Local Ablation for Hepatocellular Carcinoma: 2024 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, preprocedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.

Local ablation for hepatocellular carcinoma: 2024 expert consensus-based practical recommendation of the Korean Liver Cancer Association.

Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.

Local Ablation for Hepatocellular Carcinoma: 2024 Expert Consensus-Based Practical Recommendations of the Korean Liver Cancer Association.

Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.

Association of urinary creatinine excretion and body mass index with diabetic retinopathy in patients with type 2 diabetes.

This study aimed to determine whether urinary creatinine excretion rate (CER), a marker of muscle mass, is associated with diabetic retinopathy in individuals with type 2 diabetes and to ascertain whether this putative association depends on body mass index (BMI). This cross sectional study evaluated 2035 individuals with type 2 diabetes. Twenty-four-hour urine was collected. Individuals with diabetic retinopathy had lower CER and BMI values than those without. Patients in higher CER quartiles had higher BMI values and a lower prevalence of diabetic retinopathy. A significant relationship between CER and diabetic retinopathy persisted, even after adjusting for traditional risk factors, including glycated hemoglobin, diabetes duration, and hypertension, in multivariable analysis. Further adjustment for BMI did not significantly alter the association between CER and diabetic retinopathy. This study suggests that CER is inversely associated with diabetic retinopathy in individuals with type 2 diabetes, and this association is independent of BMI.

Relationship between plasma leucine-rich α-2-glycoprotein 1 and urinary albumin excretion in patients with type 2 diabetes.

Aims: To explore the relationship between plasma leucine-rich α-2-glycoprotein 1 (LRG1) level and the degree of urinary albumin excretion in patients with type 2 diabetes. Methods: We evaluated 332 patients with type 2 diabetes in a cross-sectional study. Result: The plasma LRG1 level differed significantly according to the quartiles of urinary albumin excretion (Q1 [<7.7 mg/g], 17.1 µg/mL; Q2 [7.7-15.0 mg/g], 17.5 µg/mL; Q3 [15.1-61.4 mg/g], 18.6 µg/mL; Q4 [≥61.5 mg/g], 22.3 µg/mL; p for trend = 0.003) under adjustment with other covariates. A positive correlation was found between plasma LRG1 level and urinary albumin excretion (ρ = 0.256, p <0.001). According to a multivariate model, the association between LRG1 and urinary albumin excretion remained significant, under adjustment for confounding factors (ß = 0.285, p <0.001). Conclusion: Plasma LRG1 level was independently associated with urinary albumin excretion in patients with type 2 diabetes. This study suggests that LRG1 may be associated with increased excretion of urinary albumin in the early stages of diabetic nephropathy.

Predicting resection margin status of pancreatic neuroendocrine tumors on CT: performance of NCCN resectability criteria.

OBJECTIVE: To test the performance of the National Comprehensive Cancer Network (NCCN) CT resectability criteria for predicting the surgical margin status of pancreatic neuroendocrine tumor (PNET) and to identify factors associated with margin-positive resection. METHODS: Eighty patients with pre-operative CT and upfront surgery were retrospectively enrolled. Two radiologists assessed the CT resectability (resectable [R], borderline resectable [BR], unresectable [UR]) of the PNET according to NCCN criteria. Logistic regression was used to identify factors associated with resection margin status. κ statistics were used to evaluate interreader agreements. Kaplan-Meier method with log-rank test was used to estimate and compare recurrence-free survival (RFS). RESULTS: Forty-five patients (56.2%) received R0 resection and 35 (43.8%) received R1 or R2 resection. R0 resection rates were 63.6-64.2%, 20.0-33.3%, and 0% for R, BR, and UR diseases, respectively (all p ≤ 0.002), with a good interreader agreement (κ, 0.74). Tumor size (<2 cm, 2-4 cm, and >4 cm; odds ratio (OR), 9.042-18.110; all p ≤ 0.007) and NCCN BR/UR diseases (OR, 5.918; p = 0.032) were predictors for R1 or R2 resection. The R0 resection rate was 91.7% for R disease <2 cm and decreased for larger R disease. R0 resection and smaller tumor size in R disease improved RFS. CONCLUSION: NCCN resectability criteria can stratify patients with PNET into distinct groups of R0 resectability. Adding tumor size to R disease substantially improves the prediction of R0 resection, especially for PNETs <2 cm. ADVANCES IN KNOWLEDGE: Tumor size and radiologic resectability independently predicted margin status of PNETs.

