Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications.

BACKGROUND: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations. RESULTS: scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naïve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs. CONCLUSION: We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.

Value of Sonazoid-enhanced ultrasonography in characterizing indeterminate focal liver lesions on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma.

PURPOSE: To evaluate the added value of contrast-enhanced ultrasonography (CEUS) using Sonazoid in characterizing focal liver lesions (FLLs) with indeterminate findings on gadoxetic acid-enhanced liver MRI in patients without risk factors for hepatocellular carcinoma (HCC). METHODS: Patients who underwent CEUS using Sonazoid for characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI were. The indeterminate FLLs were classified according to the degree of malignancy on a 5-point scale on MRI and combined MRI and CEUS. The final diagnosis was made either pathologically or based on more than one-year follow-up. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve analysis, and the net reclassification improvement (NRI) was calculated. RESULTS: A total of 97 patients (mean age, 49 years ± 16, 41 men, 80 benign and 17 malignant lesions) were included. When CEUS was added to MRI, the area under the ROC curve increased, but the difference was not statistically significant (0.87 [95% confidence interval {CI}, 0.77-0.98] for MRI vs 0.93 [95% CI, 0.87-0.99] for CEUS added to MRI, P = 0.296). The overall NRI was 0.473 (95% CI, 0.100-0.845; P = 0.013): 33.8% (27/80) of benign lesions and 41.2% (7/17) of malignant lesions were appropriately reclassified, whereas 10.0% (8/80) of benign lesions and 17.6% (3/17) of malignant lesions were incorrectly reclassified. CONCLUSIONS: Although performing CEUS with Sonazoid did not significantly improve the overall diagnostic performance in characterizing indeterminate FLLs on gadoxetic acid-enhanced liver MRI in patients without risk factors for HCC, it may increase radiologist's confidence in classifying FLLs.

Using GPT-4 for LI-RADS feature extraction and categorization with multilingual free-text reports.

BACKGROUND AND AIMS: The Liver Imaging Reporting and Data System (LI-RADS) offers a standardized approach for imaging hepatocellular carcinoma. However, the diverse styles and structures of radiology reports complicate automatic data extraction. Large language models hold the potential for structured data extraction from free-text reports. Our objective was to evaluate the performance of Generative Pre-trained Transformer (GPT)-4 in extracting LI-RADS features and categories from free-text liver magnetic resonance imaging (MRI) reports. METHODS: Three radiologists generated 160 fictitious free-text liver MRI reports written in Korean and English, simulating real-world practice. Of these, 20 were used for prompt engineering, and 140 formed the internal test cohort. Seventy-two genuine reports, authored by 17 radiologists were collected and de-identified for the external test cohort. LI-RADS features were extracted using GPT-4, with a Python script calculating categories. Accuracies in each test cohort were compared. RESULTS: On the external test, the accuracy for the extraction of major LI-RADS features, which encompass size, nonrim arterial phase hyperenhancement, nonperipheral 'washout', enhancing 'capsule' and threshold growth, ranged from .92 to .99. For the rest of the LI-RADS features, the accuracy ranged from .86 to .97. For the LI-RADS category, the model showed an accuracy of .85 (95% CI: .76, .93). CONCLUSIONS: GPT-4 shows promise in extracting LI-RADS features, yet further refinement of its prompting strategy and advancements in its neural network architecture are crucial for reliable use in processing complex real-world MRI reports.

Proton Beam Radiotherapy as a Curative Alternative to Radiofrequency Ablation for Newly Diagnosed Hepatocellular Carcinoma.

BACKGROUND/AIM: This study aimed to compare the oncological outcomes of proton beam radiotherapy (PBT) with those of radiofrequency ablation (RFA) for newly diagnosed hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study included 323 patients who underwent PBT (n=40) or RFA (n=283) as a curative treatment for previously untreated HCC between October 2016 and June 2021. The primary endpoints were local progression and toxicity. RESULTS: The median follow-up was 3.4 years (range=1.1-5.7 years). In terms of portal vein tumor thrombosis, tumor size, alpha-fetoprotein, and prothrombin-induced by vitamin K absence-II, the PBT group had significantly more severe tumor burdens than those of the RFA group (p<0.0001, p<0.0001, p=0.0004, and p<0.0001, respectively). No significant difference was observed in cumulative local progression rate (10.4% in PBT vs. 7.8% in RFA at 3-years, p=0.895). Grade 3 or higher toxicity was reported in only one patient (0.4%) after RFA. Multivariable analysis demonstrated that treatment modality was not a significant prognostic factor for local progression (hazard ratio=1.05; 95% confidence interval=0.32-3.48; p=0.934). CONCLUSION: PBT demonstrated comparable local control with acceptable toxicity to RFA in newly diagnosed HCC. Therefore, PBT may be a valid alternative.

