Reappraisal of serum retinol-binding protein as a surrogate marker for retinol and discovery of a novel retinol estimation formula.

Background & Aims: Serum retinol (ROH) is commonly used for population level assessment of vitamin A status. High-performance liquid chromatography (HPLC) is considered most accurate method for measuring ROH. However, with the technical difficulty of using HPLC for routine assays, serum retinol-binding protein (RBP) measured by immunological assays is expected to be a surrogate marker for ROH, with reports of a close correlation between serum RBP and ROH.

3D image scanning of gravel soil using in-situ X-ray computed tomography.

A typical ground investigation for characterizing geotechnical properties of soil requires sampling soils to test in a laboratory. Laboratory X-ray computed tomography (CT) has been used to non-destructively observe soils and characterize their properties using image processing, numerical analysis, or three-dimensional (3D) printing techniques based on scanned images; however, if it becomes possible to scan the soils in the ground, it may enable the characterization without sampling them. In this study, an in-situ X-ray CT scanning system comprising a drilling machine with an integrated CT scanner was developed.

Significance of a preoperative tumor marker gradient for predicting microvascular invasion in cases of hepatocellular carcinoma.

Although vascular invasion is an important factor in the progression and treatment of hepatocellular carcinoma (HCC), it remains difficult to determine, on the basis of preoperative imaging alone, whether vascular invasion, especially microvascular invasion, has occurred. The current retrospective study enrolled 292 patients who, between 2004 and 2014, underwent curative hepatectomy as an initial treatment for HCC. The patients were divided between those with (n=70) and those without (n=222) microvascular invasion.

Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs.

Pancreatic neuroendocrine tumors (PanNETs) have considerable malignant potential. Frequent somatic mutations and loss of DAXX protein expression have been found in PanNETs. DAXX is known as a transcriptional repressor; however, molecular functions underlying DAXX loss remain unclear in PanNETs.

Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors.

Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC); however, tumor-specific biomarkers still remain unclear. We performed cross-species analysis to compare gene signatures of HCC from human patients and melanocortin 4 receptor-knockout mice, which develop HCC with obesity, insulin resistance, and dyslipidemia. Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and melanocortin 4 receptor-knockout mice into two distinct subgroups, one of which included mouse HCC and was causatively associated with metabolic risk factors.

Effects of acute kidney injury after liver resection on long-term outcomes.

Background: To investigate the effects of acute kidney injury (AKI) after liver resection on the long-term outcome, including mortality and renal dysfunction after hospital discharge.

Methods: We conducted a historical cohort study of patients who underwent liver resection for hepatocellular carcinoma with sevoflurane anesthesia between January 2004 and October 2011, survived the hospital stay, and were followed for at least 3 years or died within 3 years after hospital discharge. AKI was diagnosed based on the Acute Kidney Injury Network classification within 72 hours postoperatively.

Surgical pitfalls of jejunal vein anatomy in pancreaticoduodenectomy.

Background: Pancreaticoduodenectomy (PD) is the standard surgical procedure for treating pancreatic head cancers. Considerable knowledge of proximal jejunal and pancreatic vein anatomy is a prerequisite for performing PD surgery safely, yet there appear to be no detailed descriptions of first and second jejunal vein (J1V, J2V) anatomy available in the literature.

Study Design: Adults with hepatobiliary-pancreatic disease underwent multidetector-row computed tomography with intravenous contrast (n = 155), and SYNAPSE 3D (Fujifilm Medical, Tokyo, Japan) was used to generate 3D-CT images.

Acquired Resistance with Epigenetic Alterations Under Long-Term Antiangiogenic Therapy for Hepatocellular Carcinoma.

Antiangiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma; however, they finally relapse and progress, resulting in poor prognosis. We here established drug-tolerant subclones of human hepatocellular carcinoma cells by long-term treatment with VEGF receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin β 4 (Tβ4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones.

[Practice of Disaster Medicine and Clinical Laboratory Tests].

