Publications by authors named "Hitoshi Maruyama"

190 Publications

Percutaneous Two-Dimensional Shear Wave Elastography for Diagnosis of Pancreatic Tumor.

Diagnostics (Basel) 2021 Mar 11;11(3). Epub 2021 Mar 11.

Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1 Inohan, Chuo-ku Chiba City 260-8670, Japan.

Background: To investigate the efficacy of two-dimensional shear wave elastography (2D-SWE) for the diagnosis of pancreatic mass lesions.

Methods: This ethics committee-approved cross-sectional study included 52 patients with histologically-proven pancreatic tumors (pancreatic ductal adenocarcinoma (PDAC), 36; tumor-forming pancreatitis (TFP), 15; neuroendocrine tumor, 1) and 33 control subjects. The 2D-SWE was performed for the tumor/non-tumor tissues, and SWE-mapping patterns and propagation quality were assessed.

Results: Three mapping patterns were detected based on the size and distribution of the coloring areas. Pattern A (whole coloring) was detected in all non-tumor tissues and TFP, whereas pattern C (multiple small coloring spots) was detected in PDAC only. Pattern B (partial coloring with smaller spots) was detected in other lesions. The specificity and positive predictive value of pattern A for non-PDAC and those of pattern C for PDAC were 100%. The SWE value was higher in tumor lesions than in the non-tumor tissues (38.1 vs. 9.8 kPa; < 0.001) in patients with PDAC. The SWE value in the non-tumor lesion was higher in patients with PDAC than in control (9.8 vs. 7.5 kPa; < 0.001).

Conclusions: 2D-SWE may play a role as a novel diagnostic tool for PDAC to detect a specific mapping pattern with quantitative assessment.
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http://dx.doi.org/10.3390/diagnostics11030498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001884PMC
March 2021

Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells.

Biochem Biophys Res Commun 2021 Apr 3;549:171-178. Epub 2021 Mar 3.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells. Lenvatinib-resistant HCC cell lines were established by exposure to serially escalated doses of lenvatinib over 2 months. The biological characteristics of these cells were examined by in vitro assays. To investigate the cytokine profile of lenvatinib-resistant HCC cells, the supernatant derived from lenvatinib-resistant Huh7 cells was subjected to nitrocellulose membrane-based sandwich immunoassay. Both activation of the MAPK/MEK/ERK signaling pathway and upregulation of epithelial mesenchymal transition markers were observed in lenvatinib-resistant cells. Concordant with these findings, proliferation and invasion abilities were enhanced in these cells compared with control cells. Screening of a cytokine array spotted with 105 different antibodies to human cytokines enabled us to identify 16 upregulated cytokines in lenvatinib-resistant cells. Among them, 3 angiogenic cytokines: vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and angiogenin, were increased significantly. Conditioned medium from lenvatinib-resistant cells accelerated tube formation of human umbilical vein cells. In conclusion, lenvatinib-resistant HCC cells were characterized by enhanced proliferation and invasion abilities. These findings might contribute to the establishment of new combination therapies with lenvatinib.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.097DOI Listing
April 2021

The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma.

Sci Rep 2021 Mar 5;11(1):5303. Epub 2021 Mar 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

FGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19 (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19 (n = 105) patients, there were no significant differences between FGF19 (n = 21) and FGF19 (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.
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http://dx.doi.org/10.1038/s41598-021-84117-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935880PMC
March 2021

AI-Based Radiological Imaging for HCC: Current Status and Future of Ultrasound.

Diagnostics (Basel) 2021 Feb 12;11(2). Epub 2021 Feb 12.

Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Hepatocellular carcinoma (HCC) is a common cancer worldwide. Recent international guidelines request an identification of the stage and patient background/condition for an appropriate decision for the management direction. Radiomics is a technology based on the quantitative extraction of image characteristics from radiological imaging modalities. Artificial intelligence (AI) algorithms are the principal axis of the radiomics procedure and may provide various results from large data sets beyond conventional techniques. This review article focused on the application of the radiomics-related diagnosis of HCC using radiological imaging (computed tomography, magnetic resonance imaging, and ultrasound (B-mode, contrast-enhanced ultrasound, and elastography)), and discussed the current role, limitation and future of ultrasound. Although the evidence has shown the positive effect of AI-based ultrasound in the prediction of tumor characteristics and malignant potential, posttreatment response and prognosis, there are still a number of issues in the practical management of patients with HCC. It is highly expected that the wide range of applications of AI for ultrasound will support the further improvement of the diagnostic ability of HCC and provide a great benefit to the patients.
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http://dx.doi.org/10.3390/diagnostics11020292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918339PMC
February 2021

Propofol midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

JGH Open 2021 Feb 22;5(2):273-279. Epub 2020 Dec 22.

