Ablation manual for liver cancer.

Because of recent advances in energy device technology, ablation has become popular worldwide. It is less invasive and provides faster postoperative recovery compared to surgery, and therefore, it has come to be applied to a wide range of organs, such as liver, lung, kidney, thyroid, and bone/soft tissue tumors. In order to properly guide the needle to the target area, imaging support is necessary, and ultrasound, which has the advantages of high resolution and real-time capability, is the most frequently used modality. In other words, ablation can be said to be a therapeutic method that makes the most of the advantages of ultrasound. This article outlines the role of ultrasound in ablation for liver cancer and its specific usage.

The relationship between the ratio of the supraspinatus muscle thickness measured by ultrasound imaging and glenohumeral subluxation in stroke patients: a cross-sectional study.

Introduction: Glenohumeral subluxation (GHS) is a common complication in stroke patients with hemiplegia, occurring in approximately 17-81% of cases. This study aims to evaluate the relationship between shoulder muscle thickness and the degree of subluxation using ultrasound imaging. Methods: A cross-sectional study of 61 stroke patients with hemiplegia was conducted, measuring supraspinatus muscle thickness, deltoid muscle thickness, and acromion-greater tuberosity (AGT). Logistic regression and ROC analyses were used. ROC curves, calibration plots, and decision curves were drawn on the training and validation sets. Results: According to logistic regression analysis, the ratio of supraspinatus muscle thickness was statistically significant (OR: 0.80; 95% CI: 0.70-0.92; p < 0.01), and it was an independent factor for evaluating the presence or absence of GHS. An AUC of 0.906 (95% CI, 0.802-1.000) was found in the training set; meanwhile, the AUC in the validation set was 0.857 (95% CI, 0.669-1.000), indicating good performance. According to the training set ROC curve, the most effective statistical threshold was 93%, with a sensitivity of 84% and a specificity of 96%. Discussion: The ratio of supraspinatus muscle thickness is a valuable criterion for evaluating GHS risk, supporting targeted rehabilitation interventions.

Short-term intervention effect analysis of neuromuscular joint facilitation in patients who experienced stroke with shoulder subluxation: a clinical randomized controlled trial.

[Purpose] Shoulder subluxation is a common complication of acute stroke that affects clinical rehabilitation training and hinders the recovery of upper limb motor function. This study explored the short-term interventional effects of neuromuscular joint facilitation in patients who experienced stroke with shoulder subluxation. [Participants and Methods] We recruited 36 patients who experienced stroke with shoulder subluxation. All patients were randomly divided into two groups: the neuromuscular joint facilitation group (n=18) and the control group (n=18). The control group underwent routine rehabilitation treatment. The intervention in the neuromuscular joint facilitation group involved neuromuscular joint facilitation of the shoulder joint in four modes based on conventional rehabilitation treatment. Four different interventions were administered. The thickness of the supraspinatus muscle and the acromion-greater tuberosity distance were measured using ultrasound to observe the curative effect. [Results] In neuromuscular joint facilitation group, the thickness of supraspinatus muscle, acromion-greater tuberosity distance and acromion-greater tuberosity distance difference were significantly different before and after intervention. In the control group, there were no significant difference before and after intervention. [Conclusion] Neuromuscular joint facilitation intervention improved the thickness of the supraspinatus muscle, shortened the distance between the acromion and the greater tubercle, and improved shoulder subluxation in patients who experienced stroke.

Effect of expiratory muscle training on respiratory muscle fatigue in healthy adults: a randomized controlled trial.

