Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: Postoperative pain management is challenging in patients with oral cancer, especially those undergoing reconstructive surgery. Patient-controlled analgesia (PCA) is widely used, and fentanyl (FTN) concentration adjustments may improve pain control. This study aimed to evaluate the effects of FTN PCA concentration and reconstructive surgery on postoperative pain in patients with oral cancer. Methods: This retrospective observational study analyzed 140 patients with oral cancer who underwent surgery under general anesthesia. Patients were categorized based on FTN PCA dosage (FTN 700 mcg and ketorolac 150 mg vs. FTN 1400 mcg and ketorolac 150 mg). Pain was assessed using the visual analog scale (VAS) at multiple time points postoperatively (0, 12, 24, 36, 48, 60, and 72 h). PCA usage patterns, including demand count, delivery count, and delivery/demand ratios, were compared across subgroups. Missing data were imputed using linear interpolation. Results: PCA usage and pain control were evaluated between the FTN 700 mcg (N = 40) and 1400 mcg (N = 100) groups, stratified by reconstruction status. Demographic characteristics showed no significant difference.In the reconstructive surgery subgroup, patients in the FTN 1400 mcg group showed lower PCA refill counts (1.45 ± 0.69 vs. 1.61 ± 0.58) and fewer delivery counts (17.1 ± 21.3 vs. 25.1 ± 28.5) compared to those in the FTN 700 mcg group, achieving similar or superior pain control with fewer interventions. Similarly, patients without reconstructive surgery in the FTN 1400 mcg group demonstrated lower PCA refill counts, shorter PCA usage times, and fewer delivery counts. VAS scores decreased consistently over time across all groups but remained higher in the reconstruction groups. Logistic regression analysis revealed that patients with reconstructive surgery in the FTN 1400 mcg group were more likely to achieve a VAS score of ≤ 3.0 at 72 h postoperatively (P = 0.022). These findings indicate FTN 1400 mcg’s superiority in managing postoperative pain. Conclusion Comparing FTN PCA dosages, 1400 mcg demonstrated superior pain control to 700 mcg in patients undergoing oral cancer surgery, particularly those who underwent reconstructive surgery. This finding underscores the importance of optimizing FTN dosages to enhance postoperative pain management, reduce PCA-related demands, and achieve better patient outcomes.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: Postoperative pain management is challenging in patients with oral cancer, especially those undergoing reconstructive surgery. Patient-controlled analgesia (PCA) is widely used, and fentanyl (FTN) concentration adjustments may improve pain control. This study aimed to evaluate the effects of FTN PCA concentration and reconstructive surgery on postoperative pain in patients with oral cancer. Methods: This retrospective observational study analyzed 140 patients with oral cancer who underwent surgery under general anesthesia. Patients were categorized based on FTN PCA dosage (FTN 700 mcg and ketorolac 150 mg vs. FTN 1400 mcg and ketorolac 150 mg). Pain was assessed using the visual analog scale (VAS) at multiple time points postoperatively (0, 12, 24, 36, 48, 60, and 72 h). PCA usage patterns, including demand count, delivery count, and delivery/demand ratios, were compared across subgroups. Missing data were imputed using linear interpolation. Results: PCA usage and pain control were evaluated between the FTN 700 mcg (N = 40) and 1400 mcg (N = 100) groups, stratified by reconstruction status. Demographic characteristics showed no significant difference.In the reconstructive surgery subgroup, patients in the FTN 1400 mcg group showed lower PCA refill counts (1.45 ± 0.69 vs. 1.61 ± 0.58) and fewer delivery counts (17.1 ± 21.3 vs. 25.1 ± 28.5) compared to those in the FTN 700 mcg group, achieving similar or superior pain control with fewer interventions. Similarly, patients without reconstructive surgery in the FTN 1400 mcg group demonstrated lower PCA refill counts, shorter PCA usage times, and fewer delivery counts. VAS scores decreased consistently over time across all groups but remained higher in the reconstruction groups. Logistic regression analysis revealed that patients with reconstructive surgery in the FTN 1400 mcg group were more likely to achieve a VAS score of ≤ 3.0 at 72 h postoperatively (P = 0.022). These findings indicate FTN 1400 mcg’s superiority in managing postoperative pain. Conclusion Comparing FTN PCA dosages, 1400 mcg demonstrated superior pain control to 700 mcg in patients undergoing oral cancer surgery, particularly those who underwent reconstructive surgery. This finding underscores the importance of optimizing FTN dosages to enhance postoperative pain management, reduce PCA-related demands, and achieve better patient outcomes.

Purpose: This study examined nationwide data regarding laparoscopic and robotic surgery for colorectal cancer (CRC) in Korea. Methods: Nationwide data concerning patients who underwent surgery for CRC from 2019 to 2023 were obtained from the Health Insurance Review and Assessment Service database. Results: From 2019 to 2023, a total of 109,573 patients with CRC underwent surgical resection in Korea. Among these, open, laparoscopic, and robotic surgery comprised 17.2%, 71.5%, and 11.3%, respectively. Open surgery decreased from 18.3% in 2019 to 15.2% in 2023, whereas robotic surgery increased from 10.3% in 2019 to 12.7% in 2023. Regarding rectal cancer, the rate of robotic surgery increased from 23.0% in 2019 to 28.2% in 2023, and the rate of minimally invasive surgery (MIS) increased from 86.9% in 2019 to 89.2% in 2023.Patients with National Health Insurance had significantly shorter lengths of hospital stay after surgery than those with medical aid for all surgical methods (p < 0.0001). With respect to hospital size, 74,282 CRC surgeries (67.8%) were performed in tertiary general hospitals and 33,050 (30.2%) in general hospitals. By the region, 47,140 cases (43.0%) were performed in Seoul, 19,961 (18.2%) in Gyeonggi, and 7,417 (6.8%) in Daegu. Ostomy was created in 16,222 CRC surgeries (14.8%). Conclusion The rate of MIS adoption for CRC in Korea has increased, reaching 84.7% in 2023. The rate of laparoscopic surgery exceeded 70% and has plateaued. In contrast, the rate of robotic surgery adoption has steadily increased, particularly for rectal cancer, where it surpassed 28% in 2023.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.