Department of Gastroenterology, Graduate School of Medicine Chiba University Chiba Japan.

Background And Aim: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC.

Methods: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5.

Results: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups.

Conclusion: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.
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http://dx.doi.org/10.1002/jgh3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857294PMC
February 2021

Testing the Validity of the Diamond Steps Test for Balance in Healthy Adults.

Arch Rehabil Res Clin Transl 2020 Dec 9;2(4):100091. Epub 2020 Nov 9.

Fukuoka International University of Health and Welfare, Fukuoka, Japan.

Objectives: To test the validity of the Diamond Steps Test (DST), a new test to assess balance.

Design: This cross-sectional study evaluated the validity of the DST, a brief new balance assessment tool.

Setting: The implementation site was the rehabilitation center of a hospital. Data collection was conducted from February to June 2017.

Participants: Healthy adults (N=65) between the ages of 40 and 72 years who volunteered to participate.

Interventions: Not applicable.

Main Outcome Measures: Two measures were used to assess DST: the time required to step around the diamond 5 times (5-DS) and the time required to step around the diamond twice, once using the dominant foot and the other using the non-dominant foot (LRDS).

Results: Multiple regression analysis was performed for each of the 2 methods for measuring DST. Five variables were predictive of DST as measured by the 5-DS test: the 10-Second Open Close Stepping Test, timed Up and Go (TUG) test, Y Balance Test (YBT) posterolateral reach for the left leg, Standing on One Leg with Eyes Closed (SOLEC) test for the right leg, and sex. The coefficient of determination was 0.54. For DST measured by the LRDS, 4 variables were found to be predictive: the 30-Second Chair Stand Test, YBT posterolateral reach for the left leg, TUG, and SOLEC for the right leg. The coefficient of determination was 0.49.

Conclusion: The DST was shown to assess 7 of the 9 components of balance (static stability, functional stability limits, underlying motor systems, anticipatory posture control, dynamic stability, reactive postural control, and sensory integration), suggesting that it is a valid test to use for balance assessment.
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http://dx.doi.org/10.1016/j.arrct.2020.100091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853401PMC
December 2020

Differences in the total hip rotation range of motion between sides in healthy young Japanese adults.

J Phys Ther Sci 2021 Jan 5;33(1):57-62. Epub 2021 Jan 5.

Fukuoka International University of Health and Welfare, Japan.

[Purpose] To investigate the difference by degrees in total hip rotation range of motion (ROM) between sides and with regard to gender in healthy young Japanese adults. [Participants and Methods] Data from previously published studies were used. We utilized the left and right hip rotation ROM of 205 Japanese participants aged 18 to 25 years, who satisfied the inclusion criteria and were randomly measured three times in the prone position by the double-blind method. The average value of the three measurements was used to calculate the left-right difference of the hip total rotation ROM in the hip joints, which is the sum of the hip internal and external rotation ROM. We investigated the distribution of the total hip rotation considering the flexibility factor and its relationship with gender. [Results] We confirmed that there were seven participants with 2 SD or more and two with 3 SD or more. No significant difference was found in the left-right difference in the total hip rotation ROM, regardless of gender. [Conclusion] The distribution of left-right differences in the total hip rotation ROM in healthy young adults showed the existence of a significant left-right difference of 2 SD or more.
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http://dx.doi.org/10.1589/jpts.33.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829555PMC
January 2021

Association between skeletal muscle mass index and lung function/respiratory muscle strength in older adults requiring long-term care or support.

J Phys Ther Sci 2020 Nov 11;32(11):754-759. Epub 2020 Nov 11.

Nishinasuno General Home Care Center, Department of Day Rehabilitation, Care Facility for the Elderly "Maronie-en", Japan.

