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High relative fat-free mass is important for maintaining serum albumin levels in patients with compensated liver cirrhosis

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World Journal of Gastroenterology 2005年第9期11卷 1356-1360页

作者： Kazuhiro Kotoh Makoto Nakamuta Marie Fukushima Chitose Matsuzaki Munechika Enjoji hironori sakai Hajime Nawata Department of Medicine and Bioregulatory Science Department of Gastroenterology

AIM: In patients with liver cirrhosis, hypoalbuminemia causes edema and ascites, and a reduction in the quality of life. Since musculature is catabolized to supply amino acids for albumin synthesis in malnutritional cirrhotic patients, muscular volume is hypothesized to play an important role in albumin production. Therefore, we investigated the correlation between serum albumin levels and the fat-free mass (FFM) in cirrhotic ***: Fifty-seven patients (26 males and 31 females)with compensated liver cirrhosis were evaluated. Patients with edema or ascites were excluded from the *** volunteers (n = 104; 48 males and 56 females)were also evaluated as controls. FFM was measured using 5-500 kHz multifrequency bioelectric impedance *** minimize the difference in FFM distribution between males and females, we introduced a new marker, relative FFM (rFFM), which represents the ratio of FFM in a patient relative to that in a volunteer of the same height. Following FFM measurement, the serum albumin levels of patients were assayed ***: In patients with active cirrhosis (alanine aminotransaminase [ALT] ＞50 U/L), both albumin (the difference between maximum and minimum levels) and the standard deviation of albumin levels (SD-albumin) during the observation period showed a significant correlation with rFFM. Multiple linear regression analysis using variables such as rFFM, platelet number, and serum cholesterol levels,choline esterase, albumin, bilirubin, and ALT revealed that rFFM and ALT were significant and independent factors that influenced albumin or SD-albumin in cirrhotic ***: Our results indicate that cirrhotic patients with high rFFM showed less of a decrease in albumin levels, and that the muscle volume is one of the most important factors for maintaining serum albumins level in active cirrhosis. Exercise and protein-rich nutrition at the early stage of liver cirrhosis may be advisable for maintaining or increas

关键词： Muscular volume Fat-free mass (FFM) Multifrequency bioelectric impedance analysis Albumin Liver cirrhosis

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Scattered and rapid intrahepatic recurrences after radio frequency ablation for hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第43期11卷 6828-6832页

作者： Kazuhiro Kotoh Munechika Enjoji Eiichirou Arimura Shusuke Morizono Motoyuki Kohjima hironori sakai Makoto Nakamuta Department of Medicine and Bioregulatory Science Department of Gastroenterology

AIM： To evaluate a series of patients with hepatocellular carcinoma （HCC） treated with several different protocols and devices. METHODS： We treated 138 patients [chronic hepatitis/ liver cirrhosis （Child-Pugh A/B/C）, 3/135 （107/25/3）] with two different devices and protocols： cool-tip needle [initial ablation at 60 W （standard method）（n = 37） or at 40 W （modified method）（n = 28）] or; ablation with a LeVeen needle using a standard single-step, full expansion （single-step） method （n = 39） or a multi-step, incremental expansion （multi-step） method. RESULTS： Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the ablation. Nine patients were treated by the cool-tip original protocol （60 W）（9/37 = 24%） and the other two by the LeVeen single-step method （2/39 = 5%）. The location of the recurrence was surrounding and limited to the site of ablation segment in three cases, and spread over one Iobule or both Iobules in the other eight cases. There was no recurrence in the patients treated with the modified cool-tip modified method （40 W） or the LeVeen multi-step method. CONCLUSION： There is a risk of rapid and scattered recurrence after RFA, especially when the standard cool- tip procedure is used. Because such recurrence would worsen the prognosis, we recommend that modified protocols for the cool-tip and LeVeen needle methods should be used in clinical practice.

关键词： Radio frequency ablation Hepatocellularcarcinoma Cool-tip needle LeVeen needle Recurrence

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Transcatheter arterial embolization for chest wall metastasis of hepatocellular carcinoma

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World Journal of Radiology 2013年第2期5卷 45-48页

作者： Eiki Nagao Masakazu Hirakawa Hiroyasu Soeda Satoru Tsuruta hironori sakai Hiroshi Honda Departments of Clinical Radiology Fukuoka city Hospital Yoshizukahonmachi Fukuoka 812-0046 Japan Departments of Clinical Radiology Kyushu University Beppu Hospital Beppu Oita 874-0838 Japan Departments of Clinical Radiology Beppu Medical Centor Beppu Oita 874-0011 Japan Departments of Gastrointestinal medicine Beppu Medical Centor Beppu Oita 874-0011 Japan Departments of Clinical Radiology Kyushu University Fukuoka 812-8582 Japan

