Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3 cm) hepatocellular carcinoma.

BACKGROUND AND AIM: Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3 cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. METHODS: This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3 cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10 years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. RESULTS: One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7 months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8 months, P = 0.001). Median RFS was 19.1 months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2 cm) were poor prognostic factors of OS. CONCLUSIONS: The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3 cm) HCC in CTP class A patients.

Validation of the Texas Hepatocellular Carcinoma Risk Index Predictive Model for Hepatocellular Carcinoma in Asian Cohort.

Hepatocellular carcinoma (HCC) represents a significant global health burden, with its incidence and mortality rates varying significantly across different geographic regions. This variance is largely attributed to differences in the prevalence of risk factors such as hepatitis B and C infections, and alcohol consumption, as well as genetic predispositions that are distinct between Eastern and Western populations. Moreover, the impact of racial and ethnic diversity on the disease's epidemiology further complicates the global understanding and prediction of HCC. Such disparities highlight the critical need to evaluate the applicability of predictive models across diverse populations, acknowledging that a model developed in one region may not necessarily translate with the same accuracy or effectiveness when applied to another, because of these underlying epidemiologic and genetic differences. In this study, we aimed to assess the cross-regional applicability and accuracy of an HCC prediction model (Texas hepatocellular carcinoma risk index [THCC-RI] predictive model) originally developed in Western populations, within an Eastern context.1,2.

Demographic review of aesthetic surgery for patients with facial palsy.

BACKGROUND: This study analyzed the demographic characteristics of patients with facial palsy who were treated using either dynamic or static procedures. This study aimed to compare the frequency of procedure implementation and age distribution between the two groups. METHODS: This study retrospectively analyzed the medical records of patients treated for facial palsy at a single institution from 2014 to 2022. Among cases included in our study, dynamic procedures involved cross-facial nerve graft and latissimus dorsi or gracilis muscle flap transfer. Static procedures included gold weight insertion, canthopexy, browlift, and thread lift/static slings. RESULTS: Among the 31 patients included in our study, eight (25.8%) incorporated dynamic techniques, and the average age of patients was 44.75 years (range, 24-68 years) with a male to female ratio of 1:4. The remaining 23 patients (74.2%) underwent a static procedure, of which the average age was 59.17 years (range, 23-81 years) which was statistically significantly higher than the average age of 44.75 of dynamic patients (p= 0.013). Regarding the timing of treatment after diagnosis, no patient underwent dynamic procedures more than 20 years after initial diagnosis. A greater diversity in the timing of treatment was observed in the static group. All patients who underwent dynamic procedures were treated using static procedures during the study period. CONCLUSION: Because aesthetics-based static techniques are typically quick outpatient procedures that can be performed under local anesthesia, our study shows that these are often preferred treatments for all age groups, especially for debilitated or older patients. Further research is required to investigate the long-term functional outcomes of these surgical techniques in a wider population of patients.

16S rRNA Next-Generation Sequencing May Not Be Useful for Examining Suspected Cases of Spontaneous Bacterial Peritonitis.

Background and Objectives: Ascites, often associated with liver cirrhosis, poses diagnostic challenges, particularly in detecting bacterial infections. Traditional methods have limitations, prompting the exploration of advanced techniques such as 16S rDNA next-generation sequencing (NGS) for improved diagnostics in such low-biomass fluids. The aim of this study was to investigate whether the NGS method enhances detection sensitivity compared to a conventional ascites culture. Additionally, we aimed to explore the presence of a microbiome in the abdominal cavity and determine whether it has a sterile condition. Materials and Methods: Ten patients with clinically suspected spontaneous bacterial peritonitis (SBP) were included in this study. A traditional ascites culture was performed, and all ascites samples were subjected to 16S ribosomal RNA gene amplification and sequencing. 16S rRNA gene sequencing results were interpreted by comparing them to positive and negative controls for each sample. Results: Differential centrifugation was applied to all ascites samples, resulting in very small or no bacterial pellets being harvested. The examination of the 16S amplicon sequencing libraries indicated that the target amplicon products were either minimally visible or exhibited lower intensity than their corresponding negative controls. Contaminants present in the reagents were also identified in the ascites samples. Sequence analysis of the 16S rRNA gene of all samples showed microbial compositions that were akin to those found in the negative controls, without any bacteria isolated that were unique to the samples. Conclusions: The peritoneal cavity and ascites exhibit low bacterial biomass even in the presence of SBP, resulting in a very low positivity rate in 16S rRNA gene sequencing. Hence, the 16S RNA sequencing method does little to enhance the rate of positive samples compared to traditional culture methods, including in SBP cases.

