Yoshihiro Yoshida

Long-term favorable surgical results of laparoscopic hepatic resection for hepatocellular carcinoma in patients with cirrhosis: a single-center experience over a 10-year period.

BACKGROUND We first performed laparoscopic hepatic resection (Lap-Hx) for hepatocellular carcinoma (HCC) in 1994. Here we review the long-term surgical results of Lap-Hx for HCC in patients with cirrhosis over a 10-year period at a single institution. STUDY DESIGN Between January 2000 and December 2013, 99 patients with cirrhosis underwent open hepatic resection (Open-Hx) and 63 underwent Lap-Hx for primary HCC within the Milan criteria. We compared the operative outcomes and patient survival between the 2 groups. RESULTS There were no significant differences regarding patient background characteristics or tumor-related factors between the 2 groups. The morbidity rate of the Lap-Hx group was significantly lower than that of the Open-Hx group (26% vs 10%; p = 0.0459), and the complication rate of ascites was significantly lower (7% vs 0%; p = 0.0077). The mean duration of hospital stay of the Lap-Hx group was significantly shorter than that of the Open-Hx group (16 vs 10 days; p = 0.0008). There were no significant between-group differences regarding overall or disease-free survival. CONCLUSIONS Laparoscopic-Hx for HCC in patients with cirrhosis is associated with less morbidity and shorter hospital stays, with no compromise in patient survival. It may be time to consider changing the standard operation for primary HCC within the Milan criteria to Lap-Hx in patients with cirrhosis.

Surgical results for recurrent hepatocellular carcinoma after curative hepatectomy: Repeat hepatectomy versus salvage living donor liver transplantation

The aims of this study were to evaluate the efficacy of repeat hepatectomy (Hx) and salvage living donor liver transplantation (LDLT) for recurrent hepatocellular carcinoma (HCC). A retrospective cohort study was performed to analyze the surgical results of repeat Hx and salvage LDLT for patients with recurrent HCC within the Milan criteria from 1989 to 2012. A total of 159 patients were divided into 2 groups: a repeat Hx group (n = 146) and a salvage LDLT group (n = 13). Operative results and patient prognoses were compared between the 2 groups. The operative invasiveness, including the operation time (229.1 ± 97.7 versus 862.9 ± 194.4 minutes; P < 0.0001) and blood loss (596.3 ± 764.9 versus 24,690 ± 59,014.4 g; P < 0.0001), were significantly higher in the salvage LDLT group. The early surgical results, such as morbidity (31% versus 62%; P = 0.0111) and the duration of hospital stay (20 ± 22 versus 35 ± 21 days; P = 0.0180), were significantly worse in the salvage LDLT group. There was no significant difference in the overall survival (OS) rate, but the disease‐free survival rate of the salvage LDLT group was significantly better (P = 0.0002). The OS rate of patients with grade B liver damage in the repeat Hx group was significantly worse (P < 0.0001), and the 5‐year OS rate was quite low, that is, 20% (liver damage A, 77% for the repeat Hx group and 75% for the salvage LDLT group). The prognosis of patients with grade B liver damage after repeat Hx for recurrent HCC is poor, and salvage LDLT would be a potent option for such patients. Liver Transpl 21:961‐968, 2015.

Correlation Between Portal Vein Anatomy and Bile Duct Variation in 407 Living Liver Donors

Our aim was to determine whether variant bile duct (BD) anatomy is associated with portal vein (PV) and/or hepatic artery (HA) anatomy. We examined the associations between BD anatomy and PV and/or HA anatomy in 407 living donor transplantation donors. We also examined whether the right posterior BD (RPBD) course was associated with the PV and/or HA anatomy. Variant PV, HA and BD anatomies were found in 11%, 25% and 25%, respectively, of 407 donors enrolled in this study. The presence of a variant BD was more frequently associated with a variant PV than with a normal PV (61% vs. 20%, p < 0.0001). By contrast, the presence of a variant HA was not associated with a variant BD. A supraportal RPBD was found in 357 donors (88%) and an infraportal RPBD was found in 50 donors (12%). An infraportal RPBD was significantly more common in donors with a variant PV than in donors with a normal PV (30% vs. 10%, p = 0.0004). Variant PV, but not variant HA, anatomies were frequently associated with variant BD anatomy. Additionally, an infraportal RPBD was more common in donors with a variant PV than in donors with a normal PV.

