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1. Integrated GWAS and mRNA Microarray Analysis Identified IFNG and CD40L as the Central Upstream Regulators in Primary Biliary Cholangitis

Author

Kazuko Ueno, Yoshihiro Aiba, Yuki Hitomi, Shinji Shimoda, Hitomi Nakamura, Olivier Gervais, Yosuke Kawai, Minae Kawashima, Nao Nishida, Seik‐Soon Kohn, Kaname Kojima, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ohta, Takuya Komura, Satoru Tsuruta, Kazuhiko Yamauchi, Tatsuro Kobata, Amane Kitasato, Tamotsu Kuroki, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Kiyoshi Migita, Hiromasa Ohira, Atsushi Tanaka, Hajime Takikawa, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, and PBC‐GWAS Consortium in Japan

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Genome‐wide association studies (GWASs) in European and East Asian populations have identified more than 40 disease‐susceptibility genes in primary biliary cholangitis (PBC). The aim of this study is to computationally identify disease pathways, upstream regulators, and therapeutic targets in PBC through integrated GWAS and messenger RNA (mRNA) microarray analysis. Disease pathways and upstream regulators were analyzed with ingenuity pathway analysis in data set 1 for GWASs (1,920 patients with PBC and 1,770 controls), which included 261 annotated genes derived from 6,760 single‐nucleotide polymorphisms (P 2 versus controls (P

Published
2020
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2. Prognosis of patients with liver cirrhosis: A multi‐center retrospective observational study

Author

Atsushi Naganuma, Tatsuji Komatsu, Shinji Katsushima, Yutaka Mano, Kiyohide Fushimi, Hiroshi Kamitsukasa, Taisuke Jo, Tsutomu Yamashita, Hiromasa Horiguchi, Hayato Yamana, Hideo Yasunaga, Keisuke Ario, Hiroshi Yatsuhashi, Rie Sugimoto, Shinobu Imai, Satoru Tsuruta, and Kazumi Yamasaki

Subjects
medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Proportional hazards model, Retrospective cohort study, medicine.disease, Gastroenterology, Infectious Diseases, Esophageal varices, Internal medicine, Etiology, Medicine, Risk factor, business, Liver cancer, Cohort study
Abstract

Aim Despite advances in the management of liver diseases and changes in the etiology of cirrhosis, few studies have updated the prognosis of cirrhosis. This study aimed to clarify the recent prognosis of cirrhosis and identify risk factors for death. Methods In this retrospective observational study by the Hepatic Disease Network of the National Hospital Organization in Japan, chart reviews were performed to follow patients with cirrhosis beginning in 2011. We conducted Kaplan-Meier survival time analyses stratified by Child-Pugh classification and albumin-bilirubin grade. Cox regression analysis was used to identify risk factors for death. Results We identified 444 eligible patients from 25 hospitals, including 303 (68%), 110 (25%), and 31 (7%) patients with Child-Pugh classes A, B, and C, respectively. Hepatitis C virus infection was the cause of cirrhosis for 63% of the patients. The 1-year and 5-year cumulative survival rates of patients with Child-Pugh classes A, B, and C were 90% and 61%, 78% and 42%, and 65% and 25%, respectively. The 1-year and 5-year cumulative survival rates of patients with albumin-bilirubin grades 1, 2, and 3 were 98% and 80%, 91% and 56%, and 58% and 23%, respectively. Cirrhosis classification (Child-Pugh and albumin-bilirubin), age, liver cancer, and untreated esophageal varices were associated with increased hazard of death. Conclusions Little improvement was observed in the prognosis of cirrhosis compared with previous reports, and the prognosis of Child-Pugh class C cirrhosis remained poor. Untreated esophageal varices were identified as a risk factor for death.

Published
2021

3. A Phase 1 Study of KHK4083: A Single‐Blind, Randomized, Placebo‐Controlled Single‐Ascending‐Dose Study in Healthy Adults and an Open‐Label Multiple‐Dose Study in Patients With Ulcerative Colitis

Author

Etsuji Kaneko, Hiroaki Ito, Shinji Katsushima, Risa Watanabe, Kenichi Furihata, Takuya Morishige, Munetake Shimabe, Yoh Ishiguro, Mayumi Mukai, and Naoki Yoshimura

Subjects
Adult, Male, medicine.medical_specialty, monoclonal, Pharmaceutical Science, Original Manuscript, OX40 Ligand, Antibodies, Monoclonal, Humanized, Placebo, 030226 pharmacology & pharmacy, Gastroenterology, safety and tolerability, Drug Administration Schedule, White People, 03 medical and health sciences, 0302 clinical medicine, Asian People, Japan, Pharmacokinetics, antibody, Internal medicine, medicine, Humans, OX40, Single-Blind Method, Pharmacology (medical), Adverse effect, ulcerative colitis, business.industry, Immunogenicity, Articles, Middle Aged, medicine.disease, Ulcerative colitis, Healthy Volunteers, Treatment Outcome, phase 1, Tolerability, 030220 oncology & carcinogenesis, Pharmacodynamics, Monoclonal, placebo controlled, Administration, Intravenous, Colitis, Ulcerative, Female, business, pharmacokinetics
Abstract

OX40 plays an essential role in maintaining late T‐cell proliferation and survival by suppressing apoptosis and by inducing T‐cell memory formation. Here, we report the results of the phase 1 study of KHK4083, a fully human antimonoclonal antibody specific for OX40. In this study, we aimed to assess the safety and tolerability of a single intravenous or subcutaneous administration of KHK4083 compared with placebo in healthy Japanese and Caucasian subjects and determined the pharmacokinetics (PK) and immunogenicity. Also, we assessed the preliminary efficacy and pharmacodynamics of multiple intravenous doses in Japanese patients with moderate to severe ulcerative colitis (UC). Drug‐related treatment emergent adverse events occurred in 21 healthy subjects (58.3%) and 5 patients with UC (62.5%) after administration of KHK4083. There were no serious adverse events. The PK profile of a single intravenous dose of 10 mg/kg KHK4083 was similar in healthy Japanese and Caucasian subjects. Of 8 UC patients, a clinical response was observed in 3 patients (37.5%) and clinical remission in 2 patients (25.0%) in week 6. Our study demonstrated the safety and tolerability of single and multiple administrations of KHK4083 in healthy Japanese and Caucasian subjects and Japanese patients with moderate to severe UC. It also indicated favorable pharmacological properties of the drug.

Published
2021

4. Integrated GWAS and mRNA Microarray Analysis Identified IFNG and CD40L as the Central Upstream Regulators in Primary Biliary Cholangitis

Author

Toshiki Nikami, Hitomi Nakamura, Takuya Komura, Yuki Hitomi, Kiyoshi Migita, Atsushi Naganuma, Amane Kitasato, Olivier Gervais, Hiroshi Kouno, Atsumasa Komori, Hiromasa Ohira, Minae Kawashima, Hajime Ohta, Seigo Abiru, Yosuke Kawai, Shinji Katsushima, Kaname Yoshizawa, Kazuko Ueno, Hideo Nishimura, Masao Nagasaki, Tamotsu Kuroki, Tatsuji Komatsu, Katsushi Tokunaga, Hajime Takikawa, Shinya Nagaoka, Kazuhiko Yamauchi, Tomohiko Mannami, Seik-Soon Kohn, Kouki Matsushita, Tatsuro Kobata, Hirotaka Kouno, Nao Nishida, Satoru Tsuruta, Fujio Makita, Atsushi Tanaka, Hiroshi Yatsuhashi, Shinji Shimoda, Yoshihiro Aiba, Kazuhiro Sugi, Kaname Kojima, and Minoru Nakamura

Subjects
Messenger RNA, CD40, Hepatology, Microarray analysis techniques, Cell, Genome-wide association study, Original Articles, Computational biology, Biology, medicine.anatomical_structure, Gene expression, medicine, biology.protein, lcsh:Diseases of the digestive system. Gastroenterology, Original Article, lcsh:RC799-869, Gene, Genetic association
Abstract

Genome‐wide association studies (GWASs) in European and East Asian populations have identified more than 40 disease‐susceptibility genes in primary biliary cholangitis (PBC). The aim of this study is to computationally identify disease pathways, upstream regulators, and therapeutic targets in PBC through integrated GWAS and messenger RNA (mRNA) microarray analysis. Disease pathways and upstream regulators were analyzed with ingenuity pathway analysis in data set 1 for GWASs (1,920 patients with PBC and 1,770 controls), which included 261 annotated genes derived from 6,760 single‐nucleotide polymorphisms (P 2 versus controls (P

