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

The optimal surgical approach to reduce recurrence rates after laparoscopic repair of paraesophageal hernia (PEH) is yet to be defined. The crural repair is challenged by both axial and transverse-lateral tension, which may compromise durability. The aim of this double-blind randomized clinical trial was to investigate whether a left-sided diaphragmatic relaxing incision in addition to standard crural repair and fundoplication reduces anatomical recurrence rates at one year postoperatively.

Aims & Methods

This study was conducted at two high-volume Swedish centers—Ersta Hospital (Stockholm) and Sahlgrenska University Hospital (Gothenburg)—between August 2019 and August 2023. Adult patients undergoing surgery for PEH were randomized 1:1 to either standard crural repair with total (360°) fundoplication (control) or the same procedure with the addition of a left-sided diaphragmatic relaxing incision covered by synthetic mesh (intervention). Patients with prior hiatal surgery, ASA class IV or above, type I hernia, major esophageal motility disorders, or any contraindication to fundoplication were excluded. Blinding for patients and assessors was maintained throughout follow-up. Pre- and postoperative assessments included computed tomography (CT), symptom questionnaires (Dakkak dysphagia score, Gastrointestinal Symptom Rating Scale [GSRS]), and quality of life (QoL, RAND-36). The primary outcome was radiologically confirmed PEH recurrence at 12 months.

Results

Of 103 patients screened, 76 were randomized (38 per group). Baseline characteristics were well balanced. CT was completed in 72 patients (95%) at 12 months. The recurrence rate was 66% in the control group and 54% in the intervention group (p=0.313). Three patients in the intervention group had asymptomatic CT verified herniation at the site of the diaphragmatic incision. There were no differences in recurrence size distribution (<4 cm vs >4 cm) between groups. Postoperative symptom assessment revealed significant improvements in dysphagia, reflux, indigestion, and abdominal pain in both groups, without intergroup differences. Physical QoL (PCS) improved significantlywhereas mental QoL (MCS) remained unchanged. Two deaths occurred within 90 days postoperatively (1 per group), yielding a 90-day mortality of 2.6%. Other complications included mediastinal abscess (n=1, intervention group) and need for postoperative endoscopic dilatation (n=5 in total). Operation time tended to be longer in the intervention group (150 vs 133 min; p=ns).

	Crural repair alone	Crural repair with relaxing diaphragmatic incision	P value
Completed CT chest at 1 year	35/38	37/38
Radiological recurrence	23 (66%)	20 (54%)	.313
Recurrence<4cm	12 (34%)	11 (30%)	.522
Recurrence>4cm	11 (31%)	9 (24%)	.457

Table 1: Radiological recurrences 1 year after surgical repair of PEH

Conclusion

In this randomized, double-blind trial, the addition of a left-sided diaphragmatic relaxing incision to standard laparoscopic PEH repair did not improve anatomical recurrence rates, symptom relief or QoL at 12 months after surgery and should not be recommended for routine use. Alternative strategies to improve recurrence rates after PEH need to be explored in the future.