68 Ga-FAPI PET/CT Imaging of the Pancreas in a Patient With Fulminant Type 1 Diabetes.

ABSTRACT: Fulminant type 1 diabetes is a recently recognized diabetes subtype characterized by extremely rapid destruction of the pancreatic beta cells, leading to an absolute deficiency in insulin secretion. Fulminant type 1 diabetes is clinically characterized by the drastic onset of hyperglycemia and ketoacidosis within a few days, as well as near-normal glycated hemoglobin (HbA 1c ) levels despite remarkable hyperglycemia at initial presentation. A 41-year-old woman diagnosed with fulminant type 1 diabetes underwent 68 Ga-FAPI PET/CT, which showed intense FAPI uptake throughout the pancreas, especially in the pancreatic tail. Contrast-enhanced abdominal CT failed to reveal any pancreatic abnormalities. This case indicated that 68 Ga-FAPI PET/CT might be useful for evaluating patients with fulminant type 1 diabetes.

Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance.

BACKGROUND: To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. METHODS: This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. RESULTS: The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by -0.68%±1.39% and -1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a "responder" to empagliflozin therapy. CONCLUSION: Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Plasma galectin-3 concentration and estimated glomerular filtration rate in patients with type 2 diabetes with and without albuminuria.

This study aimed to investigate the association between galectin-3 concentration and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria. In this cross-sectional study, we examined 334 patients with T2DM. The eGFR was calculated using a creatinine-based formula (eGFRcrea) and a combined creatinine-cystatin C equation (eGFRcrea-cyst). The participants were categorized into two groups based on the urinary albumin-to-creatinine ratio (UACR): patients without albuminuria (UACR < 30 mg/g) and those with albuminuria (UACR ≥ 30 mg/g). Greater concentrations of plasma galectin-3 were associated with lower eGFRcrea-cyst and eGFRcrea levels in patients with and without albuminuria. Plasma galectin-3 concentrations were negatively correlated with eGFRcrea-cyst in patients with normoalbuminuria and albuminuria (γ = - 0.405, P < 0.001; γ = - 0.525, P < 0.001, respectively). Galectin-3 concentrations were significantly associated with eGFRcrea-cyst after adjusting for sex, age, and other confounding factors, including UACR as a categorical or continuous variable in multiple regression analyses (ß = - 0.294, 95% CI - 70.804 to - 41.768, P < 0.001; ß = - 0.265, 95% CI - 65.192 to - 36.550, P < 0.001, respectively). Likewise, when eGFRcrea-cyst was treated in place of eGFRcrea, this result was replicated in the correlation and regression analyses. Galectin-3 concentration was negatively associated with eGFR in patients with T2DM, independent of albuminuria status.

Radiofrequency ablation using real-time ultrasonography-computed tomography fusion imaging improves treatment outcomes for T1a renal cell carcinoma: Comparison with laparoscopic partial nephrectomy.

PURPOSE: To determine whether real-time ultrasonography-computed tomography (US-CT) fusion imaging can improve technical feasibility versus B-mode US and provide comparable outcomes of radiofrequency ablation (RFA) for T1a renal cell carcinoma (RCC) compared with laparoscopic partial nephrectomy (LPN). MATERIALS AND METHODS: Between June 2013 and August 2016, biopsy- or pathologically confirmed stage T1a RCCs were retrospectively reviewed. Of these, 39 cases were included in the RFA group, and 46 cases were included in the LPN group. In the RFA group, we evaluated tumor visibility and technical feasibility before RFA on a four-point scale on B-mode US and US-CT fusion images. After RFA, hospital days, creatinine value, complications, and disease-free survival rate were compared between the two groups. All results were analyzed by use of the Mann-Whitney U-test and Kaplan-Meier method. RESULTS: Compared with B-mode US alone, real-time US-CT fusion significantly improved the tumor visibility score and overall mean technical feasibility grade (p<0.001). The 5-year disease-free survival rate was 97.4% and 97.8% in the RFA and LPN groups, respectively, and there was no statistically significant difference between groups (p=0.1). Mean periprocedural creatinine levels were significantly lower in the RFA group than in the LPN group. The number of hospital days was shorter in the RFA group. Minor complications were present in 5.1% of the RFA group and 13.0% of the LPN group, with no major complications. CONCLUSIONS: US-CT fusion-image-guided RFA improved tumor visibility scores and overall mean technical validity and resulted in a comparable disease-free survival rate to LPN.

A Real-World Comparative Study of Microwave and Radiofrequency Ablation in Treatment-Naïve and Recurrent Hepatocellular Carcinoma.

