INTRODUCTION:Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, and postoperative recurrence continues to limit long-term survival. Liver-resident natural killer (NK) cells are key effectors of antitumor immunity in the hepatic microenvironment. Interleukin-37 (IL-37), an anti-inflammatory cytokine, has recently been shown to modulate immune responses and enhance NK-cell activity. METHODS:Liver mononuclear cells were isolated from 24 deceased donors. For functional experiments, liver NK cells from six donors were cultured with interleukin-2 (IL-2) in the presence or absence of IL-37. Flow cytometry was used to evaluate activation markers, and cytotoxicity assays assessed NK cell-mediated tumor lysis. Serum IL-33 and IL-37 levels were measured in 120 patients undergoing liver resection for HCC, and their associations with oncological outcomes were analyzed. RESULTS:IL-37 significantly enhanced NK-cell cytotoxicity, increasing TRAIL and NKp44 expression. Clinically, patients with higher serum IL-37 levels showed improved 5-year recurrence-free survival (35.5% vs. 20.1%, p = 0.02) and a lower incidence of early recurrence. CONCLUSION:IL-37 enhanced liver NK-cell cytotoxicity in experimental analyses, and higher preoperative serum IL-37 levels were associated with improved recurrence-free survival after liver resection for HCC.
OBJECTIVES:Recurrence remains common in resectable pancreatic cancer (PC) despite multimodal treatment. We evaluated whether pretreatment contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) predicts pathological response and recurrence-free survival (RFS). METHODS:We retrospectively analyzed 52 patients with resectable PC who underwent CH-EUS before standardized multimodal treatment (neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy). Associations between CH-EUS enhancement patterns (iso- or hypoenhancement) at 20, 40, and 60 s and pathological response were assessed. Associations with RFS were analyzed using Kaplan-Meier and Cox regression analyses. RESULTS:Hypoenhancement was associated with significantly lower pathological response rates at all phases. Median RFS was significantly shorter in the hypoenhancement group at 20 s (560 vs. 1296 days; p = 0.018), 40 s (683 days vs. not reached; p = 0.013), and 60 s (779 days vs. not reached; p = 0.034). In multivariate analysis, hypoenhancement at 20 s independently predicted shorter RFS (HR 2.49, 95% CI 1.01-6.09; p = 0.047). CONCLUSIONS:Pretreatment CH-EUS predicts pathological response and recurrence risk in resectable PC. In particular, 20-s enhancement provides a simple, reproducible imaging biomarker that may support pre-treatment risk stratification and potentially guide individualized management strategies.
BACKGROUND:Cholangiolocarcinoma (CLC) is a rare liver cancer with ≥ 80% ductular configuration (DC). Given its rarity, its clinicopathological characteristics remain poorly understood, and its status as a distinct disease entity remains controversial. We conducted a nationwide multicenter study with centralized pathological review to investigate the features of CLC. METHODS:We included patients with a postoperative diagnosis of CLC at 49 participating institutions (2005-2018). All cases were re-evaluated by centralized pathology according to the WHO classification. RESULTS:Among 196 re-evaluated patients, 56 tumors were classified as CLC, 69 as intrahepatic cholangiocarcinoma (iCCA) with < 80% DC, 53 as small-duct type iCCA with DC, and 16 as mixed small- and large-duct type (SD/LD-iCCA with DC). CLC showed a low prevalence of viral hepatitis (23.2%), frequent arterial enhancement (83.9%), and characteristic apical EMA positivity. The median overall survival (OS) was 10.8 years, with 5- and 10-year OS rates of 85.0% and 73.7%, respectively, which were significantly better than those of SD/LD-iCCA with DC. Recurrence occurred in 38.2% of CLC cases with favorable outcomes following surgical resection. CONCLUSIONS:CLC exhibits distinct pathological and prognostic features, including favorable long-term survival, supporting CLC as a distinct clinicopathological entity. Further molecular research is needed to refine the classification. TRIAL REGISTRATION:This study was registered with the UMIN Clinical Trials Registry (UMIN000057919).