Association between multimorbidity and periodontal disease in Korean adults: A nationwide cross-sectional cohort study.

OBJECTIVES: This study aimed to investigate the association between multimorbidity, which refers to the presence of two or more chronic diseases, and periodontal disease in Korean adults using national survey data. METHODS: A total of 12,440 Korean adults aged ≥19 years were selected from the seventh Korea National Health and Nutrition Examination Survey (KNHANES). We investigated periodontal disease status based on various variables, including the gender, age, educational level, income level, smoking and alcohol drinking status, frequency of daily toothbrushing, and unmet dental treatment needs. Furthermore, periodontal status according to diagnosed chronic diseases, including hypertension, dyslipidaemia, stroke, myocardial infarction, angina pectoris, and diabetes, was investigated, and the association between multimorbidity and periodontal disease was analysed through multiple logistic regression using SAS 9.4. RESULTS: According to the general characteristics of the study participants, the prevalence of periodontal disease was higher in males, smokers, older age, and lower educational and income levels (p < 0.001). Moreover, as the frequency of daily toothbrushing increased, the distribution of periodontal disease decreased (p < 0.001). The prevalence of periodontal disease was higher in those with chronic diseases than in those without chronic diseases and was statistically significantly higher as the number of diagnosed chronic diseases increased (p < 0.001). Additionally, an increase in the number of chronic diseases was observed to increase the prevalence and risk of periodontal disease. CONCLUSION: These results suggest that multimorbidity significantly affects the prevalence of periodontal disease.

Harnessing Pentameric Scaffold of Cholera Toxin B (CTB) for Design of Subvirion Recombinant Dengue Virus Vaccine.

Dengue virus is an enveloped virus with an icosahedral assembly of envelope proteins (E). The E proteins are arranged as a head-to-tail homodimer, and domain III (EDIII) is placed at the edge of the dimer, converging to a pentamer interface. For a structure-based approach, cholera toxin B (CTB) was harnessed as a structural scaffold for the five-fold symmetry of EDIII. Pivoted by an RNA-mediated chaperone for the protein folding and assembly, CTB-EDIII of dengue serotype 1 (DV1) was successfully produced as soluble pentamers in an E. coli host with a high yield of about 28 mg/L. Immunization of mice with CTB-DV1EDIII elicited increased levels of neutralizing antibodies against infectious viruses compared to the control group immunized with DV1EDIII without CTB fusion. IgG isotype switching into a balanced Th1/Th2 response was also observed, probably triggered by the intrinsic adjuvant activity of CTB. Confirming the immune-enhancing potential of CTB in stabilizing the pentamer assembly of EDIII, this study introduces a low-cost bacterial production platform designed to augment the soluble production of subunit vaccine candidates, particularly those targeting flaviviruses.

Reduced-Dose or Discontinuation of Bevacizumab Might Be Considered after Variceal Bleeding in Patients with Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab: Case Reports.

Background and Objectives: Variceal bleeding (VB) is the most concerning condition that is difficult to treat after atezolizumab/bevacizumab in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: We would like to introduce the cases of two patients who underwent bevacizumab reduction or discontinuation when VB occurred after atezolizumab/bevacizumab. Results: VB occurred in two patients who showed good tumor response after atezolizumab/bevacizumab treatment, and all VBs were successfully treated with endoscopic variceal ligations. In the first patient, VB did not occur as the tumor response decreased after a 50% reduction in bevacizumab. In the second patient, VB occurred again after a 50% bevacizumab reduction, so bevacizumab was discontinued and treatment with atezolizumab alone has been successfully maintained. Conclusions: Accordingly, we would like to suggest that considering bevacizumab dose reduction instead of changing to tyrosine kinase inhibitor may be a good clinical choice in atezolizumab/bevacizumab patients who develop VB.

