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: Although the association between handgrip strength and glycemic control has been reported, studies conducted exclusively within specific occupational groups remain limited. To explore the association between handgrip strength and metabolic health in industrial settings, this study examined the relationship between relative handgrip strength and glycated hemoglobin (HbA1c) among male automobile manufacturing workers using vibration tools in South Korea. Methods: Using 66,212 occupational health examination records collected at Inha University Hospital between January 2024 and April 2025, a total of 3,365 workers with HbA1c and handgrip strength measurements were identified. After excluding duplicates (n = 1,536), female workers (n = 2), and records without Hb and estimated glomerular filtration rate, 1,823 male participants were included in the final analysis. Relative handgrip strength was calculated as the maximum value of bilateral grip strength divided by body mass index. Multiple linear regression analyses were conducted to assess the association between relative handgrip strength and HbA1c, adjusting for age, smoking status, alcohol consumption, current hypertension, current dyslipidemia, current hypoglycemic-agents use, family diabetes history, leisure-time physical activity, and resistance exercise. Results: Relative handgrip strength was inversely associated with HbA1c levels (B: –0.060; 95% confidence interval [CI]: −0.081 to −0.039; p < 0.001). The association was strongest among normoglycemic participants (B: −0.185; 95% CI: −0.305 to −0.065; p = 0.003). Effect size was reduced but significantly associated among individuals with prediabetes (B: −0.115; 95% CI: −0.180 to −0.050; p < 0.001) and further attenuated to a borderline significance in individuals with diabetes (B: −0.023; 95% CI: −0.050 to 0.003; p = 0.082). These findings indicate that greater muscle strength relative to body size is related to better glycemic control. Conclusions Handgrip strength was associated with HbA1c levels in industrial workers. This study suggests that handgrip strength may provide complementary information on metabolic health in occupational settings.

Purpose: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Materials and Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes.Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5,460 ESD cases from 5,250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

Purpose: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis. Materials and Methods: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point. Results: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage. Conclusion Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

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.

Objectives: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes. Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5460 ESD cases from 5250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.