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Spontaneous regression of hepatocellular carcinoma: A mini-review

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World Journal of Gastroenterology 2017年第21期23卷 3797-3804页

作者： Akira Sakamaki Kenya Kamimura Satoshi Abe Atsunori Tsuchiya Masaaki Takamura hirokazu kawai Satoshi Yamagiwa Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma(HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively amo ng t he 15 c as e s f or w hic h t he inf o r mat io n regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.

关键词：自发的回归 Hepatocellular 癌免疫学的反应免疫疗法组织缺氧

Shear wave velocity is a useful marker for managing nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2010年第23期16卷 2918-2925页

作者： Akihiko Osaki Tomoyuki Kubota Takeshi Suda Masato Igarashi Keisuke Nagasaki Atsunori Tsuchiya Masahiko Yano Yasushi Tamura Masaaki Takamura hirokazu kawai Satoshi Yamagiwa Toru Kikuchi Minoru Nomoto Yutaka Aoyagi Department of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata University Department of Homeostatic Regulation and Development Graduate School of Medical and Dental SciencesNiigata University Department of Laboratory Medicine Niigata University Medical and Dental Hospital

AIM:To investigate whether a noninvasive measurement of tissue strain has a potential usefulness for management of nonalcoholic steatohepatitis(NASH).METHODS:In total 26 patients,23 NASHs and 3 normal controls were enrolled in this *** was staged based on Brunt *** a region of interest(ROI),a shear wave was evoked by implementing an acoustic radiation force impulse(ARFI),and the propagation velocity was quantif ***:Shear wave velocity(SWV) could be reproducibly quantified at all ROIs in all subjects except for 4 NASH cases,in which a reliable SWV value was not calculated at several *** average SWV of 1.34 ± 0.26 m/s in fibrous stage 0-1 was significantly slower than 2.20 ± 0.74 m/s and 2.90 ± 1.01 m/s in stages 3 and 4,respectively,but was not significantly different from 1.79 ± 0.78 m/s in stage *** a cutoff value was set at 1.47 m/s,receiver operating characteristic analysis showed significance to dissociate stages 3 and 4 from stage 0-1(P=0.0092) with sensitivity,specificity and area under curve of 100%,75% and 94.2%,*** addition,the correlation between SWV and hyaluronic acid was significant(P<0.0001),while a tendency toward negative correlation was observed with serum albumin(P=0.053).CONCLUSION:The clinical implementation of ARFI provides noninvasive repeated evaluations of liver stiffness at an arbitrary position,which has the potential to shed new light on NASH management.

关键词： Nonalcoholic steatohepatitis Ultrasound Liver stiffness measurement Shear wave velocity Acoustic radiation force impulse

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

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World Journal of Clinical Cases 2017年第6期5卷 238-246页

作者： Kohei Ogawa Kenya Kamimura Yukari Watanabe Yosuke Motai Daisuke Kumaki Ryoya Seki Akira Sakamaki Satoshi Abe hirokazu kawai Takeshi Suda Satoshi Yamagiwa Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Department of Gastroenterology and Hepatology Uonuma Institute of Community Medicine Niigata Medical and Dental Hospital

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

关键词： Hepatocellular carcinoma Double platinum Transarterial oily chemoembolization Hepatic arterial infusion chemotherapy Combination

Advances in understanding and treating liver diseases during pregnancy:A review

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World Journal of Gastroenterology 2015年第17期21卷 5183-5190页

作者： Kenya Kamimura Hiroyuki Abe hirokazu kawai Hiroteru Kamimura Yuji Kobayashi Minoru Nomoto Yutaka Aoyagi Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8510Japan

Liver disease in pregnancy is rare but pregnancyrelated liver diseases may cause threat to fetal and maternal *** includes pre-eclampsia;eclampsia;haemolysis,elevated liver enzymes,and low platelets syndrome;acute fatty liver of pregnancy;hyperemesis gravidarum;and intrahepatic cholestasis of *** basic researches have shown the various etiologies involved in this disease *** these advances,rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal *** other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic ***,correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better ***,here we review and summarized recent advances in understanding the etiologies,clinical courses and management of liver disease in *** information will contribute to physicians for diagnosis of disease and optimum management of patients.

