Search

Background Hepatocellular carcinoma (HCC) in patients without hepatitis B (HBV) and -C virus (HCV) infection are increasing in Japan. Method for detecting high-risk liver diseases of HCC in general population has still not been established. Liver stiffness measurement (LSM) and Controlled Attenuation Parameter (CAP) using transient elastography (TE; FibroScan System) are useful for detecting liver fibrosis and steatosis. The aim of this study is to clarify TE for risk assessment of HCC in general population. Methods This cross-sectional study was performed for residents aged ≥ 40 years in an intermountain town in Japan with a population of 3,493. Blood laboratory testing included tumor markers, abdominal ultrasound (AUS), and TE was performed. Results Among 175 subjects (64 men, 111 women), TE was evaluated and three patients with HCC were detected by AUS. For detecting HCC, the cut-off value of LSM was 5.3 kPa sensitivity 100%, specificity 75%, AUROC 0.88). The combination of LSM and CAP (LSM > 5.3 kPa with any CAP and CAP > 248 dB/m with any LSM) could detect the high-risk liver diseases of HCC (HCC, nonalcoholic fatty liver/steatohepatitis, HBV or HCV related chronic viral hepatitis with alanine transaminase (ALT) > 30 IU/L for men or > 19 IU/L for women or cirrhosis of any cause) with high sensitivity (sensitivity 90%, specificity 55%, positive predictive value 10%, negative predictive value 99%, P = 0.006). Conclusion The combination of LSM and CAP can be useful in detecting high-risk liver diseases of HCC out of general population.

Background: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed, however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. Methods: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. Results: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. Conclusions: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH.

IntroductionNon-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker.MethodsEighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control.ResultsCompared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, and low-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism–related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379.ConclusionsSerum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.

Gastrointestinal stromal tumor (GIST) is the most common submucosal tumor of the stomach. GISTs are often detected by esophagogastroduodenal endoscopy. We have previously reported on endoscopically invisible medium-sized exophytic type GISTs. We present here a case of small exophytic GIST detected by transabdominal ultrasonography (TUS) in which the natural history of the tumor could be traced retrospectively through incidental findings obtained during follow-up for intraductal papillary mucinous neoplasm by magnetic resonance of imaging or computed tomography over about 10 years. The tumor appeared 7 years before its detection, and the doubling time was calculated as 6.9 years. In conclusion, low-risk exophytic GIST was estimated to have taken at least about 7 years to reach a size detectable by TUS.

Cholangiocarcinoma (CCA) has an increasing incidence and remains a difficult to treat malignancy. In a search for more effective treatment options, progress has been made in identifying molecular drivers of oncogenic signaling including IDH mutations and FGFR2 fusions. In addition, multiple investigators have identified increased activity of YAP, the effector protein of the Hippo pathway, in CCA. The Hippo pathway regulates organ size, cellular proliferation, and apoptosis via YAP, a transcriptional co-activator. Targeting of the pathway has been difficult due the lack of a dedicated cell-surface receptor. However, more recently, additional cross-regulatory pathways have been identified that are potentially targetable. In this review, we address the current treatment landscape for CCA, the Hippo pathway broadly, animal models of CCA with attention to Hippo-related models, and the current strategies for targeting YAP.

Aim Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end-stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. Methods Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non-CKD group), and 39 end-stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. Results Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non-CKD group and in the ESRD group, and no difference was found between the non-CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non-CKD group and the ESRD group, even when ages were matched and depth was adjusted. Conclusion Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages.