Complications of immunotherapy in advanced hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.

Auxetic Photonic Patterns with Ultrasensitive Mechanochromism.

Photonic crystals with mechanochromic properties are currently under intensive study to provide intuitive colorimetric detection of strains for various applications. However, the sensitivity of color change to strain is intrinsically limited, as the degree of deformation determines the wavelength shift. To overcome this limitation, auxetic photonic patterns that exhibit ultra-sensitive mechanochromism are designed. These patterns have a regular arrangement of cuts that expand to accommodate the strain, while the skeletal framework undergoes torsional deformation. Elastic photonic crystals composed of a non-close-packed array of colloidal particles are embedded in the cut area of the auxetic patterns. As the cut area amplifies the strains, the elastic photonic crystals show significant color change even for small total strains. The degree of local-strain amplification, or sensitivity of color change, is controllable by adjusting the width of cuts in the auxetic framework. In this work, a maximum sensitivity of up to 60 nm/% is achieved, which is 20 times higher than bulk films. It is believed that the auxetic photonic patterns with ultra-sensitive mechanochromism will provide new opportunities for the pragmatic use of mechanochromic materials in various fields, including structural health monitoring.

The prediction of liver decompensation using hepatic collagen deposition assessed by computer-assisted image analysis with Masson's trichrome stain.

BACKGROUND & AIM: The current pathologic system classifies structural deformation caused by hepatic fibrosis semi-quantitatively, which may lead to a disagreement among pathologists. We measured hepatic fibrosis quantitatively using collagen proportionate area (CPA) in compensated cirrhotic patients and assessed its impact on predicting the development of liver decompensation. METHOD: From January 2010 to June 2018, we assessed 101 patients who went through liver biopsy and received diagnosis as compensated cirrhosis with digital image analysis of CPA. Clinical and laboratory data were collected at the baseline and at the time of the last follow-up or progression to liver decompensation (LD). RESULT: The mean age was 50.8 ± 10.5 years, and the most common etiology of liver disease was chronic hepatitis B (48.5%), followed by alcoholic hepatitis (18.8%). The mean CPA was 16.91 ± 9.60%. The mean CPA values were different in patients with and without LD development (21.8 ± 11.1 vs. 15.2 ± 8.5). During the median follow-up of 60.0 months, 26 out of 101 patients experienced LD. Older age (hazard ratio [HR],1.069; p = 0.015), prolonged international normalized ratio (HR, 6.449; p = 0.019) and higher CPA (HR, 1.049; p = 0.040) were independent predictors of liver decompensation on multivariate cox-regression analysis. When patients were divided according to the optimal CPA threshold (26.8%), higher CPA predicted LD better than lower CPA. (Log-rank test: p < 0.001). CONCLUSION: CPA could be a useful quantitative prognostic value for patients with compensated cirrhosis.

Radiation Oncologists' Perspectives on Oligometastatic Disease: A Korean Survey Study.

PURPOSE: Perspectives of radiation oncologists on oligometastatic disease was investigated using multi-layered survey. MATERIALS AND METHODS: Online survey on the oligometastatic disease was distributed to the board-certified regular members of the Korean Society for Radiation Oncology. The questionnaire consisted of four domains: five questions on demographics; five on the definition of oligometastatic disease; four on the role of local therapy; and three on the oligometastatic disease classification, respectively. RESULTS: A total of 135 radiation oncologists participated in the survey. The median length of practice after board certification was 22.5 years (range, 1 to 44 years), and the vast majority (94.1%) answered affirmatively to the clinical experience in oligometastatic disease management. Nearly two-thirds of the respondents considered the number of involved organs as an independent factor in defining oligometastasis. Most frequently perceived upper limit on the numerical definition of oligometastasis was 5 (64.2%), followed by 3 (26.0%), respectively. Peritoneal and brain metastasis were nominated as the sites to be excluded from oligometastastic disease by 56.3% and 12.6% of the participants, respectively. Vast majority (82.1%) agreed on the role of local treatment in the management of oligometastatic disease. Majority (72%) of the participants acknowledged the European Society for Radiotherapy and Oncology (ESTRO)-European Organisation for Research and Treatment of Cancer (EORTC) classification of oligometastatic disease, however, only 43.3% answered that they applied this classification in their clinical practice. Underlying reasons against the clinical use were 'too complicated' (66.0%), followed by 'insufficient supporting evidence' (30.0%), respectively. CONCLUSION: While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Continued education and training on oligometastatic disease would be also required to build consensus among participating caregivers.