关键词： Pregnancy Liver injury Low platelets Haemolysis elevated liver enzymes Acute fatty liverof pregnancy Hyperemesis gravidarum Intrahepaticcholestasis of pregnancy

Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis

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World Journal of Hepatology 2011年第1期3卷 15-23页

作者： hirokazu kawai Minoru Nomoto Takeshi Suda Kenya Kamimura Atsunori Tsuchiya Yasushi Tamura Masahiko Yano Masaaki Takamura Masato Igarashi Toshifumi Wakai Satoshi Yamagiwa Yasunobu Matsuda Shogo Ohkoshi Isao Kurosaki Yoshio Shirai Masahiko Okada Yutaka Aoyagi Department of Clinical Laboratory Niigata University Medical and Dental Hospital Division of Gastroenterology and Hepatology Niigata University Graduate School of Medical and Dental Sciences Division of Digestive and General Surgery Niigata University Graduate School of Medical and Dental Sciences Department of Medical Technology Niigata University Graduate School of Health Sciences Division of Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences

AIM:To reveal the manner of hepatocellular carcinoma (HCC) development in patients with nonalcoholic steatohepatitis(NASH) focusing on multicentric occurrence (MO) of ***:We compared clinicopathological characteristics between patients with and without MO of HCC arising from NASH *** clinical features were implicated with reference to the literature ***:MO of HCC was identified with histological proof in 4 out of 12 patients with NASH-related HCC(2 males and 2 females).One patient had synchronous MO;an advanced HCC,two well-differentiated HCCs and a dysplastic nodule,followed by the development of metachronous MO of *** other three patients had multiple advanced HCCs accompanied by a well-differentiated HCC or a dysplastic *** these three patients,one had synchronous MO,one had metachronous MO and the other had both synchronous and metachronous *** were no obvious differences between the patients with or without MO in terms of liver function tests,tumor markers and anatomical extent of *** the other hand,all four patients with MO of HCC were older than 70 years old and had the comorbidities of obesity,type 2 diabetes mellitus(T2DM),hypertension and *** these conditions were not limited to MO of HCC,all the conditions were met in only one of eight patients without MO of ***,concurrence of these conditions may be a predisposing situation to synchronous MO of *** particular,old age,T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the ***:The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this *** investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.

关键词： Nonalcoholic steatohepatitis Hepatocellular carcinoma Multicentric occurrence

Active treatments are a rational approach for hepatocellular carcinoma in elderly patients

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World Journal of Gastroenterology 2013年第24期19卷 3831-3840页

作者： Takeshi Suda Aiko Nagashima Shyunsaku Takahash Tsutomu Kanefuji Kenya Kamimura Yasushi Tamura Ma-saaki Takamura Masato Igarashi hirokazu kawai Satoshi Yamagiwa Minoru Nomoto Yutaka Aoyagi Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University

AIM: To determine whether an active intervention is beneficial for the survival of elderly patients with hepa-tocellular carcinoma (HCC). METHODS: The survival of 740 patients who received various treatments for HCC between 1983 and 2011 was compared among different age groups using Cox regression analysis. Therapeutic options were principal-ly selected according to the clinical practice guidelines for HCC from the Japanese Society of Hepatology. The treatment most likely to achieve regional control capa-bility was chosen, as far as possible, in the following order: resection, radiofrequency ablation, percutaneous ethanol injection, transcatheter arterial chemoembo-lization, transarterial oily chemoembolization, hepatic arterial infusion chemotherapy, systemic chemotherapy including molecular targeting, or best supportive *** treatment was used alone, or in combination, with a clinical goal of striking the best balance be-tween functional hepatic reserve and the volume of the targeted area, irrespective of their age. The percent survival to life expectancy was calculated based on a Japanese national population survey. RESULTS: The median ages of the subjects during each 5-year period from 1986 were 61, 64, 67, 68 and 71 years and increased significantly with time (P<0.0001). The Child-Pugh score was comparable among younger (59 years of age or younger), middle-aged (60-79 years of age), and older (80 years of age or older) groups (P=0.34), whereas the tumor-node-metastasis stage tended to be more advanced in the younger group (P=0.060). Advanced disease was significantly more frequent in the younger group compared with the middle-aged group (P=0.010), whereas there was no difference between the middle-aged and elderly groups (P=0.75). The median sur-vival times were 2593, 2011, 1643, 1278 and 1195 d for 49 years of age or younger, 50-59 years of age, 60-69 years of age, 70-79 years of age, or 80 years of age or older age groups, respectively, whereas the me-di

关键词： Hepatocellular carcinoma Population ag-ing Survival Life expectancy Active intervention

Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging

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World Journal of Gastroenterology 2015年第15期21卷 4583-4591页