[Purpose] This study examined the effects of expiratory muscle training on fatigue in individual respiratory muscles. [Participants and Methods] Healthy adult males (n=31) were randomly assigned to two groups: expiratory muscle training (n=15) and normal controls (n=16). In the expiratory muscle training group, training was performed once for 15 min at 50% load of the maximum expiratory mouth pressure twice daily for 4 weeks. Respiratory muscle fatigue indicators were measured using surface electromyography as the median power frequency of each respiratory muscle at the time of measuring the maximum inspiratory mouth pressure during 20 min of inspiratory muscle loading and maximum expiratory mouth pressure. [Results] In the expiratory muscle training group, the median power frequency values of the sternocleidomastoid, rectus abdominis, and internal oblique/external oblique before expiratory muscle training significantly decreased during inspiratory muscle loading. However, no difference was observed in the median power frequency values measured before and during inspiratory muscle loading after the expiratory muscle training. In the normal controls, the median power frequency values of the sternocleidomastoid and rectus abdominis significantly decreased during inspiratory muscle loading. [Conclusion] Expiratory muscle training increased fatigue tolerance of the sternocleidomastoid, rectus abdominis, and internal and external oblique muscles in healthy individuals.

Modified multi-Rayleigh model-based statistical analysis of ultrasound envelope for quantification of liver steatosis and fibrosis.

PURPOSE: Quantitative diagnosis of the degree of fibrosis progression is currently a focus of attention for fatty liver in nonalcoholic steatohepatitis (NASH). However, previous studies have focused on either lipid droplets or fibrotic tissue, and few have reported the evaluation of both in patients whose livers contain adipose and fibrous features. Our aim was to evaluate fibrosis tissue and lipid droplets in the liver. METHODS: We used an analytical method combining the multi-Rayleigh (MRA) model and a healthy liver structure filter (HLSF) as a technique for statistical analysis of the amplitude envelope to estimate fat and fibrotic volumes in clinical datasets with different degrees of fat and fibrosis progression. RESULTS: Fat mass was estimated based on the non-MRA fraction corresponding to the signal characteristics of aggregated lipid droplets. Non-MRA fraction has a positive correlation with fat mass and is effective for detecting moderate and severe fatty livers. Progression of fibrosis was estimated using MRA parameters in combination with the HLSF. The proposed method was used to extract non-healthy areas with characteristics of fibrotic tissue. Fibrosis in early fatty liver suggested the possibility of evaluation. On the other hand, fat was identified as a factor that reduced the accuracy of estimating fibrosis progression in moderate and severe fatty livers. CONCLUSION: The proposed method was used to simultaneously evaluate fat mass and fibrosis progression in early fatty liver, suggesting the possibility of quantitative evaluation for discriminating between lipid droplets and fibrous tissue in the early fatty liver.

Use of albumin infusion for cirrhosis-related complications: An international position statement.

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.

Effects of Diamond Steps Exercises on Balance Improvement in Healthy Young and Older Adults: A Protocol Proposal.

Diamond step (DS) exercises are associated with multiple components of postural control and, thus, have the potential to efficiently improve balance ability. This study aimed to verify whether DS exercises contribute to improving balance ability. This study included 35 healthy young people and 29 older adults. DS exercises were performed continuously for 3 min, four times a week, for 1 month. Balance ability was assessed at baseline and after 1 and 2 months; eight items in total were examined: 30 s chair stand test, functional reach test, standing on one leg with eyes closed, time required for five rounds of DS, left-right DS, Y balance test, open-close stepping test, and finger-to-floor distance. The difficulty, achievement, and lightness/enjoyment of DS exercises were measured after the first practice and 1 month after beginning the exercises as subjective evaluations. Older adults showed improvement in seven of the eight items, with the exception being the one-legged stance with closed eyes. The subjective evaluation showed a decrease in the level of difficulty of DS exercises for older adults. DS exercises may improve balance by effectively utilizing various postural control strategies. These exercises can be effective and easy to implement, given their moderate difficulty level and self-efficacy.

The Impact of Partial Splenic Embolization on Portal Hypertensive Gastropathy in Cirrhotic Patients with Portal Hypertension.

This study investigated the impact of partial splenic embolization (PSE) on portal hypertensive gastropathy (PHG). We retrospectively analyzed endoscopic findings and the portal venous system of 31 cirrhotic patients with PHG. The improved group was defined as the amelioration of PHG findings using the McCormack classification. Child-Pugh scores of the improved group (18 of 31 patients) were significantly lower compared with those of the non-improved group (p = 0.018). The changes in the diameters of the portal trunk and those of the spleno-portal junction and spleen hilum in the splenic vein of the improved group were significantly larger than those of the non-improved group (p = 0.007, p = 0.025, and p = 0.003, respectively). The changes in the diameters of the portal vein and splenic hilum of the splenic vein showed significant correlations with Child-Pugh score (r = 0.386, p = 0.039; r = 0.510, p = 0.004). In a multivariate analysis of baseline factors related to the improved group, Child-Pugh grade A was significantly associated with the improvement of PHG (odds ratio 6.875, p = 0.033). PSE could be useful for PHG, especially in patients with Child-Pugh grade A, at least in the short term.