[Purpose] We focused on skeletal muscle mass index, one of the biomarkers of sarcopenia, and investigated the association between skeletal muscle mass index and the parameters of lung function and respiratory muscle strength. [Participants and Methods] After applying the exclusion criteria, we included, in this cross-sectional study, 120 community-dwelling older adults aged ≥65 years who required long-term care/support and underwent ambulatory rehabilitation under the long-term care insurance system in Japan. We measured the skeletal muscle mass index, forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow rate, maximum expiratory pressure, and maximum inspiratory pressure. The data were analyzed using Pearson correlation coefficient and multiple regression analysis. [Results] The skeletal muscle mass index was positively correlated with only maximum expiratory pressure for both male and female participants by Pearson's correlation coefficient. With the skeletal muscle mass index as a dependent variable, only the maximum expiratory pressure was significant for both male and female participants by the multiple regression analysis. [Conclusion] Therefore, the findings of this study suggested that compared with lung function tests, maximum expiratory pressure, which is an indicator of respiratory muscle strength, is related to muscle mass. Maximum expiratory pressure might be the most useful indicator for sarcopenia.
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http://dx.doi.org/10.1589/jpts.32.754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708015PMC
November 2020

The Asian working group for sarcopenia's new criteria updated in 2019 causing a change in sarcopenia prevalence in Japanese older adults requiring long-term care/support.

J Phys Ther Sci 2020 Nov 11;32(11):742-747. Epub 2020 Nov 11.

Nishinasuno General Home Care Center, Department of Day Rehabilitation, Care Facility for the Elderly "Maronie-en", Japan.

[Purpose] The Asian Working Group for Sarcopenia (AWGS) criteria were recently updated. However, whether these changes would result in a difference in sarcopenia prevalence was unclear. We therefore focused on Japanese older adults who required long-term care/support and determined the differences in sarcopenia prevalence between the new and old criteria. [Participants and Methods] This cross-sectional study included 161 Japanese older adults aged ≥65 years who required long-term care/support along with ongoing daycare. Handgrip strength, usual gait speed, and skeletal muscle mass index were measured. We analyzed the difference in sarcopenia prevalence between the 2019 and 2014 AWGS criteria using the McNemar test. [Results] The overall sarcopenia prevalence rates were 60.2% and 53.4%, and the prevalence rates of sex-specific sarcopenia were 63.6% and 55.7% among males and 56.2% and 50.7% among females when the 2019 and 2014 AWGS criteria were used, respectively. Overall, males exhibited a significantly higher prevalence with the new than criteria than with the old. [Conclusion] With the 2019 AWGS criteria, more older males who required long-term care/support were diagnosed as having sarcopenia. Conversely, the sarcopenia diagnosis in females statistically remained unchanged. Thus, a mismatch might exist between the two criteria regarding sarcopenia prevalence in males.
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http://dx.doi.org/10.1589/jpts.32.742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708002PMC
November 2020

APASL practical recommendations for the management of hepatocellular carcinoma in the era of COVID-19.

Hepatol Int 2020 Dec 11;14(6):920-929. Epub 2020 Nov 11.

Department of Gastroenterology, Yamanashi Prefectural Central Hospital, Kofu-city, Yamanashi, Japan.

Background: COVID-19 has been giving the devastating impact on the current medical care system. There are quite many guidelines on COVID-19, but only a few on the management of hepatocellular carcinoma (HCC) during COVID-19 pandemic.

Aims: We develop these recommendations to preserve adequate clinical practice for the management of HCC.

Methods: Experts of HCC in the Asia-Pacific region exchanged opinions via webinar, and these recommendations were formed.

Results: Close contact should be minimized to reduce possible exposure of both medical staff and patients to the novel coronavirus. To prevent transmission of the virus, meticulous hygiene measures are important. With the decrease in regular medical service, the medical staff may be mobilized to provide COVID-19-related patient care. However, diagnosis and treatment of HCC should not be delayed because of COVID-19 pandemic. The management of HCC should be the same as in non-pandemic circumstances. HCC is highly malignant, thus it is recommended not to delay curative treatment such as surgery and ablation. However, a kind of triage is necessary even among patients with HCC when resources are insufficient for all to be treated. Curative treatments should be periodized and cytoreductive or non-curative treatment such as vascular interventions and systemic therapy may be postponed until it can be performed safely with sufficient resources. For patients with confirmed or suspected to be infected with the novel coronavirus, diagnosis and treatment should be postponed until the virus is eliminated or they are confirmed as not being infected with it.

