Hideki Iwamoto

Kurume University · Department of Internal Medicine

“Angiogenic switch off” is one of the ideal therapeutic concepts in the treatment of cancer. However, the specific molecules which can induce “angiogenic switch off” in tumor have not been identified yet. In this study, we focused on von Hippel-Lindau protein (pVHL) in hepatocellular carcinoma (HCC) and investigated the effects of sulfoquinovosyl-a...

Inhibition of Dll4 (delta-like ligand 4)-Notch signaling-mediated tumor angiogenesis is an attractive approach in cancer therapy. However, inhibition of Dll4-Notch signaling has produced different effects in various tumors, and no biomarkers are available for predicting the anti-Dll4-Notch-associated antitumor activity. We show that human and mouse...

Inflammation and lymphangiogenesis are two cohesively coupled processes that promote tumour growth and invasion. Here we report that TNF-α markedly promotes tumour lymphangiogenesis and lymphatic metastasis. The TNF-α-TNFR1 signalling pathway directly stimulates lymphatic endothelial cell activity through a VEGFR3-independent mechanism. However, VE...

Aliment Pharmacol Ther 2010; 32: 543–550 Background Portal vein tumour thrombosis is a negative prognostic factor for hepatocellular carcinoma (HCC). Aim To assess the efficacy of cisplatin in lipiodol emulsion combined with 5-fluorouracil (5-FU) for patients with HCC and portal vein tumour thrombosis. Methods The study subjects were 51 patients wi...

Metronomic chemotherapy involves frequent, regular administration of cytotoxic drugs at nontoxic doses, usually without prolonged breaks. We investigated the therapeutic efficacies of metronomic S-1, an oral 5-fluorouracil prodrug, and vandetanib, an epidermal growth factor receptor and vascular endothelial growth factor (VEGF) receptor tyrosine ki...

Introduction In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G–CSF)–mobilized autologous peripheral blood (PB)-CD34⁺ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods Patients were ra...

In a 40-year-old woman with no history of liver disease or alcohol consumption, contrast-enhanced abdominal computed tomography of a hepatic lesion demonstrated homogeneous dark staining in the arterial phase and washout in the portal venous phase, causing suspicion about hepatocellular carcinoma (HCC). The contrast-enhanced abdominal magnetic reso...

In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related A...

Introduction The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post-hoc analyses of IMbrave-150 and metanalyses of clinical trials of PD-1/PD-L1 blockers. As a results, it is not clear whether the first-line systemic treatment atezolizu...

Introduction Overweight is a negative prognostic factor in the general population in the long term. However, the role of body mass index (BMI) in the short‐mid term in advanced tumours is unclear. The present analysis investigates the role of BMI weight classes in a large sample of patients affected by HCC and receiving atezolizumab plus bevacizuma...

Background: We previously identified 14 variants of T-cell factor (TCF)-4, a key transcriptional factor in the canonical Wnt signaling pathway, from human liver cancer cell lines (Exp Cell Res 2011). The functional analysis of the variants demonstrated that the SxxSS motif played crucial roles in high tumorigenicity, resistance to hypoxia (PLoS ONE...

INTRODUCTION: Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. METHODS AND MATERIAL: The study population included individuals from both Eastern and Western regions with a confirm...

Current approved anti-angiogenic drugs (AAD) for hepatocellular carcinoma (HCC) inhibit tumor angiogenesis, but affect the hepatic vasculature resulting in adverse effects. Tumor endothelial cells (TECs) differ from normal endothelial cells. In this study, we aimed to detect TEC-specific miRNAs and develop an anti-angiogenic treatment specific for...

Data concerning the use of lenvatinib in very old patients (≥ 80 years) are limited, although the incidence of hepatocellular carcinoma (HCC) in this patient population is constantly increasing. This analysis aimed to evaluate the efficacy and safety of lenvatinib in a large cohort of very old patients (≥ 80 years) with unresectable HCC. The study...

Based on the findings of the IMbrave150 trial, atezolizumab+bevacizumab (atezo+beva) combination therapy is currently used as a first-line treatment for unresectable hepatocellular carcinoma (HCC) in Japan. Although atezo+beva combination therapy has proved to be useful in clinical practice, reports of immune-related adverse events (irAEs) associat...

Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first‐line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance...

Background & aims Combination immunotherapy refers to the use of immune checkpoint inhibitors (ICI) and molecular-targeted agents (MTA), which have recently been approved for the treatment of advanced hepatocellular carcinoma (HCC). Owing to its relatively low antitumor effect (up to 30%), sequential therapy following ICIs treatment is required in...

Introduction Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. Methods In this multicenter international...

