Background: s/Aims: Pancreaticoduodenectomy (PD) is the standard treatment for periampullary tumors, but it is technically challenging. Evidence directly comparing open, laparoscopic, robotic, and hybrid approaches is limited. This study conducts a network meta-analysis (NMA) to compare the perioperative and oncologic outcomes of open PD (OPD), laparoscopic PD (LPD), robotic PD (RPD), and hybrid PD. Methods: We searched PubMed, EMBASE, and the Cochrane Library for studies published between January 1994 and August 2024.We included randomized controlled trials and comparative observational studies that evaluated at least two PD approaches. Perioperative outcomes were the primary endpoints, while oncologic safety served as a secondary endpoint. A random-effects NMA was performed, establishing treatment hierarchies through ranking probabilities (PROSPERO ID: CRD420250365864). Results: A total of 78 studies were included (5 randomized and 73 retrospective). RPD was associated with lower blood loss compared to OPD (mean difference [MD], –163.85 mL) and LPD (MD, –84.14 mL). Hospital stays were also shorter for RPD compared to OPD (MD, –2.50 days) and LPD (MD, –1.88 days). In contrast, OPD was the most time-efficient approach compared to LPD (MD, –77.61 minutes) and RPD (MD, –73.30 minutes). Mortality rates, severe complications, clinically relevant postoperative pancreatic fistula rates, and reoperation rates were comparable across all surgical approaches. In terms of oncologic safety, lymph node yield and R0 resection rates were similar for all modalities. Conclusions While OPD is the most time-efficient approach, RPD provides significant advantages in reducing intraoperative blood loss and shortening hospital stays compared to both LPD and OPD.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Intrahepatic cholangiocarcinoma (CCA) is the second most common primary liver cancer after hepatocellular carcinoma (HCC). However, combined HCC-CCA is a rare malignancy exhibiting hepatocytic and cholangiocytic differentiation. For both tumors, R0 resection with regional lymph node dissection remains the only potentially curative treatment. Nevertheless, key aspects of surgical management remain controversial. In this narrative review, we synthesize contemporary evidence on the surgical management of intrahepatic CCA and combined HCC-CCA. We summarize current data on lymphadenectomy, safety, and oncologic comparability of minimally invasive vs. open surgery, and integration of liver hypertrophy techniques for major hepatectomy. We also review the emerging clinical experience with immune checkpoint inhibitor-based chemoimmunotherapy as a neoadjuvant treatment and conversion surgery for advanced disease. We highlight persisting knowledge gaps and propose practical perspectives to support individualized surgical planning for this heterogeneous disease.

Objective: The Korean National Fire Agency conducted a pilot project examining Advanced Life Support (ALS) protocols, including epinephrine administration, to improve survival among patients suffering out-of-hospital cardiac arrest (OHCA). In this study, we aimed to evaluate the effects of the Korean National Fire Agency ALS protocol on prehospital return of spontaneous circulation (ROSC) in patients with OHCA. Methods: This study included patients with adult-presumed cardiac arrest between January and December 2020. The main factor of interest was ambulance type according to ALS protocol, which was divided into dedicated ALS ambulance (DA), smartphone-based ALS ambulance (SALS), and non-DA, and the main analysis factor was prehospital ROSC. Multivariate logistic regression analysis was performed. Results: During the study period, a total of 18,031 adult patients with OHCA was treated by the emergency medical services, including 7,520 DAs (41.71%), 2,622 SALSs (14.54%), and 7,889 non-DAs (43.75%). The prehospital ROSC ratio was 13.19% for DA, 11.17% for SALS, and 7.91% for non-DA (P<0.01). Compared with that of the DA group, the odds ratios (95% confidence interval) for prehospital ROSC ratio were 0.97 (0.82–1.15) in the SALS group and 0.57 (0.50–0.65) in the non-DA group. The prehospital ROSC ratio of the DA group was higher than those of the non-DA group and the SALS group. Conclusion ALS protocol intervention was associated with prehospital ROSC rates. Therefore, continuous efforts to promote systemic implementation of the ALS protocol to improve OHCA outcomes are necessary.

Recent clinical outcomes of multi-regimen chemotherapy in patients with cholangiocarcinoma (CCC) have shown benefits in terms of overall survival. However, repeated endoscopic biliary drainage (EBD) and serious adverse events negatively affect prolongation of the survival period.The aim of this study was to investigate the prevalence of massive hemobilia and the outcomes of its management with fully covered self-expandable metal stents (FC-SEMSs) in patients with hilum-involving CCC receiving multi-regimen chemotherapy. The methods and effects of FCSEMS placement were retrospectively investigated following the occurrence of massive hemobilia during EBD. A total of 356 patients with CCC received multi-regimen chemotherapy. Among them, 181 patients had hilar invasion, and seven patients (3.9%) developed massive hemobilia during repeated EBD using removable stents. In all cases, the tumor encased the right hepatic artery. In six patients (85.7%), hemostasis was immediately and completely achieved by inserting one or two FC-SEMSs proximal to the hilar invasion area. Therefore, if the tumor encases the right hepatic artery, massive hemobilia is likely to occur during multi-regimen chemotherapy.Thus, prompt placement of a FC-SEMS would be an effective treatment option for massive hemobilia in patients with hilum-involving CCC.