In recent years, Japan has been hit by natural disasters such as earthquakes, typhoons, torrential rains, and heavy snow every year without exception. When such disasters occur, human lives are put at risk. These emergency situations are an unrivaled sphere of activity for physicians, nurses, and emergency life-saving technicians, and the need for these workers becomes the focus of society; however, for advanced rescue in the acute phase of disasters and to prevent disease onset in the chronic phase, clinical laboratory tests are expected to play a major role in developing more accurate diagnoses and promoting prompt medical care.

ARID2 modulates DNA damage response in human hepatocellular carcinoma cells.

Background & Aims: Recent genomic studies have identified frequent mutations of AT-rich interactive domain 2 (ARID2) in hepatocellular carcinoma (HCC), but it is not still understood how ARID2 exhibits tumor suppressor activities.

Methods: We established the ARID2 knockout human HCC cell lines by using CRISPR/Cas9 system, and investigated the gene expression profiles and biological functions.

Results: Bioinformatic analysis indicated that UV-response genes were negatively regulated in the ARID2 knockout cells, and they were sensitized to UV irradiation.

Preoperative direct bilirubin to prothrombin time ratio index to prevent liver failure after minor hepatectomy.

Background: The most reliable index to predict the safety of hepatectomy for patients with poor liver function remains unknown. We aimed to construct a novel preoperative index to predict early liver failure (ELF) and mortality due to recurrence-free liver failure (MLF) after hepatectomy.

Methods: Between 2000 and 2012, 385 consecutive patients with hepatocellular carcinoma undergoing curative minor hepatectomy were divided into two sequential cohorts: training set (n = 143) and validation set (n = 242), and observed until 2015.

Clinical application of the biomarkers for the selection of adjuvant chemotherapy in pancreatic ductal adenocarcinoma.

Background: For the establishment of personalized therapy, we investigated biomarkers that can contribute to the selection of adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC).

Methods: Between 2005 and 2014, of 141 consecutive patients with PDAC who underwent R0 or R1 resection, 61 patients given gemcitabine and 31 patients given S-1 as adjuvant therapy were enrolled. We evaluated the correlation between treatment outcomes and the expressions of intratumoral human antigen R (HuR), human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD).

Proteasome activity is required for the initiation of precancerous pancreatic lesions.

Proteasome activity is significantly increased in advanced cancers, but its role in cancer initiation is not clear, due to difficulties in monitoring this process in vivo. We established a line of transgenic mice that carried the ZsGreen-degron(ODC) (Gdeg) proteasome reporter to monitor the proteasome activity. In combination with Pdx-1-Cre;LSL-Kras(G12D) model, proteasome activity was investigated in the initiation of precancerous pancreatic lesions (PanINs).

Macroscopic morphology for estimation of malignant potential in pancreatic neuroendocrine neoplasm.

Purpose: Pancreatic neuroendocrine neoplasm (Pan-NEN) representing approximately 1.3 % of pancreatic malignancy cases in incidence has been a so rare disease that it remains major problem to analyze the malignant potential. The aim of this study was to verify whether the macroscopic morphology of Pan-NEN, a novel pathological classification, contributes to malignant potential.

Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis.

Patients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs), but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs.

Expression of connective tissue growth factor in the livers of non-viral hepatocellular carcinoma patients with metabolic risk factors.

Background: The incidence of hepatocellular carcinoma (HCC) associated with metabolic risk factors, such as diabetes and obesity, has been increasing. However, the underlying mechanism that links these diseases remains unclear.

Methods: We performed genome-wide expression analysis of human liver tissues of non-viral HCC patients with or without metabolic risk factors.

CD73 as a therapeutic target for pancreatic neuroendocrine tumor stem cells.

Identification and purification of cancer stem cells (CSCs) lead to the discovery of novel therapeutic targets; however, there has been no study on isolation of the CSC population among pancreatic neuroendocrine tumors (pNETs). This study aimed to identify pNET CSCs and to characterize a therapeutic candidate for pNET CSCs. We identified CSCs by aldehyde dehydrogenase (ALDH) activity in pNET clinical specimens and cell lines.

The difficulty of laparoscopic liver resection.