Hemothorax due to rupture of metastatic hepatocellular carcinoma (HCC) is a very rare complication with high mortality because of uncontrollable hemorrhage. A 71-year-old man treated by transcatheter arterial embolization for HCC with massive bleeding from chest wall metastasis is reported. Enhanced computed tomography and selective intercostal angiogram showed a hypervascular mass in the right chest wall and extravasation of contrast agent. After successful transcatheter arterial embolization with gelatin sponge particles and metallic coils, the patient recovered from shock without major complication. To our knowledge, a successfully treated case of hemothorax due to rupture of metastatic HCC has not previously been described.

关键词： Hepatocellular carcinoma Chest wall metastasis Rupture Transcatheter arterial embolization Hemothorax

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Analysis of Serum Antibody Level after COVID-19 Vaccine and Side Effects after Vaccine

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Advances in Infectious Diseases 2023年第2期13卷 249-262页

作者： Hiromi Nagashima Shinji Chiba Shinnosuke Oura Itaru Fujimura Masachika Akiyama Yu Utsumi hironori sakai Wataru Hojo Takuya Iwabuchi Makoto Maemondo Department of Internal Medicine Division of Pulmonary Medicine Iwate Medical University Yahaba Japan R&D Cellspect Co. Ltd. Morioka Japan Department of Medicine Division of Pulmonary Medicine Jichi Medical University Shimotsuke Japan

Background: COVID-19 has caused a large number of deaths, in the elderly. In this situation, vaccines have been considered the main strategy to combat COVID-19 and were developed worldwide in 2020. One problem with COVID-19 vaccination is side effects after vaccination. In this report, we identify the relationship between side effects and elevation of antibodies as determined by monitoring several kinds of antibodies against COVID-19. Objective: We investigated whether the antibody level changed depending on side effects after COVID-19 vaccination. Methods: Healthy volunteers, who received two vaccinations between 10 March and 7 May 2021, were collected for this study. Information including age, gender, smoking history, medical history including allergies and side reactions after vaccination was obtained by questionnaire. Serum levels of antibodies of IgG and IgM against each S1, SP, and NP antigens of COVID-19 were evaluated frequently for 3 - 4 months after the first vaccination. Result: Ten employees working at Iwate Medical University were evaluated in this study. Side effects were observed in 7 of 10 patients, and grade 2 side effects in all 3 patients with a history of allergic disease. Serum S1 and SP IgG were elevated sufficiently in all patients. In all patients, IgG antibody titers fell below the cutoff point in approximately 3 months. No cases had elevated NP antibodies. SP IgM was elevated in three cases;all three cases with elevated IgM had allergic disease and the degree of side effects was relatively higher. Subjects with long-lasting elevated SPIgM were observed. Conclusion: S1 IgG and SP IgG exceeded the cutoff in all subjects after vaccination but decreased below the cutoff in all subjects within 4 months, regardless of side effects or allergic history. On the other hand, elevated SPIgM was suspected to be related to side effects and history of allergies, and cases with persistent elevation of SPIgM were observed.

关键词： COVID-19 Vaccination History of Allergic Disease Side Effect S1 IgG SP IgG SP IgM

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Long-term lamivudine treatment for chronic,hepatitis B in Japanese patients:A project of Kyushu University Liver Disease Study

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World Journal of Gastroenterology 2006年第4期12卷 561-567页

作者： Norihiro Furusyo Hiroaki Takeoka Kazuhiro Toyoda Masayuki Murata Yuichi Tanabe Eiji Kajiwara Junya Shimono Akihide Masumoto Toshihiro Maruyama Hideyuki Nomura Makoto Nakamuta Kazuhiro Takahashi Shinji Shimoda Koichi Azuma hironori sakai Jun Hayashi Department of General Medicine Kyushu University Hospital Department of Environmental Medicine and Infectious Diseases Graduate School of Medical Sciences. Kyushu University Fukuoka Japan Department of Medicine Fukuoka City HospitalFukuoka Japan Department of Internal Medicine Nippon SteelYawata Memorial Hospital Kitakyushu Japan Department of Medicine Yahata SaiseikaiHospital Kitakyushu Japan Department of Clinical Research NationalHospital Organization Kokura Hospital Kitakyushu Japan Department of Medicine KitakyushuMunicipal Medical Center Kitakyushu Japan Department of Internal Medicine ShinKokura Hospital Kitakyushu Japan Department of Medicine and Bioregulatory Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Medicine HamanomachiHospital Fukuoka Japan Department of Medicine and Biosystemic Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Gastroenterology National Hospital Organization Kyushu Medical Center Fukuoka Japan

