Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Background/Aims: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05). Conclusions This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Remimazolam is a novel benzodiazepine with unique pharmacokinetic and pharmacodynamic properties, making it an ideal candidate for sedation during endoscopic procedures. Distinguished by its rapid onset and short duration of action, remimazolam offers a safer and more efficient alternative to traditional sedatives, such as midazolam and propofol, with fewer side effects, such as hypotension, bradycardia, and respiratory depression. This article reviews the characteristics of remimazolam and its practical advantages, including ease of use, quick recovery time, and minimal residual sedation, emphasizing its potential to improve patient safety and procedural efficiency in clinical endoscopy settings.

Background: s/Aims: We compared the postoperative outcomes of single-incision laparoscopic cholecystectomy (SILC) with those of single-incision robotic cholecystectomy (SIRC) using the da Vinci Xi and SP systems. Methods: We retrospectively analyzed data from 206 patients who underwent these procedures by a single surgeon between August 2020 and April 2022. Propensity score matching was used to adjust for confounders and evaluate outcomes. Results: SILC exhibited shorter operation times compared to SIRC with Xi and SP (44.9 ± 14.5 min vs. 55.3 ± 12.2 min vs. 55.2 ± 16.2 min, p < 0.001). SIRC with Xi had shorter docking times (6.2 ± 2.8 min vs. 10.3 ± 2.3 min, p < 0.001), while SIRC with SP demonstrated reduced console times (11.2 ± 2.4 min vs. 18.6 ± 8.0 min, p < 0.001). Pain scores and complications did not significantly differ between the groups. Conclusions Both SILC and SIRC showed comparable outcomes, with the SP system providing advantages such as reduced console time and fully articulated arms, likely reducing surgeon stress.

Purpose: Common bile duct (CBD) stone recurrence after laparoscopic CBD exploration (LCBDE) is relatively common. No studies have been conducted evaluating the safety and feasibility of re-do LCBDE in the treatment of recurrent CBD stones. Methods: This single-center retrospective study reviewed 340 consecutive patients who underwent LCBDE for CBD stones between January 2004 and December 2020. Patients with pancreatobiliary malignancies and those who underwent other surgical procedures were excluded. Results: Of the 340 included patients, 45 experienced a recurrence after a mean follow-up period of 24.2 months. Of them, 18 underwent re-do LCBDE, 20 underwent endoscopic intervention, 2 underwent radiologic intervention, and 5 underwent observation. Re-do LCBDE and initial LCBDE showed similar surgical outcomes in terms of operative time (113.1 minutes vs. 107.5 minutes, P = 0.515), estimated blood loss (42.5 mL vs. 49.1 mL, P = 0.661), open conversion rate (2.9% vs. 0%, P = 0.461), postoperative complication (15.3% vs. 22.2%, P = 0.430), and postoperative hospital stay (6.5 days vs. 6.4 days, P = 0.921). Comparing re-do LCBDE and nonsurgical treatment (endoscopic or radiologic), no statistically significant differences were noted in posttreatment complication (22.2% vs. 13.6%, P = 0.477), hospital stay (6.4 days vs.7.3 days, P = 0.607), and recurrence (50.0% vs. 36.4%, P = 0.385). The clearance rate was higher in the re-do LCBDE group than in the nonsurgical group (100% vs. 81.8%, P = 0.057). Conclusion Compared to initial LCBDE and endoscopic or radiological treatments, re-do LCBDE for recurrent CBD stones is a treatment option worth considering in selected patients.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background: s/Aims: We compared the postoperative outcomes of single-incision laparoscopic cholecystectomy (SILC) with those of single-incision robotic cholecystectomy (SIRC) using the da Vinci Xi and SP systems. Methods: We retrospectively analyzed data from 206 patients who underwent these procedures by a single surgeon between August 2020 and April 2022. Propensity score matching was used to adjust for confounders and evaluate outcomes. Results: SILC exhibited shorter operation times compared to SIRC with Xi and SP (44.9 ± 14.5 min vs. 55.3 ± 12.2 min vs. 55.2 ± 16.2 min, p < 0.001). SIRC with Xi had shorter docking times (6.2 ± 2.8 min vs. 10.3 ± 2.3 min, p < 0.001), while SIRC with SP demonstrated reduced console times (11.2 ± 2.4 min vs. 18.6 ± 8.0 min, p < 0.001). Pain scores and complications did not significantly differ between the groups. Conclusions Both SILC and SIRC showed comparable outcomes, with the SP system providing advantages such as reduced console time and fully articulated arms, likely reducing surgeon stress.