Purpose: This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Materials and Methods: We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method. Results: Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure. Conclusion Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Purpose: Pregnant women with diabetes mellitus (DM) and their babies are affected by complications and congenital abnormalities during pregnancy. This study aimed to examine the risk factors for cardiac anomalies and the characteristics of pregestational DM and GDM in mothers and babies in Korea. Methods: This retrospective study used medical records from Bucheon St. Mary's Hospital between January 2013 and July 2021. We studied 1983 infants, with 335 neonates from mothers with DM. Results: Body weight and body mass index were high in mothers with pregestational DM at delivery (p<0.005). The rate of preterm births was lower in the pregestational DM group than in the GDM group. Furthermore, the cardiac anomaly rate was high in the pregestational DM group (p<0.001). The rate of hyperbilirubinemia in the DM group was higher than that in the control group (p<0.001). Multivariate logistic regression analysis revealed no significant risk factors for congenital heart disease. Conclusion DM in pregnant women is associated with congenital anomalies. Therefore, the appropriate management of mothers with DM is important for the prognosis of their neonates.

Objective: The cervical spine presents challenges in treating metastatic cervical spinal tumors (MCSTs). Although the efficacy of cervical pedicle screw placement (CPS) has been well established, its use in combination with 5.5-mm rods for MCST has not been reported. This study aimed to evaluate the efficacy of CPS combined with 5.5-mm rods in treating MCST and compare it with that of CPS combined with traditional 3.5-mm rods. Methods: This retrospective study analyzed 58 patients with MCST who underwent posterior cervical spinal fusion surgery by a single surgeon between March 2012 and December 2022. Data included demographics, surgical details, imaging results, numerical rating scale score for neck pain, Eastern Cooperative Oncology Group performance status, and Spine Oncology Study Group Outcomes Questionnaire responses. Results: Preoperative Spinal Instability Neoplastic Scores were significantly higher in the 5.5-mm rod group. Greater kyphotic changes in the index vertebra were observed in the 3.5-mm rod group. Neck pain reduction was significantly better in the 5.5-mm rod group. Conclusion CPS with 5.5-mm rods provides superior biomechanical stability and effectively resists forward bending momentum in posterior MCST fusion surgery. These findings support the use of 5.5-mm rods to enhance surgical outcomes.

Objective: Stereotactic radiosurgery (SRS) has been performed for spinal tumors. However, the quantitative effect of SRS on postoperative residual cervical dumbbell tumors remains unknown. This study aimed to quantitatively evaluate the efficacy of SRS for treating postoperative residual cervical dumbbell tumors. Methods: We retrospectively reviewed cases of postoperative residual cervical dumbbell tumors from 1995 to 2020 in 2 tertiary institutions. Residual tumors underwent SRS (SRS group) or were observed with clinical and magnetic resonance imaging (MRI) follow-up (observation group). Tumor regrowth rates were compared between the SRS and observation groups. Additionally, risk factors for tumor regrowth were analyzed. Results: A total of 28 cervical dumbbell tumors were incompletely resected. Eight patients were in the SRS group, and 20 in the observation group. The mean regrowth rate was not significantly lower (p = 0.784) in the SRS group (0.18 ± 0.29 mm/mo) than in the observation group (0.33 ± 0.40 mm/mo). In the multivariable Cox regression analysis, SRS was not a significant variable (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.18–1.79; p = 0.336). Conclusion SRS did not significantly decrease the tumor regrowth rate in our study. We believe that achieving maximal resection during the initial operation is more important than postoperative adjuvant SRS.

Background/Aims: Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. Methods: We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. Results: The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (p=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. Conclusions Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.

Background/Aims: With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance. Methods: Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-toplatelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR. Results: The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Timedependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC. Conclusions aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

Background: s/Aims: This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. Methods: We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Results: Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (P<0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS<0.05). Conclusions In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.