Photodynamic therapy (PDT) is a therapeutic method used to destroy tumor tissue via reactive oxygen. Notably, reactive oxygen is induced by a combination of photosensitizers, including talaporfin sodium (TS) and laser light. Gastric cancer cell lines, MKN45 and MKN74, were used to evaluate the effect of TS-PDT in vitro. The antitumor effect of TS-PDT, which was evaluated via cellular viability assay, on MKN74 was weaker than that on MKN45 cells, suggesting that MKN74 cell could be resistant to TS-PDT. However, using a higher TS concentration or setting a longer treatment time (24 h) resulted in effective TS-PDT treatment on MKN74 cells. In addition, when irradiation power of LED was raised up to 5.06 J/cm2, TS-PDT was able to induce an antitumor effect on MKN74 cells. This suggested that the difference in TS-PDT efficacy between MKN45 and MKN74 cells is based on the difference in cellular uptake of TS. As expected, uptake of TS by MKN74 cells was lower than that by MKN45 cells. The expression levels of low-density lipoprotein (LDL) receptor in MKN74 cells were lower than those in MKN45 cells. With GW3965 treatment, an agonist/activator of Liver X Receptor, LDL receptor expression was reduced, weakening the TS-PDT effect. Furthermore, as a hydroxymethylglutaryl-Coenzyme A reductase inhibitor, treatment using simvastatin increased LDL receptor expression, leading to enhancement of the TS-PDT effect on MKN74 cells. In conclusion, the difference in LDL receptor expression between the two gastric cell lines could influence TS-PDT efficacy; simvastatin may enhance the antitumor effect of TS-PDT through upregulating the LDL receptor even on PDT-resistant gastric cancer cells.

The aim of this study was to investigate the feasibility of ablative margin (AM) grading by magnetic resonance imaging (MRI) with Gd-EOB-DTPA administered prior to radiofrequency ablation (RFA), and to identify factors for achieving a sufficient AM and predictors for local tumor progression.A total of 124 hepatocellular carcinomas (HCCs) were treated by RFA after Gd-EOB-DTPA administration. MRI and enhanced CT were performed within seven hours and one month after RFA. The AM assessment was categorized using three grades: AM (+), low-intensity area with continuous high-intensity rim; AM zero, low-intensity area with discontinuous high-intensity rim; and AM (-), low-intensity area extends beyond the high-intensity rim. Patients were followed and local tumor progression was observed.AM (+), AM zero, AM (-), and indeterminate were found in 34, 33, 26, and 31 nodules, respectively. The overall agreement rate between MRI and enhanced CT for the diagnosis of AM was 56.8%. The κ coefficient was 0.326 (p0.001), indicating moderate agreement. Multivariate logistic regression analysis showed that a significant factor for the achievement of AM (+) on MRI was no contiguous vessels. The cumulative local tumor progression rates (0% at 1, 2, and 3 years) in 33 AM (+) nodules were significantly lower than those (3.6%, 11.5%, and 18.3% at 1, 2, and 3 years respectively) in 32 AM zero nodules. A multivariate Cox proportional hazards model identified tumor size as an independent predictor for local tumor progression.Gd-EOB-DTPA-MRI enabled an early assessment of RFA effectiveness in the majority ofHCC nodules. Local tumor progression was not detected in AM (+) nodules during the follow-up.

Detection of reticuloendothelial system (RES) cells is essential for the differential diagnosis of splenic hamartoma. Among the imaging techniques using contrast agents phagocytosed by RES cells, contrast-enhanced ultrasonography (CEUS) with Sonazoid is less invasive and less costly than (99m)Tc-labeled colloid scintigraphy. We report a case of non-symptomatic splenic hamartoma in a 40-year-old woman detected as an abdominal tumor by screening ultrasonography. The tumor was 4 cm in diameter, round, slightly hypoechoic, and associated with a cystic lesion. The tumor region was stained on enhanced computed tomography with prolonged enhancement, while the cystic lesion was not. The mass appeared as mainly isointense with partial hyperintensity on T1-weighted and as a mixed hypo- and hyperintense region on T2-weighted magnetic resonance images. (99m)Tc-labeled colloid scintigraphy demonstrated uptake in only the tumor region. CEUS with Sonazoid revealed that the tumor was mainly hypervascular with non-enhanced areas in the early vascular phase, but the hypervascular region appeared also as a hyperechoic area (indicating microbubble phagocytosis) in the post-vascular phase. Thus, CEUS with Sonazoid revealed all three cardinal features of splenic hamartoma: hypervascularity, presence of RES cells, and tissue heterogeneity. Splenectomy and histopathology confirmed the presence of a splenic hamartoma with associated hematoma. CEUS with Sonazoid is a promising new diagnostic tool for splenic hamartoma.

