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1. Development of a nomogram to predict survival in advanced biliary tract cancer

Author

Hiroshi Imaoka, Masafumi Ikeda, Shogo Nomura, Chigusa Morizane, Takuji Okusaka, Masato Ozaka, Satoshi Shimizu, Kentaro Yamazaki, Naohiro Okano, Kazuya Sugimori, Hirofumi Shirakawa, Nobumasa Mizuno, Sohei Satoi, Hironori Yamaguchi, Rie Sugimoto, Kunihito Gotoh, Keji Sano, Akinori Asagi, Kazuyoshi Nakamura, and Makoto Ueno

Subjects
Medicine, Science
Abstract

Abstract The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno’s concordance index was 0.661 (95% confidence interval [CI] 0.629–0.696) in the training set and 0.640 (95% CI 0.566–0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians’ prognosis-based decision-making.

Published
2023
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2. Undifferentiated embryonal sarcoma of the liver occurring in an adolescent: a case report with genomic analysis

Author

Tomonari Shimagaki, Keishi Sugimachi, Yohei Mano, Emi Onishi, Yuki Tanaka, Rie Sugimoto, Kenichi Taguchi, Masaru Morita, and Yasushi Toh

Subjects
Undifferentiated embryonal sarcoma of the liver, Surgical resection, Adjuvant chemotherapy, Cancer genomic medicine, Surgery, RD1-811
Abstract

Abstract Background Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant mesenchymal tumor that usually occurs in children and is rarely diagnosed in adults. Case presentation The case was a female in her late 20s who presented with a huge liver mass found upon the examination of fever. Imaging analysis showed a well-defined mass measuring 9 cm in the largest dimension in the right posterior segment of the liver. The patient underwent right hemi-hepatectomy. Histopathological studies revealed that the circumscribed tumor was composed of a proliferation of atypical epithelioid to spindle-shaped cells with pleomorphic nuclei arranged in haphazard pattern. Histopathological features observed in immunohistochemical analyses confirmed a final diagnosis of UESL. Genome analysis using FoundationOne CDx revealed 11 somatic mutations including TP53 (R196*) and STK11 (F354L). Adjuvant chemotherapy with ifosfamide and etoposide was performed, and the case has been followed up without recurrence for 1 year after hepatectomy. Conclusions A UESL should be considered in the differential diagnosis of large and well-defined solid liver lesions. Although the prognosis of UESL is extremely unfavorable, aggressive surgical resection with adjuvant chemotherapy and genomic analysis may be helpful for ensuring long-term survival.

Published
2022
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3. Diagnostic benefit of cytological and histopathological examinations for recurrent vaginal cancer metastasizing to the duodenum: A case report

Author

Kenzo Sonoda, Masao Okadome, Rie Sugimoto, Takahiro Fujimoto, Kenichi Taguchi, and Toshiaki Saito

Subjects
cytological diagnosis, duodenal neoplasm, immunohistochemistry, metastatic neoplasm, recurrence, vaginal neoplasm, Medicine, Medicine (General), R5-920
Abstract

Abstract This is the first case report of a vaginal squamous cell carcinoma that metastasized to the duodenum. Cytological and histopathological examinations are useful for the diagnosis of a duodenal metastasis.

Published
2020
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4. Significance of ramucirumab following atezolizumab plus bevacizumab therapy for hepatocellular carcinoma using real‐world data

Author

Shigeo Shimose, Rie Sugimoto, Atsushi Hiraoka, Masatoshi Tanaka, Hideki Iwamoto, Yuki Tanaka, Fujimasa Tada, Hideko Ohama, Takashi Niizeki, Tomotake Shirono, Etsuko Moriyama, Yu Noda, Naoki Kamachi, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, and Takumi Kawaguchi

Subjects
Infectious Diseases, Hepatology
Abstract

Few studies have reported the efficacy and safety of ramucirumab (RAM) after atezolizumab plus bevacizumab (Atezo/Beva) treatment and the overall associated outcomes. Thus, we aimed to evaluate the therapeutic effects and safety of RAM post-treatment with Atezo/Beva.This retrospective study enrolled 46 patients with unresectable hepatocellular carcinoma who were treated with RAM. The patients were classified into the RAM administered following Atezo/Beva failure (n = 12) or RAM administered following other drug failure (n = 34) groups. Progression-free survival (PFS), overall survival (OS), and adverse event (AE) rates were assessed.There were significant differences in the objective response rates and disease control rates between the RAM administered following Atezo/Beva and RAM administered following others groups (objective response rate 33.3%. vs. 0.0%, p = 0.001; disease control rate 83.3% vs. 32.3, p = 0.001). Although there was no significant difference in the OS rates, the median PFS rates in the RAM administered following Atezo/Beva group was significantly higher than in the RAM administered following others group (PFS 3.9 months. vs. 1.9 months, p = 0.047). The AE rates were comparable between the two groups; ascites was the most common AE (45.6%). Using decision tree analysis, the presence of splenomegaly and body mass index (BMI) 19.8 were the first and second splitting variables for RAM-related ascites, respectively.The therapeutic effect of RAM increased in patients with Atezo/Beva failure. Patients with splenomegaly and low BMI should be monitored for ascites during RAM treatment.