Conclusions: These are collection of measures implemented by front-line medical professionals. We would evolve these recommendations over time as more real-world data becomes available.
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http://dx.doi.org/10.1007/s12072-020-10103-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655459PMC
December 2020

Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials.

Liver Cancer 2020 Sep 22;9(5):596-612. Epub 2020 Jul 22.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden.

Aims: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs.

Methods: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC.

Results: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC.

Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
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http://dx.doi.org/10.1159/000508809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548915PMC
September 2020

Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma.

Liver Cancer 2020 Aug 5;9(4):382-396. Epub 2020 May 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial.

Methods: We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan.

Results: Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7-6.9 for first line, 4.8 months; 95% CI 3.8-5.9 for second or later line, = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin - bilirubin scores.

Conclusion: Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.
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http://dx.doi.org/10.1159/000507022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506220PMC
August 2020

Summary of respiratory rehabilitation and physical therapy guidelines for patients with COVID-19 based on recommendations of World Confederation for Physical Therapy and National Association of Physical Therapy.

J Phys Ther Sci 2020 8;32(8):545-549. Epub 2020 Aug 8.

CangZhou Medical College, China.

[Purpose] To summarize the existing official guidelines issued by the World Confederation for Physical Therapy and Associations of Physical Therapy in various countries and to clarify the recommended methods of respiratory rehabilitation and physiotherapy for patients in different stages of the coronavirus disease of 2019 (COVID-19). [Methods] An introductory literature search was conducted using the keywords "COVID-19", "respiratory rehabilitation", "physical therapy", and others in the database of the Association of Physical Therapy. [Results] Using 12 coronavirus disease-2019 rehabilitation-related articles, we summarized data on physical therapy (PT) evaluation; treatment; indications; contraindications; and termination indicators for patients in acute, stable, and post-discharge stages. [Conclusion] PT for COVID-19 patients with coronavirus disease 2019 should be formulated according to the stage of the disease and condition of the patients.
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http://dx.doi.org/10.1589/jpts.32.545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443542PMC
August 2020

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid.

J Med Ultrasound 2020 Apr-Jun;28(2):59-82. Epub 2020 May 25.

Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan.

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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http://dx.doi.org/10.4103/JMU.JMU_124_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446696PMC
May 2020

Reliability of measurement reliability and optimal number of measurements for mental arithmetic reaction time test.

J Phys Ther Sci 2020 Jul 3;32(7):463-466. Epub 2020 Jul 3.

Department of Physical Therapy, International University of Health and Welfare: 2600-1 Kitakanemaru, Ohtawara City, Tochigi 324-8501, Japan.

[Purpose] The main objective of this study was to assess the reliability of the method for testing the attention distribution ability of the elderly using mental arithmetic response time. [Participants and Methods] The participants included in the study were 30 healthy elderly people (over 65 years old), 11 males and 19 females, eight of whom had experienced falls in the past year.In the quiet standing position and the free walking state, we recorded the mental calculation response time of the participants by calculating the two-digit plus or minus one-digit values within 100. The test of the two states were tested in 24 hour intervals. [Results] In the quiet standing and free walking state, the correlation coefficient of the mental arithmetic response time group of the elderly was excellent. The intra-group correlation coefficient of mental arithmetic response time of more than three tests under free walking was greater than 0.9. [Conclusion] We found that the mental arithmetic response time can be used to objectively evaluate the ability of attention distribution in the elderly.
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http://dx.doi.org/10.1589/jpts.32.463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344278PMC
July 2020

Consensus recommendations of three-dimensional visualization for diagnosis and management of liver diseases.

Hepatol Int 2020 Jul 7;14(4):437-453. Epub 2020 Jul 7.

CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China.