The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P

Diuretics are essential for treating acute decompensated heart failure (ADHF), but the response is inconsistent. This study aimed to clarify whether kidney volume as assessed by ultrasound (US) predicts diuretic resistance in patients with ADHF.We enrolled 29 patients with ADHF and 32 controls. Height-adjusted kidney volume was assessed by US. We divided patients into two groups based on the median value of total daily use of furosemide (intravenous dose plus 0.5 × oral dose of furosemide equivalents) during 3 days from admission.Patients with ADHF had a significantly smaller left kidney volume than did control subjects (27.7 ± 10.0 vs. 32.8 ± 8.8 mL/m,Kidney volume as assessed by US is a useful predictor of diuretic resistance in patients with ADHF.

Aim The purpose of this study was to evaluate the usefulness of contrast-enhanced ultrasound (CEUS) with Sonazoid (perfluorobutane) in patients with liver abscess. Sonazoid is a contrast agent with a low mechanical index and is phagocytosed by Kupffer cells. Methods Twenty-two patients with liver abscess were evaluated with conventional US, real-time CEUS with Sonazoid, and enhanced computed tomography (CT). After 0.5 mL of Sonazoid was administrated i.v., CEUS images in the vascular and post-vascular phases were observed. Results Conventional US showed hypoechoic lesions in 13 (59.1%), isoechoic in four (18.2%), hyperechoic in two (9.1%), mixed echoic in two (9.1%) and undetected in one (4.8%) patient. CEUS showed perilesional enhancement in 19 (86.4%) lesions in the vascular phase and well-defined unenhanced areas in 22 (100%) lesions in the post-vascular phase. CEUS revealed that 18 abscesses were cystic type and three were honeycomb type. Twenty-one abscesses (95.5%) had clearer appearances on CEUS than on conventional US in regard to the extent of necrotic or liquefied lesions seen. We could confirm reduction of the lesions after therapy in 13 (92.9%) of 14 patients followed up by CEUS. Conclusion Most of the liver abscesses showed perilesional enhancement in the vascular phase and unenhanced areas in the post-vascular phase. The appearance of liver abscesses was clearer on CEUS than on conventional US. CEUS with Sonazoid can be a more effective diagnostic and therapeutic tool for liver abscess.

Background & Aims: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. Methods: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index

Aim Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome in the liver that is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The renin–angiotensin system (RAS) appears to play important roles in NASH. Direct renin inhibitors (DRI) reduce plasma renin activity (PRA) through interaction with the active site of the enzyme and reduce the formation of angiotensin-II (AT-II). Therefore, the DRI aliskiren may further suppress the RAS. This study examined the effects of aliskiren on NASH in fatty liver Shionogi (FLS)-ob/ob male mice that are the closest animal model of metabolic syndrome-related NASH in humans. Methods Aliskiren (100 mg/kg per day, aliskiren group) or a placebo (control group) was p.o. administrated to eight FLS-ob/ob mice each for 16 weeks and factors including steatosis, fibrosis, inflammation and oxidative stress were compared between the two groups. Results Amounts of hepatic fibrosis were significantly lower in the aliskiren group than in the control group. Areas of α-smooth muscle actin positivity, the numbers of F4/80 positive, 8-hydroxy-2-deoxyguanosine positive cells and immunohistochemical staining of 4-hydroxynonenal were also significantly decreased in the aliskiren group. Levels of RNA expression for transforming growth factor-β1, connective tissue growth factor and monocyte chemoattractant protein-1 were significantly lower in the aliskiren group. Conclusion Aliskiren attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate and Kupffer cells and by reducing oxidative stress.

Procalcitonin (PCT) is a known diagnostic marker of bacterial infection. There are no previous reports of PCT concerning acute liver failure (ALF). We evaluated the clinical value of serum PCT levels in patients with ALF.Forty-four patients with acute hepatitis (19 men and 25 women; median age, 40 years; range, 20-79 years) were retrospectively enrolled from January 2001 and June 2015. PCT levels were measured by saved serum samples obtained within 3 days after admission. ALF was defined as prothrombin time (PT)40% regardless of hepatic encephalopathy.Serum PCT levels were significantly higher in the patients with ALF (Serum PCT level was significantly higher in patients with ALF.

