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

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

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with limited therapeutic options available for unresectable cases. In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape. Among them, the combination of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), collectively referred to as Dur/Tre, has demonstrated significant survival benefits in patients with advanced HCC. However, robust prognostic biomarkers specific to patients receiving Dur/Tre therapy have yet to be established. The neutrophil-to-lymphocyte ratio (NLR), a systemic marker of inflammation, has been correlated with prognosis in various malignancies, including HCC [1, 2].

Aims & Methods

This study aimed to assess the prognostic significance of baseline NLR in patients with unresectable HCC treated with Dur/Tre. This multicenter retrospective cohort study included 182 patients with unresectable HCC who received Dur/Tre therapy between May 2022 and June 2024. Eligibility criteria included the availability of baseline NLR data and complete clinical records. The treatment regimen comprised a single 300 mg dose of tremelimumab on day 1, followed by 1500 mg of durvalumab administered every four weeks. Primary endpoints were progression-free survival (PFS) and overall survival (OS), assessed using the Kaplan-Meier method and Cox proportional hazards modeling. Baseline NLR values were calculated, and the optimal cutoff for OS prediction was determined using hazard ratio (HR) spline curve analysis.

Results

The median age of patients was 74 years, and 82.9% were male. The median baseline NLR was 3.13. Dur/Tre was administered as first-line therapy in 29.7% of patients and as second-line or later therapy in 70.3%. The median PFS was 3.5 months (95% confidence interval [CI]: 2.7–4.4 months), while the median OS was not reached (95% CI: 12.1 months–not reached). Multivariate analysis identified administration of Dur/Tre after second-line treatment as an independent predictor of shorter PFS (HR: 1.819; p = 0.003). Notably, an NLR ≥2.56 independently predicted poorer OS (HR: 1.919; p = 0.039). Median OS was not reached in the low-NLR group (<2.56), whereas it was 12.1 months in the high- NLR group (≥2.56) (p = 0.016). A Sankey diagram revealed that patients with higher NLR were more likely to receive best supportive care (BSC) rather than subsequent anticancer therapies post-Dur/Tre (p = 0.046). Spline curve analysis identified an optimal NLR threshold range of 2.3–3.0 for OS prediction.

Conclusion

This large, real-world, multicenter study demonstrated that baseline NLR serves as a significant and independent prognostic biomarker for overall survival in patients with unresectable HCC undergoing Dur/Tre therapy. Higher baseline NLR values (≥2.56) were associated with reduced survival and a lower likelihood of receiving subsequent anticancer treatment, whereas patients with lower NLR values were more likely to continue active therapeutic interventions. These findings suggest that NLR may function not only as a prognostic indicator but also as a practical tool for therapeutic decision-making and patient stratification in clinical settings. Further prospective studies with extended follow-up are warranted to validate these findings and refine NLR-based stratification strategies to optimize immunotherapy outcomes in HCC.

References

1. Tada T, Kumada T, Hiraoka A, et al. Neutrophil-to-lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with Lenvatinib. Liver Int. 2020; 40: 968-976.
2. Tada T, Kumada T, Hiraoka A, et al. Neutrophil-lymphocyte ratio predicts early outcomes in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab: a multicenter analysis. Eur J Gastroenterol Hepatol. 2022; 34: 698-706.

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

Post-ESD surveillance guidelines remain heterogeneous, with many centers favoring early surveillance colonoscopy (SC) despite low recurrence rates after curative resection. This study aimed to evaluate the safety and outcomes of delayed SC after R0 colorectal ESD for benign lesions and to identify risk factors for metachronous advanced neoplasia.

Aims & Methods

We retrospectively analyzed 1,097 patients who underwent colorectal ESD between 2013 and 2021. Clinical, procedural, and histological characteristics were recorded. Among 778 patients with available surveillance data, outcomes were compared between those who had early SC (<12 months) and those with delayed SC (>24 months). Rates of recurrence, advanced neoplasia, and colorectal cancer were assessed. Risk factors for metachronous advanced neoplasia were evaluated via univariate and multivariate analysis.

Results

Mean patient age was 74.3 ± 10.8 years; 54.1% were male. En bloc and R0 resection rates were 95.8% and 83.3%, respectively. Among patients with surveillance data, 82.6% underwent early SC, and 17.4% had late-only SC. The rate of advanced adenoma at first SC was low and comparable between early and late groups (3.9% vs. 6.7%, p = 0.167). The overall rate of metachronous advanced adenoma was 6.5%, with no significant difference between early and late strategies (6.1% vs. 8.9%, p = 0.25). All four colorectal cancers were detected in the early group; none occurred in the late-only group. Recurrence on the ESD scar was rare (1.5% overall), and no late recurrences occurred after a normal SC1. The only significant predictor of metachronous advanced neoplasia was the number of synchronous lesions at index colonoscopy (OR 1.16, 95% CI 1.07–1.27; p < 0.01).

Conclusion

Delayed surveillance colonoscopy 3 years after R0 colorectal ESD for benign lesions appears safe and effective in selected patients. The multiplicity of synchronous lesions could guide risk stratification. These findings support extending SC intervals after curative ESD, with potential to reduce unnecessary procedures.

References

Pimentel-Nunes P, Libânio D, Bastiaansen BAJ, Bhandari P, Bisschops R, Bourke MJ, et al. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. juin 2022;54(6):591‑622.
Dai M, Xiao X, Guo CLT, Lui RN, Yip HC, Chu S, et al. The Long‐Term Risk of Metachronous Advanced Adenoma Recurrence After Endoscopic Submucosal Dissection for Colorectal Neoplasia: A Propensity‐Score Matched Longitudinal Cohort With 5‐Year Follow‐Up. United Eur Gastroenterol J. 21 déc 2024;13(2):210‑9.
Yoshida N, Naito Y, Siah KTH, Murakami T, Ogiso K, Hirose R, et al. High incidence of metachronous advanced adenoma and cancer after endoscopic resection of colon polyps ≥20 mm in size. Dig Endosc Off J Jpn Gastroenterol Endosc Soc. mars 2016;28(2):194‑202.