Successful Identification of a Novel Therapeutic Compound for Hepatocellular Carcinoma Through Screening of ADAM9 Inhibitors.

BACKGROUND/AIM: MHC-class I-related chain A (MICA) functions as a ligand for natural killer group D, an activating receptor on natural killer (NK) cells, and its expression correlates with the carcinogenesis and progression of hepatocellular carcinoma (HCC). Although membranous MICA (mMICA) activates NK cells, soluble forms of MICA (sMICA), shed by cleaving enzymes, such as A disintegrin and metalloprotease (ADAM) 9, suppress NK cells. Therefore, the prevention of MICA shedding through the inhibition of ADAM9 has the potential to activate cancer immunity. Although we have discovered several ADAM inhibitors, many did not sufficiently activate NK cells without being cytotoxic, and, thus, new ADAM9 inhibitor candidates are needed. MATERIALS AND METHODS: To identify possible compounds for drug development, chemical library screening (a total of 741 compounds) was conducted using a fluorescence assay. Compounds with reduced fluorescence intensity were used as hit compounds in a subsequent analysis. Their impact on sMICA and mMICA in HCC cell lines was assessed using ELISA and flow cytometry, respectively. The cytotoxicity of NK cells was also evaluated by co-culturing NK cells with HCC cells. RESULTS: CCL347, a symmetrical compound with five benzene rings, was identified as a hit compound. CCL347 significantly reduced sMICA levels in the culture medium supernatant with negligible cytotoxicity. Although mMICA was also reduced, CCL347 successfully enhanced NK cell cytotoxicity in co-cultures of NK cells and HCC cells. CONCLUSION: CCL347 has potential as a novel therapeutic drug for HCC.

Body mass index combined with (waist + hip)/height accurately screened for normal-weight obesity in Chinese young adults.

OBJECTIVES: Only a few studies have explored the prevalence of normal-weight obesity in young adults or the development of a simple evaluation index for body fat percentage. Therefore, this study aimed to examine the prevalence of normal-weight obesity in young Chinese adults and use anthropometric measurements to develop an evaluation index. METHODS: In total, 1322 college students participated in the study and were divided into the normal-weight lean, normal-weight obese, and overweight and obese groups based on their body mass index and body fat percentage. The differences in body composition, circumference, and circumference ratio among these three groups were examined. RESULTS: When exploring the correlation between the circumference ratio and body fat percentage, the circumference ratio was suitable for early screening of abnormal body fat percentage, and the cutoff value was calculated. Body composition and circumference were significantly different among the three groups: (waist + hip)-to-height, hip-to-height, and waist-to-height ratios were strongly correlated with body fat percentage. CONCLUSIONS: (Waist + hip)-to-height ratio can be used as a simple evaluation index for indicating abnormal body fat percentage when higher than 1.032 in male and 1.047 in female individuals. Downregulating the normal upper limit for body mass index to 24.4 and 23.8 kg/m2 in male and female individuals, respectively, is recommended. Body mass index combined with (waist + hip)-to-height ratio allowed for more accurate screening of normal-weight obesity as an easy and cost-free evaluation measure for abnormal body fat percentage.

Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-ß/Smad pathway suppression in hepatic stellate cells.