Vitamin BWe enrolled 90 patients (57 men, 33 women) with chronic viral hepatitis and cirrhosis who admitted to our hospital as a prospective cohort study. Overall, 37 patients had chronic hepatitis and 53 had cirrhosis (Child-Pugh A 33, B 13, and C 7); 57 patients had primary liver cancer. Serum vitamin BMean total serum vitamin BFalsely elevated serum vitamin B

To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse model.Fatty liver shionogi (FLS) FLS-ob/ob mice (male, 12 wk old) received ambrisentan (2.5 mg/kg orally per day; n = 8) or water as a control (n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the liver.In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group (18.0 μg/g ± 6.1 μg/g vs 33.9 μg/g ± 13.5 μg/g liver, respectively, P = 0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, were also significantly lower in the ambrisentan group (0.46% ± 0.18% vs 1.11% ± 0.28%, respectively, P = 0.0003; and 0.12% ± 0.08% vs 0.25% ± 0.11%, respectively, P = 0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were significantly lower by 60% and 45%, respectively, in the ambrisentan group. Inflammation, steatosis, and endothelin-related mRNA expression in the liver were not significantly different between the groups.Ambrisentan attenuated the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.

Aim The fatty liver Shionogi (FLS) mouse develops hereditary fatty liver without obesity. The FLS-ob/ob mouse made by transferring the leptin(ob) gene demonstrates several metabolic disorders and marked fat deposition in the liver. The aim was to evaluate which mouse model, the FLS or FLS-ob/ob, is more useful for non-alcoholic steatohepatitis research. Methods FLS (n = 40) and FLS-ob/ob (n = 40) mice were fed a standard diet for 12, 24, 36 and 48 weeks, and then killed. The degree of fat deposition, oxidative stress, fibrosis and apoptosis were analyzed in the liver. Hepatic mRNA expression of fibrogenic and pro-inflammatory cytokines was measured. Results FLS mice developed hepatic steatosis and slight fibrosis without obesity between 12 and 48 weeks of age. Conversely, FLS-ob/ob mice developed severe steatosis at 12 weeks of age, and steatohepatitis with increased oxidative stress and advanced fibrosis between 24 and 36 weeks of age. At 48 weeks of age, some FLS-ob/ob but not FLS mice, progressed to cirrhosis. Transforming growth factor-β1, connective tissue growth factor and tumor necrosis factor-α mRNA expression levels were greater in FLS-ob/ob than FLS mice between 24 and 48 weeks of age. The number of apoptotic cells in the liver was greater at 12 weeks of age in FLS mice and at 48 weeks of age in FLS-ob/ob mice. Conclusion FLS-ob/ob mice developed more severe steatohepatitis with fibrosis than FLS mice, and had increased oxidative stress and apoptosis. These findings indicate that the FLS-ob/ob mouse is a more useful model for steatohepatitis research.

Aim: An effective therapy for non-alcoholic steatohepatitis has yet to be defined. This study examined the therapeutic effects of ezetimibe, a lipid-lowering medication, on steatosis and hepatic fibrosis in fatty liver Shionogi ob/ob (FLS-ob) mice. Methods: Low-dose (0.2 mg/kg body weight) and high-dose (1.0 mg/kg body weight) of ezetimibe were administered to FLS-ob mice orally for 12 weeks. Results: Administration of ezetimibe significantly and dose-dependently decreased liver cholesterol content. The area of hepatic fibrosis and hepatic hydroxyproline content in the low- and high-dose groups were significantly decreased compared with controls. Areas of α-smooth muscle actin positivity and F4/80 positivity were significantly decreased in a dose-dependent manner. Percentages of 8-hydroxy-2-deoxyguanosine-positive cells in low- and high-dose groups were significantly decreased compared with those in controls, and 8-hydroxy-2-deoxyguanosine DNA content and thiobarbituric acid reactive substances in the high-dose group was also significantly decreased compared to controls. Gene expression levels of procollagen I and transforming growth factor β1 mRNA levels were lower in the low- and high-dose groups than in controls. Tumor necrosis factor-α and sterol regulatory element-binding protein 1c mRNA levels were also lower in the low- and high-dose groups than in controls. Conclusions: Ezetimibe attenuated steatosis and liver fibrosis by reducing oxidative stress and lipid peroxidation and suppressing activated hepatic stellate cells and Kupffer cells.

