Tadahisa Inoue

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein levels and liver fibrosis: A meta-analysis

A reliable, non‐invasive biomarker for diagnosis of liver fibrosis in chronic liver disease patients is needed. The aim of this study was to assess by meta‐analysis the efficacy of measuring serum levels of Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein (WFA+‐M2BP), a novel and promising biomarker, for staging liver fibrosis and predicting the development of hepatocellular carcinoma and overall survival.

Ezetimibe for the treatment of non-alcoholic fatty liver disease: A meta-analysis.

Several studies on the efficacy of ezetimibe, a potent inhibitor of cholesterol absorption, in treating non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) have been published; however, the results are inconsistent. We undertook a meta‐analysis to evaluate the efficacy of ezetimibe in treating NAFLD and NASH.

Ezetimibe for the treatment of nonalcoholic fatty liver disease: a meta‐analysis

Several studies on the efficacy of ezetimibe, a potent inhibitor of cholesterol absorption, in treating non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) have been published; however, the results are inconsistent. We undertook a meta‐analysis to evaluate the efficacy of ezetimibe in treating NAFLD and NASH.

Reintervention for stent occlusion after bilateral self-expandable metallic stent placement for malignant hilar biliary obstruction

Endoscopic reintervention for stent occlusions following bilateral self‐expandable metallic stent (SEMS) placement for malignant hilar biliary obstruction (MHBO) is challenging, and time to recurrent biliary obstruction (RBO) of the revisionary stent remains unclear. We aimed to clarify a suitable reintervention method for stent occlusions following bilateral SEMS placement for MHBO.

Long-term outcomes of endoscopic gallbladder stenting in high-risk surgical patients with calculous cholecystitis (with videos)

BACKGROUND AND AIMS Recently, endoscopic gallbladder stenting (EGBS) has been performed to prevent recurrences in high-risk surgical patients with cholecystitis. However, evidence regarding the long-term outcomes of EGBS is sparse. We investigated the cholecystitis recurrence rate in high-risk surgical patients with acute calculous cholecystitis and compared the cholecystitis recurrence rates in patients in whom EGBS was performed with those in patients who were observed after percutaneous drainage. METHODS We studied 64 consecutive high-risk surgical patients with acute calculous cholecystitis who required gallbladder decompression between 2007 and 2014. We divided the patient cohort into patients who underwent observation after percutaneous drainage between 2007 and 2011 (OAPD group) and those who underwent EGBS between 2012 and 2014 (EGBS group), and we compared the groups. RESULTS The technical success rate of EGBS was 82.9% based on the intention-to-treat analysis. The cholecystitis recurrence rates were 17.2% in the OAPD group and 0% in the EGBS group, a difference that was significant (P = .043). There was also a significant difference between the groups with respect to the time to recurrent cholecystitis, which was determined by using Kaplan-Meier analysis (P = .015). The overall biliary event rates were 24.1% in the OAPD group and 9.1% in the EGBS group, and no significant difference was noted (P = .207). CONCLUSION EGBS reduced the recurrence of cholecystitis in high-risk surgical patients with calculous cholecystitis. However, stent-related adverse events may occur, and modifications are necessary to reduce these.

Local administration of amphotericin B and percutaneous endoscopic necrosectomy for refractory fungal-infected walled-off necrosis: a case report and literature review.

AbstractWalled-off necrosis (WON) caused by fungal infection is very rare, and its treatment is more difficult than that of bacterial infection. We present the first case of a patient with refractory fungal-infected WON treated with percutaneous endoscopic necrosectomy and local administration of amphotericin B.A Japanese man in his 30s was hospitalized with severe necrotizing pancreatitis and multiple organ failure. Computed tomography imaging of the abdomen 1 month after the onset of pancreatitis revealed infected WON. Percutaneous drainage revealed purulent necrotic fluid, and culture of the fluid revealed the presence of Candida albicans and C glabrata. WON was treated by percutaneous endoscopic necrosectomy and local administration of amphotericin B. Consequently, the patients condition improved, and Candida species were not detected in subsequent cultures.The combination of endoscopic necrosectomy with local administration of amphotericin B may be effective in treating refractory fungal-infected WON.

Δ40p53α suppresses tumor cell proliferation and induces cellular senescence in hepatocellular carcinoma cells.

ABSTRACT Splice variants of certain genes impact on genetic biodiversity in mammals. The tumor suppressor TP53 gene (encoding p53) plays an important role in the regulation of tumorigenesis in hepatocellular carcinoma (HCC). Δ40p53α is a naturally occurring p53 isoform that lacks the N-terminal transactivation domain, yet little is known about the role of Δ40p53α in the development of HCC. Here, we first report on the role of Δ40p53α in HCC cell lines. In the TP53+/Δ40 cell clones, clonogenic activity and cell survival dramatically decreased, whereas the percentage of senescence-associated β-galactosidase (SA-β-gal)-positive cells and p21 (also known as WAF1, CIP1 and CDKN1A) expression significantly increased. These observations were clearly attenuated in the TP53+/Δ40 cell clones after Δ40p53α knockdown. In addition, exogenous Δ40p53 expression significantly suppressed cell growth in HCC cells with wild-type TP53, and in those that were mutant or null for TP53. Notably, Δ40p53α-induced tumor suppressor activity was markedly attenuated in cells expressing the hot-spot mutant Δ40p53α-R175H, which lacks the transcription factor activity of p53. Moreover, Δ40p53α expression was associated with increased full-length p53 protein expression. These findings enhance the understanding of the molecular pathogenesis of HCC and show that Δ40p53α acts as an important tumor suppressor in HCC cells. Summary: Δ40p53 exerts tumor suppressor activity that is associated with upregulation of p53-target gene expression and induces senescence in hepatocellular carcinoma cell lines.

