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Prediction of post-progression survival in patientswith advanced hepatocellular carcinoma treated with sorafenib by using time-dependent changes inclinical characteristics

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Hepatoma Research 2018年第3期4卷 1-8页

作者： Yoshiyuki Wada Yuko Takami Hajime Matsushima Masaki Tateishi Tomoki Ryu munehiro yoshitomi Hideki Saitsu Department of Hepato-Biliary-Pancreatic Surgery Clinical Research InstituteNational Hospital Organization Kyushu Medical CenterFukuoka 810-8563Japan

Aim: Sorafenib has been shown to improve time to tumor progression (TTP) and overall survival (OS) in patients with hepatocellular carcinoma (HCC);however, post-progression survival (PPS) has not been well characterized in these patients. This study aimed to evaluate the predictors of PPS by using time-dependent and dynamic changes in radiologic progression patterns, liver function, and performance status (PS) in patients with advanced HCC receiving sorafenib treatment. Methods: We retrospectively analyzed the clinical characteristics of 128 advanced HCC patients with Child-Pugh scores ≤ 7 at the initiation of sorafenib treatment. Results: The median TTP, OS, and PPS were 3.8, 15.6, and 9.9 months, respectively. At the time of confirmation of radiologic progressive disease (PD), a total of 46 (35.6%) patients showed impairments in their PS of ≥ +1 points over time. For the Child-Pugh score, 27 (21.1%) and 26 (10.9%) patients exhibited an impairment of ≥ +1 and ≥ +2 points, respectively. Multivariate analysis identified the following independent predictors of PPS: impairment in the PS score of ≥+1 point [hazard ratio (HR) 1.81, 95% confidence interval (CI) 1.16-2.82], impairment in the Child-Pugh score of ≥ +2 points (HR 3.70, 95% CI 1.68-8.15), radiologic pattern of progression (target lesion growth and emergence of a new lesion) (HR 2.91, 95% CI 1.79-2.91), a TTP < 4 months(HR 1.87, 95% CI 1.21-2.91), second-line treatment after radiologic confirmation of PD (HR 0.16, 95% CI 0.08-0.32), and continuous sorafenib treatment after radiologic confirmation of PD (HR 1.76, 95% CI 1.06-3.00). Conclusion: PPS in patients with advanced HCC can be characterized by using time-dependent dynamic changes in clinical parameters.

关键词： Contactin-associated protein-2 Isaac neuromuscular hyperexcitability neuromyotonia voltage-gated potassium channel

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Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

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World Journal of Gastroenterology 2012年第28期18卷 3673-3680页

作者： Yoshiki Naito Hironori Kusano Osamu Nakashima Eiji Sadashima Satoshi Hattori Tomoki Taira Akihiko Kawahara Yoshinobu Okabe Kazuhide Shimamatsu Jun Taguchi Seiya Momosaki Koji Irie Rin Yamaguchi Hiroshi Yokomizo Michiko Nagamine Seiji Fukuda Shinichi Sugiyama Naoyo Nishida Koichi Higaki munehiro yoshitomi Masafumi Yasunaga Koji Okuda Hisafumi Kinoshita Masayoshi Kage Masamichi Nakayama Makiko Yasumoto Jun Akiba Hirohisa Yano Departments of Pathology Kurume University School of Medicine Kurume 830-0011 Japan Biostatistics Center Kurume University Kurume 830-0011 Japan Department of Diagnostic Pathology Kurume University Hospital Kurume 830-0011 Japan Division of Gastroenterology Department of Medicine Kurume University School of Medicine Kurume 830-0011 Japan Department of Pathology Omuta City General Hospital Omuta 836-8567 Japan Department of Pathology Asakura Medical Association Hospital Fukuoka 838-0069 Japan Department of Pathology National Hospital Organization Kyushu Medical Center Fukuoka 810-8563 Japan Department of Pathology Shin-Koga Hospital Tenjinkai 120 Tenjincho Kurume 830-0033 Japan Department of Pathology Kurume University Medical Center 155-1 Kokubumachi Kurume 839-0863 Japan Department of Surgery Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Department of Pathology Japanese Red Cross Kumamoto Hospital Kumamoto 861-8520 Japan Division of Surgery Saiseikai Kumamoto Hospital Kumamoto 861-4193 Japan Department of Pathology St Mary's Hospital Kurume 830-8543 Japan Department of Surgery Kurume University School of Medicine Kurume 830-0011 Japan