There is currently no report that has documented hepatocellular carcinoma (HCC) in a case of Cowden syndrome. Here, we present the first reported case of HCC in a 60-year-old female patient with Cowden syndrome. We diagnosed the patient using a pathognomonic criterion of the International Cowden Consortium Operational Diagnostic Criteria and performed genetic analysis. Enhanced computed tomography demonstrated a hypervascular tumor in segment VII of the liver. The patient was diagnosed with Cowden syndrome because her mucocutaneous lesions met the pathognomonic criterion. Mutational analysis confirmed a heterozygous germ line TGT→TAT transition at nucleotide 407 in exon 5 of the phosphatase and tensin homolog detected on the chromosome 10 (PTEN) gene. Needle biopsy showed a poorly differentiated HCC. We also diagnosed non-alcoholic steatohepatitis (NASH) from hepatic histological findings of Mallory's bodies and ballooning cells. PTEN-deficient mice reportedly develop HCC through NASH. This is the first reported case of Cowden syndrome complicated with HCC possibly originating from NASH.

症例は60歳代の女性．平成21年2月頃から口渇・多飲・全身倦怠感が出現し，約3カ月で5 kgの体重減少を認めた．同年5月に空腹時血糖291 mg/dl ，HbA1c 12.6％と異常を認め，糖尿病および末梢神経障害の診断にてインスリン治療およびエパルレスタット150 mg/日と高コレステロール血症に対してロスバスタチンが開始された．7月中旬にAST 246 IU/L，ALT 375 IU/Lと肝機能障害を認めたため被疑薬を中止したが，肝機能障害が悪化し当科入院となった．8月中旬に総ビリルビン2.1 mg/dl ，ALT 1166 IU/Lまで上昇した．肝生検では小葉内にspotty necrosisを散見し，門脈域にはリンパ球を主体に炎症細胞浸潤を認めた．DLSTにてエパルレスタットのみが陽性であった．その後肝機能障害は改善し9月中旬にはほぼ正常となった．エパルレスタットはアルドース還元酵素阻害薬であり，糖尿病性末梢神経障害治療薬として広く用いられている．本症例はエパルレスタットでDLSTが陽性であり本剤による薬物性肝障害と診断した．

The purpose of the present study was to compare the size and configuration of the ablation zones created by SuperSlim and CoAccess electrodes, using various ablation algorithms in ex vivo bovine liver and in clinical cases. In the experimental study, we ablated explanted bovine liver using 2 types of electrodes and 4 ablation algorithms (combinations of incremental power supply, stepwise expansion and additional low-power ablation) and evaluated the ablation area and time. In the clinical study, we compared the ablation volume and the shape of the ablation zone between both electrodes in 23 hepatocellular carcinoma (HCC) cases with the best algorithm (incremental power supply, stepwise expansion and additional low-power ablation) as derived from the experimental study. In the experimental study, the ablation area and time by the CoAccess electrode were significantly greater compared to those by the SuperSlim electrode for the single-step (algorithm 1, p=0.0209 and 0.0325, respectively) and stepwise expansion algorithms (algorithm 2, p=0.0002 and

Background: Kidney size is associated with renal function, however it is not elucidated whether kidney size is a risk for the progression of chronic kidney disease. The aim of this study was to investigate the predictive value of morphological evaluation of kidney size by ultrasonography for the progression of renal dysfunction. Methods: Morphological parameters including kidney length, volume, cortical thickness, and medullary thickness were measured by ultrasonography in 87 patients with chronic kidney disease, and adjusted by body size. Renal functions at baseline and after 2 years were measured and the associations of morphological parameters to decline in renal function over 2 years were analyzed. Results: Height-adjusted cortical thickness was correlated to decline in renal function (r = 0.426, p &lt, 0.001). Height-adjusted cortical thickness could predict renal dysfunction with the area under the curve of 0.786, and height-adjusted cortical thickness of 4.0 mm/cm was a cut off value with a sensitivity of 72.5% and a specificity of 80.0% for the risk of a more than 30% decline in renal function or initiation of dialysis. Conclusions: We provide new insights into the utility of measuring cortical thickness by ultrasonography for predict future renal impairment.