Published
2020

5. AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

Author

Katsuyoshi Matsuoka, Mamoru Watanabe, Toshihide Ohmori, Koichi Nakajima, Tetsuya Ishida, Yoh Ishiguro, Kazunari Kanke, Kiyonori Kobayashi, Fumihito Hirai, Kenji Watanabe, Hidehiro Mizusawa, Shuji Kishida, Yoshiharu Miura, Akira Ohta, Toshifumi Kajioka, Toshifumi Hibi, Satoshi Motoya, Atsuo Maemoto, Mikihiro Fujiya, Toshifumi Ashida, Mitsuru Goto, Takayuki Matsumoto, Yasuo Suzuki, Yukihiro Hamahata, Tomoo Nakagawa, Naoya Kato, Jun Kato, Yutaka Endo, Ryoichi Suzuki, Koichiro Matsuda, Naoki Ohmiya, Shinji Katsushima, Shuhei Hosomi, Ken-ichi Tarumi, Chiyuki Watanabe, Mitsuru Saito, Yuichiro Yokoyama, Tomoki Inaba, Yasuhisa Sakata, Hitoshi Hongo, Tomoyoshi Shibuya, Kazuhiko Kawakami, Yoichi Kakuta, Atsushi Irisawa, Naoki Yoshimura, Katsuyuki Fukuda, Takayuki Shirai, Hitoshi Ichikawa, Junko Nagata, Takayoshi Suzuki, Kaoru Yokoyama, Takashi Tomidokoro, Yuichiro Kojima, Masahiro Yamada, Hideko Yamamoto, Takayuki Yamamoto, Noriyuki Horiki, Hirozumi Obata, Satoko Inoue, Shinji Tanaka, Tatsuya Toyokawa, Masaki Kunihiro, Takashi Hisabe, Shinichi Ogata, Fuminao Takeshima, Kayoko Matsushima, Nobuyuki Matsuhashi, Hirotake Sakuraba, Masahiro Iwabuchi, Akihiko Tsuchiya, Kan Uchiyama, Takanori Kanai, Masanao Nakamura, Tadashi Yokoyama, Nobuyuki Hida, Keiichi Mitsuyama, Taro Osada, Sakiko Hiraoka, Tomoyuki Tsuzuki, Takashige Masuo, Ryota Hokari, Taku Kobayashi, Masayuki Saruta, Masao Araki, Hiroshi Araki, Masahito Shimizu, Masakazu Kikuchi, Takahiro Nishikawa, Hidetoshi Takedatsu, Kunihiko Aoyagi, Toshiaki Ochiai, Nobuo Toda, Yuji Mizokami, Masakazu Nagahori, Kazuhiro Matsueda, Hitoshi Kino, Akira Kanamori, Tsunehiro Suzuki, Toshiharu Sakurai, Masatoshi Kudo, Atsuo Kitano, Tadakazu Hisamatsu, Shinji Kumagai, Tomoyuki Ninomiya, Kenichiro Mori, Shun-ichi Yoshida, and Mitsuhide Goto

Subjects
Treatment Outcome, Hepatology, Nasopharyngitis, Integrin alpha4, Phenylalanine, Gastroenterology, Humans, Colitis, Ulcerative, Induction Chemotherapy, Mesalamine, Quinazolinones
Abstract

AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis.This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment.Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug.AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis.EA Pharma and Kissei Pharmaceutical.For the Japanese translation of the abstract see Supplementary Materials section.

Published
2021

6. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581]

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byun, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, Maria Consiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton V.J. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris D.J. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom J.W. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch'ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, and Charles Millson

Subjects
Science & Technology, Hepatology, Gastroenterology & Hepatology, Italian PBC Study Group, Japan-PBC-GWAS Consortium, UK-PBC Consortium, Chinese PBC Consortium, 1103 Clinical Sciences, US PBC Consortium, Canadian PBC Consortium, Life Sciences & Biomedicine, PBC Consortia, 1117 Public Health and Health Services
Published
2021

7. IgG4-related disease in the Japanese population: a genome-wide association study

Author

Naoki Kanda, Shigeyuki Kawa, Takahiro Nakazawa, Hideyuki Shiomi, Osamu Hasebe, Takayoshi Nishino, Shuji Kawaguchi, Kazuyoshi Matsumura, Yukitaka Yamashita, Shinji Katsushima, Yoshiya Tanaka, Hisanori Umehara, Mitsuhiro Kawano, Shujiro Yazumi, Toshiyuki Kimura, Fumihiko Matsuda, Terumi Kamisawa, Kenji Hirano, Kozo Kajimura, Hiroshi Tatsuta, Tetsuro Inokuma, Masao Ota, Masaya Ohana, Yasufumi Masaki, Masakazu Shimizu, Atsushi Azumi, Chikashi Terao, Tooru Shimosegawa, Kazushige Uchida, Meiko Takahashi, Ichiro Moriyama, Shoko Matsui, Koh ichi Ohshima, Katsutoshi Kuriyama, Keita Fujikawa, Koichiro Higasa, Yoshitaka Nakai, Takahisa Kawaguchi, Takefumi Nakamura, Hiroyuki Maguchi, Kazuya Setoh, Takashi Akamizu, Tomoki Origuchi, Atsushi Kanno, Seiji Nakamura, Takeshi Iwasaki, Kensuke Kubota, Tsutomu Chiba, Hiroki Takahashi, Mitsushige Shibatoge, Masahiro Shiokawa, Norimoto Gotoh, Yoichiro Kamatani, Kazuo Inui, Eisuke Iwasaki, Izumi Yamaguchi, Takako Saeki, Chiharu Kawanami, Akio Ido, Shigeo Nakamura, Motohisa Yamamoto, Yuzo Kodama, Tsuneyo Mimori, Jun Mimura, Kazuichi Okazaki, Takanobu Tsutsumi, Yasuharu Tabara, Yoshihiro Okabe, and Nobumasa Mizuno

Subjects
Genetics, Linkage disequilibrium, business.industry, Immunology, Single-nucleotide polymorphism, Genome-wide association study, Disease, Human leukocyte antigen, Rheumatology, Immunology and Allergy, Medicine, Allele, business, Genotyping, Imputation (genetics)
Abstract

Summary Background IgG4-related disease is a newly recognised immunopathological entity that includes autoimmune pancreatitis, IgG4-related sialadenitis, and IgG4-related kidney disease. To understand the genetic landscape of IgG4-related disease, we did a genome-wide association study. Methods We did a genome-wide association study of Japanese individuals, initially screening 857 patients with IgG4-related disease at 50 Japanese research institutions and DNA samples from 2082 healthy control participants from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience. From Oct 27, 2008, to July 22, 2014, we enrolled 835 patients and used data from 1789 healthy participants. Only patients with confirmed diagnosis of IgG4-related disease according to the international diagnostic criteria were included. Genotyping was done with the Infinium HumanOmni5Exome, HumanOmni2.5Exome, or HumanOmni2.5 Illumina arrays, and genomic distributions were compared between case and control samples for 958 440 single nucleotide polymorphisms. The HLA region was extensively analysed using imputation of HLA alleles and aminoacid residues. Fine mapping of the FCGR2B region was also done. Associations between clinical manifestations of disease and the genetic variations identified in these two genes were examined. Findings We identified the HLA-DRB1 (p=1·1×10−11) and FCGR2B (p=2·0×10−8) regions as susceptibility loci for IgG4-related disease. We also identified crucial aminoacid residues in the β domain of the peptide-binding groove of HLA-DRB1, in which the seventh aminoacid residue showed the strongest association signal with IgG4-related disease (p=1·7×10−14), as has been reported with other autoimmune diseases. rs1340976 in FCGR2B showed an association with increased FCGR2B expression (p=2·7×10−10) and was in weak linkage disequilibrium with rs1050501, a missense variant of FCGR2B previously associated with systemic lupus erythematosus. Furthermore, rs1340976 was associated with the number of swollen organs at diagnosis (p=0·011) and IgG4 concentration at diagnosis (p=0·035). Interpretation Two susceptibility loci for IgG4-related disease were identified. Both FCGR2B and HLA loci might have important roles in IgG4-related disease development. Common molecular mechanisms might underlie IgG4-related disease and other immune-related disorders Funding The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, and Kyoto University Grant for Top Global University Japan Project.