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

关键词： Intraductal biliary neoplasm Intraductal papillary neoplasm of the bile duct Intraductal tubular neoplasm of the bile duct Intraductal tubulopapillary neoplasm of the bile duct Mucin expression

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Clinicopathological utility of sialoglycoconjugates in diagnosing and treating colorectal cancer

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World Journal of Gastroenterology 2014年第20期20卷 6123-6132页

作者： Yoshinori Inagaki Jianjun Gao Peipei Song Norihiro Kokudo munehiro Nakata Wei Tang Hepato-Biliary-Pancreatic Surgery Division Department of Surgery Graduate School of Medicine the University of Tokyo Tokyo 113-8655 Japan Department of Applied Biochemistry Tokai University Hiratsuka Kanagawa 259-1292 Japan

Aberrant expression of glycoconjugates occurs during malignant transformation of cancer *** of sialoglycoconjugates in particular may play an important role in the progression,i.e.,invasion or metastasis,of *** types of sialoglycoconjugates have been investigated to clarify their biological significance and clinical utility in diagnosing and treating colorectal *** review focuses specifically on expression of mucin(MUC)1 and it suggests that MUC1with the specific structure of a sialo-oligosaccharide has biological significance in determining the metastatic potential of colorectal cancer cells and clinicopathological utility in evaluating the effectiveness of treatments and the prognosis for patients with colorectal *** studies are expected to contribute to the expanded use of cancer-associated sialoglycoconjugates in cancer diagnosis and therapy.

关键词： Sialoglycoconjugates Sialic acid Mucin 1 Colorectal cancer Invasion Metastasis

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Effectiveness of Somatic Balance Restoration Therapy to Alleviate Pain of Musculoskeletal System

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Health 2017年第10期9卷 1390-1403页

作者： munehiro Mike Kayo Yoshiaki Ohkami Institute of System Design and Management Yokohama Japan

Chronic pain and general physical discomfort are common symptoms among those seeking medical or physiotherapy treatment, as it relates to disorders found in the Human Musculoskeletal System (HMS). Since this system is highly complex and large in scale, clinical pain research has been confounded by many complex factors. The goal of our research is to overcome these obstacles by applying multidisciplinary approaches including systems engineering, traditional oriental techniques, conventional medicine and related sciences. To pursue such an integrated approach this paper examines the therapist-guided exercise for restoring human musculoskeletal balance called the Somatic Balance Restoration Therapy (SBRT). The SBRT is a simple but effective self-exercise therapy with minimal assistance by a trained therapist. This therapy is analyzed by a mechanical engineering method by modeling the human body as a multi-body subject to a static equilibrium condition. In addition, the wording has been rewritten in functional anatomical terms, enabling smooth communication between specialists of three different disciplines: therapy, conventional medicine and systems engineering. Examples will be given to demonstrate an integrated and systematic approach for identifying and remedying malfunctions within the HMS.

关键词： Integrated Medicine Self-Exercise Therapy Musculoskeletal Pain Systems Approach

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Modifying oxygen tension affects bone marrow stromal cell osteogenesis for regenerative medicine

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World Journal of Stem Cells 2017年第7期9卷 98-106页

作者： Yusuke Inagaki Manabu Akahane Takamasa Shimizu Kazuya Inoue Takuya Egawa Tsutomu Kira munehiro Ogawa Kenji Kawate Yasuhito Tanaka Department of Orthopedic Surgery Nara Medical University Department of Public Health Health Management and PolicyNara Medical UniversityFaculty of Medicine Departments of Artificial Joint and Regenerative Medicine for Bone and Cartilage Nara Medical University

AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells(MSCs) using osteogenic matrix cell sheets(OMCSs).METHODS Rat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia(21% O_2) for 14 d(NN), normoxia for 7 d followed by hypoxia(5% O_2) for 7 d(NH), hypoxia for 7 d followed by normoxia for 7 d(HN), or hypoxia for 14 d(HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion(ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements,and real-time quantitative *** In the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12(P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type Ⅰ?messenger RNA expression as compared with the NN *** The results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.

