Objective Response by mRECIST Is an Independent Prognostic Factor for Overall Survival in Hepatocellular Carcinoma Treated with Sorafenib in the SILIUS Trial.

Objective: In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and OS in the sorafenib group, in the combination group, and in all patients in the SILIUS trial.

Methods: Association between objective response and OS in patients treated with sorafenib ( = 103) or combination ( = 102) and all patients ( = 205) were analyzed.

Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial.

Background: Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma.

Leucine-rich α2-glycoprotein overexpression in the brain contributes to memory impairment.

We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg.

A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization.

This randomized, double-blind, placebo-controlled trial evaluated dexamethasone efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo). The primary endpoint was complete response, defined as the absence of grade ≥1 fever, anorexia, or nausea/vomiting according to the Common Terminology Criteria for Adverse Events (version 4.

Prognostic Significance of Concurrent Hypovascular and Hypervascular Nodules in Patients with Hepatocellular Carcinoma.

Background: Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC.

Post-progression survival in patients with advanced hepatocellular carcinoma resistant to sorafenib.

Background: Since the approval of sorafenib, no other agent has been proven to show survival benefits in clinical trials involving patients with advanced hepatocellular carcinoma (HCC) resistant to sorafenib. Prognostic factors for survival after tumor progression in sorafenib-treated patients are critical for designing second-line trials.

Methods: To determine the factors affecting the post-progression survival (PPS) after sorafenib treatment, additional analyses were conducted using fixed data obtained from our previous prospective study.

Intensity-Based Assessment of Microbubble-Enhanced Ultrasonography: Phase-Related Diagnostic Ability for Cellular Differentiation of Hepatocellular Carcinoma.

This prospective study aimed to elucidate the effect of phase-related quantitative parameters of contrast-enhanced ultrasound (CEUS) with perflubutane microbubble agent to assess the cellular differentiation of hepatocellular carcinoma (HCC). Intensity was analyzed in 94 lesions (19.4 ± 4.

Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway.

The model animal of renal cell carcinoma (RCC), the Eker rat, has a germline mutation in the tuberous sclerosis 2 (Tsc2) gene. Heterozygous mutants develop RCCs by second hit in the wild-type Tsc2 allele, whereas homozygous mutants are embryonic lethal. In the present study, a new cell differentiation model was developed to study the mechanism of Tsc2 mutation-associated pathogenesis by generating Tsc2-deficient embryonic stem cells (ESCs) from Eker rats.

Sorafenib treatment in Child-Pugh A and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors.

Background: We aimed to evaluate the safety, efficacy and prognostic impact of baseline and early clinical markers in both Child-Pugh A and B patients with advanced hepatocellular carcinoma (HCC).

Methods: We prospectively studied 89 Japanese patients with HCC (Child-Pugh A, n = 59; Child-Pugh B, n = 30) who were started with sorafenib between May 2010 and July 2013.

Results: Frequency of sorafenib-related adverse events was almost similar between Child-Pugh score 5, 6, and 7 patients.

Natural history of large regenerative nodules and dysplastic nodules in liver cirrhosis: 28-year follow-up study.

Background And Aims: Some follow-up studies of large regenerative nodules (LRNs) and dysplastic nodules (DNs) were reported previously. However, the pre-malignant potentiality of LRNs has remained controversial up to now. No LRNs showed malignant transformation in our previous study.

Establishment of Tsc2‑deficient rat embryonic stem cells.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by TSC1 or TSC2 mutations. TSC causes the development of tumors in various organs such as the brain, skin, kidney, lung, and heart. The protein complex TSC1/2 has been reported to have an inhibitory function on mammalian target of rapamycin complex 1 (mTORC1).

Partial splenic embolization with transarterial chemoembolization in patients with hepatocellular carcinoma accompanied by thrombocytopenia.