This study aimed to evaluate the effect of lenvatinib (LEN) combined with transcatheter intra-arterial therapy (TIT) for advanced-stage hepatocellular carcinoma (HCC) after propensity score matching (PSM). This retrospective study enrolled 115 patients with advanced-stage HCC who received LEN treatment. The patients were categorized into the LEN co...

Background: Immune checkpoint inhibitors (ICIs) are emerging treatments for advanced hepatocellular carcinoma (HCC); however, evidence has shown they may induce hyperprogressive disease via unexplained mechanisms. Methods: In this study, we investigated the possible stimulative effect of ICIs on programmed cell death-ligand 1 (PD-L1)-harboring live...

Background: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of...

Background/purpose of the study In drug-induced liver injury, vascular endothelial progenitor cells, specifically the CD34⁺ cell fractions, have been found to decrease liver fibrosis and promote regeneration. However, it is unclear whether CD34⁺ cell transplantation has anti-fibrogenic effects on NASH, which has been treated effectively with anti-a...

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab. Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients receive...

Background and aims: We aimed to validate the predictive factors for tumor response and the prognostic impact of conversion therapy aimed at cancer- and drug-free states in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing atezolizumab plus bevacizumab (Atez/Bev) therapy. Methods: This retrospective study enrolled 156 patien...

Simple Summary The safety of bevacizumab administration immediately after central venous (CV) port placement, a minor surgery, is still unknown. We investigated whether Bevacizumab is safe when administered early after CV port placement. Bevacizumab therapy after CV port implantation did not affect the frequency of complications, regardless of the...

Background: We previously identified 14 isoforms of T-cell factor (TCF)-4, a key transcriptional factor in the Wnt signaling pathway, from human hepatocellular carcinoma (HCC) cell lines (Exp Cell Res 2011). The TCF-4J and K pair has been characterized based on the presence (K) or absence (J) of a conserved SxxSS motif at the head of exon 9. TCF-4J...

Background: Combination therapy with anti-programmed death-ligand 1 and anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for un-resectable hepatocellular carcinoma (uHCC). We aimed to identify predictive circulating biomarkers for the outcome/response of the combination therapy in uHCC patients. Methods:...

Introduction The best first-line treatment for patients with advanced hepatocellular carcinoma (HCC) and Child–Pugh (CP) class B remains unknown. The aim of the present study was to perform a real-world analysis on a large sample of patients with unresectable HCC with CP B treated with atezolizumab plus bevacizumab Vs Lenvatinib. Methods The study...

Striking advances in systemic therapy for unresectable advanced hepatocellular carcinoma (HCC) have improved the average prognosis of patients with HCC. As a result, the guidelines for the treatment of HCC have changed significantly. However, various issues have emerged in clinical practice. First, there is no established biomarker that can predict...

Background: Atezolizumab plus bevacizumab has recently been approved as a new first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Objective: We performed a real-world study to evaluate the impact of the IMbrave150 trial inclusion criteria on the safety and efficacy of treatment outside of clinical trials....

Background and aim: This study aimed to investigate whether telephone follow-up by clinical pharmacists for unresectable hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN) contributes to improved adherence and treatment duration for LEN. Methods: This retrospective study enrolled 132 patients with HCC who were treated with LEN...

Background: Antiangiogenic tyrosine kinase inhibitors (TKIs) provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma (HCC). However, patients with HCC often develop resistance toward antiangiogenic TKIs, and the underlying mechanisms are not understood. The aim of this study was to determine the mechanisms un...

Recently, treatments for unresectable hepatocellular carcinoma (HCC) have undergone remarkable development. Various systemic chemotherapy drugs have been approved and are recommended by clinical guidelines worldwide. Although systemic treatments are effective and contribute to prolonged patient survival, their effects are unsatisfactory for some sp...

Introduction: The prognostic nutritional index (PNI) is a multiparametric score introduced by Onodera based on the blood levels of lymphocytes and albumin in patients with gastrointestinal neoplasms. Regarding hepatocellular carcinoma (HCC), its prognostic role has been demonstrated in patients treated with sorafenib and lenvatinib. The aim of thi...

For advanced hepatocellular carcinoma, an 80's woman underwent right inguinal reservoir port implantation and hepatic arterial infusion chemotherapy. The patient developed sepsis caused by methicillin-resistant Staphylococcus aureus 40 days after starting treatment. After the reservoir port was removed, an infected pseudoaneurysm developed. Interve...

Purpose: The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting. Methods: Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea). Results: 1312 p...

Background A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. Materials and methods We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib...

Background and aims Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomized controlled trial. We conducted a retrospective multi-center study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario....