Objective Peribiliary cysts are usually benign, although severe complications and mortality may occur, and they may be confounded with other diseases. No classification delineating their different characteristics exists. Design We performed a systematic review of the frequency and clinical manifestations of peribiliary cysts. Two reviewers identified studies after searching multiple databases on 2 August 2017. Results These cysts were prevalent in cirrhosis (9%). A total of 135 patients were reported in 72 papers with sufficient clinical data (10 countries, 65% from Japan, median age 63 years (range: 4–88), and 80% were males). Symptoms were present in 70%. Misdiagnosis occurred in 40%, and 33% underwent therapeutic misadventures. Cysts were solitary in 10%. Obstructive features and cholangitis were observed in 36% and 12.5%, respectively. Cysts progression was observed in 37.5% over a median of 18 months. Mortality was 24%, mostly due to cirrhosis. A classification framework is proposed, wherein type I includes hepatic, type II extrahepatic and type III mixed hepatic and extrahepatic cysts, each having distinct features. Specifically, type II was more frequent in females, solitary, without cirrhosis, presenting with obstructive jaundice, more difficult to diagnose and required more surgical interventions (all p Conclusion Although rarely studied in the literature, peribiliary cysts were frequent in studies designed to evaluate their prevalence, and were mostly asymptomatic. Inaccurate diagnosis, therapeutic misadventures, cysts progression and cysts-related complications are frequent. In a novel classification framework based on location, extrahepatic peribiliary cysts have distinct characteristics and require a special approach for diagnosis and management.

異性間性交渉を契機に感染したアメーバ性肝膿瘍の2例を経験したため報告する．症例はそれぞれ28歳と29歳の男性で，性風俗店での口肛門性交の経験を有していた．両症例とも慢性の下痢・下血を契機に発症しており，腹部超音波検査，腹部CT検査にて肝S8に膿瘍を認めた．1例は胸腔への穿破を合併していた．膿汁の塗抹検査や糞便からはアメーバ原虫は確認されなかったが，抗アメーバ抗体が陽性であり，メトロニダゾール750 mg-1500 mg/日の内服を開始したところ，速やかに解熱し回復した．海外渡航歴が無くても，20代から60代までの男女で慢性の下痢・下血が認められる場合，性行為感染症としての赤痢アメーバ感染症を念頭において，性交渉歴について詳しく問診し，積極的に内視鏡検査の実施やアメーバ抗体を検査し，特に男性には肝膿瘍の合併が多い為に腹部超音波検査を実施する事が大切である．

This study investigated whether contrast-enhanced sonography can accurately predict the ablated area by radiofrequency ablation using virtual sonography by computed tomography as a gold standard. Thirty-one hepatocellular carcinoma nodules were treated by radiofrequency ablation and then examined. The defect of contrast-enhanced sonography (puncture direction: r=.868, P

症例は54歳，男性．全身倦怠感を主訴に受診し，胆道系酵素の著明な上昇を認めた．肝炎ウイルスマーカー，抗核抗体は陰性であったが，梅毒血清反応が陽性で，陰茎に硬結を認めた．腹腔鏡検査では，肝表面に白色調小結節を認め，肝組織では肉芽腫性炎症を認めた．早期梅毒性肝炎と診断し，amoxicillin（AMPC）内服を開始後，胆道系酵素は速やかに改善した．早期梅毒性肝炎の報告は比較的稀であり，組織学的に肉芽腫性炎症を認める例も少なく，若干の文献的考察を加えて報告する．

Background and Aim This study evaluated the outcomes of antiviral therapy with nucleotide analogs for hepatitis B virus infection-related hepatocellular carcinoma. Methods Thirty patients orally received nucleotide analogs and, as a matched control group, 20 patients who were not treated with nucleotide analogs were selected. We compared changes in liver function, HCC recurrence and survival rate between both groups. Results In the nucleotide analog group, serum albumin, AST and ALT were significantly improved compared with baseline values. The Child-Pugh score was significantly decreased in the nucleotide analog group. Furthermore, of the 36 patients curatively treated with the initial treatment, more patients in the nucleotide analog group improved or maintained their Child-Pugh score at the time of recurrent HCC than in the control group (p=0.023). The cumulative recurrent-free survival rate of HCC did not significantly differ between the two groups; however, the cumulative survival rates of not only curative-treated patients but also all patients in the nucleotide analog group were significantly higher than those of patients in the control group (p=0.047 and p=0.02, respectively). Conclusion The results suggest that nucleotide analog treatment increases the survival rate in patients with HCC by contributing to the improvement of remnant liver function.