The efficacy and safety of microwave ablation (MWA) compared to radiofrequency ablation (RFA) for patients with treatment-naïve and recurrent hepatocellular carcinoma (HCC) has not been clarified in Korea. There were 150 HCC patients (100 in the RFA group and 50 in the MWA group) enrolled in our study. The primary outcome was one- and two-year disease-free survival (DFS). Secondary outcomes were complete response (CR) rate, two-year survival rate, risk factors for DFS and complication rate. Treatment outcomes were also assessed using propensity-score matching (PSM). The MWA group had better one- and two-year DFS than the RFA group (p = 0.035 and p = 0.032, respectively), whereas the CR rate, two-year survival rate, and complication rate were similar between the two groups with fewer major complications in the MWA group (p = 0.043). Patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. MWA was also an independent factor for favorable one- and two-year DFS. Finally, the MWA group still showed better one- and two-year DFS than the RFA group after PSM. In conclusion, MWA could be an alternative treatment to RFA especially in patients with a high risk of recurrence, perivascular tumors, and small tumor size.

Relationship Between Fibroblast Growth Factor 19 and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus.

AIM: This study aimed to evaluate whether fibroblast growth factor 19 (FGF19) is associated with the risk of diabetic retinopathy in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 357 patients with T2DM were investigated in this cross-sectional study. Logistic regression analysis was performed to assess the association between FGF19 level and diabetic retinopathy. RESULTS: Serum FGF19 level was significantly lower in patients with diabetic retinopathy in those without diabetic retinopathy. The multivariable analysis revealed a significant association between serum FGF19 level and diabetic retinopathy (odds ratio for every 1 standard deviation increase in logarithmic value = 0.69, 95% confidence interval 0.51-0.94, p = 0.019). CONCLUSION: Serum FGF19 level was negatively associated with diabetic retinopathy in patients with T2DM.

Dlx5 Represses the Transcriptional Activity of PPARγ.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master transcription factor in adipocyte differentiation, while distal-less homeobox 5 (Dlx5) is essential for initiating osteoblast differentiation by driving Runt-related transcription factor 2 expression. Considering that adipocytes and osteoblasts share common progenitors, there is a reciprocal correlation between bone and fat formation. However, the mechanism by which Dlx5 controls PPARγ remains unclear. We elucidated that Dlx5 physically binds to PPARγ during immunoprecipitation; in particular, the ligand-binding and DNA-binding domains of PPARγ were involved in the interaction. Transcriptional activity of PPARγ was significantly decreased by Dlx5 overexpression, whereas the opposite results were detected with Dlx5 knockdown. Rosiglitazone, a PPARγ agonist, further enhanced the PPARγ-induced transcriptional activity; however, Dlx5 overexpression effectively repressed the rosiglitazone-mediated increase in activity. Finally, DNA-binding affinity assay revealed that Dlx5 interrupts the interaction of PPARγ with the PPARγ response element promoter. In conclusion, our findings indicate that Dlx5 impedes PPARγ-induced activity, and it may be useful for managing diabetes drug-mediated obesity.

Relationship between plasma growth differentiation factor-15 level and estimated glomerular filtration rate in type 2 diabetes patients with and without albuminuria.

AIM: To assess the relationship between growth differentiation factor-15 (GDF-15) levels and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus (DM) patients with and without albuminuria. METHODS: We examined 324 patients with type 2 DM in a cross-sectional study. eGFR was determined using equations from creatinine (eGFRcr) and the combination of creatinine and cystatin C (eGFRcr-cys). The patients were classified into two groups based on urinary albumin: creatinine ratio (ACR): the normoalbuminuria group (urinary ACR < 30 mg/g) and the albuminuria group (urinary ACR ≥ 30 mg/g). RESULTS: In individuals both with and without albuminuria, higher GDF-15 levels were associated with lower eGFRcr and eGFRcr-cys. Plasma GDF-15 levels were inversely correlated with eGFRcr in individuals both with and without albuminuria (γ = -0.624, p < 0.001 and γ = -0.509, p < 0.001, respectively). A multiple regression analysis showed that GDF-15 levels were significantly associated with eGFRcr after adjusting for age, sex and other confounders, including urinary ACR as a continuous or categorical variable (ß = -0.309, p < 0.001 and ß = -0.318, p < 0.001, respectively). Similarly, these results were replicated when eGFRcr-cys was considered instead of eGFRcr in correlation and regression analyses. CONCLUSION: GDF-15 levels were inversely associated with eGFR in patients with type 2 DM. This relationship was independent of albuminuria status.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study.

BACKGROUND: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). METHODS: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. RESULTS: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, -1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. CONCLUSION: This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Relationship between plasma growth differentiation factor-15 levels and diabetic retinopathy in individuals with type 2 diabetes.

