent liver biopsy from April 2015 to November 2022. The cohort was divided into two groups based on TLS neogenesis (TLS- vs TLS+). A comparison of the severity of cholangitis between two groups was performed. Bulk RNA sequencing was performed between the groups of TLS- and TLS+ in liver biopsy. Sphingosine-1-phosphate receptor agonist FTY720 was administrated to suppress TLSs formation in dnTGFβRII mice, in which liver TLSs were developed.

Results

In total, 70 patients were included in the study cohort, of which 50 patients with TLSs formation and 20 patients without TLSs formation. The group of TLS+ showed a higher level of serum liver function compared with TLS- (Table1). The level of IgM and the proportion of liver cirrhosis were higher in the group of TLS+. Transcriptomic analysis in liver biopsy indicated a group of 1,548 significantly upregulated genes and 1,365 downregulated genes comparing the group of TLS+ with TLS-. The KEGG pathway identified liver with TLS expression signatures associated with phospholipase D signaling pathway and B cell receptor signaling pathway. GO assessment of DEGs confirmed the activation of immune system process and leukocyte migration. FTY720 significantly attenuated serum liver function and reduced the levels of inflammation cytokines in dnTGFβRII mice. Notably, TLSs were significantly smaller in FTY720-treated mice, with the levels of TLS-related chemokine and lymphotoxin decreasing significantly. Flow cytometry indicated the percentage of CD19⁺ B cells and CD4⁺ T cells out of the liver CD45⁺population was reduced significantly in FTY720-treated liver.

_{Table1: Clinical and demographic characteristics in patients of tertiary lymphoid structures at the time of biopsy}

	TLS+ (n=50)	TLS-(n=20)	P Value
Female, n (%)	44 (88.0)	19 (95.0)	0.445
Age at liver biopsy	54.5 (48.0-62.5)	50.0 (46.0-55.0)	0.528
ALT (U/L)	46.5 (31.0-79.5)	26.0 (12.0-39.0)	0.018*
AST (U/L)	50.5 (30.0-90.3)	27.0 (22.0-40.0)	0.005*
ALP (U/L)	196.0 (114.3-305.5)	107.0 (72.0-154.0)	0.008*
GGT (U/L)	150.0 (62.5-299.0)	153.0 (61.0-306.0)	0.826
IgG (g/L)	1765.0 (1507.5-2037.5)	1770.0 (1290.0-1890.0)	0.207
IgM (g/L)	342.0 (187.8-507.3)	206.0 (138.0-338.0)	0.013*
Liver cirrhosis, n (%)	14 (28.0)	0	0.007*

Note: Data are presented as a percentage or as the median (25th-75th percentile). Comparisons between the groups were performed by chi-squared tests or nonparametric tests. *P < 0.05.
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, gamma glutamyl transpeptidase;IgG, immunoglobulin G; IgM, immunoglobulin M.

Conclusion

Our results suggest the potential role of TLSs in building the severity of cholangitis and this understanding may guide therapeutic interventions of PBC.

References

[1]Sato Y, Silina K, van den Broek M, Hirahara K, Yanagita M. The roles of tertiary lymphoid structures in chronic diseases. Nat Rev Nephrol. 2023 : 1-13.
[2]Zhang QY, Ye XP, Zhou Z, et al. Lymphocyte infiltration and thyrocyte destruction are driven by stromal and immune cell components in Hashimoto's thyroiditis. Nat Commun. 2022. 13(1): 775.
[3]Al-Diwani A, Theorell J, Damato V, et al. Cervical lymph nodes and ovarian teratomas as germinal centres in NMDA receptor-antibody encephalitis. Brain. 2022. 145(8): 2742-2754.

Disclosure

Nothing to disclosure

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.