Published
2019

8. Reducing the risk of developing walled-off necrosis in patients with acute necrotic collection using recombinant human soluble thrombomodulin

Author

Toshinao Itani, Toshihiro Kusaka, Dai Inoue, Masanori Asada, Yoshihisa Tsuji, Tsuyoshi Sanuki, Kosuke Iwane, Takaaki Eguchi, Eiji Funatsu, Kazuki Ikeda, Hitoshi Someda, Y. Takada, Masataka Yokode, Arata Sakai, Hironobu Tokumasu, Kazuyoshi Matsumura, Shujiro Yazumi, Akihiko Okada, Toshihiro Morita, Katsutoshi Kuriyama, Yojiro Sakuma, Hiroshi Seno, Norimitsu Uza, Takao Mikami, Yoshitaka Nakai, Yugo Sawai, Yasushi Kudo, Yoshito Uenoyama, Koichi Fujita, Shinji Katsushima, Chiharu Kawanami, Yuzo Kodama, and Yukimasa Yamashita

Subjects
medicine.medical_specialty, Hepatology, business.industry, Thrombomodulin, Significant difference, medicine.disease, Soluble thrombomodulin, Inverse probability of treatment weighting, Necrosis, Multicenter study, Pancreatitis, hemic and lymphatic diseases, Internal medicine, Walled off necrosis, Acute Disease, medicine, Acute pancreatitis, Humans, Surgery, In patient, business, Retrospective Studies
Abstract

BACKGROUND/PURPOSE The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P

Published
2021

9. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .

Subjects
Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Published
2021

10. [Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography]

Author

Kiyonori, Kusumoto, Yoshitaka, Nakai, Yoshio, Itokawa, Kentaro, Aoki, Masahito, Kawamura, Mitsuya, Kikuchi, Mari, Teramura, Yoko, Oiwa, Toshihiro, Kusaka, Hiroyuki, Kokuryu, Toshihide, Yamaoka, Osamu, Inatomi, and Shinji, Katsushima

Subjects
Cholangiopancreatography, Endoscopic Retrograde, Pancreatitis, Humans, Retrospective Studies
Abstract

The aim of this study was to determine if the difference in serum amylase levels prior to, and two hours following, an endoscopic retrograde cholangiopancreatography (ERCP), or the ratio of the two-hour post-ERCP amylase level to the pre-ERCP amylase level was a better predictor of post-ERCP pancreatitis (PEP).This was a retrospective, single-center study of consecutive patients, who underwent ERCP between April 2015 and August 2018. Serum amylase was measured before and two hours following ERCP. We compared the difference and the ratio of the two levels in predicting PEP using a receiver operating characteristic (ROC) curve analysis.A total of 1029 patients underwent ERCP, with PEP occurring in 118 (11.5%). Multivariate analysis revealed that an elevated two-hour post-ERCP serum amylase level was a significant predictor of PEP. ROC analysis of the difference and the ratio of the two levels found good performance for both parameters, with an area under the curve (AUC) of 0.861 (95% confidence interval [CI], 0.823-0.900) and 0.847 (95% CI, 0.809-0.886), respectively. The difference between the values was a significantly more effective predictor of PEP, based on the AUC analysis (P = 0.011).The difference between pre and two-hour post-ERCP amylase levels is a better predictor of PEP than the ratio of the two.

Published
2020

11. Long‐term safety and efficacy of lanreotide autogel in Japanese patients with neuroendocrine tumors: Final results of a phase II open‐label extension study

Author

Susumu Hijioka, Akira Fukutomi, Atsushi Kudo, Akira Shimatsu, Yasutoshi Kimura, Tetsuhide Ito, Akihiro Nakajima, Shinji Katsushima, Seiichi Hisamatsu, Nao Fujimori, and Yoshitaka Honma

Subjects
medicine.medical_specialty, Phases of clinical research, Antineoplastic Agents, somatostatin, Neuroendocrine tumors, Lanreotide, Peptides, Cyclic, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Japan, Internal medicine, medicine, Humans, 030212 general & internal medicine, Adverse effect, business.industry, clinical trial, Original Articles, General Medicine, medicine.disease, Clinical trial, Neuroendocrine Tumors, Somatostatin, Oncology, chemistry, 030220 oncology & carcinogenesis, Japanese, Original Article, lanreotide, business, neuroendocrine tumor, Progressive disease, Adverse drug reaction
Abstract

Aim The aim of this study was to describe the long‐term safety and efficacy of lanreotide in Japanese patients with neuroendocrine tumors. Methods The final analyses of a 48‐week open‐label phase II study (n = 32) and its extension study (n = 17) were conducted. Patients received 4‐weekly subcutaneous injections of lanreotide autogel 120 mg. Safety was evaluated by adverse events. Efficacy endpoints included tumor response by RECIST and change in tumor size. Post hoc analyses including tumor growth rate were performed. Results The median (range) of lanreotide exposure in the safety analysis set (n = 17) and efficacy analysis set (n = 28) were 151.4 (52–181) and 52.7 (12–181) weeks, respectively. Sixteen patients developed adverse drug reaction; of these, upper abdominal pain and urticaria were not reported before 48 weeks. No patient discontinued lanreotide or died from an adverse event. Two serious events of bile duct stones in one patient were drug‐related. Partial response was observed in 2 patients (7.1%; at 60 and 108 weeks), stable disease in 20 (71.4%) and progressive disease in 6 (21.4%). The mean of the greatest change from baseline in the sum of diameters of target lesions was −5.5%. The mean (standard deviation) tumor growth rate before treatment and from baseline to last observation was 25.3% (35.7%)/month and 6.4% (9.6%)/month, respectively. Conclusion Lanreotide treatment had an acceptable safety profile and was effective over long‐term treatment in Japanese patients with neuroendocrine tumors. No unexpected serious adverse events developed during prolonged use of lanreotide.

Published
2020

12. Contents Vol. 35, 2017

Author

Hobyung Chung, Midori Ando, Takanori Ito, Kayo Seo, Toshiharu Sakurai, Yujiro Nozawa, Natsuko Kobayashi, Toshifumi Tada, Aya Ohtani, Ryuichiro Iwasaki, Soo Ki Kim, Yasuharu Imai, Tomonari Okudaira, Noritomo Shimada, Etsuko Iio, Keiichi Seki, Osamu Nakashima, Ken Kamata, Tadaaki Arizumi, Tomohiro Watanabe, Koji Joko, Hirofumi Izumoto, Michitaka Imai, Hiroshi Ida, Kenichi Harada, Yuka Saijo, Takayuki Iwamoto, Tomohiro Minami, Mamoru Takenaka, Takeshi Okanoue, Akito Iwanaga, Yasuko Umehara, Akemi Tsutsui, Shigeya Hirohata, Yoshitake Hayashi, Takashi Owaki, Shogo Kitahata, Eiji Tsubouchi, Hirokazu Chishina, Soo Ryang Kim, Osakuni Morimoto, Aya Fujinami, Chi Wan Kim, Miho Kaneto, Taisei Murakami, Ke Ih Kim, Koichi Takaguchi, Nobuhura Tamaki, Norihiko Fujita, Yasuhito Tanaka, Yoriaki Komeda, Tomoyuki Ninomiya, Masatoshi Kudo, Tetsuo Takehara, Takashi Kumada, Masashi Kono, Kunihiko Tsuji, Hiroki Sato, Sachiyo Kogita, Susumu Imoto, Hidenori Toyoda, Kazuto Fukuda, Mana Kobayashi, Kazuomi Ueshima, Seitetsu Yoon, Masayoshi Kage, Takumi Igura, Satoko Nakamura, Naoshi Nishida, Shinji Katsushima, Masato Kishida, Atsushi Hiraoka, Toru Ishikawa, Satoru Hagiwara, Takuya Nagano, Kosuke Minaga, Druckerei Stückle, Koichi Mizobuchi, Hidetaro Ueki, Kazuto Tajiri, Akihiro Deguchi, Yoshiyuki Sawai, Terasu Honma, Hironori Ochi, Masahiro Takita, Hideomi Tomida, Eri Morimoto, Hiroyuki Kokuryu, Masanori Nakahara, Keisuke Amano, Toshiaki Yoshida, Marie Ochi, Toyokazu Fukunaga, Yasushi Matsumoto, Tomonori Senoh, Yuji Miyamoto, Masashi Hirooka, Hideki Miyata, Toshiki Komeda, Takashi Hatae, Koichi Tsuneyama, Hiroka Yamago, Kenichiro Mori, Yoichi Hiasa, Airi Kato, Yoshitaka Yamaguchi, Yohei Koizumi, Tomoe Sano, Kojiro Michitaka, Hiroshi Ohashi, Yasunori Minami, Norihisa Yada, Toshihiko Aibiki, Namiki Izumi, Yutaka Horie, and Yoshihiko Yano

Subjects
Traditional medicine, business.industry, Gastroenterology, Medicine, General Medicine, business
Published
2017

13. Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C

Author

Susumu Imoto, Aya Fujinami, Yasuhito Tanaka, Soo Ki Kim, Shigeya Hirohata, Hiroyuki Kokuryu, Toru Ishikawa, Seitetsu Yoon, Toshiki Komeda, Takashi Hatae, Yutaka Horie, Yoshihiko Yano, Shinji Katsushima, Soo Ryang Kim, Keisuke Amano, Masatoshi Kudo, Toyokazu Fukunaga, Hobyung Chung, and Etsuko Iio

Subjects
Innate immune system, medicine.diagnostic_test, business.industry, Hepatitis C virus, Gastroenterology, Single-nucleotide polymorphism, General Medicine, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Interferon, 030220 oncology & carcinogenesis, Immunoassay, Immunology, medicine, 030211 gastroenterology & hepatology, Acute hepatitis C, business, Gene, Genetic association, medicine.drug
Abstract

Background: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown. Aim: This study is aimed at clarifying the factors affecting IFNL3 production and assessing the roles of IFNL3 in AHC. Materials and Methods: A total of 21 AHC patients who visited the hospital within 10 days after symptom onset were assessed. As controls, 23 healthy volunteers (HVs) were examined. Serum IFNL3 levels were quantified using an in-house, IFNL3-specific chemiluminescence enzyme immunoassay (CLEIA) kit. Serum IFNL1, IFN-α, IFN-β, and IFN-γ induced protein-10 (IP-10) levels were assayed using commercial enzyme-linked immunosorbent assay (ELISA) kits. Results: At baseline, serum IFNL3 levels were higher in AHC patients than in HVs (p < 0.0001). The higher levels in AHC patients did not differ between patients with the rs8099917 TT genotype and those with the non-TT (TG/GG) genotype (p = 0.546). Serial measurement of serum IFNL3 levels did not predict the outcome of conventional AHC. However, serum IFNL3 levels at baseline correlated positively with the HCV RNA levels (p = 0.005). Following HCV eradication, serum IFNL3 levels reduced to within the range obtained for HVs. Baseline serum IFNL1 levels did not differ significantly between AHC patients and HVs (p = 0.284). Serum levels of IFNL1 and IFNL3 at baseline also showed no correlative power (p = 0.288). Serum IFN-α and IFN-β were detected together with remarkably high serum IFNL3 levels in only one patient who progressed to acute liver failure (ALF). Conclusion: These findings indicate that serum IFNL3 levels at baseline are higher in AHC patients regardless of the rs8099917 polymorphism, and primary HCV infection triggers the production of IFNL3. As a first line of defense in the innate immune system against invading HCV, increased IFNL3 levels play an important role, but serum IFNL3 levels are not the principal determinant of the clinical course of conventional AHC.

Published
2017

14. Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study

Author

Haruhiro Yamashita, Noriko Watanabe, Toraji Amano, Mototsugu Kato, Masayoshi Ono, Hiroshige Hamada, Yoichiro Iboshi, Shinji Katsushima, Yasuo Takahashi, Kimitoshi Kubo, Hideki Mori, Tatsuya Toyokawa, Hitoshi Nishiyama, Yoshito Ogura, Naohiko Harada, Mio Matsumoto, Nobuyuki Ara, Takashi Kagaya, Hiroki Saito, Yuko Sakakibara, Katsuhiro Mabe, Eiji Masuda, and Toshio Kuwai

Subjects
medicine.medical_specialty, Antiplatelet drug, Endoscopic Mucosal Resection, medicine.drug_class, medicine.medical_treatment, Administration, Oral, Endoscopic mucosal resection, Endoscopy, Gastrointestinal, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Humans, Retrospective Studies, Rivaroxaban, business.industry, Anticoagulant, Gastroenterology, Warfarin, Anticoagulants, Polypectomy, Surgery, 030220 oncology & carcinogenesis, Therapeutic endoscopy, 030211 gastroenterology & hepatology, Apixaban, business, medicine.drug
Abstract

Background/Aims: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. Methods: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. Results: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. Conclusion: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

Published
2019

15. POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33

Author

Takeaki Sato, Hironori Sakai, Tatsuki Ichikawa, Atsushi Naganuma, Atsushi Tanaka, Tatsuo Kanda, Hirotoshi Ebinuma, Masataka Seike, Hidetaka Shibata, Tatsuji Komatsu, Mikio Zeniya, Shinji Uemoto, Toshiki Nikami, Yoko Nakamura, Osamu Yokosuka, Yoshiyuki Ueno, Masaru Harada, Masao Nagasaki, Keisuke Ario, Yuki Hitomi, Haruhiro Yamashita, Yutaka Mano, Michio Senju, Makiko Taniai, Kazuhiko Yamauchi, Satoshi Yamagiwa, Makoto Nakamuta, Fujio Makita, Kazuhiro Sugi, Kouki Matsushita, Kiyoshi Migita, Masahiro Ito, Noriaki Naeshiro, Hajime Takikawa, Kaname Kojima, Noboru Hirashima, Norihiro Kokudo, Shinji Katsushima, Shinya Nagaoka, Hironao Takahashi, Kuniaki Arai, Kazumoto Murata, Etsuko Hashimoto, Masanori Abe, Tsutomu Yamashita, Naohiko Masaki, Minoru Nakamura, Hiroshi Kouno, Atsumasa Komori, Kiyoshi Furuta, Shinji Shimoda, Kaname Yoshizawa, Yoshihiko Maehara, Iwao Yabuuchi, Seigo Abiru, Shotaro Sakisaka, Rie Sugimoto, Hideo Nishimura, Takashi Himoto, Yasuaki Takeyama, Yosuke Kawai, Hiromasa Ohira, Satoru Joshita, Yusuke Shimada, Katsushi Tokunaga, Masahiro Kikuchi, Minae Kawashima, Masao Honda, Hiroshi Kamitsukasa, Toshiki Komeda, Yoshihiro Aiba, Eiji Mita, Hajime Ohta, Nao Nishida, Kazuhiko Nakao, Hiroshi Yatsuhashi, Takeji Umemura, Masaharu Koda, Seiji Tsunematsu, Hirotaka Kouno, Teruko Arinaga-Hino, Kazuko Ueno, Masaaki Shimada, Hitomi Nakamura, Shuichi Kaneko, and Akinobu Takaki

Subjects
0301 basic medicine, Adult, Male, In silico, lcsh:Medicine, Genome-wide association study, Locus (genetics), Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, Pathogenesis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Japan, SNP, Humans, lcsh:Science, Gene, Aged, Genetics, Aged, 80 and over, Multidisciplinary, Effector, Liver Cirrhosis, Biliary, lcsh:R, Middle Aged, 030104 developmental biology, Glucosyltransferases, lcsh:Q, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Article, Scientific reports.9 :102(2019)

Published
2019

17. Double Common Bile Duct

Author

Yoshiyuki Ota, Bunji Endoh, Shinji Katsushima, and Naoki Esaka

Subjects
medicine.medical_specialty, Common bile duct, business.industry, General Medicine, bile duct anomaly, Gastroenterology, medicine.anatomical_structure, Pictures in Clinical Medicine, double common bile duct, Internal medicine, accessory common bile duct, Internal Medicine, medicine, business
Published
2018

18. Selection of regimens for patients with hepatitis C virus genotype/serotype discrepancy

Author

Shinji, Katsushima, Tatsuro, Kobata, Toshiki, Komeda, Seiko, Hamada, Kouki, Chikugo, Shigeharu, Nakano, Tsubasa, Shimogama, Ken, Kumagai, Yoshiyuki, Ohta, Bunji, Endoh, Naoki, Esaka, Satoru, Iwamoto, Katsuhiro, Kasahara, Nobuko, Shima, and Yoshinori, Mizumoto

Subjects
Male, Genotype, Humans, Female, Hepacivirus, Middle Aged, Serogroup, Antiviral Agents, Hepatitis C, Aged, Retrospective Studies
Abstract

In the present study, the usefulness of the resistance-associated variant (RAV) analysis to select direct acting antiviral (DAA) drugs for patients with hepatitis C virus (HCV) genotype/serotype discrepancy was evaluated. The core-genotype and serotype were determined in the 559 patients recruited in the study. The RAV analysis and NS5B-genotype determination were performed in the eight patients who exhibited a genotype/serotype discrepancy. One of these patients exhibited a core-genotype 1b/serotype 2, and detection by RAV analysis was possible in this patient. The other seven patients demonstrated a core-genotype 2/serotype 1, and detection using the RAV analysis was possible in four of them. The NS5B-genotype was 1b in all patients in whom detection using the RAV analysis was possible and was other than 1b in patients in whom detection using the RAV analysis was impossible. The RAV analysis could detect RNA sequences specific to genotype 1b in the NS5A region. Therefore, in patients with genotype/serotype discrepancy in whom detection using the RAV analysis is possible, the treatment regimens should be selected based on the assumption that HCV with genome that is highly homologous to genotype 1b is present in the NS5A region.

