Introduction

Since 2029 national curricula for sedation and emergency management in endoscopy has established for endoscopy staff. NAPS are trained in three-day courses. After a baseline assessment in 2013, the effect of the training was evaluated in a survey in 2018.

Results & Findings

The questionnaire was completed by 356 endoscopy departments (95% in hospitals, 6% in private practice).

• Most departments operate in a multidisciplinary manner (85% gastroenterology, 59% TEE, 13% cardiology, 1.12% urology).
• In 52% of departments, 100% of staff have been trained, while 30% have trained 75-100% of staff. Refresher courses are completed every 2-5 years by 77% of units, while annual resuscitation courses are established in 93% od units.
• 98% have examination rooms equipped with BB, pulse oximeter, ECG, and oxygen supply. The second suction is available in 80%, and capnography in 9%. 83% have their own recovery room, 16% use other recovery rooms.
• ASA classification is used in 80% of unit for risk assessment, while Mallampati score is used in 7% only. 38% developed department specific scores. 63% perform the sign-in for all patients, 16% for 75-100% of patients. Only 10% of departments never perform a sign-in.
• 35% of units perform team-time-out (TTO) for all patients, 11% for 75-100% of patients. Only 26% of departments never use TTO.
• In 47% of departments, a dedicated person for patient monitoring and sedation is available. 30% have this person in 75-100% of patients, and 14% have this person in 25-50% of cases.
• Propofol mono sedation by bolus application is used in 88% of units, TCI in 17% of units, combination Propofol and Midazolam is used in 27%.
• In 77% of units, inpatients and outpatient are equally monitored in the recovery area while 21% of units only use the recovery area for outpatients.
• In 73% of units, physicians discharge the patient, in 12% nurses discharge patients.
• In 80% of departments, patients are only allowed to leave the endoscopy with an accompanying person.
• 70% of departments document all complications, but only 42% evaluate the complication rate statistically.
• 42% of units reported to have no problems to establish all requirements for sedation and patient monitoring. 37% reported about staff shortage. 12% could not find new staff, 25% reported about financial problems. 44% reported about resistance in their own department or with hospital management to establish improvements.

Summary & Discussion

• Comparing data from 2013, 2018 and 2024, improvements could be identified in the establishment of riss assessment by using ASA Score and individual checklists, Malampati score is still not well-known. The establishment of TTO increased from 20 to 35% in all patients, but still needs to be improved.
• The availability of a sedating person remains unchanged with 40 to 47% in all patients and 30% in 75-100% of patients. The recovery situation remains unchanged.

Conclusion

Staff shortage and resistance within the own team are the main challenges when establishing safe sedation and patient monitoring in Endoscopy.

Disclosure

no conflict of interest

Introduction

Lymphocytes inhibit the progression of hepatocellular carcinoma (HCC) through immune surveillance within an immunosuppressive microenvironment. Reduced lymphocyte counts, often associated with systemic inflammation, have been implicated in facilitating tumor progression. In contrast, elevated monocyte counts have been reported to be associated with microvascular invasion and poor prognosis in patients with HCC. Therefore, a high lymphocyte-to-monocyte ratio (LMR), calculated by dividing the lymphocyte count by the monocyte count, is considered a favorable prognostic indicator and is associated with improved clinical outcomes in patients with HCC.

Aims & Methods

We assessed the utility of the LMR in predicting the prognosis of patients with unresectable hepatocellular carcinoma who were treated with atezolizumab plus bevacizumab (Atezo/Bev). The study involved 941 patients who received Atezo/Bev treatment between September 2020 and February 2025. The median age was 74.0 years, and 754 were male. Performance status (PS) was distributed as follows: 741 patients with PS 0, 169 with PS 1, and 31 with PS ≥2. The liver background conditions were as follows: 149 patients with hepatitis B, 282 with hepatitis C, and 449 with non-hepatitis B or C (NBNC). Child-Pugh scores were distributed as follows: 522 patients with a score of 5, 254 with a score of 6, 67 with a score of 7, and 37 with a score of ≥8. The Barcelona Clinic Liver Cancer (BCLC) stages were as follows: 77 patients with stage ≤A, 317 with stage B, and 547 with stage ≥C. The median values of key biomarkers were as follows: LMR: 3.33, NLR: 2.63, AFP: 34.1 ng/mL. The median observation period was 14.3 months. NLR was included in Model 1, and LMR was incorporated in Model 2 of the multivariate analysis.