In vitro action of prothoracicotropic hormone on RNA-synthesis in the prothoracic gland of the silkworm, Bombyx mori

Abstract Prothoracic glands of dauer pupae of the silkworm, Bombyx mori , were maintained in organ culture, and in vitro activation of prothoracic glands with prothoracicotropic hormone (PTTH) was studied. The PTTH purified from adult heads of Bombyx mori induced a significant stimulation of uridine incorporation into the RNA of cultured prothoracic glands. This stimulating effect showed an apparent dose-response relationship. On the basis of the inhibitory effect of actinomycin D on this RNA synthesis, it became apparent that the increase in uridine incorporation induced by PTTH action depends on a true stimulation of the RNA synthesis in prothoracic glands. The PTTH exerted no effect on the in vitro uridine incorporation into the RNA of both salivary glands and suboesophageal ganglia of dauer pupae of Bombyx mori . The RNA pattern of prothoracic glands stimulated with the PTTH as judged by polyacrylamide gel electrophoresis demonstrated the predominant increase in the synthesis of ribosomal RNA.

p62 Promotes Amino Acid Sensitivity of mTOR Pathway and Hepatic Differentiation in Adult Liver Stem/Progenitor Cells

Autophagy is a homeostatic process regulating turnover of impaired proteins and organelles, and p62 (sequestosome‐1, SQSTM1) functions as the autophagic receptor in this process. p62 also functions as a hub for intracellular signaling such as that in the mammalian target of rapamycin (mTOR) pathway. Liver stem/progenitor cells have the potential to differentiate to form hepatocytes or cholangiocytes. In this study, we examined effects of autophagy, p62, and associated signaling on hepatic differentiation. Adult stem/progenitor cells were isolated from the liver of mice with chemically induced liver injury. Effects of autophagy, p62, and related signaling pathways on hepatic differentiation were investigated by silencing the genes for autophagy protein 5 (ATG5) and/or SQSTM1/p62 using small interfering RNAs. Hepatic differentiation was assessed based on increased albumin and hepatocyte nuclear factor 4α, as hepatocyte markers, and decreased cytokeratin 19 and SOX9, as stem/progenitor cell markers. These markers were measured using quantitative RT‐PCR, immunofluorescence, and Western blotting. ATG5 silencing decreased active LC3 and increased p62, indicating inhibition of autophagy. Inhibition of autophagy promoted hepatic differentiation in the stem/progenitor cells. Conversely, SQSTM1/p62 silencing impaired hepatic differentiation. A suggested mechanism for p62‐dependent hepatic differentiation in our study was activation of the mTOR pathway by amino acids. Amino acid activation of mTOR signaling was enhanced by ATG5 silencing and suppressed by SQSTM1/p62 silencing. Our findings indicated that promoting amino acid sensitivity of the mTOR pathway is dependent on p62 accumulated by inhibition of autophagy and that this process plays an important role in the hepatic differentiation of stem/progenitor cells. J. Cell. Physiol. 232: 2112–2124, 2017.

Graft selection strategy in adult‐to‐adult living donor liver transplantation: When both hemiliver grafts meet volumetric criteria

To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipients body surface area (BSA), Model for End‐Stage Liver Disease (MELD) score, and the donors age were higher in the RL group. The donors BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6‐month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six‐month and 12‐month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914–922 2016 AASLD

Prognostic Impact of Des-γ-carboxyl Prothrombin in Living-Donor Liver Transplantation for Recurrent Hepatocellular Carcinoma