Three-dimensional (3D) visualization involves feature extraction and 3D reconstruction of CT images using a computer processing technology. It is a tool for displaying, describing, and interpreting 3D anatomy and morphological features of organs, thus providing intuitive, stereoscopic, and accurate methods for clinical decision-making. It has played an increasingly significant role in the diagnosis and management of liver diseases. Over the last decade, it has been proven safe and effective to use 3D simulation software for pre-hepatectomy assessment, virtual hepatectomy, and measurement of liver volumes in blood flow areas of the portal vein; meanwhile, the use of 3D models in combination with hydrodynamic analysis has become a novel non-invasive method for diagnosis and detection of portal hypertension. We herein describe the progress of research on 3D visualization, its workflow, current situation, challenges, opportunities, and its capacity to improve clinical decision-making, emphasizing its utility for patients with liver diseases. Current advances in modern imaging technologies have promised a further increase in diagnostic efficacy of liver diseases. For example, complex internal anatomy of the liver and detailed morphological features of liver lesions can be reflected from CT-based 3D models. A meta-analysis reported that the application of 3D visualization technology in the diagnosis and management of primary hepatocellular carcinoma has significant or extremely significant differences over the control group in terms of intraoperative blood loss, postoperative complications, recovery of postoperative liver function, operation time, hospitalization time, and tumor recurrence on short-term follow-up. However, the acquisition of high-quality CT images and the use of these images for 3D visualization processing lack a unified standard, quality control system, and homogeneity, which might hinder the evaluation of application efficacy in different clinical centers, causing enormous inconvenience to clinical practice and scientific research. Therefore, rigorous operating guidelines and quality control systems need to be established for 3D visualization of liver to develop it to become a mature technology. Herein, we provide recommendations for the research on diagnosis and management of 3D visualization in liver diseases to meet this urgent need in this research field.
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http://dx.doi.org/10.1007/s12072-020-10052-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366600PMC
July 2020

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid.

Ultrasonography 2020 Jul 27;39(3):191-220. Epub 2020 Apr 27.

Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan.

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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http://dx.doi.org/10.14366/usg.20057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315291PMC
July 2020

Clinical course of COVID-19 in patients with pre-existing decompensated cirrhosis: initial report from China.

Hepatol Int 2020 Jul 22;14(4):478-482. Epub 2020 May 22.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

Background: The clinical characteristics and disease course in COVID-19 patients with pre-existing decompensated cirrhosis has not been described so far.

Methods: In this case series, we report three patients with confirmed COVID-19 and pre-existing decompensated cirrhosis from three hospitals in Hubei, the epicenter of the outbreak in China.

Result: Patient 1 was a 53-year-old man with hepatitis B virus-related cirrhosis, portal hypertension, and ascites. Though receiving intensive support, he died of irreversible multiple organ dysfunction syndrome 48 days after the onset of the illness. Patient 2 was a 75-year-old woman with a history of schistosomiasis-related cirrhosis, portal hypertension, and ascites. Her family members requested that invasive rescue measures not be undertaken, and she died of acute respiratory distress syndrome 40 days after presenting with COVID-19 infection. Patient 3 was an 87-year-old man with alcohol-related cirrhosis, portal hypertension, and esophageal variceal hemorrhage. He was discharged from the hospital 29 days after illness onset.

Conclusion: The case series raise the possibility that decompensated cirrhosis may be a risk factor for a poor outcome in patients with COVID-19.
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http://dx.doi.org/10.1007/s12072-020-10051-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242176PMC
July 2020

Antioxidant therapy on ischemic hepatitis: here we are and where do we go?

Hepatol Int 2020 Jul 29;14(4):456-459. Epub 2020 Apr 29.

Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

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http://dx.doi.org/10.1007/s12072-020-10044-yDOI Listing
July 2020

Long-term administration of Tolvaptan to patients with decompensated cirrhosis.

Int J Med Sci 2020 15;17(7):874-880. Epub 2020 Mar 15.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