Published
2017

19. Antithrombin III for portal vein thrombosis in patients with liver disease: A randomized, double-blind, controlled trial

Author

Takahiro Sato, Keiji Tsuji, Shoichi Matsutani, Shingo Asahara, Kazuo Notsumata, Shozo Hirota, Yukio Osaki, Namiki Izumi, Hisashi Hidaka, Hirofumi Kawanaka, Takumi Igura, Shigehiro Kokubu, Shinji Katsushima, and Tomohiko Akahoshi

Subjects
medicine.medical_specialty, Hepatology, business.industry, Antithrombin, Lumen (anatomy), medicine.disease, Gastroenterology, Confidence interval, law.invention, Portal vein thrombosis, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Infectious Diseases, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, Thrombus, business, Adverse effect, medicine.drug
Abstract

Aim Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT-III). We designed this randomized, double-blind, placebo-controlled trial comparing the safety and efficacy of AT-III for PVT in liver disease patients with those who received no treatment. Methods Eligible patients were diagnosed with the association of thrombus, without tumor thrombus, and thrombus in more than 50% of the cross-sectional lumen of the portal vein. Patients with 70% or less serum level of AT-III were included. The study drug was given up to three times in a 5-day consecutive infusion interval if the thrombus decreased in size. Efficacy was evaluated by contrast enhanced computed tomography using a five-grade scale (complete response, partial response, slight response, no response, and progression). From October 2014 through to March 2016, 36 patients were randomly assigned to the AT-III group and 37 patients to the placebo group. Results The proportion of patients with complete response or partial response of PVT was significantly higher in the AT-III group (55.6%; 20/36 patients; 95% confidence interval, 38.1–72.1) than in the placebo group (19.4%; 7/36 patients, 95% confidence interval, 8.2–36.0) (P = 0.003). The overall incidence of adverse events and adverse drug reactions did not differ significantly between the two groups. Conclusion Antithrombin III is one of the essential therapies for patients with PVT in cases with lower concentration levels of AT-III.

Published
2017

20. Inhibition of hepatocellular carcinoma by PegIFNα-2a in patients with chronic hepatitis C: a nationwide multicenter cooperative study

Author

Kazuaki Chayama, Mie Inao, Tsutomu Kawai, Yoichi Hiasa, Yasuhiro Asahina, Eiji Tanaka, Gotaro Yamada, Makoto Oketani, Hiroshi Yatsuhashi, Namiki Izumi, Osamu Yokosuka, Shinji Katsushima, Yukishige Okamura, Hisataka Moriwaki, Masatoshi Kudo, Takayuki Takeuchi, Hiromitsu Kumada, Kouichi Takaguchi, Hiroshi Adachi, Eiji Kajiwara, Kazuya Kariyama, Joji Toyoda, and Masayuki Kurosaki

Subjects
Male, medicine.medical_specialty, Pathology, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Alpha interferon, Chronic hepatitis C, Gastroenterology, Antiviral Agents, Drug Administration Schedule, Polyethylene Glycols, Japan, Interferon, Surgical oncology, Risk Factors, Internal medicine, medicine, Humans, In patient, Peginterferon, Aged, Retrospective Studies, Original Article—Liver, Pancreas, and Biliary Tract, business.industry, Incidence (epidemiology), Incidence, Liver Neoplasms, Interferon-alpha, Retrospective cohort study, Hepatology, Hepatitis C, Chronic, Middle Aged, medicine.disease, digestive system diseases, Recombinant Proteins, Treatment Outcome, Female, business, medicine.drug
Abstract

Background We investigated whether the administration of maintenance doses of interferon prevented hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Methods Study 1: A multicenter, retrospective, cooperative study was carried out to determine whether long-term administration of low-dose peginterferon alpha-2a (PegIFNα-2a) prevented HCC development in patients with chronic hepatitis C. In total, 594 chronic hepatitis C patients without a history of HCC were enrolled and treated with 90 μg PegIFNα-2a administered weekly or bi-weekly for at least 1 year. Study 2: HCC developed in 16 of 99 additional patients without PegIFNα-2a treatment during 3.8 years of observation. A propensity-matched control study was then carried out to compare the incidence of HCC between the 59 patients who received low-dose PegIFNα-2a (PegIFNα-2a group) and 59 patients who did not receive PegIFNα-2a treatment (control group), matched for sex, age, platelet count, and total bilirubin levels. Results Study 1: HCC developed in 49 patients. The risk of HCC was lower in patients with undetectable hepatitis C virus RNA, ≤40 IU/L alanine aminotransferase (ALT), or ≤10 ng/L alpha-fetoprotein (AFP) 24 weeks after the start of therapy. Study 2: The incidence of HCC was significantly lower in the PegIFNα-2a group than in the control group. Conclusions Low-dose and long-term maintenance administration of PegIFNα-2a decreased the incidence of HCC in patients with normalized ALT and AFP levels at 24 weeks compared with patients without normal ALT and AFP levels.

Published
2012

21. Erratum to: Early diagnosis of pancreatic necrosis based on perfusion CT to predict the severity of acute pancreatitis

Author

Masahiro Shiokawa, Tsukasa Yoshida, Tetsuro Inokuma, Chiharu Kawanami, Sho Koyasu, Nobuyuki Kakiuchi, Yuzo Kodama, Miho Sekimoto, Tsutomu Chiba, Akihiro Okano, Naoki Esaka, Shinji Katsushima, Yoshihiro Nishikawa, Naoki Takahashi, Hiroshi Yamamoto, Ichiro Moriyama, Takafumi Kajitani, Yoshikazu Kinoshita, Yuichi Imanaka, Osamu Kikuchi, Masanori Asada, Yoshihisa Tsuji, Hiroyoshi Isoda, Shujiro Yazumi, and Koji Koizumi

Subjects
medicine.medical_specialty, Necrosis, business.industry, Gastroenterology, medicine.disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Acute pancreatitis, 030211 gastroenterology & hepatology, medicine.symptom, business, Perfusion
Published
2017

22. Low-dose PEG-IFNα2a maintenance therapy significantly reduces serum levels of ALT and AFP in chronic hepatitis C patients compared to glycyrrhizin

Author

Tatsuro Kobata, Yoshio Sumida, Takehiro Sando, Nakamura T, Kawasaki T, Shinji Katsushima, Hirokazu Oyamada, Motoshige Nabeshima, and Masahiro Arai

Subjects
medicine.medical_specialty, Hepatology, business.industry, Low dose, Gastroenterology, chemistry.chemical_compound, Chronic hepatitis, chemistry, Maintenance therapy, Internal medicine, PEG ratio, Immunology, medicine, Glycyrrhizin, business
Abstract

ペグインターフェロン（PEG-IFN）α2aまたはグリチルリチン製剤（強力ネオミノファーゲンC：SNMC）を投与開始し，24週以上継続可能であったC型慢性肝炎64例を対象とし，有効性・安全性をretrospectiveに比較検討した．平均観察期間（中央値，週）はPEG群154，SNMC群145，ALT値（中央値，IU/L）は投与前，24週，48週時点において，PEG群64，34，30，SNMC群80，47，52，AFP値（中央値，ng/mL）は投与前，24週，48週時点において，PEG群12，9.2，7.2，SNMC群12，12.5，18であった．投与中の血小板，Hb，好中球数はSNMC群と比較しPEG群で有意に低値を示したが，減量により全例継続可能であった．PEG群で3例（8％），SNMC群で3例（11％）にHCCが発現した．肝発癌抑制を目的としたPEG-IFNα2a少量及びSNMC療法は，共に肝機能改善効果を認めたが，PEG群で有意にALT値，AFP値が改善した．

Published
2011

23. Early diagnosis of pancreatic necrosis based on perfusion CT to predict the severity of acute pancreatitis

Author

Yoshikazu Kinoshita, Naoki Takahashi, Ichiro Moriyama, Naoki Esaka, Yoshihiro Nishikawa, Masanori Asada, Yuichi Imanaka, Miho Sekimoto, Takafumi Kajitani, Akihiro Okano, Tsutomu Chiba, Hiroshi Yamamoto, Chiharu Kawanami, Yuzo Kodama, Nobuyuki Kakiuchi, Sho Koyasu, Tsukasa Yoshida, Koji Koizumi, Shujiro Yazumi, Yoshihisa Tsuji, Osamu Kikuchi, Shinji Katsushima, Masahiro Shiokawa, Tetsuro Inokuma, and Hiroyoshi Isoda