Results

The progression-free survival (PFS) was 6.8 months, and the overall survival (OS) was 23.6 months. The optimal cutoff for LMR, determined via time-dependent receiver operating characteristic (ROC) analysis based on median OS, was 3.6. The objective response rate (ORR) and disease control rate (DCR) were 27.3% and 76.5%, respectively. In the multivariate analysis of PFS, Model 1 identified the following factors as significant: BMI (HR: 0.98), Child-Pugh score ≥7 (HR: 1.34), BCLC stage C or higher (HR: 1.23), Log AFP (HR: 1.16), second or later treatment line (HR: 1.19). In Model 2, LMR was included as a significant factor (HR: 0.94). For OS, the following factors were identified as significant: age (HR: 1.01), Child-Pugh score ≥7 (HR: 2.09), BCLC stage C or higher (HR: 1.24), Log AFP (HR: 1.28), second or later treatment line (HR: 1.24), and NLR (HR: 1.03). The integrated discrimination improvement (IDI) for NLR and LMR at PFS (at 3 and 6 months) was 0.012 (95% CI: 0.012). The net reclassification improvement (NRI) was 0.016 (95% CI: 0.006-0.030, p<0.001) at 3 months, 0.023 (95% CI: 0.006-0.030, p<0.001) at 6 months, and 0.023 (95% CI: 0.004-0.024, p<0.001) at 12 months. The IDI for NLR and LMR at OS (12 and 24 months) was 0.027 (95% CI: 0.011-0.049, p=0.002) and 0.034 (95% CI: 0.012-0.064, p<0.001), with LMR demonstrating superior performance. The NRI for OS at 12 and 24 months was 0.036 (95% CI: 0.016-0.062, p<0.001) and 0.053 (95% CI: 0.020-0.091, p<0.001), respectively, both favoring LMR. In the time-dependent ROC analysis, the area under the curve (AUROC) was higher for LMR compared to NLR throughout the study period, with the exception of PFS at 3 months and OS at 18 months.

Conclusion

The LMR serves as a valuable biomarker for predicting prognosis in patients receiving Atezo/Bev.

Disclosure

Toshifumi Tada: lecture fees from AbbVie, AstraZeneca, Eisai, and Chugai
Atsushi Hiraoka: lecture fees from Eisai, Bayer, Eli Lilly, and Otsuka
Hidenori Toyoda: lecture fees from AbbVie, Eisai, Gilead, Terumo, and Bayer

Introduction

Gastric mucosal visibility is essential for high-quality upper gastrointestinal (GI) endoscopy. While simethicone and N-acetylcysteine (NAC) have been shown to improve mucosal visibility, the optimal time interval between preparation and endoscopy remains undefined.

Aims & Methods

This randomized controlled trial evaluated the effect of timing on mucosal visibility and explored the upper limit beyond which visibility begins to decline.
In this single-center, randomized controlled trial, adult patients undergoing elective upper GI endoscopy were randomized into four groups: placebo, simethicone + NAC with endoscopy performed after 10–20 minutes, 20–30 minutes, and >30 minutes. The primary outcome was the proportion of patients achieving adequate gastric mucosal visibility (GMV), defined as a score of <7 on a validated visibility scale. A pre-specified subgroup analysis of the >30 minute group was performed by stratifying patients into 20-minute intervals (31–50, 51–70, and 71–90 minutes) to assess the durability of mucosal clarity over time.

Results

Comparison	Adequate gastric mucosal visibility (%)	P
10–20 min vs 20–30 min	27% vs 62%	0.001
10–20 min vs >30 min	27% vs 67%	0.001
10–20 min vs Placebo	27% vs 2.6%	0.001
20–30 min vs >30 min	62% vs 67%	0.174
20–30 min vs Placebo	62% vs 2.6%	0.001

1,140 patients (median age 42years, 63.2% males) were included in the study. Adequate GMV was significantly higher in all preparation groups compared to placebo (p < 0.001). The 20–30 minute and >30 minute groups demonstrated the highest rates of adequate visibility (61.5% and 73.5%, respectively), both significantly superior to the 10–20 minute group (26.9%) and placebo (2.6%). In the >30 minute subgroup analysis, the 31–50 minute interval demonstrated the highest adequacy (73.5%). The 51–70 minute group showed moderate adequacy (52.1%), which was not significantly different from the 20–30 minute group (p = 0.207). However, the 71–90 minute group had reduced adequacy (43.8%) and did not differ significantly from the 10–20 minute group (p = 0.145). No adverse events were reported across study arms.