: Tolvaptan, an oral vasopressin-2 antagonist, sometimes improves hepatic edema including ascites in patients with decompensated cirrhosis. In this study, we examined the effectiveness and survival advantage in patients with the long-term administration of tolvaptan. : A total of 115 patients with refractory ascites who were treated with tolvaptan were retrospectively analyzed based on their clinical records. Patients with a decrease in body weight of ≥1.5 kg from the baseline on day 7 were determined as responders. Re-exacerbation was defined as a return to the baseline BW, dose escalation of conventional diuretics, or abdominal drainage. : Of the 115 patients, 84 were included in this analysis. Response to tolvaptan treatment was observed in 55 out of the 84 patients (65.5%), with a mean weight reduction of 2.52 kg. Multivariate analyses demonstrated that body mass index (≥24) and urinary specific gravity (≥1.018) were significant predictors of the response to tolvaptan. However, cumulative re-exacerbation rates in responders at 6 and 12 months were 42.4 and 60.1%, respectively. Child-Pugh (classification C), HCC complication, and serum sodium levels (≥133 mEq/L) were determined as independent prognostic factors impacting overall survival (OS). Although there were no significant differences in OS between tolvaptan responders and non-responders, the responders without re-exacerbation within 3 months showed significantly longer OS than those with re-exacerbation within 3 months. : A persistent therapeutic response, but not early response to tolvaptan, was associated with favorable survival of decompensated cirrhotic patients.
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http://dx.doi.org/10.7150/ijms.41454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163362PMC
February 2021

Reliability of ultrasonographic measurement of the supraspinatus thickness at different angles of shoulder abduction in patients with stroke.

J Phys Ther Sci 2020 Mar 11;32(3):257-259. Epub 2020 Mar 11.

Department of Judo Therapy, Teikyo University of Science, Japan.

[Purpose] The primary purpose of this study was to evaluate the usefulness of the intraclass correlation coefficient for evaluating the reliability of the measurement of the supraspinatus thickness on shoulder ultrasonography at different angles in a resting position in patients with stroke. [Participants and Methods] The study included 20 patients with stroke. The supraspinatus thickness was measured on both sides on ultrasonography, with the participants' shoulders in abduction at 3 testing angles (0°, 30°, and 60° abduction). Each measurement was performed three times, and the average of the three measurements was recorded. The intraclass correlation coefficient was calculated, with the supraspinatus thickness measured twice at an interval of 24 hours as the factor. [Results] All intraclass correlation coefficients for the hemiplegic and normal sides were greater than 0.93 when the shoulders were at the three testing angles. [Conclusion] In this investigation, the reliability of measuring the supraspinatus thickness on shoulder ultrasonography at each angle for 3 times was evaluated and was found to be excellent.
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http://dx.doi.org/10.1589/jpts.32.257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064348PMC
March 2020

Relationship between walking ability of patients with stroke and effect of body weight-supported treadmill training.

J Phys Ther Sci 2020 Mar 11;32(3):206-209. Epub 2020 Mar 11.

Graduate School, International University of Health and Welfare, Japan.

[Purpose] Reports on the amount of unloading maximizing walking ability in patients with stroke are limited. The effect of body weight-supported treadmill training (BWSTT) in patients with stroke has not been clarified. We aimed to investigate the effects of unloading rate during BWSTT on the gait of patients with stroke and the relationship between BWSTT and walking ability on flat ground. [Participants and Methods] We performed BWSTT in 17 patients at three unloading rates: 0%, 20%, and 40%. Then, we examined the walking speed and rate, number of steps, single-leg support time ratio, and root mean square before and after unloading. Furthermore, we examined the relationship between walking ability on flat ground and immediate effects of BWSTT at each unloading rate. [Results] We observed no significant improvement under all conditions. However, walking ability improved at unloading rates of 20% and 40%, with poor temporal symmetry while walking on flat ground. [Conclusion] Our results revealed that BWSTT has diverse effects depending on the unloading rate and the ability to walk on flat ground. In particular, it tends to be highly effective for those who have poor sway and symmetry, which may serve as an index for prescribing BWSTT.
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http://dx.doi.org/10.1589/jpts.32.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064355PMC
March 2020

Absolute reliability of tongue pressure measurement in young healthy adults and elderly patients with certification of needing long-term care or support.

Geriatr Gerontol Int 2020 May 16;20(5):488-493. Epub 2020 Mar 16.

Nishinasuno General Home Care Center, Department of Day Rehabilitation, Care Facility for the Elderly "Maronie-en", Tochigi, Japan.

Aim: We aimed to determine systematic bias and the range of random error in tongue pressure measurements among young healthy adults and elderly patients with certification of requiring long-term care or support, considering sex, and to establish a measurement method.

Methods: Subjects were 226 adults (88 young healthy adults and 138 elderly patients with certification of requiring long-term care or support). Tongue pressure was measured thrice. Bland-Altman analysis was performed for the first and second trials, and second and third trials.