AIM： To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS： In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 （median 21） mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS： Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL （P〈 0.0001）, HBeAg negativity （P〈 0.0001）, a platelet count of 100×10^9/L or more （P= 0.0162） at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment （P= 0.0003） to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥15 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION： Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

关键词： Hepatitis B virus Lamivudine HBeAg Cirrhosis

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Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2:A project of the Kyushu University Liver Disease Study Group

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World Journal of Gastroenterology 2006年第5期12卷 784-790页

作者： Norihiro Furusyo Masaki Katoh Yuichi Tanabe Eiji Kajiwara Toshihiro Maruyama Junya Shimono hironori sakai Makoto Nakamuta Hideyuki Nomura Akihide Masumoto Shinji Shimoda Kazuhiro Takahashi Koichi Azuma Jun Hayashi Kyushu University Liver Disease Study Group Department of General Medicine Kyushu University HospitalFukuokaJapan Department of Medicine Fukuoka City HospitalFukuokaJapan Department of Internal Medicine Nippon Steel Yawata Memorial HospitalKitakyushuJapan Department of Medicine Kitakyushu Municipal Medical CenterKitakyushuJapan Department of Medicine Yahata Saiseikai HospitalKitakyushuJapan Department of Gastroenterology National Hospital Organization Kyushu Medical CenterFukuokaJapan Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Internal Medicine ShinKokura HospitalKitakyushuJapan Department of Clinical Research National Hospital OrganizationKokura HospitalKitakyushuJapan Department of Medicine and Biosystemic Science Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Medicine Hamanomachi HospitalFukuokaJapan Department of Medicine and Clinical Science Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16

关键词： Hepatitis C virus Interferon Ribavirin Genotype 2

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Relationship between body surface area and ALT normalization after long-term lamivudine treatment

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World Journal of Gastroenterology 2005年第44期11卷 6948-6953页

作者： Makoto Nakamuta Shusuke Morizono Yuichi Tanabe Eiji Kajiwara Junya Shimono Akihide Masumoto Toshihiro Maruyama Norihiro Furusyo Hideyuki Nomura hironori sakai Kazuhiro Takahashi Koichi Azuma Shinji Shimoda Kazuhiro Kotoh Munechika Enjoji Jun Hayashi Kyushu University liver Disease Study Group Department of Medicine and Bioregulatory Science Department of Medicine Department of Internal Medicine Department of Clinical Research Department of Environmental Medicine and Infectious Diseases Department of Gastroenterology Department of Medicine and Clinical Science Department of Medicine and Biosystemic Science

AIM： To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS： We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year （n = 249）, two years （n = 147）, and three years （n = 72） were evaluated from the levels of serum ALT and HBVoDNA, as biological and virological effects （undetectable levels by PCR）, respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBVoDNA, and HBeAg were analyzed. RESULTS： For 1-year treatment, multivariate analysis revealed that BSA （P = 0.0002） was the only factor for the biological effect, and that ALT （P = 0.0017）, HBV- DNA （P = 0.0004）, and HBeAg （P = 0.0021） were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA （P = 0.0147） was the only factor for the biological effect, and that ALT （P = 0.0192） and HBeAg （P = 0.0428） were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA （P = 0.0730） as a factor for the normalization of ALT levels. CONCLUSION： BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.

关键词： Lamivudine Hepatitis B virus Body surface area Dose Long-term treatment

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Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma

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World Journal of Gastroenterology 2013年第20期19卷 3161-3164页

作者： Ichiro Onishi Hirohisa Kitagawa Kenichi Harada Syogo Maruzen Seisyo sakai Isamu Makino hironori Hayashi Hisatoshi Nakagawara Hidehiro Tajima Hiroyuki Takamura Takashi Tani Masato Kayahara Hiroko Ikeda Tetsuo Ohta Yasuni Nakanuma Department of Gastroenterologic Surgery Graduate School of Medical ScienceKanazawa UniversityKanazawa 920-8641Japan Department of Human Pathology Graduate School of Medical ScienceKanazawa UniversityKanazawa 920-8650Japan Pathology Division Kanazawa University HospitalKanazawa 920-8650Japan