Conclusion

Endoscopy performed between 20 and 50 minutes after mucosal preparation yields optimal gastric mucosal visibility. A decline in visibility beyond 50 minutes suggests a practical upper limit for endoscopy timing following preparation. These findings support structured, time-sensitive scheduling following mucosal cleansing to enhance procedural quality.

Disclosure

None

Introduction

Primary sclerosing cholangitis (PSC) is a progressive autoimmune cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis [1]. In PSC, reduced expression and function of the bile acid receptor GPBAR1 (TGR5) in cholangiocytes is associated with a dysfunctional gut–liver immune axis and impaired resolution of inflammation [2,3]. Parallelly, the transcription factor RORγt in Th17 cells sustains IL-17 perpetuating IL-23-driven intestinal [4] and liver inflammation [5]. While GPBAR1 mediates anti-inflammatory responses to secondary bile acids, RORγt governs Th17 differentiation and cytokine secretion. Recent clinical studies have demonstrated that IL-23 inhibitors, such as risankizumab [6] and mirikizumab [7], are effective in treating IBD, highlighting the significance of the IL-23/IL-17 axis. GPBAR1/RORγt dual simultaneous modulation represents a novel strategy to counteract the fibrotic and inflammatory environment characteristic of PSC.

Aims & Methods

We evaluated the therapeutic efficacy of PBT002, a dual GPBAR1 agonist and RORγt inverse agonist, in modulating immune and fibrotic pathways in PSC. Transcriptomic distribution of target genes was assessed using publicly available single-cell RNA-sequencing datasets from healthy human livers [8]. Differential gene expression was validated in two independent cohorts of patients with PSC and PBC, and further confirmed in an external validation cohort (GSE159676). Functional studies were performed in vitro using primary human cholangiocytes (NHC), immortalized hepatic stellate cells (LX-2), primary monocyte-derived macrophages and CD4+ T lymphocytes. In vivo efficacy was assessed in Abcb4^⁻/⁻ mice treated with PBT002 (10 mg/kg/day) for 12 weeks.

Results

Single-cell transcriptomic analysis revealed that IL-17 and IL-23 cytokines are predominantly expressed by immune cells, whereas their receptors (IL23R, IL17RA, IL17RC, IL17RE) are enriched in epithelial cells, including hepatocytes and cholangiocytes. Deconvolution analysis of liver bulk transcriptomes from PSC and PBC cohorts showed features of immune exhaustion, with a mild upregulation of pro-inflammatory markers and IL-17 receptor subunits, along with prominent overexpression of PD-L1, a known pro-fibrotic mediator. In vitro, exposure of hepatic stellate cells, macrophages, and CD4+ T cells to supernatants from inflamed cholangiocytes induced strong activation, which was reversed by PBT002 treatment. In vivo, PBT002 significantly reduced hepatocellular damage, as shown by decreased serum ALT, AST, ALP, and bilirubin levels. Histological analyses revealed marked reductions in periductal inflammation and liver fibrosis. Gene expression profiling confirmed significant downregulation of M1 and Th17-associated genes (Rorc, Il17f, Il22, Il23a) in colon and liver. Bile acid profiling showed restoration of key GPBAR1 agonists and RORγt antagonists (DCA, 3-oxo-DCA, allo-LCA), while microbiota analysis demonstrated increased abundance of protective taxa (e.g., Blautia, Sutterellaceae), inversely associated with disease severity.

Conclusion

PBT002 exerts potent immunomodulatory effects in experimental PSC by rebalancing M1/M2 and Th17/Treg homeostasis through dual GPBAR1 activation and RORγt inhibition. These effects correlate with restoration of bile acid and microbiota profiles, confirming the key role of the microbiota–bile acid–immune axis in PSC and supporting PBT002’s clinical development for immune-mediated cholangiopathies, particularly in PSC-IBD overlap.

References

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3. Reich, M. et al. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis. J. Hepatol. 75, 634–646 (2021).
4. Biagioli, M. et al. Development of dual GPBAR1 agonist and RORγt inverse agonist for the treatment of inflammatory bowel diseases. Pharmacol. Res. 208, 107403 (2024).
5. Garcia Moreno, A. S. et al. IL-17 signaling in primary sclerosing cholangitis patient-derived organoids. Hepatol. Commun. 8, (2024).
6. Louis, E. et al. Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials. JAMA 332, 881–897 (2024).
7. D’Haens, G. et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N. Engl. J. Med. 388, 2444–2455 (2023).
8. Andrews, T. S. et al. Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity. Hepatol. Commun. 6, 821–840 (2022).