This study aimed to compare the tissue stiffness of pancreatic ductal adenocarcinoma (PDAC) with that of pancreatic parenchyma using virtual touch quantification (VTQ). SWV was measured in 34 PDAC lesions and in pancreatic parenchyma of both controls and patients. SWVs in PDAC lesions were significantly higher than in pancreatic parenchyma in both healthy controls and in patients with PDAC. The area under the ROC for diagnosis of PDAC was 0.94 for pancreatic parenchyma in healthy controls, and 0.85 for pancreatic parenchyma in patients with PDAC. VTQ can provide a useful and additional information for diagnosis of PDAC.

Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end-stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors.Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non-CKD group), and 39 end-stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared.Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non-CKD group and in the ESRD group, and no difference was found between the non-CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non-CKD group and the ESRD group, even when ages were matched and depth was adjusted.Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages.

Aims: The kidney becomes atrophic in advanced chronic kidney disease, and renal size and parenchymal volume correlate with renal function. However, alterations in renal parenchymal volume have not been adequately studied in terms of the renal cortex and medulla. We investigated the relationship between the changes in the renal cortex and medulla and renal function. Methods: Renal ultrasound (US) parameters including renal length, parenchymal thickness, cortical thickness and medullary thickness were assessed in 176 subjects, who were categorized into 4 groups based on the estimated glomerular filtration rate (ml/min/1.73 m2): group 1, ≥90; group 2, ≥60 but Results: We found stepwise associations in renal length, cortical thickness and parenchymal thickness with decreased renal function. Medullary thickness showed no changes among groups 1-3. Multiple linear regression analysis including sex, age and renal US parameters showed that only renal length was an independent predictor of renal function. When analyzed in groups 1-3, cortical thickness was the strongest associated parameter. Lower cortical left/right ratio (left cortical thickness/right cortical thickness) showed a stepwise association with a decrease in renal function. Conclusion: Renal length and cortical thickness measured by US were correlated with renal function. In particular, left cortical thickness could help to detect early changes in renal function.

Gastrointestinal stromal tumors (GISTs) are the most common submucosal tumors of the stomach. GISTs are often detected by esophagogastroduodenal endoscopy (EGD). However, the exophytic GIST type is relatively rare and difficult to detect by EGD. Most exophytic GISTs found are large and symptomatic. We present three cases with exophytic GISTs less than 5 cm in diameter detected by transabdominal ultrasound (TUS). All patients were asymptomatic and TUS revealed hypoechoic solid masses 2–3 cm in diameter between the stomach and left lobe of the liver. In contrast, no tumor in the stomach was detected by esophagogastroduodenal endoscopy. Endoscopic ultrasound and enhanced CT showed gastric tumors protruding outward. All three cases underwent partial gastrectomy, and the excised tumor was diagnosed as low-grade GIST. In conclusion, TUS can be a starting point for diagnosing exophytic GISTs of the stomach.

