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BACKGROUND: Neoadjuvant therapy has been increasingly adopted for resectable pancreatic ductal adenocarcinoma (PDAC) in Japan following the Prep-02/JSAP-05 trial. However, real-world evidence regarding effectiveness and underlying pathological mechanisms remains limited. This retrospective study evaluated neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) impacts on resectable PDAC patient oncological and pathological outcomes. METHODS: Consecutive resectable PDAC patients treated with NAC-GS (n = 60) or upfront surgery (UFS) (n = 101) between 2013 and 2023 were retrospectively analyzed (total diagnosed during the study period, n = 186). An intention-to-treat principle assessed overall survival (OS) and recurrence-free survival (RFS). Propensity score matching using six baseline variables (1:1) minimized selection bias. RESULTS: Fifty-four patients were included in each group. The NAC-GS group demonstrated significantly longer OS than the UFS group (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90; P = 0.023). Among resected cases, NAC-GS was associated with improved OS (HR, 0.42; 95% CI, 0.20-0.90; P = 0.026). Pathologically, the NAC-GS group showed significantly lower lymph node stage and less lymphatic invasion. Pathological complete response was observed in 4.0% of NAC-GS patients. DISCUSSION: Neoadjuvant chemotherapy with GS was associated with prolonged survival in resectable PDAC, potentially through lymphatic spread suppression. Pathological complete response was rare but may represent a clinically meaningful benefit of neoadjuvant treatment in selected patients.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. While curative resection offers the best chance for long-term survival, the high postoperative recurrence rate suggests a persistent need for effective perioperative therapies. We investigated a multimodal approach, combining sequential lenvatinib with transarterial chemoembolization (TACE), as a presurgical treatment (PST) for resectable HCC. METHODS: This retrospective study included 19 patients with technically resectable HCC who underwent the PST protocol followed by surgery between March 2022 and September 2024. The protocol involved four phases: Pre-TACE lenvatinib administration (Pre-LEN), TACE, Post-TACE lenvatinib administration, and surgery. We assessed the feasibility, safety, and pathological response of the protocol. Liver function was evaluated using the albumin-bilirubin (ALBI) score, modified ALBI (mALBI) grade, and tumor response was assessed using the Response Evaluation Criteria in Cancer of the Liver (RECICL). RESULTS: The PST protocol demonstrated high efficacy and safety. The median tumor reduction rate was 22.9%, and the median pathological tumor necrosis rate was 95%. The preoperative overall RECICL response was a complete response in 84.2% of patients. With a median follow-up of 22 months, the 2-year recurrence-free survival rate was 84.6%, and the overall survival rate was 100%. A significant association was found between mALBI grade and the decision to proceed with surgery at two time points: Pre-LEN (p = 0.023) and before surgery (p = 0.006). CONCLUSION: Presurgical sequential lenvatinib-TACE therapy is a feasible and safe strategy for resectable HCC. This protocol achieved a high pathological response and favorable survival outcomes, suggesting that it may mitigate the risk of early recurrence. Our findings highlight the importance of mALBI grade monitoring for patient selection and provide a rationale for larger, prospective studies.