Diagnostic Performance of Endoscopic Ultrasound Elastography for Differential Diagnosis of Gallbladder Polyp.

BACKGROUND AND AIMS: It is difficult to differentiate between neoplastic and non-neoplastic gallbladder (GB) polyps before surgery. Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method. The utility of EUS-EG in the differential diagnosis of GB polyps has not been investigated. We aimed to investigate the diagnostic performance of EUS-EG for the differential diagnosis of GB polyps. METHODS: Patients with GB polyps were prospectively enrolled from June 2020 until November 2022. EUS-EG and semi-quantitative evaluation of the strain ratio (SR) were performed for differential diagnosis of GB polyps. Fifty-three eligible patients were divided into two groups based on the final diagnosis after surgery. Patient demographics, EUS characteristics, and SR values were compared. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff SR value that discriminates between neoplastic and non-neoplastic GB polyps. RESULTS: The median SR value for neoplastic polyps (32.93 [interquartile range: 22.37-69.02]) was significantly higher than for non-neoplastic polyps (5.40 [2.36-14.44]; p<0.001). There were significant differences in SR values between non-neoplastic, benign neoplastic (23.38 [13.62-39.04]), and malignant polyps (49.25 [27.90-82.00]). The optimal cut-off SR value to differentiate between neoplastic and non-neoplastic polyps was 18.4. In multivariable logistic regression, SR value >18.4 (odds ratio 33.604, 95% confidence interval 2.588-436.292) was an independent predictor of neoplastic polyps. CONCLUSIONS: EUS-EG and SR values can be used as a supplementary method for evaluating GB polyps.

Prognostic value of initial and longitudinal changes in body composition in metastatic pancreatic cancer.

BACKGROUND: Sarcopenia or visceral adipose tissue has been reported to be related to pancreatic cancer prognosis. However, clinical relevance of the comprehensive analysis of body compositions and their longitudinal changes is lacking. This study analysed the association between body composition changes after chemotherapy and survival in patients with metastatic pancreatic cancer. METHODS: We retrospectively included 456 patients (mean age ± standard deviation, 61.2 ± 10.0 years; 272 males and 184 females) with metastatic pancreatic cancer who received palliative chemotherapy from May 2011 to December 2019. Using deep learning-based, fully automated segmentation of contrast-enhanced computed tomography (CT) at the time of diagnosis, cross-sectional areas of muscle, subcutaneous adipose tissue and visceral adipose tissue were extracted from a single axial image of the portal venous phase at L3 level. Skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI) and mean skeletal muscle attenuation (MA) were calculated, and their effect on overall survival (OS) was analysed. Longitudinal changes in body composition and prognostic values were also analysed in a subgroup of patients with 2- and 6-month follow-up CT (n = 349). RESULTS: A total of 452 deaths occurred during follow-up in the entire cohort. The survival rate was 49.3% (95% confidence interval [CI], 44.9-54.2) at 1 year and 3.7% (95% CI, 2.0-6.8) at 5 years. In multivariable analysis, higher MA (≥44.4 HU in males and ≥34.8 HU in females) at initial CT was significantly associated with better OS in both males and females (adjusted hazard ratio [HR], 0.706; 95% CI, 0.538-0.925; P = 0.012 for males, and HR, 0.656; 95% CI, 0.475-0.906; P = 0.010 for females), whereas higher SATI (≥42.8 cm2/m2 in males and ≥65.8 cm2/m2 in females) was significantly associated with better OS in female patients only (adjusted HR, 0.568; 95% CI, 0.388-0.830; P = 0.003). In longitudinal analysis, SMI, VATI and SATI significantly decreased between initial and 2-month follow-up CT, whereas mean MA significantly decreased between 2- and 6-month follow-up CT. In multivariable Cox regression analysis of longitudinal changes, which was stratified by disease control state, SATI change was significantly associated with OS in male patients (adjusted HR, 0.513; 95% CI, 0.354-0.745; P < 0.001), while other body composition parameters were not. CONCLUSIONS: In patients with metastatic pancreatic cancer, body composition mostly changed during the first 2 months after starting chemotherapy, and the prognostic factors associated with OS differed between males and females. Initial and longitudinal changes of body composition are associated with OS of metastatic pancreatic cancer.

