Michihito Asanoma

Specific miRNA expression profiles of non‐tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma

It is reasonable to investigate non‐tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific miRNA expression profiles associated with a risk for multicentric (MC) HCC.

Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutinin‐reactive fraction of alpha‐fetoprotein

Aim:  Lens culinaris agglutinin A‐reactive fraction of α‐fetoprotein (AFP‐L3) status has been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). In this study, we evaluated the clinical usefulness of measuring preoperative AFP‐L3 to predict the recurrence and prognosis of HCC after curative hepatectomy.

ALTA injection sclerosing therapy:non-excisional treatment of internal hemorrhoids.

BACKGROUND/AIMS Aluminum potassium sulfate and tannic acid (ALTA) is a new sclerosing therapy for internal hemorrhoids. This injection therapy is a four-step direct injection sclerosing procedure intended to shrink and harden internal hemorrhoids to eliminate hemorrhoidal prolapse and bleeding. The aim of this study was to assess the short term efficacy of this treatment. METHODOLOGY The procedure was conducted using a four-step injection process under perianal local anesthesia. The entry point for the four-step injection of ALTA is the submucosa of the superior pole, the submucosa in the central part, the mucous lamina propria in the central part and the submucosa at the inferior pole of hemorrhoid. RESULTS From January 2009 to March 2010, we performed the ALTA sclerosing therapy on 28 patients (14 men and 14 women; mean age, 64.6 years), including 5 second-degree, 16 third-degree and 7 fourth-degree hemorrhoids. There were 6 postoperative complications (2 cases of low grade fever, 2 anal pains, 1 necrosis at injection site and 1 perianal dermatitis). All symptoms of prolapse or bleeding disappeared after 29 postoperative days. There were 3 recurrent cases (10.7%). CONCLUSIONS ALTA sclerosing therapy is a useful and less invasive treatment for internal hemorrhoids.

Visualization and hypervascularization of the haemorrhoidal plexus in vivo using power Doppler imaging transanal ultrasonography and three-dimensional power Doppler angiography

The purpose of this study was to demonstrate the distribution of haemorrhoidal arteries and the relationship between vascularity and growth of haemorrhoids.

Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells

Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4+ T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling in T cells to EAU pathogenesis because Notch signaling regulates various aspects of CD4+ T cell functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj-deficient mice correlated with low levels of IL-22 production from CD4+ T cells, although IRBP-specific CD4+ T cell proliferation and Th17 differentiation were unaffected. Administration of recombinant IL-22 during the late phase, but not the early phase, of EAU increased EAU clinical scores in T cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP with a γ-secretase inhibitor (GSI) suppressed EAU progression, even when GSI was administered as late as 13 days after IRBP immunization. Our data demonstrate that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role in the late phase of EAU, and suggest that Notch blockade might be a useful therapeutic approach for treating EAU.

Cytokine expression in spleen affects progression of liver cirrhosis through liver–spleen cross‐talk

It is unclear whether the spleen affects the progression of liver cirrhosis (LC) through “liver–spleen cross‐talk”. Transforming growth factor‐β1 (TGF‐β1) is reported to be the most potent cytokine of liver fibrosis, and interleukin‐6 (IL‐6) is an important factor of liver regeneration. In this study, we investigated the expression of cytokines in the spleens of LC patients in order to attempt to prove the existence of liver–spleen cross‐talk.

Beneficial effects of enteral nutrition containing with hydrolyzed whey peptide on warm ischemia/reperfusion injury in the rat liver

This study examined the efficacy of enteral nutrition containing hydrolyzed whey peptide (HWP) on warm ischemia/reperfusion (I/R) injury in the rat liver.

Clinical role of Foxp3+ regulatory T cell in Living donor related liver transplantation for prediction of life-threatening complications.

PURPOSES It is no doubt that regulatory T cells (Foxp3(+)CD4(+)CD25(+)T cells: Treg) play important roles in transplant immunity. We investigated the significance of Treg expression in acute stage of living donorrelated liver transplantation (LDLT) for the possibility of the sensitive marker for immunological state and homeostatic stress after liver transplantation. METHODS Peripheral blood was drawn from 5 recipients of LDLT preoperatively and on post operative 1, 4, 7, and 14 days. The peripheral blood mononuclear cells (PBMCs) were stained with CD4, CD25, Foxp3, and were analyzed with FACScan. This data was compared with clinical output of LDLT. RESULT The populations of Treg were significantly decreased in all patients on day 1 after LDLT and significantly increased in patients who had early postoperative complications compared with patients who had no complications. CONCLUSIONS The population of Treg in peripheral blood may reflect the surgical stress such as life-threatening complications after LDLT.

Usefulness of peripheral regulatory T-cells induced by Notch signaling pathway-driven indoleamine 2, 3-dioxygenase positive dendritic cell as a biomarker for the decision for IPMN surgical indications.

181 Background: This study was performed to elucidate the expression of the Notch signaling pathway regulated by dendetric cell (DC) and their correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs) as a new biomarker for surgical indications. We already reported that regulatory T cells (Tregs) play an important role in tumor immunity (Pancreas 2006, ASCO-GI 2009), however, the whole mechanism of control of peripheral Tregs remains unclear. It is reported that Indoleamine 2, 3-dioxygenase (IDO) induces active Treg from naive CD4+Tcells through dendritic cells. Otherwise, we also reported that the Notch signaling pathway is involved in tumor growth and DC function (JI 2010). Thus we focused that Indoleamine 2,3-deoxygenase(IDO)-Treg axis driven by Notch signaling in IPMNs. Methods: Peripheral blood samples and resected specimens from 20 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemical...

The impact of pegylated-interferon α-2b on partial and massive hepatectomy model in rats.

BACKGROUND/AIMS The impact of pegylated-interferon (PEG-IFN) α-2b on liver regeneration has not yet been elucidated. METHODOLOGY Rats were divided into the following four groups: 70% hepatectomy (Hx); 70% Hx+PEG-IFN; 90% Hx and 90% Hx+PEG-IFN group (n=6 each). Rats were pretreated with subcutaneous of PEGIFN α-2b (1.5 μg/kg) administration 24 hours before Hx. Samples were taken 24, 48 and 72 hours after Hx and the following parameters were investigated: blood analysis (AST, WBC, PLT); liver weight to body weight ratio (Lw/Bw ratio); survival and PCNA labeling index (LI). RESULTS In the 90% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group in blood analysis; AST after postoperative 24 hours (2511 vs. 2466 IU/L), WBC (1200 vs. 1290) and PLT (107 vs. 111 x 10⁴/mm³), in Lw/Bw ratio at postoperative 0, 24, 48, 72 hours, respectively (0.38, 0.60, 1.14, 1.69 vs. 0.37, 0.64, 1.12, 1.63), in postoperative survival (40% vs. 45%), and in PCNA LI at postoperative 0, 24, 48, 72 hours, respectively (10.4%, 16.8%, 14.6%, 12.8% vs. 10.0%, 17.1%, 15.6%, 13.7%). In the 70% Hx model, there was no significant difference between the Hx+PEG-IFN group and the Hx alone group for all parameters. CONCLUSIONS Our data demonstrated that PEG-IFN α-2b did not affect liver regeneration and the early use of PEG-IFN α-2b would cause no problems after liver transplantation using partial grafts including living donor liver transplantation.