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