Comparison of Surgical Resection and Radiofrequency Ablation in Elderly Patients with Hepatocellular Carcinoma.

BACKGROUND/AIMS: The aim of this study was to examine whether the efficacy of radiofrequency ablation (RFA) and surgical resection (SR) are comparable for hepatocellular carcinoma (HCC) less than 3 cm in elderly individuals aged 65 years or older. METHODS: We used the National Health Insurance Service claims data in Korea, which was linked with liver cancer stage data from the Central Cancer Registry of the National Cancer Center, as well as death data from the National Statistical Office. Out of the 9213 registrants, we focused on 141 patients who underwent SR and 225 patients who underwent RFA when they were 65 years or older. To ensure comparability, a 1:1 propensity score (PS) matching was conducted. RESULTS: The SR group had lower performance status and better liver function compared to the RFA group. Tumor diameter was larger in the SR group than in the RFA group (2.1 cm vs. 1.7 cm), and the proportion of stage II cases was higher (62.4% vs. 33.8%). After PS matching, the mortality rate in the RFA group did not significantly differ from the SR group (HR 1.33, 95% CI 0.86-2.06, P = 0.19). Also, liver related mortality was similar between the SR and RFA group after matching (log rank P = 0.13). However, recurrence free survival was significantly longer in the SR group than RFA group before and after matching (log rank P = 0.03). CONCLUSION: In patients aged 65 years or older with resectable HCC, RFA demonstrates a therapeutic effect comparable to SR.

Vitreous Opacity Following Intravitreal Brolucizumab Injection: A Case Series Review.

PURPOSE: To investigate cases of vitreous opacity (VO) similar to asteroid hyalosis (AH) after intravitreal brolucizumab injection. METHODS: A retrospective chart review was conducted to identify cases showing VO similar to AH among patients who received intravitreal brolucizumab injections at our retinal clinic from January 2022 to January 2023. RESULTS: A total of 220 brolucizumab injections were administered at our hospital. VO, showing yellow-white brilliant reflective particles, was found in six patients (2.7%). When VO occurred, all patients complained of floaters, although none of them complained of other symptoms including decreased visual acuity, pain, or conjunctival redness. The mean number of brolucizumab injections was 2.57 ± 2.38. No significant visual impairment was observed while VO was present. VO improved in all cases, and four cases improved without any treatment. The mean interval from onset to disappearance of VO was 8.0 ± 3.1 weeks. CONCLUSIONS: VO, similar to AH, can occur with a relatively high probability after intravitreal brolucizumab injections. Patients complained of severe floaters, but VO was not accompanied by other symptoms including vision impairment, injection, and pain. The VO disappeared after approximately 4 to 14 weeks. In case that other inflammatory findings are not severe, close follow-up without treatment may be sufficient. If a patient complains of floaters after an intravitreal brolucizumab injection, close fundus observation is necessary to evaluate the VO.

Superb Microvascular Imaging in Pediatric Focal Nodular Hyperplasia.

OBJECTIVE: To investigate superb microvascular imaging (SMI), a novel Doppler ultrasound technique that can visualize low-velocity microvascular flow, for assessing pediatric focal nodular hyperplasia (FNH). PATIENTS AND METHODS: Nine FNH lesions in 6 patients were enrolled. On SMI and color Doppler imaging (CDI), intralesional vascularity was assessed visually and categorized as typical spoke-wheel pattern (central vessel radiating from the center to the periphery), multifocal spoke-wheel pattern, and nonspecific pattern. We compared the vascular features of the lesions between SMI and CDI and evaluated vascular patterns according to lesion size. RESULTS: In terms of vascularity pattern, the typical spoke-wheel pattern of FNH was noted more frequently on SMI (67%) than on CDI (11%; P < 0.05). In addition, a multifocal spoke-wheel pattern was noted in all remaining lesions (33%) on SMI. On the contrary, a nonspecific vascular pattern was detected in the majority (78%) of CDI. Regarding the lesion size and vascularity on SMI, the typical spoke-wheel pattern was seen more frequently in the small FNH group than in the large FNH group. The intralesional vascular signal was detected more frequently on SMI (100%) than on CDI (89%). CONCLUSION: SMI is feasible in evaluating FNH in children and has a greater ability to demonstrate the spoke-wheel pattern than CDI.