BACKGROUND Although the Milan criteria are widely accepted for liver transplantation (LT) in patients for hepatocellular carcinoma (HCC), they have not been fully evaluated for salvage LT in patients with recurrent HCC. We have previously reported outcomes of living-donor LT (LDLT) for HCC and identified 2 risk factors affecting recurrence-free survival (RFS): tumor size >5 cm and des-γ-carboxyl prothrombin (DCP) concentration >300 mAU/mL (Kyushu University criteria). This study was designed to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. METHODS Outcomes in 114 patients who underwent LDLT for recurrent HCC were analyzed retrospectively. RFS rates after LDLT were calculated, and risk factors for tumor recurrence were identified. RESULTS The 1-, 3-, and 5-year RFS rates after LDLT were 90.6%, 80.4%, and 78.8%, respectively. Univariate analysis showed that tumor recurrence was associated with alpha-fetoprotein concentration ≥ 300 ng/mL, DCP concentration ≥ 300 mAU/mL, tumor number ≥ 4, tumor size ≥ 5 cm, transarterial chemotherapy before LDLT, duration of last treatment of HCC to LDLT <3 months, bilobar distribution, exceeding Milan criteria, exceeding Kyushu University criteria, poor differentiation, and histologic vascular invasion. Multivariate analysis showed that DCP ≥ 300 mAU/mL (P = .03) and duration from last treatment to LDLT <3 months (P = .01) were independent predictors of RFS. CONCLUSIONS DCP concentration and time between last treatment and LDLT are prognostic of RFS in patients undergoing LDLT for HCC.

MicroRNA-125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection

Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection.

Liver transplantation for cryptogenic liver failure caused by diffuse hepatic angiosarcoma: case report

BackgroundPrimary hepatic angiosarcoma is a non-epithelial malignancy derived from sinusoidal endothelial cells, accounting for approximately 1.8% of primary hepatic malignancies. Diagnosis of primary hepatic angiosarcoma is complicated by difficulties in the qualitative radiological assessment of these tumors. Prognosis is very poor due to local recurrence and distant metastasis after liver resection or liver transplantation (LT).Case presentationThis case report describes two patients with primary hepatic angiosarcoma who were diagnosed by histopathological examination of the explanted liver after LT. One patient had undergone living donor LT, and the other had undergone deceased donor LT. Neither showed evidence of malignancy on the pre-operative imaging tests.ConclusionsHepatic angiosarcoma has a very high relapse rate after LT. Pre-transplant liver biopsy may be necessary to distinguish diffuse hepatic angiosarcoma from tumors of other origin in patients with cryptogenic liver failure.

rs8099917 and Viral Genotyping as Indications for Living Donor Liver Transplantation for Hepatitis C: A Case Report

INTRODUCTION Appropriate antiviral treatment is essential for living donor liver transplantation (LDLT) to be effective for treating hepatitis C. However, it has never been reported that pre-LDLT genetic analyses of both host and virus, with prediction of the outcome of post-LDLT antiviral treatment, indicated LDLT for a borderline case. CASE REPORT We have reported the case of a 68-year-old woman with liver cirrhosis caused by genotype 1b hepatitis C, a history of ruptured esophageal varices, and adequately controlled minor ascites. Her liver function was classified as Child-Pugh grade B. The donor was a 42-year-old woman with an estimated left lobe graft volume (GV) of 33.8% based on the standard liver volume of the recipient. Molecular analyses used to confirm the indication of LDLT for this combination revealed the following: The rs8099917 genotype was T/T in the donor and recipient, the HCV core protein was double wild type, there were no mutations in the interferon sensitivity-determining region, and 8 mutations were found in the interferon/ribavirin resistance-determining region. LDLT was performed because very high sensitivity to interferon treatment was predicted. DISCUSSION Six months after LDLT and uneventful post-LDLT courses, pegylated interferon-α2a and ribavirin were administered under immunosuppression with cyclosporine and mycophenolate mofetil. This regimen was continued for 48 weeks, resulting in a viral response at 10 weeks and a sustained viral response, as predicted. CONCLUSIONS We have reported the usefulness of molecular analyses of host and viral factors for indicating LDLT to treat hepatitis C in a borderline case.