Non-alcoholic steatohepatitis is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The dipeptidyl peptidase‑IV enzyme is important in glucose metabolism, as well as lipid accumulation, extracellular matrix metabolism and immune stimulation. Furthermore, the enzyme activity of dipeptidyl peptidase‑IV is known to be increased in non‑alcoholic steatohepatitis. Therefore, dipeptidyl peptidase‑IV inhibitors are potential therapeutic agents for non‑alcoholic steatohepatitis. The present study assessed the therapeutic effects of sitagliptin, a dipeptidyl peptidase‑IV inhibitor, on non‑alcoholic steatohepatitis using fatty liver Shionogi‑ob/ob male mice. Sitagliptin (2 mg/kg/day; n=10) or placebo (control; n=10) was orally administered to fatty liver Shionogi‑ob/ob mice for 12 weeks, and hepatic steatosis, fibrosis, inflammation and oxidative stress were assessed in comparison with the controls. Sitagliptin administration reduced body weight and blood glucose levels, and improved hepatic fibrosis. It also inhibited the gene expression levels of fatty acid synthase, transforming growth factor‑β1, tissue inhibitor of metalloproteinases‑1, procollagen‑type 1, tumor necrosis factor‑α, monocyte chemoattractant protein‑1 and enhanced peroxisome proliferator activated receptor‑α. Furthermore, a marked attenuation of hepatic stellate cell activation and Kupffer cells was observed in the sitagliptin group. A decrease in oxidative stress and apoptosis was also observed. Sitagliptin attenuated the progression of hepatic fibrosis by improving lipid metabolism, inflammation and oxidative stress in non-alcoholic steatohepatitis.

The purpose of this study was to evaluate the usefulness of contrast-enhanced ultrasound (CEUS) with Sonazoid (perfluorobutane) in patients with liver abscess. Sonazoid is a contrast agent with a low mechanical index and is phagocytosed by Kupffer cells.Twenty-two patients with liver abscess were evaluated with conventional US, real-time CEUS with Sonazoid, and enhanced computed tomography (CT). After 0.5 mL of Sonazoid was administrated i.v., CEUS images in the vascular and post-vascular phases were observed.Conventional US showed hypoechoic lesions in 13 (59.1%), isoechoic in four (18.2%), hyperechoic in two (9.1%), mixed echoic in two (9.1%) and undetected in one (4.8%) patient. CEUS showed perilesional enhancement in 19 (86.4%) lesions in the vascular phase and well-defined unenhanced areas in 22 (100%) lesions in the post-vascular phase. CEUS revealed that 18 abscesses were cystic type and three were honeycomb type. Twenty-one abscesses (95.5%) had clearer appearances on CEUS than on conventional US in regard to the extent of necrotic or liquefied lesions seen. We could confirm reduction of the lesions after therapy in 13 (92.9%) of 14 patients followed up by CEUS.Most of the liver abscesses showed perilesional enhancement in the vascular phase and unenhanced areas in the post-vascular phase. The appearance of liver abscesses was clearer on CEUS than on conventional US. CEUS with Sonazoid can be a more effective diagnostic and therapeutic tool for liver abscess.

A 61-year-old woman with a hepatocellular carcinoma located in the subphrenic region was treated by radiofrequency ablation (RFA) under artificial pleural effusion. During RFA, B-mode ultrasonography showed a swirling high echoic lesion in the artificial pleural effusion. A real-time scan performed using contrast-enhanced ultrasonography (CEUS) revealed a jet-like extravasation of contrast medium and pooling of microbubbles in the pleural cavity, which were confirmed by angiography. CEUS successfully identified the site of bleeding and can be regarded an effective tool for detecting active bleeding in an emergency.

Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome in the liver that is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The renin-angiotensin system (RAS) appears to play important roles in NASH. Direct renin inhibitors (DRI) reduce plasma renin activity (PRA) through interaction with the active site of the enzyme and reduce the formation of angiotensin-II (AT-II). Therefore, the DRI aliskiren may further suppress the RAS. This study examined the effects of aliskiren on NASH in fatty liver Shionogi (FLS)-ob/ob male mice that are the closest animal model of metabolic syndrome-related NASH in humans.Aliskiren (100 mg/kg per day, aliskiren group) or a placebo (control group) was p.o. administrated to eight FLS-ob/ob mice each for 16 weeks and factors including steatosis, fibrosis, inflammation and oxidative stress were compared between the two groups.Amounts of hepatic fibrosis were significantly lower in the aliskiren group than in the control group. Areas of α-smooth muscle actin positivity, the numbers of F4/80 positive, 8-hydroxy-2-deoxyguanosine positive cells and immunohistochemical staining of 4-hydroxynonenal were also significantly decreased in the aliskiren group. Levels of RNA expression for transforming growth factor-β1, connective tissue growth factor and monocyte chemoattractant protein-1 were significantly lower in the aliskiren group.Aliskiren attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate and Kupffer cells and by reducing oxidative stress.