Radiofrequency Ablation versus Surgical Resection in Elderly Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Although the disease burden of elderly cancer patients is rapidly increasing, reliable scientific information, value and preference information of domestic patients, and standardized guidelines for determining the treatment of elderly cancer patients are lacking. The aim of this study is to compare the therapeutic effects of radiofrequency ablation (RFA) and surgery in hepatocellular carcinoma (HCC) patients aged 65 years or older. For the meta-analysis, the databases including PubMed (MEDLINE), EMBASE, OVID Medline, and the Cochrane Library were systematically searched. After the abstract-based review by two investigators, selected manuscripts were read in detail. The surgery group showed higher overall survival (OS) (HR 1.44, 95% CI 1.22-1.70) and disease-free survival (DFS) (HR 1.40, 95% CI 1.00-1.97) than the RFA group. This was also shown in small HCC of less than 3 cm (OS, HR 1.42, 95% CI 1.00-2.03; DFS, HR 1.32, 95% CI 0.91-1.91). This might be related to the high local recurrence in the RFA group (OR 4.90, 95% 2.16-11.08). On the other hand, adverse events were significantly lower in the RFA group (OR 0.22, 95% CI 0.14-0.36), which led to a decrease in the duration of hospital stay (mean difference -14.88 days, 95% CI -22.44--7.32). In elderly HCC patients, survival in the surgery group was significantly higher than in the RFA group, but various complications tended to increase; so, appropriate patient selection is required.

Clinical Significance of Venous Thromboembolism in Patients with Advanced Cholangiocarcinoma.

Background/Aims: Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA. Methods: We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA. Results: During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02; p<0.001) was associated with poor overall survival. Conclusions: Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

Side-by-side placement of fully covered metal stents versus conventional 7F plastic stents in malignant hilar biliary obstruction: Prospective randomized controlled trial.

OBJECTIVES: We aimed to evaluate the efficacy and safety of metal stents compared with plastic stents when bilateral side-by-side stents were deployed for malignant hilar biliary obstruction (MHBO). METHODS: Fifty patients with unresectable advanced MHBO were randomly assigned to the metal stent (MS, n = 25) or plastic stent group (PS, n = 25). Fully covered self-expandable metal stents with 6 mm diameter and plastic stents with either 7F straight or double pigtail were used for MS and PS groups, respectively. Time to recurrent biliary obstruction (TRBO) was evaluated as the primary outcome. RESULTS: Both groups had 100% technical success rates; 88% and 76% of clinical success rates were obtained in MS and PS, respectively. Although stent migrations were more frequent in MS than PS (48% vs. 16%, P = 0.02), the mean TRBO was significantly longer in MS (190 days; 95% confidence interval [CI] 121-260 days vs. 96 days; 95% CI 50-141 days, P = 0.02). The placement of plastic stents (hazard ratio 2.42; 95% CI 1.24-4.73; P = 0.01) was the only significant risk factor associated with TRBO in multivariable analysis. The rates of adverse events were similar between the two groups (difference 0%; 95% CI -25% to 25%; P > 0.99). CONCLUSIONS: During bilateral side-by-side deployment in MHBO, the use of metal stents appears to be preferable to plastic stents in terms of TRBO, despite a higher frequency of stent migration.

LI-RADS category is associated with treatment outcomes of small single HCC: surgical resection vs. radiofrequency ablation.

OBJECTIVES: To assess whether the Liver Imaging Reporting and Data System (LI-RADS) category is associated with the treatment outcomes of small single hepatocellular carcinoma (HCC) after surgical resection (SR) and radiofrequency ablation (RFA). METHODS: This retrospective study included 357 patients who underwent SR (n = 209) or RFA (n = 148) for a single HCC of ≤ 3 cm between 2014 and 2016. LI-RADS categories were assigned. Overall survival (OS), recurrence-free survival (RFS), and local tumor progression (LTP) rates after treatment were compared according to the LI-RADS category (LR-4/5 vs. LR-M) before and after propensity score matching (PSM). Prognostic factors for treatment outcomes were assessed. RESULTS: In total, 357 patients (mean age, 59 years; men, 272) with 357 HCCs (294 LR-4/5 and 63 LR-M) were included. After PSM (n = 78 in each treatment group), there were 10 and 11 LR-M HCCs in the SR and RFA group, respectively. There were no significant differences in OS or RFS. However, SR provided a lower 5-year LTP rate than RFA (1.4% vs. 14.9%, p = 0.001). SR provided a lower 5-year LTP rate than RFA for LR-M HCCs (0% vs. 34.4%, p = 0.062) and LR-4/5 HCCs (1.5% vs. 12.0%, p = 0.008). The LI-RADS category was the sole risk factor associated with poor OS (hazard ratio [HR] 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032). CONCLUSION: LI-RADS classification is associated with the treatment outcome of HCC, supporting favorable outcomes of SR over RFA for LTP, especially for HCCs categorized as LR-M. CLINICAL RELEVANCE STATEMENT: Liver Imaging Reporting and Data System category has a potential prognostic role, supporting favorable outcomes of surgical resection over radiofrequency ablation for local tumor progression, especially for hepatocellular carcinoma categorized as LR-M. KEY POINTS: • SR provided a lower 5-year LTP rate than RFA for HCCs categorized as LR-M (0% vs. 34.4%, p = 0.062) and HCCs categorized as LR-4/5 (1.5% vs. 12.0%, p = 0.008). • There is a steeply increased risk of LTP within 1 year after RFA for LR-M HCCs, compared to SR. • The LI-RADS category was the sole risk factor associated with poor OS (HR 3.79, p = 0.004), RFS (HR 2.12; p = 0.001), and LTP (HR 2.89; p = 0.032) in patients with HCC of ≤ 3 cm treated with SR or RFA.