Results: Fixed bias was revealed for the first and second trials among young healthy adults. Systematic bias was not found for the second and third trials. Fixed bias was revealed for the first and second trials among elderly patients, with a proportional bias with a negative slope for the second and third trials. For young healthy adults, the minimal detectable change was 6.0 and 5.4 kPa in males and females, respectively. For elderly patients, the limit of agreement ranged from -5.9 to 8.6 and from -5.4 to 8.8 kPa in males and females, respectively.

Conclusions: There was a difference in systematic bias in tongue pressure measurement between young healthy adults and elderly patients with certification of needing long-term care or support. In young healthy adults, the third trial results showed stability, whereas they decreased in elderly patients. In elderly patients, it was suggested that the number of measurements reduced from three to two when a maximum value was adopted. No differences were observed among sexes in either young or elderly patients. Geriatr Gerontol Int 2020; 20: 488-493.
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http://dx.doi.org/10.1111/ggi.13902DOI Listing
May 2020

Immediate effects of lumbar spine patterns after neuromuscular joint facilitation on balance in stroke patients.

J Phys Ther Sci 2019 Dec 3;31(12):979-982. Epub 2019 Dec 3.

Department of Physical Therapy, International University of Health and Welfare: 2600-1 Kitakanemaru Otawara city, Tochigi 324-8501, Japan.

[Purpose] The present study investigated changes in the balance function of stroke patients after neuromuscular joint facilitation treatment. [Participants and Methods] Fourteen stroke patients were randomly subjected to neuromuscular joint facilitation intervention (neuromuscular joint facilitation intervention group) and no intervention (control group), with a 1-day interval between treatments. The interventions were performed consecutively. The order of interventions was completely randomized. Before and after one neuromuscular joint facilitation and control intervention, the functional reach test, and body sway were measured. [Results] Functional reach test values were significantly increased and peripheral area was significantly reduced in the neuromuscular joint facilitation intervention group than in the control group. [Conclusion] These results suggest that neuromuscular joint facilitation of the trunk has an immediate effect on balance and function in stroke patients.
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http://dx.doi.org/10.1589/jpts.31.979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893158PMC
December 2019

Free fatty acid-based low-impedance liver image: a characteristic appearance in nonalcoholic steatohepatitis (NASH).

Eur Radiol Exp 2020 01 23;4(1). Epub 2020 Jan 23.

Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: To examine in vitro acoustic property of nonalcoholic fatty disease in mouse and human liver to identify nonalcoholic steatohepatitis (NASH).

Methods: The acoustic impedance (× 10 kg/m/s) was measured in 35 free fatty acids (FFAs, 500 mmol/L) and histologically-diagnosed liver samples of twelve mice (four control, four simple steatosis [SS], and four NASH) and eight humans (two control, three SS, and three NASH), using 80-MHz acoustic microscopy. The sum of percentage (SP) composition of FFAs (SP-FFAs) was also assessed.

Results: Median impedance of all FFAs was 0.7 (5 FFAs with impedance 0.7); 17 FFAs with impedance < 0.7 were classified as low-impedance group; and, 13 FFAs with impedance > 0.7 were classified as high-impedance group. The median impedance of the mouse liver decreased from control (1.715), to SS (1.68), to NASH (1.635) (control versus NASH, p = 0.039 without significant differences for the other comparisons, p ≥ 0.1). Similarly, the median impedance of human liver showed decreased from control (1.825), to SS (1.788), to NASH (1.76) (control versus SS, p = 0.023; control versus NASH, p = 0.003; SS versus NASH, p = 0.050). The ratio of SP-FFAs between the low-impedance and high-impedance groups showed an increase in both mice and humans, with significant differences in mice (control versus SS, p < 0.001; control versus NASH, p < 0.001; SS versus NASH, p = 0.003), without significant differences in humans (p ≥ 0.671).

Conclusion: Lower acoustic impedance based on the intrahepatic composition of FFAs may be characteristic of NASH.
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http://dx.doi.org/10.1186/s41747-019-0137-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977798PMC
January 2020

Incidence and hemodynamic feature of risky esophageal varices with lower hepatic venous pressure gradient.

Int J Med Sci 2019 9;16(12):1614-1620. Epub 2019 Nov 9.

Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

To examine the incidence of cirrhosis patients with high-risk esophageal varices (EV) who show hepatic venous pressure gradient (HVPG) < 10 mmHg and to identify their hemodynamic features. This prospective study consisted of 110 cirrhosis patients with EV, all with the candidate for primary or secondary prophylaxis. Sixty-one patients had red sign, and 49 patients were bleeders. All patients underwent both Doppler ultrasound and HVPG measurement. There were 18 patients (16.4%) with HVPG < 10 mmHg. The presence of venous-venous communication (VVC) was more frequent in patients with HVPG < 10 mmHg (10/18) than in those with HVPG ≥ 10 mmHg (19/92; p = 0.0021). The flow volume in the left gastric vein (LGV) and the incidence of red sign were higher in the former (251.9 ± 150.6 mL/min; 16/18) than in the latter (181 ± 100.5 mL/min, p = 0.02; 45/92; p = 0.0018). The patients with red sign had lower HVPG (13.3 ± 4.5) but advanced LGV hemodynamics (velocity 13.2 ± 3.8 cm/s; flow volume 217.5 ± 126.6 mL/min), whereas those without red sign had higher HVPG (16.2 ± 4.6, p = 0.001) but poorer LGV hemodynamics (10.9 ± 2.3, p = 0.002; 160.1 ± 83.1, p = 0.02). Patients with high-risk EV with HVPG < 10 mmHg showed 16.4% incidence. Although low HVPG may be underestimated by the presence of VVC, the increased LGV hemodynamics compensates for the severity of portal hypertension, which may contribute to the development of red sign.
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http://dx.doi.org/10.7150/ijms.37040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909812PMC
April 2020

Serum fibroblast growth factor 19 serves as a potential novel biomarker for hepatocellular carcinoma.

BMC Cancer 2019 Nov 12;19(1):1088. Epub 2019 Nov 12.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA).

Methods: The serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined.

Results: The median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called "double negative HCC") exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment.

Conclusion: Our findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment.
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http://dx.doi.org/10.1186/s12885-019-6322-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849282PMC
November 2019

Contrast-enhanced ultrasonography: is it an ideal tool for hepatocellular carcinoma surveillance?

Quant Imaging Med Surg 2019 Sep;9(9):1611-1614

Department of Gastroenterology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan.

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http://dx.doi.org/10.21037/qims.2019.08.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785512PMC
September 2019

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Invest New Drugs 2020 02 6;38(1):172-180. Epub 2019 Jun 6.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.
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http://dx.doi.org/10.1007/s10637-019-00801-8DOI Listing
February 2020

Genome-Wide Mapping of Bivalent Histone Modifications in Hepatic Stem/Progenitor Cells.

Stem Cells Int 2019 1;2019:9789240. Epub 2019 Apr 1.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

The "bivalent domain," a distinctive histone modification signature, is characterized by repressive trimethylation of histone H3 at lysine 27 (H3K27me3) and active trimethylation of histone H3 at lysine 4 (H3K4me3) marks. Maintenance and dynamic resolution of these histone marks play important roles in regulating differentiation processes in various stem cell systems. However, little is known regarding their roles in hepatic stem/progenitor cells. In the present study, we conducted the chromatin immunoprecipitation (ChIP) assay followed by high-throughput DNA sequencing (ChIP-seq) analyses in purified delta-like 1 protein (Dlk) hepatic stem/progenitor cells and successfully identified 562 genes exhibiting bivalent domains within 2 kb of the transcription start site. Gene ontology analysis revealed that these genes were enriched in developmental functions and differentiation processes. Microarray analyses indicated that many of these genes exhibited derepression after differentiation toward hepatocyte and cholangiocyte lineages. Among these, 72 genes, including and , were significantly upregulated after differentiation toward hepatocyte or cholangiocyte lineages. Knockdown of in Dlk cells suppressed colony propagation and resulted in increased numbers of albumin/cytokeratin 7 progenitor cells in colonies. These findings implicate that derepression of expression is required to induce normal differentiation processes. In conclusion, combined ChIP-seq and microarray analyses successfully identified bivalent genes. Functional analyses of these genes will help elucidate the epigenetic machinery underlying the terminal differentiation of hepatic stem/progenitor cells.
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http://dx.doi.org/10.1155/2019/9789240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466853PMC
April 2019