Transforming growth factor (TGF)-ß/Smad pathway is implicated in the pathogenesis of liver fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) proteins such as collagen in response to chronic inflammation. It has been reported that ceramide regulates collagen production through TGF-ß/Smad pathway activation. In this study, we examined whether miglustat, an inhibitor of glucosylceramide synthase, can suppress liver fibrosis by reducing TGF-ß/Smad pathway activity. Human hepatic stellate cells (HHSteCs) were cultured with TGF-ß and multiple miglustat concentrations to examine dose-dependent effects on the expression levels of ECM-related genes and Smad proteins. To evaluate the efficacy of miglustat for fibrosis mitigation, C57BL/6 mice were treated with carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis, followed by combined CCl4 plus miglustat for a further 2 weeks. To examine if miglustat can also prevent fibrosis, mice were treated with CCl4 for 2 weeks, followed by CCl4 plus miglustat for 2 weeks. Miglustat dose-dependently downregulated expression of α-smooth muscle actin and ECM components in TGF-ß-treated HHSteCs. Both phosphorylation and nuclear translocation of Smad2 and Smad3 were also suppressed by miglustat treatment. Sirius-Red staining and hydroxyproline assays of model mouse liver samples revealed that miglustat reduced fibrosis, an effect accompanied by decreased expression of ECM. Our findings suggest that miglustat can both prevent and reverse liver fibrosis by inhibiting TGF-ß/Smad pathway.

Ablation for Benign Liver Tumors: Current Concepts and Limitations.

Percutaneous ablation under imaging guidance is a curative treatment that can induce complete tumor necrosis with advantages of minimal invasiveness and a low risk of complications. Thermal ablation, which includes radiofrequency ablation and microwave ablation, is a representative technique that has sufficient antitumor effects in cases of hepatocellular carcinoma with ≤3 lesions measuring ≤3 cm and preserved liver function. The short- and long-term outcomes of patients are comparable with those achieved with surgical resection. Despite their nonmalignant nature, some benign liver tumors require treatment for symptoms caused by the presence of the tumor and/or continuous enlargement. Ablation may be the treatment of choice because it has lower burden on patients than surgical treatment. This review describes the recent concepts, progress, and limitations of ablation-based treatment for benign liver tumors.

The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells.

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and HBx-overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of ELAVL1 resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in ELAVL1-knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.

Diagnostic accuracy of transient elastography in diagnosing clinically significant portal hypertension in patients with chronic liver disease: a systematic review and meta-analysis.

PURPOSE: Liver stiffness measurement using transient elastography (TE-LSM) is a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for diagnosing clinically significant portal hypertension (CSPH). However, previous studies have yielded conflicting results. We evaluated the correlation between TE-LSM and HVPG and the performance of TE-LSM in diagnosing CSPH (HVPG ≥ 10 mmHg). METHODS: We conducted a systematic review and meta-analysis by searching PubMed and Scopus databases for relevant literature evaluating the clinical usefulness of TE for diagnosing CSPH in patients with chronic liver disease. RESULTS: Twenty-six studies (4337 patients with valid TE and HVPG) met our inclusion criteria. The median correlation coefficient of TE with HVPG was 0.70 (range 0.36-0.86). The weighted mean of optimal cut-off of liver stiffness value for diagnosing CSPH was 22.8 kPa (95% CI 22.7-23.0 kPa). The summary sensitivity and specificity were 79% (95% CI 74-84%) and 88% (95% CI 84-91%), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.91 (95% CI 0.88-0.93) according to the bivariate model. One limitation of the study was significant heterogeneity in the results of summary sensitivity and specificity (I2 83 and 74%, respectively). The heterogeneity could be explained by the variable liver stiffness cut-offs used in studies. The meta-regression plot revealed that as the optimal cut-off increased, the sensitivity decreased, the specificity increased, and vice versa. CONCLUSIONS: Liver stiffness measurement using TE correlates well with HVPG, and a liver stiffness cut-off value of 22.8 kPa shows a high accuracy for diagnosing CSPH. Thus, use of TE should be integrated into clinical practice for noninvasive diagnosis of CSPH.

Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring CTNNB1 Mutation in Early Clinical Experience.