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Combined Transarterial Chemoembolization and Radiofrequency Ablation for Hepatocellular Carcinoma Infeasible for Ultrasound-Guided Percutaneous Radiofrequency Ablation: A Comparative Study with General Ultrasound-Guided Radiofrequency Ablation Outcomes.

OBJECTIVES: This study aimed to evaluate the therapeutic outcomes of transarterial chemoembolization combined with radiofrequency ablation (TACE + RFA) for hepatocellular carcinomas (HCC) measuring ≤3 cm infeasible for ultrasound (US)-guided percutaneous RFA. METHODS: Twenty-four patients who underwent fluoroscopy-guided TACE + RFA for single HCC between January 2012 and December 2016 were screened. To evaluate the TACE + RFA outcomes compared with those of US-guided RFA, 371 patients who underwent US-guided RFA during the same period were screened. We compared local tumor progression (LTP) and intrahepatic distant recurrence (IDR) between the two groups before and after propensity score (PS) matching, and performed univariable and multivariable Cox proportional hazard regression analyses for all patients. RESULTS: PS matching yielded 21 and 42 patients in the TACE + RFA and US-guided RFA groups, respectively. Cumulative LTP rates after PS matching were not significantly different between the two groups at 1 (0.0% vs. 7.4%, p = 0.072), 2 (10.5% vs. 7.4%, p = 0.701), and 5 years (16.9% vs. 10.5%, p = 0.531). IDR rates did not differ significantly between the two groups at 1 (20.6% vs. 10%, p = 0.307), 2 (25.9% vs. 25.9%, p = 0.999), or 5 years (49.9% vs. 53%, p = 0.838). Multivariable analysis showed that treatment type was not a significant factor for LTP or IDR. CONCLUSION: The outcomes of TACE + RFA for HCC were similar to those of general US-guided RFA. Fluoroscopy-guided TACE + RFA may be an effective treatment when US-guided RFA is not feasible.

Synergistic Effect of Saccharin and Caffeine on Antiproliferative Activity in Human Ovarian Carcinoma Ovcar-3 Cells.

The purpose of this study was to confirm the antiproliferative and apoptotic induction potential of a saccharin and caffeine combination in ovarian cancer cells. The cell line used was Ovcar-3, and the cell viability was measured through a WST-8 assay, while a Chou-Talalay assay was used to confirm the synergistic effect of saccharin and caffeine on the ovarian cancer cells. A clonogenic assay, annexin V-FITC/PI-PE double-staining, and RT-PCR were performed to confirm the expression of genes that induce colony formation, cell viability, and apoptosis in ovarian cancer cells treated with the saccharin-caffeine combination. It was demonstrated that both saccharin and caffeine decreased the viability of Ovcar-3 cells, and the cell viability decreased even more significantly when the cells were treated with the combination of saccharin and caffeine. The clonogenic assay results showed that the number of colonies decreased the most when saccharin and caffeine were combined, and the number of colonies also significantly decreased compared to the single-treatment groups. Based on flow cytometry analysis using annexin V-FITC/PI-PE double-staining, it was confirmed that the decrease in cell viability caused by the combination of saccharin and caffeine was correlated with the induction of apoptosis. The results of the RT-PCR confirmed that the combined treatment of saccharin and caffeine promoted cell apoptosis by regulating the expression of apoptosis-inducing genes. These results demonstrate that the combination of saccharin and caffeine more efficiently inhibits the proliferation of Ovcar-3 cells and induces apoptosis in vitro.