Application of surface-guided radiation therapy in prostate cancer: comparative analysis of differences with skin marking-guided patient setup.

PURPOSE: Surface-guided radiation therapy is an image-guided method using optical surface imaging that has recently been adopted for patient setup and motion monitoring during treatment. We aimed to determine whether the surface guide setup is accurate and efficient compared to the skin-marking guide in prostate cancer treatment. MATERIALS AND METHODS: The skin-marking setup was performed, and vertical, longitudinal, and lateral couch values (labeled as "M") were recorded. Subsequently, the surface-guided setup was conducted, and couch values (labeled as "S") were recorded. After performing cone-beam computed tomography (CBCT), the final couch values was recorded (labeled as "C"), and the shift value was calculated (labeled as "Gap (M-S)," "Gap (M-C)," "Gap (S-C)") and then compared. Additionally, the setup times for the skin marking and surface guides were also compared. RESULTS: One hundred and twenty-five patients were analyzed, totaling 2,735 treatment fractions. Gap (M-S) showed minimal differences in the vertical, longitudinal, and lateral averages (-0.03 cm, 0.07 cm, and 0.06 cm, respectively). Gap (M-C) and Gap (S-C) exhibited a mean difference of 0.04 cm (p = 0.03) in the vertical direction, a mean difference of 0.35 cm (p = 0.52) in the longitudinal direction, and a mean difference of 0.11 cm (p = 0.91) in the lateral direction. There was no correlation between shift values and patient characteristics. The average setup time of the skin-marking guide was 6.72 minutes, and 7.53 minutes for the surface guide. CONCLUSION: There was no statistically significant difference between the surface and skin-marking guides regarding final CBCT shift values and no correlation between translational shift values and patient characteristics. We also observed minimal difference in setup time between the two methods. Therefore, the surface guide can be considered an accurate and time-efficient alternative to skin-marking guides.

Open Reduction of an Isolated Anterior Nasal Spine Fracture: A Case Report and Review of the Literature.

A 14-year-old girl had a midfacial trauma event caused by hitting against an opening door and experienced discomfort and swelling of the columella and upper lip. Physical examination revealed mild tenderness on light palpation without any discomfort with upper lip movement. A computed tomography scan of the maxillofacial bones with three-dimensional reconstruction showed a fracture of the anterior nasal spine with obvious leftward displacement, mild-deviation of the caudal aspect of the nasal septum, and no sign of nasal bone fracture. Open reduction and internal fixation was performed with regard to aesthetic and functional concerns, including nasal septum deviation. The postoperative course was uneventful, and healing proceeded normally without complications. Herein, we emphasize the importance of differential diagnosis of isolated anterior nasal spine fractures in patients with midfacial trauma and clinicians' strategic decision-making in treatment modalities.

Prevalence, incidence, and outcomes of hepatitis E virus coinfection in patients with chronic hepatitis C.

