Gun Hyung Na

Background/Objectives: The American Joint Committee on Cancer (AJCC) 8th edition subdivides node-positive periampullary adenocarcinoma into N1 and N2 by the number of positive nodes. We quantified how much this subdivision and the lymph node ratio (LNR) each add to nodal positivity, and how the nodal yield affects the comparison. Methods: This retrospective cohort comprised 147 consecutive pancreatoduodenectomies for pancreatic head (n = 49), distal bile duct (n = 63), ampullary (n = 31) or duodenal (n = 4) adenocarcinoma. In covariate-adjusted Cox models stratified by origin, the N1/N2 subdivision and the LNR were tested over nodal positivity and over each other with nested likelihood-ratio tests, overall, with the examined-node count in the model and by the period of resection. Results: The median nodal yield was 17 (10 in 2013–2016, 19 in 2017–2024). Beyond nodal positivity, the N1/N2 subdivision added χ² 0.25 (p = 0.61; adjusted N2-versus-N1 hazard ratio 1.21, 95% confidence interval [CI] 0.59–2.45) and the LNR added χ² 9.60 (p = 0.002; hazard ratio 1.41 per 0.1, 95% CI 1.22–1.62). The LNR added to the N category (p = 0.002; optimism-corrected C-index gain 0.020, 95% CI 0.002–0.041), whereas the N category did not add detectably to the LNR (p = 0.54). With the examined-node count in the model, the LNR increment was attenuated (p = 0.045) and the subdivision’s increment rose (χ² 3.65, p = 0.056). From 2017 onward (n = 113), the LNR and the positive-node count were nearly collinear among the node-positive patients (ρ 0.90 versus −0.02 before 2017), and neither the subdivision (p = 0.49) nor the LNR (p = 0.17) added significantly to positivity. Conclusions: The N1/N2 subdivision added little beyond nodal positivity, although imprecisely estimated, and its increment rose when the examined-node count was in the model. The LNR added prognostic information mainly when the yield was low or variable; where the yield was higher and more uniform, the ratio and the count-based category conveyed nearly the same information, and no additional value of the ratio was demonstrated.

Seo CH, et al. Ann Surg Treat Res. 2024 Mar;106(3):155-168. https://doi.org/10.4174/astr.2024.106.3.155

Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from PGC-1α-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. Upon achieving a cellular confluence of 70-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vivo mouse models. In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to control-secretome (Ctrl-Sec). In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum pro-inflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, OPA1 (a mitochondrial function marker), and PPARα (an anti-fibrogenic marker) in the PGC-Sec-treated group, along with reduced Collagen 1A expression (a pro-fibrogenic marker). These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

Park SE, et al. Ann Surg Treat Res. 2022 Sep;103(3):145-152. https://doi.org/10.4174/astr.2022.103.3.145

Although methyl-tertiary butyl ether (MTBE) is the only clinical topical agent for gallstone dissolution, its use is limited by its side effects mostly arising from a relatively low boiling point (55 °C). In this study, we developed the gallstone-dissolving compound containing an aromatic moiety, named 2-methoxy-6-methylpyridine (MMP) with higher boiling point (156 °C), and compared its effectiveness and toxicities with MTBE. The dissolubility of MTBE and MMP in vitro was determined by placing human gallstones in glass containers with either solvent and, then, measuring their dry weights. Their dissolubility in vivo was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after directly injecting each solvent into the gallbladder in hamster models with cholesterol and pigmented gallstones. In the in vitro dissolution test, MMP demonstrated statistically higher dissolubility than did MTBE for cholesterol and pigmented gallstones (88.2% vs. 65.7%, 50.8% vs. 29.0%, respectively; P < 0.05). In the in vivo experiments, MMP exhibited 59.0% and 54.3% dissolubility for cholesterol and pigmented gallstones, respectively, which were significantly higher than those of MTBE (50.0% and 32.0%, respectively; P < 0.05). The immunohistochemical stains of gallbladder specimens obtained from the MMP-treated hamsters demonstrated that MMP did not significantly increase the expression of cleaved caspase 9 or significantly decrease the expression of proliferation cell nuclear antigen. This study demonstrated that MMP has better potential than does MTBE in dissolving gallstones, especially pigmented gallstones, while resulting in lesser toxicities.