Subjects
Adult, Male, medicine.medical_specialty, endocrine system diseases, Perfusion Imaging, Severity of Illness Index, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Medicine, Humans, Prospective Studies, Stage (cooking), Medical diagnosis, Aged, Receiver operating characteristic, business.industry, Pancreatitis, Acute Necrotizing, Gastroenterology, Area under the curve, Hepatology, Middle Aged, medicine.disease, Early Diagnosis, ROC Curve, Acute pancreatitis, 030211 gastroenterology & hepatology, Female, Radiology, business, Tomography, X-Ray Computed, Perfusion, Abdominal surgery
Abstract

Perfusion CT can diagnose pancreatic necrosis in early stage of severe acute pancreatitis, accurately. However, no study to date has examined whether early diagnosis of pancreatic necrosis is useful in predicting persistent organ failure (POF). We performed a multi-center prospective observational cohort study to investigate whether perfusion CT can predict the development of POF in the early stage of AP, based on early diagnosis of the development of pancreatic necrosis (PN). From 2009 to 2012, we examined patients showing potential early signs of severe AP (n = 78) on admission. Diagnoses for the development of PN were made prospectively by on-site physicians on the admission based on perfusion CT (diagnosis 1). Blinded retrospective reviews were performed by radiologists A and B, having 8 and 13 years of experience as radiologists (diagnosis 2 and 3), respectively. Positive diagnosis for the development of PN were assumed equivalent to positive predictions for the development of POF. We then calculated the area under the curve (AUC) of the receiver operating characteristic for POF predictions. Fourteen (17.9%) and 23 patients (29.5%) developed PN and POF, respectively. For diagnoses 1, 2, and 3, AUCs for POF predictions were 74, 68, and 73, respectively. Perfusion CT diagnoses pancreatic necrosis and on that basis predicts the development of POF; http://www.umin.ac.jp/ctr/index-j.htm,UMIN000001926 .

Published
2015

24. The usefulness of laparoscopy-assisted distal gastrectomy in comparison with that of open distal gastrectomy for early gastric cancer

Author

Takushi Monden, Yoshiaki Nakano, Hiroshi Yano, Takashi Iwazawa, Shinji Katsushima, Shigeo Matsui, Masakatsu Kinuta, Takeshi Tono, and Toshiyuki Kanoh

Subjects
Male, Cancer Research, medicine.medical_specialty, Distal gastrectomy, Postoperative Complications, Blood loss, Gastrectomy, Stomach Neoplasms, Surgical oncology, Humans, Medicine, Laparoscopy, Retrospective Studies, Laparotomy, medicine.diagnostic_test, business.industry, Mortality rate, Gastroenterology, General Medicine, Length of Stay, Middle Aged, Surgery, Early Gastric Cancer, Treatment Outcome, Oncology, Female, Morbidity, business, Hospital stay, Abdominal surgery
Abstract

Background. The technique of laparoscopy-assisted distal gastrectomy (LADG) was developed for early gastric cancer, but its feasibility and the associated clinical outcome remain unclear. Methods. We reviewed 24 patients who underwent LADG (LADG group) and 35 patients who underwent traditional open distal gastrectomy (ODG group) for early gastric cancer in our hospital, and compared the clinical data of the two groups. Results. The clinical and pathological backgrounds of the patients in the two groups were similar. The duration of surgery was not significantly different between the two groups, but the blood loss in the LADG group was significantly less than that in the ODG group. The number of removed lymph nodes was not significantly different between the two groups. The times to the first passing of flatus, first walking, and the restarting of oral intake; the length of hospital stay; and the duration of epidural analgesia were significantly shorter in the LADG group. The morbidity rate in the LADG group was lower than that in the ODG group. Conclusions. LADG is a safe and minimally invasive surgical technique, after which we can expect a faster recovery.

Published
2001

25. Acute Hepatic Failure following Transcatheter Arterial Embolization for the Treatment of Hepatocellular Carcinoma

Author

Junji Konishi, Teturou Inokuma, Ryo Takeuchi, Yasuhiro Iida, Chohei Shigeno, Hiromichi Oi, Shinji Katsushima, Akinari Hidaka, Jyun Okamura, and Tatsuya Higashi

Subjects
Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Chronic liver disease, Gastroenterology, Risk Factors, Internal medicine, medicine, Humans, Hepatic artery embolization, Embolization, Chemoembolization, Therapeutic, Hepatic encephalopathy, Serum Albumin, Aged, Aged, 80 and over, business.industry, Arterial Embolization, Acute kidney injury, Bilirubin, Acute Kidney Injury, Liver Failure, Acute, Middle Aged, medicine.disease, Surgery, Doxorubicin, Evaluation Studies as Topic, Hepatocellular carcinoma, Multivariate Analysis, Prothrombin Time, Female, Pulmonary Embolism, business, Complication
Abstract

We conducted a retrospective analysis to evaluate the risk factors associated with the occurrence of acute hepatic failure following transcatheter arterial embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a total of 623 embolization procedures in 369 patients with both hepatocellular carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%) experienced hepatic failure as characterized by a rapid increase in serum bilirubin levels and the development of hepatic encephalopathy of grade 2 or higher. These results indicated that the following are risk factors for acute hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.

Published
1997

26. Risk factors for developing colorectal cancer in Japanese patients with ulcerative colitis: a retrospective observational study—CAPITAL (Cohort and Practice for IBD total management in Kyoto-Shiga Links) study I

Author

Shinji Katsushima, Takuya Yoshino, Teruki Oki, Takafumi Kogawa, Yuji Naito, Shigeki Bamba, Tomohisa Takagi, Toshihiro Kusaka, Takuji Kawamura, Tomoyuki Tsujikawa, Hiroshi Nakase, Hirozumi Obata, Chiharu Kawanami, Akira Andoh, and Yusuke Okuyama

Subjects
medicine.medical_specialty, Colorectal cancer, Gastroenterology, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, SURVEILLANCE, medicine, Family history, Colitis, COLORECTAL CANCER, business.industry, Inflammatory Bowel Disease, Retrospective cohort study, medicine.disease, Ulcerative colitis, digestive system diseases, ULCERATIVE COLITIS, 030220 oncology & carcinogenesis, Concomitant, Cohort, 030211 gastroenterology & hepatology, business
Abstract

Background and Aims Patients with ulcerative colitis (UC) are at risk for developing colorectal cancer (CRC), despite the development of new therapeutic agents. Stratification of the individual UC-patient9s risk would be helpful to validate the risk factors for CRC. The aim of this study was to evaluate the risk factors for the development of CRC in a large cohort of patients with UC. Methods Data were obtained from 12 hospitals in the Kyoto-Shiga region during 2003–2013. We performed a retrospective cohort study of 2137 patients with UC. Results In total, 60 lesions of CRC were detected in 43 (2.0%) of 2137 patients. 30 of the 43 patients were male. The median age was 53 years. The median duration of disease was 13 years, and 67.4% of these patients had a disease duration >10 years. Of the 43 patients, 34 (79.1%) had extensive colitis. Primary sclerosing cholangitis was detected in 2 patients (4.7%). The median corticosteroids (CS) dose was 6.4 g, and 4 patients were treated with a total of more than 10 g of CS. 18 of these patients underwent more than 1 year CS treatment. Of all 60 CRC lesions, 43 (71.7%) were located in the distal colon and 35 (58.3%) were of the superficial type. Moreover, the stage of CRC was stage 0 or I in 55.8% of the 43 patients with CRC. Multivariate analysis suggested that extensive colitis could be a risk factor for the development of advanced CRC in patients with UC. Conclusions Our findings indicated that male, extensive colitis, long-term duration of UC and family history of CRC, but not concomitant primary sclerosing cholangitis, are important factors for predicting CRC in Japanese patients with UC. Moreover, long-standing extensive colitis might contribute to the progression of CRC. Further studies are required to establish CRC surveillance in Japanese patients with UC.

