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.

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.

Background: s/Aims: Minimally invasive pancreatoduodenectomy (MIPD), such as totally laparoscopic pancreatoduodenectomy (TLPD) or robot-assisted pancreatoduodenectomy (RAPD), is increasingly performed worldwide. This study aimed to compare the perioperative outcomes of TLPD and RAPD, and compare the oncologic outcomes between MIPD and open pancreatoduodenectomy (OPD) for malignant disease. Methods: This retrospective study was conducted at two hospitals that followed similar oncological surgical principles, including the extent of resection. RAPD was performed at Seoul National University Hospital, and TLPD at Seoul National University Bundang Hospital. Patient demographics, perioperative outcomes, and oncological outcomes were analyzed. Propensity score matching (PSM) analysis was performed to compare oncologic outcomes between MIPD and OPD. Results: Between 2015 and 2020, 332 RAPD and 178 TLPD were performed. The rates of Clavian–Dindo grade ≥ 3 complications (19.3% vs. 20.2%, p = 0.816), clinically relevant postoperative pancreatic fistula (9.9% vs. 11.8%, p = 0.647), and open conversions (6.6% vs. 10.5%, p = 0.163) were comparable between the two groups. The mean operation time (341 minutes vs. 414 minutes, p < 0.001) and postoperative hospital stay were shorter in the RAPD group (11 days vs. 14 days, p = 0.034). After PSM, the 5-year overall survival rate was comparable between MIPD and OPD for overall malignant disease (58.4% vs. 55.5%, p = 0.180). Conclusions Both RAPD and TLPD are safe and feasible, and MIPD has clinical outcomes that are comparable to those of OPD. Although RAPD exhibits some advantages, its perioperative outcomes are similar to those associated with TLPD. A surgical method may be selected based on the convenience of surgical movements, medical costs, and operator experience.

Background: s/Aims: Minimally invasive pancreatoduodenectomy (MIPD), such as totally laparoscopic pancreatoduodenectomy (TLPD) or robot-assisted pancreatoduodenectomy (RAPD), is increasingly performed worldwide. This study aimed to compare the perioperative outcomes of TLPD and RAPD, and compare the oncologic outcomes between MIPD and open pancreatoduodenectomy (OPD) for malignant disease. Methods: This retrospective study was conducted at two hospitals that followed similar oncological surgical principles, including the extent of resection. RAPD was performed at Seoul National University Hospital, and TLPD at Seoul National University Bundang Hospital. Patient demographics, perioperative outcomes, and oncological outcomes were analyzed. Propensity score matching (PSM) analysis was performed to compare oncologic outcomes between MIPD and OPD. Results: Between 2015 and 2020, 332 RAPD and 178 TLPD were performed. The rates of Clavian–Dindo grade ≥ 3 complications (19.3% vs. 20.2%, p = 0.816), clinically relevant postoperative pancreatic fistula (9.9% vs. 11.8%, p = 0.647), and open conversions (6.6% vs. 10.5%, p = 0.163) were comparable between the two groups. The mean operation time (341 minutes vs. 414 minutes, p < 0.001) and postoperative hospital stay were shorter in the RAPD group (11 days vs. 14 days, p = 0.034). After PSM, the 5-year overall survival rate was comparable between MIPD and OPD for overall malignant disease (58.4% vs. 55.5%, p = 0.180). Conclusions Both RAPD and TLPD are safe and feasible, and MIPD has clinical outcomes that are comparable to those of OPD. Although RAPD exhibits some advantages, its perioperative outcomes are similar to those associated with TLPD. A surgical method may be selected based on the convenience of surgical movements, medical costs, and operator experience.

Background: s/Aims: Minimally invasive pancreatoduodenectomy (MIPD), such as totally laparoscopic pancreatoduodenectomy (TLPD) or robot-assisted pancreatoduodenectomy (RAPD), is increasingly performed worldwide. This study aimed to compare the perioperative outcomes of TLPD and RAPD, and compare the oncologic outcomes between MIPD and open pancreatoduodenectomy (OPD) for malignant disease. Methods: This retrospective study was conducted at two hospitals that followed similar oncological surgical principles, including the extent of resection. RAPD was performed at Seoul National University Hospital, and TLPD at Seoul National University Bundang Hospital. Patient demographics, perioperative outcomes, and oncological outcomes were analyzed. Propensity score matching (PSM) analysis was performed to compare oncologic outcomes between MIPD and OPD. Results: Between 2015 and 2020, 332 RAPD and 178 TLPD were performed. The rates of Clavian–Dindo grade ≥ 3 complications (19.3% vs. 20.2%, p = 0.816), clinically relevant postoperative pancreatic fistula (9.9% vs. 11.8%, p = 0.647), and open conversions (6.6% vs. 10.5%, p = 0.163) were comparable between the two groups. The mean operation time (341 minutes vs. 414 minutes, p < 0.001) and postoperative hospital stay were shorter in the RAPD group (11 days vs. 14 days, p = 0.034). After PSM, the 5-year overall survival rate was comparable between MIPD and OPD for overall malignant disease (58.4% vs. 55.5%, p = 0.180). Conclusions Both RAPD and TLPD are safe and feasible, and MIPD has clinical outcomes that are comparable to those of OPD. Although RAPD exhibits some advantages, its perioperative outcomes are similar to those associated with TLPD. A surgical method may be selected based on the convenience of surgical movements, medical costs, and operator experience.

Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.

Background: Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. Methods: Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. Results: PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. Conclusion This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.