Aim: Few studies have reported the efficacy and safety of ramucirumab (RAM) after atezolizumab plus bevacizumab (Atezo/Beva) treatment and the overall associated outcomes. Thus, we aimed to evaluate the therapeutic effects and safety of RAM post-treatment with Atezo/Beva. Methods: This retrospective study enrolled 46 patients with unresectable h...

This study aimed to investigate the clinical characteristics of patients with unresectable hepatocellular carcinoma (HCC), who were eligible for sequential systemic therapy. We evaluated 365 patients with HCC who underwent systemic therapy after 2017. The overall survival (OS) was 13.7 months, 19.2 months, and 35.6 months in the first-line, second-...

Background: Systemic treatments are recommended for advanced hepatocellular carcinoma (HCC) in preserved liver function. However, their effects are unsatisfactory in some tumor conditions, particularly macrovascular invasion (MVI) including major portal vein tumor thrombus (PVTT). We compared the efficacy of hepatic arterial infusion chemotherapy...

Background: /Aims: Lenvatinib is used to treat advanced hepatocellular carcinoma (HCC). Metabolic dysfunction-associated fatty liver disease (MAFLD) is becoming a major etiology of HCC. We aimed to evaluate the impact of MAFLD on the efficacy of lenvatinib. Methods: We enrolled 320 patients with HCC who were treated with lenvatinib. All patients...

This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longe...

Background: The identification of new prognostic factors able to stratify HCC patients candidate to first line therapy is an urgent. In the present work we validated the prognostic value of the LEP index. Matherials and methods: Data of Eastern and Western patients treated with lenvatinib as first-line for BCLC stage B or C HCC were recollected....

Recently, a combined regimen of atezolizumab and bevacizumab (AB) treatment has been approved as a first-line treatment in patients with advanced hepatocellular carcinoma (HCC), contributing to prolonged survival. However, we often encounter cases where treatment must be discontinued due to the occurrence of adverse events. One of these events, whi...

Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective co...

Introduction: In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes. Methods: The study p...

Background/Purpose: Although macrovascular invasion (MVI), particularly major portal vein tumor thrombus (PVTT), is a critical tumor condition in hepatocellular carcinoma (HCC), determining the optimal treatment is an unmet medical need. We aimed to compare the efficacy of hepatic arterial infusion chemotherapy (HAIC) regimens New-FP (fine-powder c...

In 2013 and 2014, the development of microcatheters with balloons for the 4-Fr system and new embolization materials provided various options for transarterial chemoembolization (TACE), expanding the range of treatment strategies. At our hospital, balloon-occluded TACE (B-TACE), conventional TACE (C-TACE), and drug-eluting bead TACE (DEB-TACE) have...

Background and Aims Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) progresses with a highly multicentric occurrence (MO) even after radical hepatectomy. Despite several efforts to clarify the pathogenesis of MO, the underlying molecular mechanism remains elusive. The aim of this study was to evaluate alterations in DNA methylation i...

Hepatocellular carcinoma is one of the leading causes of cancer-related death not only in Japan, but also worldwide. In the advanced stage, hepatic arterial infusion chemotherapy (HAIC) is one of the most commonly used treatment options for liver cancer in Japan and implantation of a catheter system (called a port system) in the body is a treatment...

Simple Summary In patients with hepatitis C virus-related liver disease, direct-acting antivirals (DAAs) suppress the development of hepatocellular carcinoma (HCC). However, it is unclear whether their use after curative HCC treatment suppresses its recurrence in patients with hepatitis C virus-related liver disease. We retrospectively evaluated th...

Fontan-associated liver disease (FALD) caused by long-term systemic venous congestion following the Fontan procedure may eventually lead to hepatocellular carcinoma (HCC). Treatment strategies for HCC due to FALD (FALD-HCC) remain unclear. We herein report a 35-year-old man with FALD-HCC that was well controlled by 3 cycles of continuous infusion o...

Introduction: Although many treatment options are available for patients with advanced hepatocellular carcinoma and Child-Pugh class A, those for patients with Child-Pugh class B remain limited. We aimed to assess the safety and efficacy of hepatic arterial infusion chemotherapy using 5-fluorouracil and cisplatin in patients with advanced hepatoce...

Hepatocellular carcinoma is the most common type of malignant tumor in Asia. Treatment is decided according to the staging system with information on tumor burden and liver function. The Barcelona Clinic Liver Cancer staging system is the most commonly used staging system for the selection of appropriate treatments worldwide, and although it is hig...

Background Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the under...