We present the first case of an intraductal papillary neoplasm of the bile duct(IPNB) accompanying a mixed adenoneuroendocrine carcinoma(MANEC).A 74-yearold woman presented with fever of unknown *** data revealed jaundice and liver ***-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct,which exhibited early enhancement and papillary *** gastrointestinal endoscopy revealed mucus production from the papilla of Vater,characterized by its protruding and dilated *** ultrasonography visualized the polypoid tumor in the distal bile duct,but no invasive region was suggested by diagnostic ***,the initial diagnosis was *** endoscopic nasobiliary drainage,a pylorus-preserving pancreaticoduodenectomy was *** examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia,indicating pancreaticobiliary-type *** addition,solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were *** revealed expression of the neuroendocrine marker synaptophysin in this solid component,diagnosing it as a neuroendocrine tumor(NET).Furthermore,the MIB-1 proliferation index of NET was higher than that of IPNB,and microinvasion of the NET component was found,indicating neuroendocrine carcinoma(NET G3).This unique case of MANEC,comprising IPNB and NET,provides insight into the pathogenesis of biliary NET.

关键词： Neuroendocrine tumor Intraductal papillary neoplasm of bile duct Intraductal papillary neoplasm of the bile duct Bile duct

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Elevation of the glycated albumin to glycated hemoglobin ratio during the progression of hepatitis C virus related liver fibrosis

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World Journal of Hepatology 2012年第1期4卷 11-17页

作者： Nobuhiro Aizawa Hirayuki Enomoto Hiroyasu Imanishi Masaki Saito Yoshinori Iwata hironori Tanaka Naoto Ikeda Yoshiyuki sakai Tomoyuki Takashima Takashi Iwai Ei-ichiro Moriwaki Soji Shimomura Hiroko Iijima Hideji Nakamura Shuhei Nishiguchi Division of Hepatobiliary and Pancreatic Disease Department of Internal Medicine Hyogo College of Medicine Department of Gasteroenterology Nissay Hospital

AIM: To analyze the relationship between the glycated albumin (GA) to glycated hemoglobin (HbA1c) ratio and the histological grading of liver ***: The study retrospectively included consecutive hepatitis C virus positive chronic liver disease patients (n = 142) who had undergone percutaneous liver biopsy between January 2008 and March 2010 at our institution. The ratios of GA/HbA1c were calculated in all patients to investigate the relationship with the degree of the liver fibrosis. The values of the aspartate aminotransferase-to-platelet ratio index (APRI), an excellent marker for the evaluation of liver fibrosis, were also calculated. In addition, we combined the ratio of GA/HbA1c and the APRI in order to improve our ability to detect the presence of significant liver fibrosis. RESULTS: Sixty-one (43%) patients had either no fibrosis or minimal fibrosis (METAVIR score: F0-F1), while 25 (17%) had intermediate fibrosis (F2). Fifty-six (39%) patients had severe fibrosis (F3-F4) and 27 of them had cirrhosis (F4). The mean values of the GA/HbA1c increased with the progression of the fibrosis (F0-1: 2.83 ± 0.24, F2: 2.85 ± 0.24, F3: 2.92 ± 0.35, F4: 3.14 ± 0.54). There was a significant dif- ference between the F0-F1 vs F4, F2 vs F4, and F3 vs F4 groups (P 3.0) was as follows: its sensitivity

关键词： Glycated albumin Glycated hemoglobin Liver fibrosis Liver biopsy Hepatitis C virus

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Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

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Cancer Communications 2023年第4期43卷 415-434页

作者： Hiroyuki Suzuki Hideki Iwamoto Takahiro Seki Toru Nakamura Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Yasuko Imamura Takashi Niizeki Masahito Nakano Shigeo Shimose Tomotake Shirono Yu Noda Naoki Kamachi Miwa sakai Kazutoyo Morita Masamichi Nakayama Tomoharu Yoshizumi Ryoko Kuromatsu Hirohisa Yano Yihai Cao hironori Koga Takuji Torimura Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume CityFukuokaJapan Liver Cancer Research Division Research Center for Innovative Cancer TherapyKurume UniversityKurume CityFukuokaJapan Iwamoto Internal Medicine Clinic Kitakyushu CityFukuokaJapan Department of Microbiology Tumor and Cell biologyKarolinska InstitutetStockholmSweden Department of Surgery and Science Graduate School of Medical ScienceKyushu UniversityFukuoka CityFukuokaJapan Department of Pathology Kurume University School of MedicineKurume CityFukuokaJapan

Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not *** aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in ***:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC *** evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC *** on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were ***,in vivo genetic and pharmacological gain-and loss-of-function experiments were ***:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall ***,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor ***-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase ***,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib ***:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic *** TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 *** data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

关键词： hepatocellular carcinoma hypoxia IGFBP-1 lenvatinib molecular targeting resistance tyrosine kinase inhibitors

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