三木 厚

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.

BACKGROUND/AIM: The Albumin-Bilirubin (ALBI) score was initially developed to estimate prognosis in patients with hepatocellular carcinoma. Recently, its prognostic relevance has been extended to intrahepatic cholangiocarcinoma; however, its impact on perihilar cholangiocarcinoma remains unclear. PATIENTS AND METHODS: A total of 71 patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2007 and 2024 at Jichi Medical University were retrospectively analyzed. Preoperative blood samples were obtained within two weeks before surgery, after effective jaundice control. Survival outcomes were evaluated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for overall survival. RESULTS: Patients with ALBI Grade 1 had a significantly longer median survival time compared to those with ALBI Grade 2 or 3 (not reached vs. 45 months vs. 13 months, respectively; p=0.001). The prognostic nutritional index (PNI) was significantly lower in ALBI Grade 2/3 than in Grade 1 (41.6±5.7 vs. 49.5±5.9, p<0.001). Similarly, carbohydrate antigen 19-9 (CA19-9) levels were higher in ALBI Grade 2/3 compared to Grade 1 (493±129 vs. 98±176 U/mL, p=0.002). Multivariable analysis identified ALBI Grade 2/3 as an independent negative prognostic factor for overall survival (HR=2.14, 95% CI=1.01-4.54, p=0.047). Regression analysis showed a strong inverse correlation between ALBI score and serum albumin levels (R=-0.9624, p=0.001). CONCLUSION: ALBI score may provide valuable prognostic information for long-term outcomes in patients undergoing hepatectomy for perihilar cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma with large hepatic resection is associated with high risk for morbidity and mortality. To improve outcomes, assessment of remnant liver function is crucial. METHODS: A total of 70 patients with perihilar cholangiocarcinoma were examined retrospectively. Liver function was evaluated <1 month preoperatively by hepatic clearance of remnant liver using 99mTc-galactosyl serum albumin (GAS) scintigraphy and computed tomography, and clinicopathological data and outcomes were analyzed in comparison GSA scintigraphy with liver function test based on computed tomography volumetry. RESULTS: There was no postoperative 90-day mortality, with 10 patients of posthepatectomy liver failure (PHLF) Grade A, 10 of Grade B, and 1 of Grade C. Area under the curve of receiver operating curve showed better prediction power for PHLF compared to remnant liver volume/body surface area or future liver remnant/body weight, especially in patients with incomplete change of liver function. In univariable analysis, <150 ml/min ml/min cutoff of hepatic clearance of remnant liver and >1750 ml intra-operative blood loss were significant risk factors for PHLF. In multivariable analysis, <150 ml/min cutoff was a significant risk factor for PHLF. The area under the curve of hepatic clearance of remnant liver indicated better predictivity in patients with incomplete change of liver function compared with complete change of liver function. CONCLUSIONS: The hepatic clearance of remnant liver may have predictive power in patients with incomplete changes in liver function compared to computed tomography-based methods. Preoperative measurement of hepatic clearance of remnant liver may assist in risk stratification for surgical management.

BACKGROUND: The aim of this study was to elucidate the association of pancreatic fluid cytology with intrapancreatic recurrence of intraductal papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS: A total of 68 patients with IPMN who underwent pancreatectomy and obtained cytologic analysis of pancreatic fluid at Jichi Medical University Hospital were included in this study. Computed tomography scan and magnetic resonance cholangiopancreatography were performed preoperatively. Endoscopic retrograde cholangiopancreatography was used to obtain pancreatic fluid. The association of recurrence with variables was determined by logistic regression multivariate analysis. RESULTS: Class V cytology was found in 7/68 patients preoperatively. Metachronous intrapancreatic recurrences occurred in 6/68 patients, including one branched type, main pancreatic duct type in two and mixed pancreatic duct type in three. Four of seven patients with class V cytology developed intra-pancreatic recurrences as a new lesion. Class V cytology was significantly associated with intrapancreatic recurrence, compared to those with class IV or lower cytology. In univariate analysis, patients with pathological findings with high-grade dysplasia or adenocarcinoma (P = 0.0392, odds ratio (OR) 10.2, 95 % confidence interval (CI) 1.12-93.6) and class V pancreatic fluid cytology (P = 0.0005, OR 38.7, 95 % CI 4.94-302) were significant risk factors. In multivariate analysis, class V pancreatic fluid cytology was significantly associated with developing intrapancreatic recurrence (P = 0.0149, OR 22.7, 95 % CI 1.83-279). CONCLUSION: Preoperative class V pancreatic fluid cytology is associated with intra-pancreatic recurrence after resection of IPMN.