The aim of the present study was to investigate whether the degree of contrast enhancement on contrast-enhanced (CE)-CT can predict the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). A total of 67 consecutive patients with LEN-treated HCC were retrospectively analysed. In the pretreatment CE-CT, the CT valu...

An indwelling arterial access system via the brachial artery, System-i, has been previously reported. We have modified the technique for the femoral artery approach. This study aimed to evaluate the feasibility and safety of the modified System-i for patients with malignant liver tumors. The modified System-i is an indwelling catheter that provides...

Background and Aims Sequential therapy with molecular-targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first-line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver...

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled...

BACKGROUND Advanced Hepatocarcinoma (HCC) is an important health problem world-wide. Recently, the REFLECT trial demonstrated the non-inferiority of Lenvatinib compared to Sorafenib in I line setting, thus leading to the approval of new first-line standard of care, along with Sorafenib. AIMS AND METHODS With aim to evaluate the optimal choice betw...

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled...

Background & Aims: Intermediate hepatocellular carcinoma (HCC) treatment has become complicated due to the development of various molecular-targeted agents (MTAs). We aimed to determine whether the administration of MTAs in patients with intermediate-stage HCC contributed to the prevention of progression to an advanced stage. Methods: We enrolled...

Macroscopic vascular invasion (MVI) is a poor prognostic factor in hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in MVI-HCC. However, it is not clear which regimens are suitable for HAIC. In this study, we aimed to compare the therapeutic effects between New FP (a fine-powder cisplatin suspen...

Background Invasion beyond inferior vena cava (IVC) to right atrium (RA) is a rare complication in patients with advanced hepatocellular carcinoma (HCC), and results in fatal oncologic emergencies, including pulmonary embolism and right heart failure. Aim As there is no gold standard treatment for unresectable HCC with tumor thrombi involving IVC...

Objective: Although sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus so...

Background & Aim Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in HCC patients treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. Methods We performed a retrospective analysis of 606...

Background The antitumor effect of a drug is considered to be associated with a decrease in tumor blood flow. Aims We investigated whether the efficacy of lenvatinib (LEN) could be accurately assessed by measuring blood flow in hepatocellular carcinoma (HCC) during early treatment stages. Methods and results Blood flow changes and treatment resul...

Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC. Materials and methods: This is a...

Prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is unsatisfactory. Tumor, host, and treatment factors including hepatic arterial infusion chemotherapy (HAIC) are intricately involved in the progression of ICC. We aimed to identify profiles associated with disease control rate (DCR) and the prognosis of patients with unresectable IC...

Severe ascites is an adverse event of ramucirumab (RAM), a second-line treatment for hepatocellular carcinoma (HCC). Ascites can be associated with various factors, including nutritional status and muscle quality. The aim of the present study was to investigate the prevalence and profiles of RAM-associated severe ascites in patients with HCC. This...

Backround: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. M...

Background The immunological inflammatory biomarkers for advanced hepatocellular carcinoma are unclear. We aimed to investigate the association of immunity and inflammatory status with treatment outcomes in patients with advanced hepatocellular carcinoma who received molecular-targeted agents as primary treatment. Patients and methods We enrolled...

PurposeTo examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock.Materials and Methods Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin s...

Simple Summary This study aimed to investigate the efficacy of alternating lenvatinib (LEN) and trans-arterial therapy (AT) in patients with intermediate-stage hepatocellular carcinoma (HCC) after propensity score matching analysis. AT and albumin-bilirubin (ALBI) grade 1 were identified as independent factors for overall survival in patients with...

Hepatocellular carcinoma (HCC) is usually accompanied by chronic liver damage, which sometimes influences the selection of HCC treatment. The Barcelona Clinic Liver Cancer (BCLC) staging system, which was first introduced in 1999, is the most commonly used worldwide. Although the intermediate-stage (BCLC stage B) includes the largest number and het...

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Therefore, identification of biomarkers for early diagnosis of PDAC is crucial. Several studies have reported that exosomes in blood derived from patients with PDAC might contain the tumor-specific microRNAs, but such microRNAs have...

Background: We previously identified a unique Wnt target gene CLAUDIN-2, whose expression level was regulated by isoforms of the Wnt signal transcription factor T-cell factor-4 (Exp Cell Res 2011, Liver Int 2013). CLAUDIN-2 () was highly expressed in combined hepatocellular-cholangiocarcinoma cell lines, and the molecule contributed to high cellula...

Therapeutic strategies for unresectable and advanced hepatocellular carcinoma (HCC) are considerably limited worldwide. We experienced a case with unresectable advanced HCC treated with hepatectomy after down-sizing with hepatic arterial infusion therapy (new FP therapy) and transcatheter arterial chemoembolization (TACE). HCC recurred early after...