Assessment of Factors Affecting the Usefulness and Diagnostic Yield of Core Biopsy Needles with a Side Hole in Endoscopic Ultrasound-Guided Fine-Needle Aspiration

Background/Aims A barbed puncture needle with a side hole was recently developed to improve sample quality and quantity in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). In this study, we retrospectively assessed the usefulness of this puncture needle. Methods Factors affecting diagnostic yield, safety, and diagnostic accuracy were investigated in 76 patients who consecutively underwent EUS-FNA for neoplastic lesions at our hospital between January and December 2013. Results The procedure was successful in all cases; the rates of sample collection and determination of the correct diagnosis were 92.1% and 89.5%, respectively. The mean number of needle passes required for diagnosis was 1.1. Complications included mild intraluminal bleeding in two patients (2.6%). Multivariate analysis revealed that lesion size (≤20 mm) was significantly associated with a decreased chance of determining the correct diagnosis. Conclusions Core biopsy needles with a side hole are safe and provide a satisfactory diagnostic yield. However, the side hole may potentially reduce the rate of making the correct diagnosis in small lesions.

Feasibility of the placement of a novel 6-mm diameter threaded fully covered self-expandable metal stent for malignant hilar biliary obstructions (with videos)

BACKGROUND AND AIMS Uncovered self-expandable metal stents (USEMSs) are used to treat unresectable malignant hilar biliary obstructions (MHBOs). However, ingrowth is not prevented, and reintervention is often troublesome. A novel 6-mm threaded fully covered self-expandable metal stent (T-FCSEMS) is available that may mitigate these issues. We aimed to clarify the safety and efficacy of T-FCSEMS placement for MHBO. METHODS Thirty patients underwent T-FCSEMS placements for MHBOs between 2014 and 2015. T-FCSEMSs were used for initial stenting in 17 patients (initial group) and for reinterventions for USEMS occlusions caused by ingrowth in 13 patients (reintervention group). The technical success rates, times to recurrent biliary obstruction, and the reintervention success rates were evaluated. RESULTS The technical success rates were 94% (16/17) and 92% (12/13) in the initial group and reintervention group, respectively. Intrahepatic bile duct occlusions caused liver abscesses 8 days and 22 days after T-FCSEMS placements in 2 cases (7%) in the initial group, in which T-FCSEMSs were placed across the intrahepatic bile duct bifurcation. The median times to recurrent biliary obstruction were 210 days in the initial group after bilateral placement and 112 days and 152 days in the reintervention group after bilateral and unilateral placements, respectively. During reintervention, T-FCSEMS removal was successful in all patients in whom it was attempted, and the success rate of endoscopic reintervention was 100% in both groups. CONCLUSIONS T-FCSEMS placement is a promising option for both initial stenting and reintervention for MHBO. However, we should consider the possibility of intrahepatic bile duct occlusion.

Conophylline inhibits non-alcoholic steatohepatitis in mice

Conophylline (CnP), a vinca alkaloid extracted from the leaves of the tropical plant Ervatamia microphylla, attenuates hepatic fibrosis in mice. However, little is known about whether CnP inhibits steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) in mice. A methionine-choline-deficient (MCD) diet was administered to male db/db mice as a NASH model, and CnP (1 μg/kg/d) was co-administered. Eight weeks after the commencement of the MCD diet, hepatic steatosis, inflammation, and fibrosis, and hepatic fat metabolism-, inflammation-, and fibrosis-related markers were examined. Feeding on an MCD for 8 weeks induced hepatic steatosis, inflammation, and fibrosis. CnP significantly attenuated the MCD-induced increases in hepatic steatosis, as well as hepatic inflammation and fibrosis. The MCD diet increased hepatic transforming growth factor-β (TGF-β) mRNA levels, which are correlated with hepatic steatosis, inflammation, and fibrosis. The diet also attenuated acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1 (CPT1) mRNA levels, which are involved in β-oxidation. The putative mechanism of the CnP effect involves reduced hepatic TGF-β mRNA levels, and increased mRNA levels of hepatic peroxisome proliferator-activated receptor (PPAR) α and its target genes ACOX1 and CPT1. The results of this study indicate that CnP inhibits steatohepatitis, possibly through the inhibition of hepatic TGF-β mRNA levels, and induces an increase in PPARα mRNA levels, resulting in the attenuation of hepatic steatosis, inflammation, and fibrosis in mice. CnP might accordingly be a suitable therapeutic option for NASH.