A nationwide study on the current treatment status and natural prognosis of hepatocellular carcinoma in elderly.

The aim of this study was to identify the treatment status and natural prognosis of hepatocellular carcinoma (HCC) patients aged 65 years or older in Korea. We analyzed 3,492 patients' data from the liver cancer stage of the Central Cancer Registry of National Cancer Center. The most common etiology of HCC was hepatitis B (32.7%), followed by hepatitis C. 2624 patients (69.2%) received first-line active treatment for HCC. The most frequently selected treatment was transarterial chemoembolization (TACE), followed by surgical resection and radiofrequency ablation (RFA). The proportion of patients receiving supportive care increased with age. Second-line treatment was performed in only 36.7% of cases, with all others choosing supportive care. Among the various treatments, liver transplantation was found to have the greatest effect in reducing the risk of death (HR [hazard ratio] 0.164, 95% CI [confidence interval] 0.061-0.444), followed by resection, RFA, radioembolization, and TACE. A similar pattern was observed when sub-analyzing the age group over 75 years old. The median survival for untreated HCC in Barcelona Clinic Liver Cancer stage 0/A/B/C/D was 3.7 years, 2.3 years, 7.9 months, 3.9 months, and 2.9 months, respectively. This study highlights the current status of elderly patients with HCC in Korea. While the proportion of patients receiving supportive care is high among the elderly, effective treatment can improve their survival rate.

No-Touch Radiofrequency Ablation for Early Hepatocellular Carcinoma: 2023 Korean Society of Image-Guided Tumor Ablation Guidelines.

Radiofrequency ablation (RFA) has been widely used to manage hepatocellular carcinomas (HCCs) equal to or smaller than 3 cm. No-touch RFA has gained attention and has recently been implemented in local ablation therapy for HCCs, despite its technical complexity, as it provides improved local tumor control compared to conventional tumor-puncturing RFA. This article presents the practice guidelines for performing no-touch RFA for HCCs, which have been endorsed by the Korean Society of Image-Guided Tumor Ablation (KSITA). The guidelines are primarily designed to assist interventional oncologists and address the limitations of conventional tumor-puncturing RFA with describing the fundamental principles, various energy delivery methods, and clinical outcomes of no-touch RFA. The clinical outcomes include technical feasibility, local tumor progression rates, survival outcomes, and potential complications.

Treatment Outcomes of Percutaneous Radiofrequency Ablation for Hepatocellular Carcinomas: Effects of the Electrode Type and Placement Method.

OBJECTIVE: To investigate the association among the electrode placement method, electrode type, and local tumor progression (LTP) following percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) and to assess the risk factors for LTP. MATERIALS AND METHODS: In this retrospective study, we enrolled 211 patients, including 150 males and 61 females, who had undergone ultrasound-guided RFA for a single HCC < 3 cm. Patients were divided into four combination groups of the electrode type and placement method: 1) tumor-puncturing with an internally cooled tip (ICT), 2) tumor-puncturing with an internally cooled wet tip (ICWT), 3) no-touch with ICT, and 4) no-touch with ICWT. Univariable and multivariable Cox proportional-hazards regression analyses were performed to evaluate the risk factors for LTP. The major RFA-related complications were assessed. RESULTS: Overall, 83, 34, 80, and 14 patients were included in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. The cumulative LTP rates differed significantly among the four groups. Compared to tumor puncturing with ICT, tumor puncturing with ICWT was associated with a lower LTP risk (adjusted hazard ratio [aHR] = 0.11, 95% confidence interval [CI] = 0-0.88, P = 0.034). However, the cumulative LTP rate did not differ significantly between tumor-puncturing with ICT and no-touch RFA with ICT (aHR = 0.34, 95% CI = 0.03-1.62, P = 0.188) or ICWT (aHR = 0.28, 95% CI = 0-2.28, P = 0.294). An insufficient ablative margin was a risk factor for LTP (aHR = 6.13, 95% CI = 1.41-22.49, P = 0.019). The major complication rates were 1.2%, 0%, 2.5%, and 21.4% in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. CONCLUSION: ICWT was associated with a lower LTP rate compared to ICT when performing tumor-puncturing RFA. An insufficient ablation margin was a risk factor for LTP.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines From the Korean Society of Radiology and the Korean Society of Abdominal Radiology.

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.