Published
2022
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5. Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Author

Takashi Niizeki, Takayuki Tokunaga, Yuko Takami, Yoshiyuki Wada, Masaru Harada, Michihiko Shibata, Kazuhiko Nakao, Ryu Sasaki, Fumihito Hirai, Satoshi Shakado, Tomoharu Yoshizumi, Shinji Itoh, Hiroshi Yatsuhashi, Shigemune Bekki, Akio Ido, Seiichi Mawatari, Koichi Honda, Rie Sugimoto, Takeshi Senju, Hirokazu Takahashi, Takuya Kuwashiro, Tatsuji Maeshiro, Makoto Nakamuta, Yoshifusa Aratake, Tsutomu Yamashita, Yuichiro Otsuka, Shuichi Matsumoto, Tetsuro Sohda, Shigeo Shimose, Kenta Murotani, and Yasuhito Tanaka

Subjects
Bevacizumab, Cancer Research, Carcinoma, Hepatocellular, Oncology, Liver Neoplasms, Humans, Pharmacology (medical), Propensity Score, Retrospective Studies
Abstract

A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear.This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC.This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed.After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007).ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.

Published
2022
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6. Switching to tenofovir alafenamide for nucleos(t)ide analogue‐experienced patients with chronic hepatitis B: week 144 results from a real‐world, multi‐centre cohort study

Author

Eiichi, Ogawa, Makoto, Nakamuta, Toshimasa, Koyanagi, Aritsune, Ooho, Norihiro, Furusyo, Eiji, Kajiwara, Kazufumi, Dohmen, Akira, Kawano, Takeaki, Satoh, Kazuhiro, Takahashi, Koichi, Azuma, Nobuyuki, Yamashita, Naoki, Yamashita, Rie, Sugimoto, Hiromasa, Amagase, Masami, Kuniyoshi, Yasunori, Ichiki, Chie, Morita, Masaki, Kato, Shinji, Shimoda, Hideyuki, Nomura, and Jun, Hayashi

Subjects
Adult, Alanine, Hepatology, Adenine, Gastroenterology, Antiviral Agents, Hepatitis B, Chronic, Treatment Outcome, DNA, Viral, Humans, Pharmacology (medical), Renal Insufficiency, Chronic, Tenofovir, Retrospective Studies
Abstract

Tenofovir alafenamide (TAF) may be preferable to other nucleos(t)ide analogues (NA) regarding outcomes against chronic hepatitis B virus (HBV) infection.To evaluate the longer term virological/biochemical effectiveness of TAF and the renal safety of sequential therapy to TAF in real-world settings METHODS: This multi-centre, retrospective cohort study included consecutive adult patients who were switched from other NAs to TAF. We assessed the virological and biochemical responses up to 144 weeks. We performed sensitivity analyses for a subgroup with chronic kidney disease (CKD) at baseline.We analysed the data of 391 patients with chronic hepatitis B previously treated with entecavir (ETV) (n = 174), tenofovir disoproxil fumarate (TDF) (n = 116) or an NA combination (n = 101) for ≥ 24 months. HBV DNA 10 IU/ml at week 144 was found for 99% of patients, regardless of prior NA regimen or HBV DNA level at baseline. For patients who switched from TDF to TAF, total, low-density lipoprotein, high-density lipoprotein cholesterol and triglycerides were significantly increased after the switch. Patients who switched from a nucleotide analogue to TAF had an improved estimated glomerular filtration rate, although the rate of hypophosphataemia (2.5 mg/dl) remained 9.7% at week 144. The virological and biochemical responses of patients with CKD were similar to the overall results.Switching to TAF remained effective and safe for up to 3 years. Given the increasing comorbidities related to ageing, it will be important to carefully follow the change in the lipid levels of patients with a prior TDF-based regimen.

