Background: In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery. Methods: Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day 1. Results: A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups. Conclusions OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.

Background: In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery. Methods: Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day 1. Results: A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups. Conclusions OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Purpose: BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. Materials and Methods: Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. Results: Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. Conclusion BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.

Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Background: In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery. Methods: Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day 1. Results: A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups. Conclusions OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.

Objectives: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. Methods: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the correspondingsampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic ofKorea were estimated by applying the algorithms and weighted PPV and NPV to the 2018National Health Insurance Service claims data. Results: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. Conclusion This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

Background: In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery. Methods: Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day 1. Results: A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups. Conclusions OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.

Purpose: Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. Methods: A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. Results: Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients’ quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. Conclusions Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB.

Purpose: For precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers. Materials and Methods: To verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment. Results: In the baseline ctDNAs, 14 patients (93%) harbored more than one genetic alteration. A number of mutations in wellknown cancer-related genes, such as KRAS and PIK3CA, were identified. Copy number alterations were identified in eight GCs (53.3%), and amplification of the ERBB2 gene (6/15, 40.0%) was the most recurrent. When we calculated the mean variant allele frequency (VAF) of mutations in each ctDNA as the molecular tumor burden index (mTBI), the mTBI trend was largely consistent with the VAF profiles in both responder and non-responder groups. Notably, in the longitudinal analysis of ctDNA, mTBI provided 2–42 weeks (mean 13.4 weeks) lead time in the detection of disease progression compared to conventional follow-up with CT imaging. Conclusion Our data indicate that the serial genetic alteration profiling of ctDNA is feasible to predict treatment response in HER2-positive GC patients in a minimally invasive manner. Practically, ctDNA profiles are useful not only for the molecular diagnosis of GC but also for the selection of GC patients with poor prognosis for systemic treatment (ClinicalTrials.gov identifier:NCT02901301).