BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition that increase the risk of simple steatosis to hepatocellular carcinoma. This study aimed to investigate the biological effects of camphorquinone (CQ) in a high-fat diet (HFD)-fed and low dose streptozotocin (STZ)-induced mouse model, widely used to mimic the concurrent development of NAFLD pathological conditions in vivo, and a free fatty acid-induced hepatic steatosis cell model in vitro. METHODS: CQ (10 or 30 mg/kg/day; i.p.) was injected for three weeks, and fasting blood glucose levels, glucose tolerance, and liver lipid metabolism were assessed. RESULTS: CQ administration alleviated the increase in body and liver weights and improved glucose tolerance in NAFLD mice model. CQ also reduced the gene expression levels of lipid biosynthesis and inflammation markers, while increasing the levels of fatty acid oxidation markers in liver tissues and HepG2 cells. These beneficial effects of CQ were mediated via activation of the sirtuin 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway in vitro and in vivo. CONCLUSION Collectively, our data suggest that CQ improves liver lipid metabolism and reduces blood glucose levels via activation of the SIRT1/serine/threonine kinase 11 (STK11/LKB1)/AMPK axis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition that increase the risk of simple steatosis to hepatocellular carcinoma. This study aimed to investigate the biological effects of camphorquinone (CQ) in a high-fat diet (HFD)-fed and low dose streptozotocin (STZ)-induced mouse model, widely used to mimic the concurrent development of NAFLD pathological conditions in vivo, and a free fatty acid-induced hepatic steatosis cell model in vitro. METHODS: CQ (10 or 30 mg/kg/day; i.p.) was injected for three weeks, and fasting blood glucose levels, glucose tolerance, and liver lipid metabolism were assessed. RESULTS: CQ administration alleviated the increase in body and liver weights and improved glucose tolerance in NAFLD mice model. CQ also reduced the gene expression levels of lipid biosynthesis and inflammation markers, while increasing the levels of fatty acid oxidation markers in liver tissues and HepG2 cells. These beneficial effects of CQ were mediated via activation of the sirtuin 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway in vitro and in vivo. CONCLUSION Collectively, our data suggest that CQ improves liver lipid metabolism and reduces blood glucose levels via activation of the SIRT1/serine/threonine kinase 11 (STK11/LKB1)/AMPK axis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition that increase the risk of simple steatosis to hepatocellular carcinoma. This study aimed to investigate the biological effects of camphorquinone (CQ) in a high-fat diet (HFD)-fed and low dose streptozotocin (STZ)-induced mouse model, widely used to mimic the concurrent development of NAFLD pathological conditions in vivo, and a free fatty acid-induced hepatic steatosis cell model in vitro. METHODS: CQ (10 or 30 mg/kg/day; i.p.) was injected for three weeks, and fasting blood glucose levels, glucose tolerance, and liver lipid metabolism were assessed. RESULTS: CQ administration alleviated the increase in body and liver weights and improved glucose tolerance in NAFLD mice model. CQ also reduced the gene expression levels of lipid biosynthesis and inflammation markers, while increasing the levels of fatty acid oxidation markers in liver tissues and HepG2 cells. These beneficial effects of CQ were mediated via activation of the sirtuin 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway in vitro and in vivo. CONCLUSION Collectively, our data suggest that CQ improves liver lipid metabolism and reduces blood glucose levels via activation of the SIRT1/serine/threonine kinase 11 (STK11/LKB1)/AMPK axis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition that increase the risk of simple steatosis to hepatocellular carcinoma. This study aimed to investigate the biological effects of camphorquinone (CQ) in a high-fat diet (HFD)-fed and low dose streptozotocin (STZ)-induced mouse model, widely used to mimic the concurrent development of NAFLD pathological conditions in vivo, and a free fatty acid-induced hepatic steatosis cell model in vitro. METHODS: CQ (10 or 30 mg/kg/day; i.p.) was injected for three weeks, and fasting blood glucose levels, glucose tolerance, and liver lipid metabolism were assessed. RESULTS: CQ administration alleviated the increase in body and liver weights and improved glucose tolerance in NAFLD mice model. CQ also reduced the gene expression levels of lipid biosynthesis and inflammation markers, while increasing the levels of fatty acid oxidation markers in liver tissues and HepG2 cells. These beneficial effects of CQ were mediated via activation of the sirtuin 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway in vitro and in vivo. CONCLUSION Collectively, our data suggest that CQ improves liver lipid metabolism and reduces blood glucose levels via activation of the SIRT1/serine/threonine kinase 11 (STK11/LKB1)/AMPK axis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition that increase the risk of simple steatosis to hepatocellular carcinoma. This study aimed to investigate the biological effects of camphorquinone (CQ) in a high-fat diet (HFD)-fed and low dose streptozotocin (STZ)-induced mouse model, widely used to mimic the concurrent development of NAFLD pathological conditions in vivo, and a free fatty acid-induced hepatic steatosis cell model in vitro. METHODS: CQ (10 or 30 mg/kg/day; i.p.) was injected for three weeks, and fasting blood glucose levels, glucose tolerance, and liver lipid metabolism were assessed. RESULTS: CQ administration alleviated the increase in body and liver weights and improved glucose tolerance in NAFLD mice model. CQ also reduced the gene expression levels of lipid biosynthesis and inflammation markers, while increasing the levels of fatty acid oxidation markers in liver tissues and HepG2 cells. These beneficial effects of CQ were mediated via activation of the sirtuin 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK) signalling pathway in vitro and in vivo. CONCLUSION Collectively, our data suggest that CQ improves liver lipid metabolism and reduces blood glucose levels via activation of the SIRT1/serine/threonine kinase 11 (STK11/LKB1)/AMPK axis.

Background: s/Aims: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC. Methods: A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon–Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location. Results: Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location. Conclusions NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.

Purpose: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette–Guérin (BCG) therapy. Materials and Methods: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. Results: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively;p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien– Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). Conclusions Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.

Background: s/Aims: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC. Methods: A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon–Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location. Results: Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location. Conclusions NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.

Background: s/Aims: Systematic investigations into the prognostic impact of the longitudinal tumor location in gallbladder cancer (GBC) remain insufficient. To address the limitations of our pilot study, we conducted a multicenter investigation to clarify the impact of the longitudinal tumor location on the oncological outcomes of GBC. Methods: A retrospective multicenter study was conducted on 372 patients undergoing radical resections for GBC from January 2010 to December 2019 across seven hospitals that belong to the Daejeon–Chungcheong branch of the Korean Association of Hepato-Biliary-Pancreatic Surgery. Patients were divided into GBC in the fundus/body (FB-GBC) and GBC in the neck/cystic duct (NC-GBC) groups, based on the longitudinal tumor location. Results: Of 372 patients, 282 had FB-GBC, while 90 had NC-GBC. NC-GBC was associated with more frequent elevation of preoperative carbohydrate antigen (CA) 19-9 levels, requirement for more extensive surgery, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and worse 5-year overall and disease-free survival rates. Propensity score matching analysis confirmed these findings, showing lower R0 resection rates, higher recurrence rates, and worse survival rates in the NC-GBC group. Multivariate analysis identified elevated preoperative CA 19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, but not longitudinal tumor location. Conclusions NC-GBC exhibits more frequent elevation of preoperative CA 19-9 levels, more advanced histologic grade and tumor stages, lower R0 resection rates, and poorer overall and disease-free survival rates, compared to FB-GBC. However, the longitudinal tumor location was not analyzed as an independent prognostic factor.

Purpose: Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. Materials and Methods: Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. Results: UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. Conclusion Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.