Grading of difficulty is needed for laparoscopic liver resection (LLR). Indications for LLR are expanding worldwide from minor to major resections, particularly in institutions having surgeons with advanced skills. If the degrees of surgical difficulty were defined, it would serve as a useful guide when introducing LLR and stepping up to the more advanced LLR.

Distinct clinicopathological phenotype of hepatocellular carcinoma with ethoxybenzyl-magnetic resonance imaging hyperintensity: association with gene expression signature.

Background: Although hepatocellular carcinoma (HCC) is mostly a lower intensity lesion in the hepatobiliary phase on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, some HCCs were shown as a higher intensity lesion (high HCC). This study aimed to reveal the clinicopathological and biological properties of high HCC.

Methods: Patients who underwent curative hepatectomy as the first treatment for HCC were included.

Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma.

We previously identified Aurora B kinase as the only independent factor predictive of the aggressive recurrence of hepatocellular carcinoma (HCC). In this preclinical study, JNJ-28841072, a novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor, was evaluated for treatment of HCC. In vitro and in vivo effects of JNJ-28841072 were analyzed using human HCC cell cultures and xenograft models.

A novel therapeutic combination sequentially targeting aurora B and Bcl-xL in hepatocellular carcinoma.

Background: Effective therapeutic combinations targeting the oncogenic pathway still are unknown in human hepatocellular carcinoma (HCC). The authors previously identified aberrant expression of aurora B kinase as the independent predictor for the lethal recurrence of HCC, showing that AZD1152 induced in vitro and in vivo apoptosis with polyploidy in human HCC cells. In this preclinical study, the combined effects of molecular-targeted therapies were evaluated based on the cellular response of aurora B inhibition.

Advances in reduced port laparoscopic liver resection.

Reduced port surgery has been attracting attention in the field of minimally invasive surgery. Although the use of SILS is becoming widespread, technical difficulty has delayed its adoption for laparoscopic liver resection. Recently, advances in laparoscopic liver resection have been made in tandem with advances in surgical skill and devices.

Prognostic role of Child-Pugh score 5 and 6 in hepatocellular carcinoma patients who underwent curative hepatic resection.

Background: It is unclear whether Child-Pugh score discriminates a prognosis of the Child-Pugh A patients who underwent hepatic resection for hepatocellular carcinoma.

Methods: Between April 2000 and March 2011, 361 patients with Child-Pugh A who underwent curative hepatectomy were divided into 2 groups: Child-Pugh score 5 points group (CPS5) and Child-Pugh score 6 points group (CPS6); both CPS5 (n = 274) and CPS6 (n = 87) groups were compared.

Results: Overall survival rates (1/2/5 years of the CPS5 and CPS6 groups were 90.

Age-related clinicopathologic and molecular features of patients receiving curative hepatectomy for hepatocellular carcinoma.

Background: Age-related differences of clinicopathologic features, outcomes, and molecular properties of hepatocellular carcinoma remain unclarified.

Methods: We classified patients who underwent hepatectomy for hepatocellular carcinoma into 3 groups by age bracket; younger group (<50 years), middle-aged group (50 to 79 years), and elderly group (≥80 years) and compared age-related features.

Results: Hepatitis viral infection was dominant in the younger group (hepatitis B virus [HBV]; 67%) and middle-aged group (hepatitis C virus [HCV]; 56%), whereas the elderly group showed a significantly higher rate without hepatitis virus infection (absence of HBV and HCV infection, 66%; P = .

Does the preoperative alpha-fetoprotein predict the recurrence and mortality after hepatectomy for hepatocellular carcinoma without macrovascular invasion in patients with normal liver function?

Aim: It has been highly controversial whether elevated serum α-fetoprotein (AFP) level before hepatectomy predicts recurrence and mortality of patients with hepatocellular carcinoma (HCC) or not. This study is to identify whether the index predicts recurrence and mortality after hepatectomy in HCC.

Methods: Of 568 consecutive patients, 342 with normal liver function (Child-Pugh score, 5) and no macrovascular invasion were enrolled between April 2000 and March 2013.