Background: Thrombocytopenia often makes the introduction of systemic treatment difficult in patients with cirrhosis and hepatocellular carcinoma (HCC). We retrospectively evaluated the long-term effects of partial splenic embolization (PSE) with transarterial chemoembolization (TACE) in patients with HCC patients accompanied by thrombocytopenia.

Patients And Methods: Twenty-one patients with HCC complicated by severe thrombocytopenia (platelet count, <5.

Efficacy of sorafenib in intermediate-stage hepatocellular carcinoma patients refractory to transarterial chemoembolization.

Objective: We compared the benefits of sorafenib therapy with continued transarterial chemoembolization (TACE) in TACE-refractory patients with intermediate-stage hepatocellular carcinoma (HCC).

Methods: This retrospective study reviewed intermediate-stage HCC patients who underwent the first TACE. Patients were defined as TACE-refractory and divided into two cohorts: (1) patients who switched from TACE to sorafenib and (2) those who continued TACE.

Efficacy of transarterial chemoembolization targeting portal vein tumor thrombus in patients with hepatocellular carcinoma.

Aim: We aimed to retrospectively examine the tolerability and efficacy of transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Patients And Methods: Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 4.0.

A phase I/II trial of capecitabine combined with peginterferon α-2a in Patients with sorafenib-refractory advanced hepatocellular carcinoma.

Background: Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon α-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II).

Methods: Capecitabine was administered daily on days 1-14, while peginterferon α-2a was administered on days 1, 8, and 15.

A phase I/II study of S-1 with sorafenib in patients with advanced hepatocellular carcinoma.

Background: Sorafenib is the sole molecular-targeted agent showing a survival benefit in patients with advanced hepatocellular carcinoma (HCC). We evaluated the tolerability and effectiveness of a combination of S-1 with sorafenib in patients with advanced HCC.

Methods: S-1 was administered during days 1-14 and sorafenib was administered every day.

An open-label phase I/II study of tamibarotene in patients with advanced hepatocellular carcinoma.

Aim: Tamibarotene is a synthetic retinoid expected to inhibit tumor-cell proliferation and to induce apoptosis by selective interaction with retinoic acid receptor α/β. We conducted an open-label phase I/II study to determine the maximum tolerated dose (MTD) and recommended dose (RD), and to evaluate the pharmacokinetics, efficacy, and safety profiles for advanced hepatocellular carcinoma (HCC).

Methods: Patients with histologically confirmed, measurable, unresectable HCC of Child-Pugh classification A or B and with no effective systemic or local therapies were eligible.

Successful non-surgical treatment of ruptured pyogenic liver abscess.

A 72-year-old man with a fever and abdominal pain was referred to our hospital. On admission, the patient exhibited the clinical signs of septic shock. Computed tomography revealed a rim-and septal-enhanced lesion in the left lobe of the liver with hemorrhage along the hepatic capsule.

Natural history of postvascular-phase iso-enhanced lesions on the sonogram in chronic liver diseases.

Background And Aim: This study examined the natural history of postvascular-phase iso-enhanced lesions (PIELs) on contrast-enhanced sonograms to determine the potential risk and predictive factors for developing hepatocellular carcinoma (HCC) in chronic liver diseases.

Methods: This prospective study included 87 PIELs on contrast-enhanced sonograms (postvascular-phase: 10 min post-injection of perflubutane microbubbles) in 72 patients with chronic liver diseases (45 males and 27 females; age 65.0 ± 10.

Clinical features and natural history of portal vein thrombosis after radiofrequency ablation for hepatocellular carcinoma in Japan.

Purpose: Little is known about portal vein thrombosis (PVT) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to determine the incidence, background, and natural history of RFA-related PVT.

Methods: This is a retrospective study of 317 patients (219 males and 98 females) with HCC treated by RFA.

Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells.

Metformin has been widely used as an oral drug for diabetes mellitus for approximately 60 years. Interestingly, recent reports showed that metformin exhibited an anti-tumor action in a wide range of malignancies including hepatocellular carcinoma (HCC). In the present study, we investigated its impact on tumor-initiating HCC cells.