关键词： Hypoxia Osteogenesis Tissue engineering Marrow stromal cells Regenerative medicine

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Clinical therapeutic strategies for early stage of diabetic kidney disease

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World Journal of Diabetes 2014年第3期5卷 342-356页

作者： munehiro Kitada Keizo Kanasaki Daisuke Koya Departmen of Diabetology and Endocrinology Kanazawa Medical University

Diabetic kidney disease(DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuousscreening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression.

关键词： Diabetic kidney disease Glycemic control Renin-angiotensin system inhibitor Multifactorial therapy Remission and regression of albuminuria

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Estimation of mineral and trace element intake in vegans living in Japan by chemical analysis of duplicate diets

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Health 2011年第11期3卷 672-676页

作者： munehiro Yoshida Noriko Ogi Yuki Iwashita Laboratory of Food and Nutritional Sciences Faculty of ChemistryMaterials and BioengineeringKansai UniversitySuitaJapan

Thirty-six daily duplicate diet samples were collected from 12 healthy female Japanese vegans and sodium, potassium, calcium, magnesium, phosphorus, iron, zinc, copper, manganese, iodine, selenium, chromium and molybdenum in the diets were measured to estimate mineral and trace element intake by Japanese vegans. Significantly higher intake of potassium, magnesium, phosphorus, iron, copper, manganese and molybdenum was observed in vegans than in general Japanese women, but no difference was observed in sodium, iodine, selenium and chromium intake. Vegan calcium intake tended to be low compared to that of general women but the difference was not significant. Since high potassium, magnesium and iron intakes cannot be achieved by general Japanese diets and high intake of potassium and magnesium may prevent hyperextension and cardiovascular disease in vegans, there are few problems with Japanese vegan diets regarding mineral and trace element intake, except for calcium intake, which is low as it is in the general Japanese people.

关键词： Vegan Mineral intake Trace Element Intake Duplicate Diets Japan

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Dietary Combination of Fish Oil and Hemoglobin Hydrolysates Alters Serum and Liver Lipid Contents in Rat

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Food and Nutrition Sciences 2013年第9期4卷 86-93页

作者： Kenji Fukunaga Noriko Yukawa Ryota Hosomi Toshimasa Nishiyama munehiro Yoshida Department of Life Science and Biotechnology Faculty of Chemistry Materials and Bioengineering Kansai University Suita Japan Department of Life Science and Biotechnology Faculty of Chemistry Materials and Bioengineering Kansai University Suita Japan Department of Public Health Kansai Medical University Hirakata Japan. Division of Food Science and Nutrition Tottori College Kurayoshi Japan

Fish oil has been shown to have anti-inflammatory and anti-cancer effects, and to reduce serum triacylglycerol (TAG) levels by stimulating lipid oxidation and inhibiting lipogenesis in the liver. A small number of studies have demonstrated the synergistic effect of fish oil and other bioactive components. This study examined the effect of fish oil in combination with porcine hemoglobin (Hb) hydrolysates on serum and liver lipid contents in rats. Male Wistar rats were divided into four groups;one group was fed a casein and soybean oil-based semi-purified basal diet and other three groups were fed the basal diet supplemented with 2% fish oil, 0.175% Hb hydrolysates, and 2% fish oil plus 0.175% Hb hydrolysates, respectively, for 4 weeks. The fish oil diet decreased serum and liver TAG contents but did not change serum and liver cholesterol levels. The dietary combination of fish oil and Hb hydrolysates decreased serum and liver TAG and cholesterol contents owing to the additive effect of both compounds, and this diet reduced the serum non-high-density lipoprotein cholesterol content as a result of a synergistic effect. This hypolipidemic effect was in part caused by enhanced excretion of fecal fatty acids, neutral steroids, and acidic steroids. The results of this study suggest that the combined intake of fish oil and Hb hydrolysates may play beneficial roles in the prevention of cardiovascular disease as compared with fish oil alone.