This study aimed to elucidate the anti-hepatitis E virus (HEV) immunoglobulin G (IgG) prevalence and incidence of seroconversion and seroreversion as well as its risk factors and to analyze the clinical outcomes of HEV and hepatitis C virus (HCV) coinfected patients compared to those of HCV-monoinfected patients. We prospectively enrolled 502 viremic HCV patients with paired plasma samples (at intervals of ≥ 12 months) from 5 tertiary hospitals. Anti-HEV IgG positivity was tested using the Wantai ELISA kit in all paired samples. Mean age was 58.2 ± 11.5 years old, 48.2% were male, 29.9% of patients had liver cirrhosis, and 9.4% of patients were diagnosed with hepatocellular carcinoma (HCC). The overall prevalence of anti-HEV IgG positivity at enrollment was 33.3%, with a higher prevalence in males and increasing prevalence according to the subject's age. During the 916.4 person-year, the HEV incidence rate was 0.98/100 person-years (9/335, 2.7%). Hepatic decompensation or liver-related mortality was not observed. There were six seroreversion cases among 172 anti-HEV-positive patients (1.22/100 person-years). In conclusion, approximately one-third of the adult Korean chronic HCV patients were anti-HEV IgG positive. The HEV incidence rate was 1 in 100 persons per year, without adverse hepatic outcomes or mortality.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

A model for predicting poor survival in patients with cirrhosis undergoing portosystemic shunt embolization.

BACKGROUND AND AIM: Portosystemic shunt embolization (PSSE) is a promising treatment for hepatic encephalopathy (HEP) and gastric varix (GV) in cirrhotic patients with a spontaneous portosystemic shunt. However, PSSE may worsen portal hypertension causing hepatorenal syndrome, liver failure, and mortality. This study aimed to develop and validate a prognostic model that helps identify patients with a risk of poor short-term survival after PSSE. METHODS: We included 188 patients who underwent PSSE for recurrent HEP or GV at a tertiary center in Korea. To develop a prediction model for 6-month survival after PSSE, Cox proportional-hazard model was used. The developed model was validated in a separate cohort of 184 patients from two other tertiary centers. RESULTS: In multivariable analysis, the 1-year overall survival after PSSE was significantly associated with baseline levels of serum albumin, total bilirubin, and international normalized ratio (INR). We therefore developed the albumin-bilirubin-INR (ABI) score by assigning 1 point each for albumin < 3.0 g/dL, total bilirubin ≥ 1.5 mg/dL, and INR ≥ 1.5. Time-dependent areas under the curve of the ABI score for predicting 3-month and 6-month survival were 0.85 and 0.85 in the development cohort and 0.83 and 0.78 in the validation cohort, indicating good discrimination performance. The ABI score showed a better discrimination and calibration performance than the model for end-stage liver disease and the Child-Pugh scores, especially in high-risk patients. CONCLUSIONS: The ABI score is a simple prognostic model that helps decide whether to proceed with PSSE for the prevention of HEP or GV bleeding in patients with spontaneous portosystemic shunt.

Current status of ultrasonography in national cancer surveillance program for hepatocellular carcinoma in South Korea: a large-scale multicenter study.

Background/Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. Methods: This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. Results: In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. Conclusions: This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Focal Segmental Glomerulosclerosis Followed by Acute Hepatitis A Infection: Case Report.

Background and Objectives: Chronic viral hepatitis such as hepatitis B or hepatitis C is frequently related to nephropathies, yet acute hepatitis A virus (HAV) infection is an exception. Materials and Methods: A 43-year-old male presented with jaundice accompanied by nausea and vomiting. The patient was diagnosed with acute HAV infection. Although the liver function improved after conservative treatment, various symptoms such as proteinuria, hypoalbuminemia, generalized edema and pleural effusion persisted. Due to nephrotic syndrome, the patient was referred to the clinic of the nephrology department and a renal biopsy was performed. Results: The result of the renal biopsy was focal segmental glomerulosclerosis (FSGS) based on histology, electron microscopy and immunohistochemistry. Therefore, based on the clinical history and biopsy results, the patient was diagnosed as having FSGS aggravated by acute HAV infection. Proteinuria, hypoalbuminemia and generalized edema were improved after prednisolone treatment. Conclusions: Although less common, acute HAV infection can also present with an extrahepatic manifestation, for example, FSGS. Hence, clinical attention is required if proteinuria or hypoalbuminemia persists in patients with acute HAV infection.