Objective: The Korean National Fire Agency conducted a pilot project examining Advanced Life Support (ALS) protocols, including epinephrine administration, to improve survival among patients suffering out-of-hospital cardiac arrest (OHCA). In this study, we aimed to evaluate the effects of the Korean National Fire Agency ALS protocol on prehospital return of spontaneous circulation (ROSC) in patients with OHCA. Methods: This study included patients with adult-presumed cardiac arrest between January and December 2020. The main factor of interest was ambulance type according to ALS protocol, which was divided into dedicated ALS ambulance (DA), smartphone-based ALS ambulance (SALS), and non-DA, and the main analysis factor was prehospital ROSC. Multivariate logistic regression analysis was performed. Results: During the study period, a total of 18,031 adult patients with OHCA was treated by the emergency medical services, including 7,520 DAs (41.71%), 2,622 SALSs (14.54%), and 7,889 non-DAs (43.75%). The prehospital ROSC ratio was 13.19% for DA, 11.17% for SALS, and 7.91% for non-DA (P<0.01). Compared with that of the DA group, the odds ratios (95% confidence interval) for prehospital ROSC ratio were 0.97 (0.82–1.15) in the SALS group and 0.57 (0.50–0.65) in the non-DA group. The prehospital ROSC ratio of the DA group was higher than those of the non-DA group and the SALS group. Conclusion ALS protocol intervention was associated with prehospital ROSC rates. Therefore, continuous efforts to promote systemic implementation of the ALS protocol to improve OHCA outcomes are necessary.

Recent clinical outcomes of multi-regimen chemotherapy in patients with cholangiocarcinoma (CCC) have shown benefits in terms of overall survival. However, repeated endoscopic biliary drainage (EBD) and serious adverse events negatively affect prolongation of the survival period.The aim of this study was to investigate the prevalence of massive hemobilia and the outcomes of its management with fully covered self-expandable metal stents (FC-SEMSs) in patients with hilum-involving CCC receiving multi-regimen chemotherapy. The methods and effects of FCSEMS placement were retrospectively investigated following the occurrence of massive hemobilia during EBD. A total of 356 patients with CCC received multi-regimen chemotherapy. Among them, 181 patients had hilar invasion, and seven patients (3.9%) developed massive hemobilia during repeated EBD using removable stents. In all cases, the tumor encased the right hepatic artery. In six patients (85.7%), hemostasis was immediately and completely achieved by inserting one or two FC-SEMSs proximal to the hilar invasion area. Therefore, if the tumor encases the right hepatic artery, massive hemobilia is likely to occur during multi-regimen chemotherapy.Thus, prompt placement of a FC-SEMS would be an effective treatment option for massive hemobilia in patients with hilum-involving CCC.

Recent clinical outcomes of multi-regimen chemotherapy in patients with cholangiocarcinoma (CCC) have shown benefits in terms of overall survival. However, repeated endoscopic biliary drainage (EBD) and serious adverse events negatively affect prolongation of the survival period.The aim of this study was to investigate the prevalence of massive hemobilia and the outcomes of its management with fully covered self-expandable metal stents (FC-SEMSs) in patients with hilum-involving CCC receiving multi-regimen chemotherapy. The methods and effects of FCSEMS placement were retrospectively investigated following the occurrence of massive hemobilia during EBD. A total of 356 patients with CCC received multi-regimen chemotherapy. Among them, 181 patients had hilar invasion, and seven patients (3.9%) developed massive hemobilia during repeated EBD using removable stents. In all cases, the tumor encased the right hepatic artery. In six patients (85.7%), hemostasis was immediately and completely achieved by inserting one or two FC-SEMSs proximal to the hilar invasion area. Therefore, if the tumor encases the right hepatic artery, massive hemobilia is likely to occur during multi-regimen chemotherapy.Thus, prompt placement of a FC-SEMS would be an effective treatment option for massive hemobilia in patients with hilum-involving CCC.

Objective: The Korean National Fire Agency conducted a pilot project examining Advanced Life Support (ALS) protocols, including epinephrine administration, to improve survival among patients suffering out-of-hospital cardiac arrest (OHCA). In this study, we aimed to evaluate the effects of the Korean National Fire Agency ALS protocol on prehospital return of spontaneous circulation (ROSC) in patients with OHCA. Methods: This study included patients with adult-presumed cardiac arrest between January and December 2020. The main factor of interest was ambulance type according to ALS protocol, which was divided into dedicated ALS ambulance (DA), smartphone-based ALS ambulance (SALS), and non-DA, and the main analysis factor was prehospital ROSC. Multivariate logistic regression analysis was performed. Results: During the study period, a total of 18,031 adult patients with OHCA was treated by the emergency medical services, including 7,520 DAs (41.71%), 2,622 SALSs (14.54%), and 7,889 non-DAs (43.75%). The prehospital ROSC ratio was 13.19% for DA, 11.17% for SALS, and 7.91% for non-DA (P<0.01). Compared with that of the DA group, the odds ratios (95% confidence interval) for prehospital ROSC ratio were 0.97 (0.82–1.15) in the SALS group and 0.57 (0.50–0.65) in the non-DA group. The prehospital ROSC ratio of the DA group was higher than those of the non-DA group and the SALS group. Conclusion ALS protocol intervention was associated with prehospital ROSC rates. Therefore, continuous efforts to promote systemic implementation of the ALS protocol to improve OHCA outcomes are necessary.

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values.CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression.The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300–CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.