BACKGROUND:To determine the impact of symptomatic status on perioperative outcomes and assess optimal surgical timing for asymptomatic children with prenatally diagnosed congenital biliary dilatation (CBD). METHODS:This retrospective cohort study analyzed prenatally diagnosed CBD cases from 2015 to 2024, classified as symptomatic or asymptomatic. Demographics, liver fibrosis grade, and perioperative outcomes were compared between groups. Then, asymptomatic patients were subdivided into early (≤ 30 days) and delayed (> 30 days) surgery groups for further comparison. RESULTS:Of the 574 patients, 305 were symptomatic and 269 were asymptomatic. The symptomatic group had a longer operative time [180.0 (150.0, 223.5) vs. 160.0 (133.0, 190.0) min, p < 0.001], higher incidence of liver fibrosis (34.1% vs. 24.2%, p = 0.019), longer drainage duration [4 (3.5) vs. 3 (3.4) days, p < 0.001], and longer postoperative stay [7 (6.9) vs. 7 (6.8) days, p < 0.001] compared with the asymptomatic group. Among asymptomatic infants, no significant differences were observed in operative time[154.0 (132.5, 197.0) vs. 160.0 (133.0, 190.0) min, p = 0.890] or short-term complications (p > 0.05) between the early and delayed surgery groups. However, all eight cases of stage F4 liver fibrosis occurred in the delayed surgery group. CONCLUSION:Surgery after symptom onset in prenatally diagnosed CBD increases fibrosis risk. Asymptomatic early surgery is safe and may reduce advanced fibrosis.
BACKGROUND/PURPOSE:This study evaluated the association between institutional advanced hepatobiliary-pancreatic (HBP) surgical volume and operative mortality for pancreaticoduodenectomy (PD) and advanced hepatectomy using data from the Japanese National Clinical Database. METHODS:Patients undergoing PD or advanced hepatectomy between 2018 and 2021 were identified. Hospital volume was defined as the mean annual number of advanced HBP procedures performed at each institution. Volume-mortality associations were assessed using thin-plate spline regression with hospital volume as a continuous variable, followed by categorical analyses using four predefined groups (≤ 19, 20-29, 30-49, and ≥ 50 cases/year). The primary outcome was the operative mortality. RESULTS:We analyzed 47 088 patients undergoing PD and 27 358 undergoing hepatectomy. Mortality decreased with increasing institutional advanced HBP surgical volume for both procedures and plateaued at approximately 50 annual procedures. Compared with 30-49-case institutions, ≤ 19-case hospitals had significantly higher adjusted mortality for PD and hepatectomy, whereas ≥ 50-case hospitals had significantly lower mortality. CONCLUSIONS:Higher institutional advanced HBP surgical volume was associated with lower operative mortality for both procedures. Although both procedures appeared to achieve stable outcomes at similarly high institutional volumes, their volume-mortality curves differed in shape, suggesting the value of incorporating procedure-specific considerations into future quality assessment frameworks.
BACKGROUND:Common bile duct stones (CBDSs) can cause severe conditions. Endoscopic retrograde cholangiopancreatography (ERCP) is recommended but has a high rate of adverse events. However, some suspected cases do not have stones, requiring accurate evaluation in even high-likelihood patients. Endoscopic ultrasonography (EUS) offers high diagnostic performance. This study aimed to clarify the utility of EUS for diagnosing CBDSs in patients with strong suspicion of CBDSs. METHODS:This multicenter prospective exploratory study included patients with a high likelihood of CBDSs according to the American Society of Gastrointestinal Endoscopy guidelines, in whom CBDSs were not detected on initial imaging. EUS was subsequently performed, and diagnostic performance was assessed using ERCP findings or clinical course. RESULTS:Forty-eight patients were analyzed. EUS identified CBDSs in 21 and no stones in 27. A final diagnosis of CBDS was confirmed in 19 patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS (95% confidence interval) were 95.8% (85.7%-99.5%), 100% (75.1%-100%), 93.1% (77.2%-99.2%), 90.5% (69.6%-98.8%), and 100% (81.7%-100%). Among patients without CBDSs at final diagnosis, unnecessary ERCP was avoided in 79.3%. CONCLUSIONS:EUS would accurately diagnose CBDSs in high-likelihood patients with negative initial imaging, potentially reducing unnecessary ERCPs.