作者： Tsutomu Kanefuji Toru Takano Takeshi Suda Kouhei Akazawa Takeshi Yokoo Hiroteru Kamimura Kenya Kamimura Atsunori Tsuchiya Masaaki Takamura hirokazu kawai Satoshi Yamagiwa Hidefumi Aoyama Minoru Nomoto Shuji Terai Deparatment of Gastro-enterology and Hepatology Uonuma Institute of Community Medicine Niigata University Medical and Dental Hospital 4132 Urasa Minami--Uonuma Department of Radiation Oncology Graduate School of Medical and Dental Sciences Niigata University Niigata Department of Medical Informatics Graduate School of Medical and Dental Sciences Niigata University Niigata Department of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Niigata

AIM: To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules(NHNs) with higher aggressiveness from less hazardous one. METHODS: Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaaceticacid magnetic resonance imaging(Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew thatthe patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, α-fetoprotein, des-γ-carboxy prothrombin, α-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations. RESULTS: During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm(interquartile range: 8-12 mm) grew or shrank by 68.5%(fifty nodules) or 20.5%(fifteen nodules), respectively, whereas hypervascularity developed in 38.4%(twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0%(eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-γ-carboxy prothrombin, and-4.05 for fat d

关键词： Hepatocellular carcinoma Magnetic resonanceimaging Ethoxybenzyl moiety Non-hypervascular hepaticnodule Fate prediction

显示出与肝炎 B 病毒感染联系的微分表示的细胞的基因的鉴定

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World Journal of Hepatology 2012年第4期4卷 139-148页

作者： Yasuo Fukuhara Takeshi Suda Makoto Kobayashi Yasushi Tamura Masato Igarashi Nobuo Waguri hirokazu kawai Yutaka Aoyagi Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University 1-757 Asahimachi-dori Chuo-ku Niigata Niigata 951-8122 Japan

AIM: To investigate the impact of hepatitis B virus (HBV) infection on cellular gene expression, by conducting both in vitro and in vivo studies. METHODS: Knockdown of HBV was targeted by stable expression of short hairpin RNA (shRNA) in huH-1 cells. Cellular gene expression was compared using a human 30K cDNA microarray in the cells and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR) (qRT-PCR) in the cells, hepatocellular carcinoma (HCC) and surrounding non-cancerous liver tissues (SL). RESULTS: The expressions of HBsAg and HBx protein were markedly suppressed in the cells and in HBx transgenic mouse liver, respectively, after introduction of shRNA. Of the 30K genes studied, 135 and 103 genes were identified as being down- and up-regulated, respectively, by at least twofold in the knockdown cells. Functional annotation revealed that 85 and 62 genes were classified into four up-regulated and five down-regulated functional categories, respectively. When gene expression levels were compared between HCC and SL, eight candidate genes that were confirmed to be up- or down-regulated in the knockdown cells by both microarray and qRT-PCR analyses were not expressed as expected from HBV reduction in HCC, but had similar expression patterns in HBV- and hepatitis C virus-associated cases. In contrast, among the eight genes, only APM2 was constantly repressed in HBV non-associated tissues irrespective of HCC or SL.

关键词： Hepatitis B virus Differential gene expression Hepatocellular carcinoma Gene expression signature Adipose most abundant 2

The Intermediary Roles of Public Health Nurses (PHNs) in Utilizing Communication Robots (CRs) in Community Health Care Practice

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Health 2019年第12期11卷 1598-1608页

作者： Chihiro kawai Feni Betriana Tetsuya Tanioka Yuko Yasuhara hirokazu Ito Ryuichi Tanioka Yoko Nakano Tomoya Yokotani Kyoko Osaka Rozzano Locsin Graduate School of Health Sciences Tokushima University Tokushima Japan Department of Nursing Institute of Biomedical Sciences Graduate School Tokushima University Tokushima Japan Department of Psychiatric Nursing Graduate School of Integrated and Sciences Kochi University Kochi Japan

Robot technology is expected to reduce the burden of medical professionals, a concern in the super-aged society. The aim of this article is to determine the intermediary roles of Public Health Nurses (PHNs) in using Communication Robots (CRs) in Community Health care. It is necessary to consider who will manage, and how to draw lines of responsibility when a problem occurs when using robots in the future. Regarding the mediator or intermediary role of PHNs in the use of CRs, PHNs are expected to be cognizant of varieties of robots for use with persons of diverse ages and health levels, as well as of robot performances. As one of the community healthcare workers who service the elderly living in the community, the role of PHNs as mediators or intermediaries is to pay attention to ethical and moral issues while working with CRs to manage the health of the community. Lack of understanding of the intermediary role might create possible ethico-moral issues in the future. Therefore, it is critical for PHNs to understand their role as intermediaries. In doing so, it is expected that older people at home will be able to live peaceful lives, as well as be physically and mentally healthy.

关键词： Intermediary Roles Public Health Nurses Communication Robots Community Health Care Practice