关键词： Fish Oil n-3 Polyunsaturated Fatty Acid Hemoglobin Hydrolysates Lipid Metabolism

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Correlation between Mineral Intake and Urinary Excretion in Free-Living Japanese Young Women

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Food and Nutrition Sciences 2012年第1期3卷 123-128页

作者： munehiro Yoshida Tsutomu Fukuwatari Junya Sakai Tomiko Tsuji Katsumi Shibata Laboratory of Food and Nutritional Sciences Faculty of Chemistry Materials and Bioengineering Kansai University Laboratory of Food Science and Nutrition Department of Lifestyle Studies School of Human Cultures The University of Shiga Prefecture

To clarify whether the urinary excretion of calcium, magnesium, phosphorus, iron, zinc, copper, manganese, selenium and molybdenum can be used as an index of their intake, the association between urinary excretion and intake in free-living individuals was examined. A total of 102 healthy free-living female university dietetics students aged 18 - 33 years voluntarily participated in this study, of which 76 students were eligible for this assessment. All food consumed for four consecutive days was recorded accurately by a weighed food record method. A 24-h urine sample was collected on the fourth day, and the urinary levels of sodium, potassium, calcium, magnesium, phosphorus, iron, zinc, copper, manganese, selenium and molybdenum were measured. Significant correlation between urinary excretion and intake was observed in sodium (r = 0.596, p < 0.001), potassium (r = 0.583, p < 0.001), calcium (r = 0.402, p < 0.001), magnesium (r = 0.365, p < 0.01), phosphorus (r = 0.509, p < 0.001), selenium (r = 0.349, p < 0.01) and molybdenum (r = 0.265, p < 0.01). On the other hand, urinary excretion was very low and completely independent of the intake in iron, zinc, copper and manganese. These results indicate that urinary calcium, magnesium, phosphorus, selenium and mo-lybdenum can be used as an index of their intake, similarly to sodium and potassium.

关键词： Mineral Intake Trace Elements Urinary Excretion Assessment Japanese Young Women

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Efficient hemostatic method for endoscopic submucosal dissection of colorectal tumors

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World Journal of Gastroenterology 2010年第33期16卷 4180-4186页

作者： Naohisa Yoshida Yuji Naito munehiro Kugai Ken Inoue Naoki Wakabayashi Nobuaki Yagi Akio Yanagisawa Toshikazu Yoshikawa Department of Molecular Gastroenterology and Hepatology Kyoto Prefectural University of MedicineGraduate School of Medical Science Department of Surgical Pathology Kyoto Prefectural University of MedicineGraduate School of Medical Science

AIM:To evaluate a new hemostatic method using hemostatic forceps to prevent perforation and perioperative hemorrhage during colonic endoscopic submucosal dissection(ESD).METHODS:We studied 250 cases,in which ESD for colorectal tumors was performed at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and *** developed a new hemostatic method using hemostatic forceps in December 2008 for the efficient treatment of submucosal thick *** was performed on 126 cases after adoption of the new method(the adopted group)and the new method was performed on 102 of these *** was performed on 124 cases before the adoption of the new method (the unadopted group).The details of the new method are as follows:firstly,a vessel was coagulated using the hemostatic forceps in the soft coagulation mode according to the standard procedure,and the coagulated vessel was removed using the forceps in the"endocut" mode without perioperative ***,the partial surrounding submucosa was dissected using the forceps in the endocut *** the current study,we evaluated the efficacy of this ***:Coagulated vessels were successfully removed using the hemostatic forceps in all 102 cases without severe perioperative *** perioperative hemorrhage occurred in five cases(4.9%);however,it was stopped by immediately reuse of the hemostatic *** partial surrounding submucosa was dissected using the forceps in all 102 *** the adopted group,the median operation time was 105 *** proportion of endoscopic en bloc resection was 92.8%(P<0.01)compared to 80.6%in the unadopted *** postoperative hemorrhage and perforation rates were 2.3%and 2.3%.The rate of perforation was significantly lower than that in the unadopted group (9.6%,P<0.01).We evaluated the ease of use of this method by allowing our three trainees to performed ESD on 46 cases,which were accomplished without any severe ***:The new

关键词： Endoscopic submucosal dissection Colorectal tumor Hemostatic forceps Perforation Perioperative hemorrhage

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