The purpose of our study was to investigate the relationship between plasma growth differentiation factor-15 (GDF-15) concentrations and diabetic retinopathy in patients with type 2 diabetes mellitus (DM). We evaluated 235 patients with type 2 DM in a cross-sectional study. Significantly increased levels of the plasma GDF-15 were found in individuals with diabetic retinopathy versus those without. According to the degree of diabetic retinopathy, there was a significant difference in the average plasma GDF-15 levels (no diabetic retinopathy, 1114 ng/L; nonproliferative diabetic retinopathy, 1327 ng/L; proliferative diabetic retinopathy, 1445 ng/L; p for trend = 0.035) after adjustments for confounders. Logistic regression analyses indicated that plasma GDF-15 concentrations were significantly associated with diabetic retinopathy (odds ratio per 1 standard deviation increment in the log-transformed value, 1.78; 95% confidence interval, 1.05-3.03, p = 0.032). Our study showed a significant positive relationship between plasma GDF-15 concentrations and diabetic retinopathy in type 2 DM patients.

Plasma sphingosine 1-phosphate concentrations and cardiovascular autonomic neuropathy in individuals with type 2 diabetes.

The aim of this study was to test the hypothesis that plasma sphingosine 1-phosphate (S1P) levels are associated with the risk of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes patients. This cross-sectional study included 287 individuals with type 2 diabetes. CAN was evaluated using cardiovascular reflex tests. Logistic regression analyses were conducted to assess the relationship between plasma S1P levels and CAN. Plasma S1P concentrations were significantly lower in individuals with CAN than in those without CAN. There was a significant interaction between plasma S1P levels and sex with respect to CAN (p for interaction = 0.003). When stratified by sex, the association between plasma S1P levels and CAN exhibited a sex difference; in multivariable analysis, plasma S1P levels were significantly associated with CAN in women (odds ratio per standard deviation increase in the log-transformed value, 0.40; 95% confidence interval, 0.23-0.70, p = 0.001). However, there was no significant association between plasma S1P and CAN in men. Plasma S1P concentrations were inversely associated with CAN only in women with type 2 diabetes.

Serum myostatin levels are positively associated with diabetic retinopathy in individuals with type 2 diabetes mellitus.

AIM: To examine the relationship between serum myostatin levels and diabetic retinopathy in individuals with type 2 diabetes mellitus (DM). METHODS: This cross-sectional study evaluated 246 individuals with type 2 DM. Analysis of covariance was performed after adjusting for confounders. A logistic regression model was used to evaluate the relationship between serum myostatin levels and diabetic retinopathy. RESULTS: Serum myostatin levels were significantly higher in individuals with diabetic retinopathy than in those without. After adjusting for other covariates, the mean serum myostatin levels were significantly different according to the severity of retinopathy (without diabetic retinopathy, 2234 pg/mL; non-proliferative diabetic retinopathy, 2698 pg/mL; and proliferative diabetic retinopathy, 3076 pg/mL; p for trend = 0.004). The multivariate analysis showed that serum myostatin levels were significantly associated with diabetic retinopathy (odds ratio for every 1 standard deviation-increase in logarithmic value, 1.77; 95% confidence interval: 1.21-2.59; p = 0.003). CONCLUSION: Serum myostatin levels were positively associated with diabetic retinopathy in individuals with type 2 DM.

Reference Intervals for Bone Turnover Markers in Korean Healthy Women.

BACKGROUND: Adequate suppression of bone turnover rate is important to decrease fracture risk without mineralization defect due to oversuppression. This study was performed to determine reference intervals (RIs) for 2 bone turnover markers, serum C-terminal telopeptide of type I collagen (CTX) and osteocalcin, in Korean women. METHODS: A total of 461 Korean women (287 premenopausal and 174 postmenopausal) without any disease or drug history affecting bone metabolism was included. Serum CTX and osteocalcin were measured after overnight fasting. Bone mineral density (BMD) was measured at the 1st to 4th lumbar vertebra using dual energy X-ray absorptiometry. Subjects with normal spinal BMD (T-score ≥-1.0) were included in this study. RESULTS: After stable concentrations were maintained, both CTX and osteocalcin were abruptly increased in 50 to 59 years, and then decreased with increasing age. Median levels and interquartile range of serum CTX and osteocalcin in all subjects were 0.322 (0.212-0.461) ng/mL and 15.68 (11.38-19.91) ng/mL. RIs for serum CTX and osteocalcin in all subjects were 0.115 to 0.861 ng/mL and 6.46 to 36.76 ng/mL. Those were higher in postmenopausal women (CTX, 0.124-1.020 ng/mL, osteocalcin, 5.42-41.57 ng/mL) than in premenopausal women (CTX, 0.101-0.632 ng/mL, osteocalcin, 6.73-24.27 ng/mL). If we use target reference levels as lower half of premenopausal 30 to 45 years in patients with antiresorptive drugs, those were 0.101 to 0.251 ng/mL and 6.40 to 13.36 ng/mL. CONCLUSIONS: We established RIs for serum CTX and osteocalcin in healthy Korean women with normal lumbar spine BMD. Premenopausal RIs for serum CTX and osteocalcin would be useful to monitor patients with low bone mass using osteoporosis drugs.