Published
2016

27. Mo1901 Long-Term Efficacy and Safety of Thiopurines in Patients With Biologic-Naïve Ulcerative Colitis: A Multicenter Cohort Study

Author

Takafumi Kogawa, Shigeki Bamba, Toshihiro Kusaka, Tomohisa Takagi, Takuji Kawamura, Hiroshi Nakase, Shinji Katsushima, Yuji Naito, Minoru Matsuura, Hirozumi Obata, and Akira Andoh

Subjects
medicine.medical_specialty, Hepatology, business.industry, Internal medicine, Gastroenterology, Medicine, In patient, business, medicine.disease, Ulcerative colitis, Cohort study, Term (time)
Published
2016

28. [A case of epithelioid hemangioendothelioma of the liver: detection by FDG-PET]

Author

Shinji, Katsushima, Toshiki, Komeda, Bunji, Endoh, Yoshinori, Mizumoto, Toru, Watanabe, Nobuko, Shima, Eishi, Adachi, Syuji, Kitaoka, Masamitsu, Hashiba, Teruko, Tomono, Naoki, Esaka, Yoshiyuki, Ohta, Yoshihito, Tanaka, Hiroyuki, Morimoto, Eriko, Kuroda, Rei, Ohta, Takama, Maekawa, and Sachiko, Minamiguchi

Subjects
Fluorodeoxyglucose F18, Positron-Emission Tomography, Liver Neoplasms, Hemangioendothelioma, Epithelioid, Humans, Female, Middle Aged
Abstract

A 57 year-old woman was admitted for focal accumulation of 18F-fluorodeoxyglucose (FDG) in the liver detected by positron emission tomography (PET). A 25- mm hypovascular tumor was detected by computed tomography. Tumor biopsy revealed many atypical cells with positive staining for factor VIII-related-antigen in sinusoids. Right lobectomy was performed and the tumor was diagnosed as epithelioid hemangioendothelioma (EHE) pathologically. We demonstrated that FDG-PET was useful for the diagnosis of EHE and making deciding on therapeutic strategy.

Published
2009

29. Endotoxemia in Patients on Hemodialysis

Author

Shinji Katsushima, Akinari Hidaka, Yoshio Kawaguchi, Junji Konishi, Hiroshi Ideguchi, Toshio Taniguchi, and Kaechoong Lee

Subjects
Adult, Liver Cirrhosis, Male, Amebocyte, medicine.medical_specialty, Resuscitation, Cirrhosis, medicine.medical_treatment, Malignancy, Gastroenterology, Predictive Value of Tests, Renal Dialysis, Neoplasms, Internal medicine, medicine, Humans, False Positive Reactions, Cellulose, Limulus Test, Dialysis, Aged, Aged, 80 and over, biology, business.industry, Membranes, Artificial, Bacterial Infections, Middle Aged, medicine.disease, biology.organism_classification, Endotoxins, Predictive value of tests, Limulus, Immunology, Kidney Failure, Chronic, Female, Reagent Kits, Diagnostic, Hemodialysis, business
Abstract

We examined endotoxins and limulus amebocyte lysate-reactive material (LAL-RM) in serum from 87 patients on hemodialysis, using the conventional chromogenic limulus test (CCLT) and a new specific endotoxin assay with factor G-free LAL (endotoxin-specific test: EST). All patients with regenerated cellulose dialyzers had increased CCLT values, whereas the EST values were not higher than in controls. This discrepancy can be explained by the LAL-RM which is cellulose-derived and cross-reacts with LAL via factor G. Using EST for measurements of endotoxin, 6 patients out of 87 had pathological endotoxemia and all of these patients were associated with either cirrhosis, infection, or malignancy. Some patients who had no complications showed fever before or during dialysis, but they did not have high endotoxin levels. EST is useful for the diagnosis of endotoxemia in patients on hemodialysis because of the presence of LAL-RM in serum. Endotoxemia is rare in patients on hemodialysis, if they are not associated with infection, cirrhosis, or other complications.

Published
1990

31. [Gastrointestinal stromal tumor successfully treated with re-administration of STI571 despite of serious skin rash: a case report]

Author

Hirotoshi, Takemoto, Takeshi, Tono, Shigeo, Matsui, Shinji, Katsushima, Takashi, Iwazawa, Tadashi, Ohnishi, Yoshiaki, Nakano, Hiroshi, Yano, Sigeru, Okamoto, and Takushi, Monden

Subjects
Gastrointestinal Stromal Tumors, Antineoplastic Agents, Piperazines, Pyrimidines, Chemotherapy, Adjuvant, Benzamides, Imatinib Mesylate, Humans, Female, Mesentery, Drug Eruptions, Neoplasm Recurrence, Local, Peritoneal Neoplasms, Aged
Published
2005

32. Risk of HCV transmission after needlestick injury, and the efficacy of short-duration interferon administration to prevent HCV transmission to medical personnel

Author

Katsuji Kohigashi, Takashi Kumada, Takefumi Nakamura, Yukio Osaki, Shinji Katsushima, Akihiro Okano, Yukitaka Yamashita, Shinichi Nishiuma, Hobyung Chung, Hideshi Komori, and Masatoshi Kudo

Subjects
medicine.medical_specialty, Infectious Disease Transmission, Patient-to-Professional, Time Factors, Needlestick injury, Hepatitis C virus, Health Personnel, Alpha interferon, Lower risk, medicine.disease_cause, Antiviral Agents, Risk Assessment, Drug Administration Schedule, Internal medicine, medicine, Humans, Needlestick Injuries, Retrospective Studies, Transmission (medicine), business.industry, Gastroenterology, virus diseases, Interferon-alpha, Retrospective cohort study, Hepatitis C, Hepatology, medicine.disease, digestive system diseases, Immunology, business
Abstract

Background. We carried out this study to assess the risk of hepatitis C virus (HCV) transmission after needlestick injuries in medical personnel, and to evaluate the efficacy of short-duration interferon administration to prevent HCV transmission. Methods. A total of 684 personnel who had been occupationally exposed to an anti-HCV-positive source and followed for more than 3 months were retrospectively examined. Results. Of the 684 subjects, 279 (41%) were treated with 1 to 3 days of interferon either just after or 1 to 12 days after the injury. One case of HCV infection was found in each of the treated (1/279; 0.4%) and nontreated (1/405; 0.2%) groups. There was no significant difference in the transmission of HCV between the two groups. Both infected patients were treated with interferon after developing acute hepatitis, and HCV was subsequently cleared. Conclusions. There is a lower risk of HCV transmission after needlestick accident than previously reported, and short-duration interferon administration at an early stage after the needlestick injury, to prevent HCV transmission, is unnecessary.

Published
2003

33. Risk factors for developing colorectal cancer in Japanese patients with ulcerative colitis: a retrospective observational study--CAPITAL (Cohort and Practice for IBD total management in Kyoto-Shiga Links) study I.

Author

Takuya Yoshino, Hiroshi Nakase, Tomohisa Takagi, Shigeki Bamba, Yusuke Okuyama, Takuji Kawamura, Teruki Oki, Hirozumi Obata, Chiharu Kawanami, Shinji Katsushima, Toshihiro Kusaka, Tomoyuki Tsujikawa, Yuji Naito, Akira Andoh, and Takafumi Kogawa

Published
2016
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34. Dual therapy for third-lineHelicobacter pylorieradication and urea breath test prediction

Author

Toshifumi Hibi, Masahiro Kawanishi, Kenji Noguchi, Norio Kawamura, Masahiko Takahashi, Toshio Kuwai, Hideo Tsuruta, Toshiyuki Yoshio, Takama Maekawa, Toshihiro Nishizawa, Shunsuke Katayama, Eiji Masuda, Takahiro Suzuki, Munehiro Tanaka, Shinji Katsushima, Naohiko Harada, Masanori Ohara, Yuko Nishizawa, Tatsuya Toyokawa, and Hidekazu Suzuki

Subjects
Adult, Male, medicine.medical_specialty, medicine.drug_class, Urea breath test, Rabeprazole, Proton-pump inhibitor, Microbial Sensitivity Tests, macromolecular substances, Sensitivity and Specificity, Gastroenterology, 2-Pyridinylmethylsulfinylbenzimidazoles, Helicobacter Infections, Letters To The Editor, Predictive Value of Tests, Internal medicine, medicine, Humans, Urea, Prospective Studies, Aged, Breath test, Helicobacter pylori, biology, medicine.diagnostic_test, business.industry, Amoxicillin, General Medicine, Middle Aged, Anti-Ulcer Agents, biology.organism_classification, Anti-Bacterial Agents, Surgery, Regimen, Breath Tests, Tolerability, Drug Therapy, Combination, Female, business, medicine.drug
Abstract

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

Published
2012

35. Cholecystokinin-induced regulation of muscarinic receptor on dispersed pancreatic acini

Author

Toyohiko Honda, Shinji Katsushima, Shunsuke Sato, Hideki Adachi, Junji Konishi, Shuichi Onishi, Aoki E, and Masato Noguchi

Subjects
Male, medicine.medical_specialty, Carbachol, Scopolamine Derivatives, Stimulation, Tritium, digestive system, Sincalide, Internal medicine, Muscarinic acetylcholine receptor, medicine, Animals, Secretion, Amylase, Receptor, Pancreas, EC50, Cholecystokinin, Binding Sites, biology, Chemistry, digestive, oral, and skin physiology, Gastroenterology, Rats, Inbred Strains, N-Methylscopolamine, Receptors, Muscarinic, Rats, Endocrinology, Amylases, biology.protein, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract

We have examined the effect of cholecystokinin octapeptide (CCK-8) on the ability of carbamylcholine (carbachol) to inhibit binding of 3H-N-methylscopolamine (3H-NMS) to muscarinic receptors on dispersed acini from rat pancreas. Carbachol bound to muscarinic receptors on rat dispersed pancreatic acini with two different Kd values. EC50 value for the stimulation of amylase secretion by carbachol was well compatible to the calculated Kd value of high affinity binding site of carbachol, suggesting that high affinity binding sites were mainly involved in the secretory response. Simultaneous addition of CCK-8 decreased the ability of carbachol to inhibit binding of 3H-NMS to acini due to an apparent disappearance of high affinity binding site of carbachol. The effective range of concentrations of CCK-8 for such a receptor regulation, as well as the time course of CCK-8 effect, were in good agreement with those for the restriction of carbachol-induced amylase secretion by CCK-8. These findings suggest that the restriction of carbachol-stimulated amylase secretion by CCK-8 is mainly a result of the disappearance of high affinity binding site of muscarinic receptor as a result of CCK-8 administration.