Published
2022
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7. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Robin Kate Kelley, Makoto Ueno, Changhoon Yoo, Richard S Finn, Junji Furuse, Zhenggang Ren, Thomas Yau, Heinz-Josef Klümpen, Stephen L Chan, Masato Ozaka, Chris Verslype, Mohamed Bouattour, Joon Oh Park, Olga Barajas, Uwe Pelzer, Juan W Valle, Li Yu, Usha Malhotra, Abby B Siegel, Julien Edeline, Arndt Vogel, Mehmet Akce, Immaculada Ales Diaz, Gustavo Alves, Sumitra Anand, Cagatay Arslan, Jamil Asselah, Eric Assenat, Francine Aubin, Li-Yuan Bai, Yuxian Bai, Susan Bates, Stephen Begbie, Irit Ben-Aharon, Nina Beri, Marie-Luise Berres, Jean-Frederic Blanc, Ivan Borbath, Robert Bordonaro, Giovanni Brandi, Adam Burgoyne, Kritiya Butthongkomvong, Ke Cao, Marcela Carballido, Marcos Camandaroba, Stephan Lam Chang, Jen-Shi Chen, Ming-Huang Chen, Xiaoming Chen, Ashley Cheng, Tai-Jan Chiu, Hye Jin Choi, Hong Jae Chon, Joelle Collignon, Antonio Cubillo Gracian, Sarah Davis, Ricardo Saraiva de Carvalho, D.J.A. de Groot, Anne Demols, Judith De Vos, Maria Diab, Jacob Easaw, Martin Eatock, Rawad Elias, Fredericus Eskens, Alfredo Falcone, Plinio Fernandez, Richard Finn, Fabio Franke, Masayuki Furukawa, Olumide Gbolahan, Karen Geboes, Keri-Lee Geneser, Zhimin Geng, Ravit Geva, Roopinder Gillmore, Thorsten Goetze, Hongfeng Gou, Julieta Grasselli, Shanzhi Gu, Mahmut Gumus, Nadia Haj Mohammad, Chunyi Hao, Hakan Harputluoglu, Hassan Hatoum, Volker Heinemann, Wang Kwong Ho, Chiun Hsu, Ayala Hubert, Juneul Hwang, Mevlude Inanc, Soledad Iseas, Vaishnavi Jeyasingam, Paula Jimenez Fonseca, Warren Joubert, Jitlada Juengsamarn, Diego Kaen, Masahi Kanai, Stefan Kasper-Virchow, Ghazaleh Kazemi, Fergal Kelleher, Robin Kelley, Jin Won Kim, Jong Gwang Kim, Ana Beatriz Kinupe Abrahao, Heinz Klumpen, Mark Kochenderfer, Fatih Kose, Ho Ching Lam, Choong-kun Lee, Hyun Woo Lee, Margaret Lee, Myung Ah Lee, Wai Man Sarah Lee, Samuel Le Sourd, Dongliang Li, Wei Li, Houjie Liang, Tingbo Liang, Chun Sen Lim, Brian Lingerfelt, Charles Lopez, John Low, Teresa Macarulla Mercade, David Malka, Yimin Mao, Gianluca Masi, Steven McCune, Ray McDermott, Elaine McWhirter, Guillermo Mendez, Michele Milella, Tomonori Mizutani, Camila Moniz, Luisa Morales, Andres Jesús Munoz Martin, Bruno Nervi, Nuttapong Ngamphaiboon, Sang Cheul Oh, Berna Oksuzoglu, Darryl Outlaw, Mustafa Ozguroglu, Ozgur Ozyilkan, Claudio Painemeal, Yueyin Pan, Chuang Peng, Caroline Petorin, Denis Pezet, Derek Power, Shukui Qin, Aflah Roohullah, Hyewon Ryu, Pamela Salman, Rita Sasidharan, Taroh Satho, Kornelius Schulze, Martin Scott-Brown, Ruben Segovia, Thomas Seufferlin, Salvatore Siena, Isabelle Sinapi, Cristina Smolenschi, Tianqiang Song, Aumkhae Sookprasert, Nopadol Soparattanapaisarn, Naureen Starling, Stacey Stein, Salomon Stemmer, Haichuan Su, Rie Sugimoto, Thatthan Suksombooncharoen, Vincent Tam, Ai Lian Tan, Chih Kiang Tan, Suebpong Tanasanvimon, Giuseppe Tonini, Giampaolo Tortora, Akihito Tsuji, Rodrigo Uribe, Marino Venerito, Helena Verdaguer Mata, Ana Paula Victorino, James Wade, Dirk Thomas Waldschmidt, Lu Wang, Wan Zamaniah Wan Isahk, Harpeet Wasan, Rui Weschenfelder, Chun Yin Wong, Yoke Fui Wong, Suayib Yalcin, Patricio Yanez Weber, Xuezhong Yang, Hisateru Yasui, Ozan Yazici, Chia-Jui Yen, Jieer Ying, Wenchang Yu, Haitao Zhao, Helen Diller Family Comprehensive Cancer Center [San Francisco], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Kyorin University School of Medicine [Tokyo, Japan], Kyorin University [Tokyo, Japan], The University of Hong Kong (HKU), The Chinese University of Hong Kong [Hong Kong], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], University of Manchester [Manchester], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA., and Internal medicine