BACKGROUND:Acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP), known as post-ERCP pancreatitis (PEP), is a major adverse event. Although risk factors for PEP incidence have been widely studied, factors associated with severe PEP remain unclear. AIM:To identify risk factors, including body composition, associated with severe PEP. METHODS:A retrospective cohort study was conducted in patients who underwent ERCP at two tertiary care centers in Japan between January 2013 and October 2021. PEP severity was defined according to the American Society of Gastrointestinal Endoscopy Workshop criteria (2010). Patients were divided into mild and moderate-to-severe groups. Body composition parameters, including skeletal muscle index, subcutaneous adipose tissue, and visceral adipose tissue (VAT), were assessed using CT. Multivariate analysis was performed to identify factors associated with severe PEP. RESULTS:Among 3087 patients who underwent ERCP for biliary disease, 85 (2.75%) developed PEP. VAT was significantly higher in the severe than mild group (132.7 vs. 80.1 cm2, p < 0.01). VAT > 95 cm2 was the only independent risk factor for severe PEP (OR 2.79, p = 0.04). CONCLUSION:VAT may be associated with severe PEP. ERCP should be performed with awareness of the increased risk of severe PEP in patients with high visceral adiposity.
BACKGROUND:Steatotic liver disease (SLD) is an unrecognized complication after pancreaticoduodenectomy (PD) and may affect nutrition and long-term recovery. This meta-analysis estimated the incidence of SLD after PD and identified its clinical and surgical risk factors. METHODS:MEDLINE and EMBASE were searched through March 2025 for studies reporting incident SLD after PD. Random-effects models generated pooled incidence and risk estimates. Subgroup, meta-regression, and sensitivity analyses assessed heterogeneity. RESULTS:Forty-seven studies, including 6271 patients (mean age 65.8 ± 3.8 years; 42.9% female), predominantly from Asia, were included. The pooled incidence of SLD after PD was 26.2% (95% CI 22.6-30.3; I2 = 90.5), with similar estimates across regions. Meta-regression demonstrated that the timing of postoperative imaging influenced reported incidence. A higher risk of SLD was observed in women (OR 2.11), patients with obesity (OR 1.88) or hyperlipidemia (OR 1.57), and those undergoing PD for pancreatic ductal adenocarcinoma (OR 2.78). The classical Whipple procedure (RR 1.64, 95% CI 1.36-1.97) and adjuvant chemotherapy (RR 1.62, 95% CI: 1.28-2.07) were also associated with increased risk, whereas pancreatic enzyme replacement showed no significant protective effect. CONCLUSIONS:Approximately a quarter of patients develop SLD after PD. These findings support longitudinal postoperative liver assessment and early nutrition-focused management in surgical practice.
BACKGROUND:Cryopreserved venous allografts, which we pioneered in 1999 for use in living donor liver transplantation and hepato-biliary-pancreatic surgery, are widely used and are believed to preserve vascular architecture with minimal anticoagulation or immunosuppression requirements and patency comparable to autologous grafts. However, in contrast to arterial and heart valve grafts, their detailed histopathological characteristics remain unclear. METHODS:Histopathological and immunohistochemical analyses were performed in 19 non-transplanted and 15 explanted cryopreserved venous allografts. Cell viability was assessed by culture, and tissue chimerism was evaluated using fluorescence in situ hybridization. RESULTS:The normal trilaminar vascular architecture and presence of viable endothelial cells were confirmed in both groups. No findings of immunologic rejection, including medial cell loss, cellular infiltration in the adventitia, or intimal thickening, were observed. Long-term culture demonstrated sustained viability and proliferative capacity of donor cells. In situ hybridization confirmed persistent tissue chimerism with both donor- and recipient-derived cells. CONCLUSIONS:Cryopreserved venous allografts maintained viability and showed no histological evidence of active immunologic rejection after long-term implantation. These findings may help explain the favorable clinical performance and provide foundational insights to improve outcomes of venous reconstruction and the development of novel biologic vascular grafts.