Published
1990

36. Episodic fluctuation in serum intact parathyroid hormone concentration in men

Author

Chohei Shigeno, Teruki Sone, Shigeharu Dokoh, Itsuo Yamamoto, Shuichi Ohta, Tadako Kousaka, Eiji Tadamura, Shiomi K, Junji Konishi, Shinji Katsushima, Kaechoong Lee, and Nobuyasu Kitamura

Subjects
Adult, Male, medicine.medical_specialty, Periodicity, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Pulsatile flow, Parathyroid hormone, Biology, Biochemistry, Time, Eating, Endocrinology, Internal medicine, Gastrins, medicine, Humans, Magnesium, Circadian rhythm, Ultradian rhythm, Whole blood, Calcium metabolism, Immunoradiometric assay, Analysis of Variance, Minerals, Biochemistry (medical), Radioimmunoassay, Phosphorus, Parathyroid Hormone, Immunoradiometric Assay, hormones, hormone substitutes, and hormone antagonists
Abstract

To evaluate the temporal features of physiological fluctuation in serum PTH concentration, we sampled peripheral blood at 4-min intervals for 24 h from five normal men (32.8 yr; range, 26-40 yr) and measured serum PTH levels using a two-site immunoradiometric assay with the exquisite sensitivity and specificity for human PTH-(1-84) (intact PTH). The resultant 24-h time series of serum intact PTH levels were assessed by contemporary techniques in chronophysiology for rhythmic and episodic peak detection. Cosinor analysis disclosed a significant circadian rhythm in serum intact PTH concentrations in all five men, with the mean circadian amplitude and acrophase of 7.2 +/- 4.4 ng/L and 2305 +/- 401 h, respectively (mean +/- SD; n = 5). No apparent fixed ultradian periodicity was found by autocorrelation and spectral analyses. Evaluation of episodic intact PTH pulsatility by Cluster analysis revealed 23.0 +/- 4.4 discrete PTH pulses/24 h (P less than 0.01 vs. signal-free noise), which occurred at an interpulse interval of 61.6 +/- 11.1 min. The average duration of a serum intact PTH peak was 42.8 +/- 7.3 min, and its mean incremental amplitude was 12.6 +/- 1.3 ng/L, which corresponded to a 31.8 +/- 5.2% increase above the preceding nadir. Discrete PTH peaks were separated by nonpulsatile valleys which lasted for 17.9 +/- 4.4 min. Cross-correlation between the time series of serum intact PTH and whole blood ionized calcium (Ca2+) was at its maximum (-0.5) at concurrent time points in three subjects, while significant positive correlation between serum intact PTH and simultaneous serum inorganic phosphorus concentrations was observed in four of five subjects. There was no apparent correlation between the levels of serum intact PTH and serum magnesium. Our data show that serum levels of intact PTH, the only biologically active form of PTH in the blood, is characterized by a significant circadian periodicity, spontaneous episodic pulsatility with distinct peak properties, and a significant temporal coupling with Ca2+ and inorganic phosphorus concentrations. We conclude that PTH secretion, as judged by the temporal pattern of serum intact PTH levels, is pulsatile in normal men.

Published
1990

39. Development of an adrenal cortical carcinoma in systemic lupus erythematosus: A case report

Author

Akinari Hidaka, Yoshio Kawaguchi, Toyohiko Honda, Shinji Katsushima, Toshio Taniguchi, Kaoru Matsuda, Junko Omoto, Yasutaka Tokuda, Tetsuro Inokuma, and Yoshio Onishi

Subjects
Adult, business.industry, General Medicine, medicine.disease, Adrenal Cortex Neoplasms, Text mining, Adrenal Cortex Hormones, Immunology, Carcinoma, Humans, Lupus Erythematosus, Systemic, Medicine, Female, business, Anti-SSA/Ro autoantibodies
Abstract

全身性エリテマトーデス(SLE)の経過中に,機能性副腎皮質癌を発症した1例を経験したので報告する.症例は41才,女性.昭和56年6月, SLEと診断されステロイド療法を受けていたが, 2年5カ月後に高血圧の精査のため施行した腹部超音波, CT検査にて左副腎部に径4cmの腫瘤を認めた.内分泌学的にはmixed syndromeを呈し,術後の組織学的検索の結果は副腎皮質癌であつた.患者は術後約1年で再発のため死亡した. SLEにはリンパ網内系腫瘍の合併が多く,副腎皮質癌の合併は極めてまれと考えられるが,自己免疫疾患の患者に対しては,種々の悪性腫瘍の発生を念頭におき慎重に経過観察する必要があると思われた.

Published
1986

40. Risk of HCV transmission after needlestick injury, and the efficacy of short-duration interferon administration to prevent HCV transmission to medical personnel.

Author

Hobyung Chung, Marisa, Masatoshi Kudo, Marisa, Takashi Kumada, Marisa, Shinji Katsushima, Marisa, Akihiro Okano, Marisa, Takefumi Nakamura, Marisa, Yukio Osaki, Marisa, Katsuji Kohigashi, Marisa, Yukitaka Yamashita, Marisa, Hideshi Komori, Marisa, and Shinichi Nishiuma, Marisa

Subjects
HEPATITIS C virus, INTERFERONS, MEDICAL personnel
Abstract

Background. We carried out this study to assess the risk of hepatitis C virus (HCV) transmission after needlestick injuries in medical personnel, and to evaluate the efficacy of short-duration interferon administration to prevent HCV transmission. Methods. A total of 684 personnel who had been occupationally exposed to an anti­HCV­positive source and followed for more than 3 months were retrospectively examined. Results. Of the 684 subjects, 279 (41%) were treated with 1 to 3 days of interferon either just after or 1 to 12 days after the injury. One case of HCV infection was found in each of the treated (1/279; 0.4%) and nontreated (1/405; 0.2%) groups. There was no significant difference in the transmission of HCV between the two groups. Both infected patients were treated with interferon after developing acute hepatitis, and HCV was subsequently cleared. Conclusions. There is a lower risk of HCV transmission after needlestick accident than previously reported, and short-duration interferon administration at an early stage after the needlestick injury, to prevent HCV transmission, is unnecessary. [ABSTRACT FROM AUTHOR]

Published
2003
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41. [Changes in blood coagulation and fibrinolysis after transcatheter arterial chemoembolization in hepatocellular carcinoma]

Author

Tetsurou Inokuma, Akinari Hidaka, Yoshio Kawaguchi, Hiromichi Natori, R. Takeuchi, Shinji Katsushima, Kaoru Matsuda, Kenichi Nakagawa, Masaoki Fujino, and Hiromichi Ohi

Subjects
Disseminated intravascular coagulation, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, business.industry, medicine.medical_treatment, Fibrinolysis, Liver Neoplasms, General Medicine, Disseminated Intravascular Coagulation, Middle Aged, medicine.disease, Gastroenterology, Embolization, Therapeutic, Internal medicine, Hepatocellular carcinoma, medicine, Coagulation (water treatment), Humans, Female, business, Transcatheter arterial chemoembolization, Blood Coagulation
Abstract

DICは頻度は少ないが重篤な経カテーテル的動脈塞栓術(以下TAE)の合併症である.我々はTAE後のDIC合併死亡例を2例経験する機会を得,この経験からTAEによる凝固線溶系の変動を検討した.対象はchemoembolizationを施行した原発性肝癌45例で, TAE前と1, 2, 4および7日目に凝固線溶検査を行なった.血小板数はTAE翌日より著明に低下し, 2日目には56.9±4.3%(p

Published
1987

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