Atezolizumab plus bevacizumab (ATZ/BV) treatment is a combined immunotherapy consisting of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor monoclonal antibody, which has brought a major paradigm shift in the treatment of unresectable hepatocellular carcinoma (HCC). Gain-of-function mutation of CTNNB1 contributes to resistance of ICI monotherapy through the framework of non-T-cell-inflamed tumor microenvironment. However, whether CTNNB1 mutation renders resistance to ATZ/BV similar to ICI monotherapy remains to be elucidated. In this study, a liquid biopsy sample in plasma of 33 patients with HCC treated with ATZ/BV was subjected to droplet digital PCR for detecting hotspot mutations at the exon 3 of CTNNB1 locus. A total of eight patients (24.2%) exhibited at least one CTNNB1 mutation. The objective response rate (ORR) in patients with wild-type (WT) and mutant (MT) CTNNB1 was 8.0% and 12.5%, respectively, and the disease control rate (DCR) was 68.0% and 87.5%, respectively. No significant difference in both ORR and DCR has been observed between the two groups. The median progression-free survival in patients with WT and MT CTNNB1 was 6.6 and 7.6 months, respectively (not statistically significant). Similarly, no significant difference in overall survival has been observed between patients with WT and MT CTNNB1 (13.6 vs. 12.3 months). In conclusion, the treatment effect of ATZ/BV in patients with HCC with MT CTNNB1 was comparable to those patients with WT CTNNB1. These results implicate that BV added to ATZ might improve immunosuppressive tumor microenvironment caused by CTNNB1 mutation.

The Efficacy of Expiratory Muscle Training during Inspiratory Load in Healthy Adult Males: A Randomized Controlled Trial.

This study aimed to evaluate the effects of expiratory muscle training (EMT) on respiratory muscle strength and respiratory distress during inspiratory load. Thirty-one healthy adult males were randomly divided into an EMT group who underwent EMT (n = 15) and a control group who did not undergo EMT (n = 16). The EMT group underwent EMT with a 50% load of maximum expiratory mouth pressure (PEmax) for 15 min, twice a day, every day, for 4 weeks. The parameter of respiratory muscle fatigue was a decrease in maximum inspiratory mouth pressure (PImax) and PEmax during 20 min of inspiratory load; thus, PImax and PEmax during inspiratory load were measured. Respiratory distress during inspiratory load was assessed using the Borg scale. These assessments were performed on the same subjects in each group before and after the 4 week study. In the EMT group, the PEmax values after the study were significantly higher than those before the study (p < 0.01). Furthermore, before the study, the PImax and PEmax values for the EMT group during inspiratory load were significantly lower than those before inspiratory load (p < 0.01). However, after the study, there was no difference in these values between during and before inspiratory load. In the EMT group, the Borg scale value during inspiratory load from 6 to 20 min was significantly lower after the study than before the study (p < 0.05). EMT increases expiratory muscle strength, thereby attenuating decreased respiratory muscle strength (PImax and PEmax) and respiratory distress during inspiratory load in healthy subjects.

Body Fat Percentage and Normal-Weight Obesity in the Chinese Population: Development of a Simple Evaluation Indicator Using Anthropometric Measurements.

Few studies explore the associations between body fat percentage (BFP) prediction and evaluation indicators for Chinese with normal-weight obesity. We aimed to explore convenient and cost-free BFP evaluation indicators to routinely monitor BFP status in Chinese patients with normal-weight obesity. Participants (N = 164) were divided into three groups according to body mass index (BMI) and BFP: normal-weight lean, normal-weight obese, and overweight and obese. Differences in body composition and circumference were compared to examine the relationship between BFP and circumference, determine a simple evaluation indicator reflecting BFP, and identify cutoff values for normal-weight obesity circumference. Significant differences in body composition and circumference were observed among the three groups. The correlation between thigh/height, hip/height, (hip + waist)/height, and BFP was stronger than that with BMI. The (hip + waist)/height ratio was the indicator most reflective of BFP (95% confidence interval: 3.004−9.018, p = 0.013), and a ratio above 1.115 (95% confidence interval: 0.936−0.992, p < 0.001) was predictive of normal-weight obesity. Furthermore, we suggest that the upper value for a normal BMI in Chinese individuals be lowered to 23.4 kg/m2 (95% confidence interval: 0.984−0.999, p < 0.001). The (hip + waist)/height ratio can be used with body mass index for a more accurate evaluations of BFP abnormalities and health risks.