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine
Abstract

Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. Methods: KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Findings: Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72–0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Interpretation: Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Published
2023
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9. Long‐term hepatic function of patients with compensated cirrhosis following successful direct‐acting antiviral treatment for hepatitis C virus infection

Author

Nobuyuki Yamashita, Aritsune Ooho, Shinji Shimoda, Hideyuki Nomura, Chie Morita, Jun Hayashi, Yasunori Ichiki, Eiji Kajiwara, Eiichi Ogawa, Koichi Azuma, Toshimasa Koyanagi, Takeaki Satoh, Makoto Nakamuta, Kimihiko Yanagita, Naoki Yamashita, Masami Kuniyoshi, Kazuhiro Takahashi, Akira Kawano, Kazufumi Dohmen, Norihiro Furusyo, Masaki Kato, and Rie Sugimoto

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Hepatitis C virus, medicine.disease_cause, Antiviral Agents, Gastroenterology, Cohort Studies, Hepatic function, Internal medicine, medicine, Humans, Decompensation, Stage (cooking), Aged, Hepatology, business.industry, medicine.disease, Hepatitis C, Confidence interval, Treatment Outcome, Cohort, Female, business, Cohort study
Abstract

BACKGROUND AND AIM Direct-acting antivirals (DAAs) have contributed to the improvement of outcomes for all patients with chronic hepatitis C. The aim of this study was to evaluate the long-term hepatic benefits of hepatitis C virus (HCV) cure by DAAs in patients with compensated cirrhosis. METHODS This multicenter cohort study consisted of consecutive patients with compensated cirrhosis who initiated interferon-free DAA treatment before September 2016. The impact of treatment on long-term hepatic function was followed for at least 4 years after the end of treatment, and the progression to decompensation was evaluated. RESULTS The data of 394 patients were available for study. The median age was 70, and 41% had modified albumin-bilirubin (ALBI) grade 2b. During a short-term follow-up 1 year after the end of treatment, FIB-4 index and ALBI score significantly improved. The achievement rates of FIB-4

Published
2021
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10. 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
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11. Factors Contributing to the Prognosis after Second-line Therapy with Ramucirumab in Advanced Hepatocellular Carcinoma

Author

Rie, Sugimoto, Kenta, Motomura, Aritsune, Ooho, Yoshifusa, Aratake, Akihiro, Ueda, Takeshi, Senju, Yuki, Tanaka, Masayoshi, Yada, Kohsuke, Tanaka, Akifumi, Kuwano, Yuusuke, Morita, Shigehiro, Nagasawa, Mari, Ooe, Taiji, Mutsuki, Tsuyoshi, Yoshimoto, Naoki, Yamashita, Mai, Nakashima, Tomonobu, Hioki, Toshimasa, Koyanagi, Nobito, Higuchi, Tsukasa, Nakamura, Shigeru, Harada, Masatake, Tanaka, Seiya, Tada, Takeaki, Satoh, Koutarou, Uchimura, Masami, Kuniyoshi, Makoto, Nakamuta, and Motoyuki, Kohjima

Subjects
Carcinoma, Hepatocellular, Liver Neoplasms, Humans, Bilirubin, alpha-Fetoproteins, Sorafenib, Prognosis, Retrospective Studies
Abstract

Objective Multiple therapeutic agents exist for advanced hepatocellular carcinoma (HCC), but prognostic factors in second-line and subsequent therapies are unclear. Ramucirumab is a molecular-targeted agent effective against hepatocytes with alpha-fetoprotein (AFP)400 ng/mL after sorafenib failure. We examined the prognostic factors and efficacy of ramucirumab with prior therapy other than sorafenib. Methods In our retrospective multicenter study, 33 patients were treated with ramucirumab for HCC with prior therapy other than sorafenib, including 1 patient who received 2 lines of ramucirumab. We analyzed background factors, liver reserve, the prognosis, and treatment duration and efficacy. Results The median albumin-bilirubin (ALBI) value showed little change during ramucirumab treatment. The ALBI value improved in 32% of patients, and their prognoses were better than in those who did not improve. Response and efficacy rates were not as high as those in the REACH-2 study but were similar when limited to patients with 2,500 ng/mL AFP. Thirteen patients received further treatment after ramucirumab failure and they had a significantly better prognosis from ramucirumab administration and also had a significantly better prognosis from the start of the first tyrosine kinase inhibitor than who did not received further treatment. In univariate and multivariate analyses of prognostic factors, the continuation of treatment with another drug after ramucirumab failure and a good ALBI value at initiation were significant. The presence of a ramucirumab response and treatment duration were not associated with the prognosis. A good ALBI value at initiation and ALBI value improvement during treatment were also identified as independent factors associated with eligibility for further treatment after ramucirumab failure. The treatment line did not correlate with the availability of treatment with another drug after treatment failure. Conclusions ALBI value improvement with ramucirumab treatment allows for subsequent treatment after failure and an improved overall prognosis.

Published
2022

12. Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma progressing after molecular targeted therapy: A multicenter prospective observational study

Author

Rie, Sugimoto, Takeaki, Satoh, Akihiro, Ueda, Takeshi, Senju, Yuki, Tanaka, Shinsaku, Yamashita, Toshimasa, Koyanagi, Tomoyuki, Kurashige, Nobito, Higuchi, Tsukasa, Nakamura, Masatake, Tanaka, Yuuki, Azuma, Akari, Ohno, Aritsune, Ooho, Mari, Ooe, Taiji, Mutsuki, Koutarou, Uchimura, Masami, Kuniyoshi, Seiya, Tada, Yoshifusa, Aratake, Tsuyoshi, Yoshimoto, Naoki, Yamashita, Shigeru, Harada, Makoto, Nakamuta, Kenta, Motomura, and Motoyuki, Kohjima

Subjects
Bevacizumab, Carcinoma, Hepatocellular, Phenylurea Compounds, Liver Neoplasms, Quinolines, Humans, Antineoplastic Agents, Molecular Targeted Therapy, Sorafenib, Antibodies, Monoclonal, Humanized
Abstract

To evaluate the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma (HCC) previously treated with molecular targeted agents (MTAs). Thirty-one patients treated with atezolizumab plus bevacizumab for unresectable HCC and previously treated with MTAs were enrolled in this study. The treatment lines ranged from second to sixth lines. The treatment effect on HCC differed from that during first-line treatment. The treatment effect was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST. The treatment response was different for each MTA immediately prior to atezolizumab + bevacizumab treatment. Tumors treated with lenvatinib followed by atezolizumab + bevacizumab showed rapid growth for a short period of time followed by shrinkage. However, patients who received ramucirumab, sorafenib, and regorafenib did not show such changes. This was likely because of differences in the mechanism of action of the MTA administered immediately beforehand. The side-effect profile differed from that observed in the IMbrave150 phase 3 study of atezolizumab plus bevacizumab, which showed more adverse events related to hepatic reserve. Patients treated with the combination of atezolizumab and bevacizumab after lenvatinib therapy may experience rapid tumor growth and subsequent shrinkage.

Published
2022

13. High performance CO2-facilitated transport membrane fabricated by compounding amine-terminated dendrimer in composite of polyvinyl alcohol and water-absorbing agent

Author

Fuminori Ito, Misato Mori, Hidetaka Yamada, Rie Sugimoto, and Yuriko Nishiyama

Subjects
Materials science, integumentary system, Polymers and Plastics, Facilitated diffusion, Composite number, technology, industry, and agriculture, General Chemistry, Polyvinyl alcohol, chemistry.chemical_compound, Membrane, chemistry, Chemical engineering, Compounding, Dendrimer, parasitic diseases, Composite polymer, Materials Chemistry, Ceramics and Composites, Amine gas treating
Abstract

In this study, a high-performance CO2 separation membrane was fabricated by compounding amine-based additives with composite polymers composed of polyvinyl alcohol (PVA) and water-absorbing agents....

Published
2021
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14. Improved indocyanine green retention after short-term lenvatinib withdrawal in three patients with hepatocellular carcinoma

Author

Tomohiro Iguchi, Yoshifusa Aratake, Yuki Tanaka, Hiroki Inada, Yoshihiro Matsumoto, Masami Miki, Masayuki Furukawa, Takeshi Senju, Keishi Sugimachi, Yukihiko Okumura, Akira Nakanishi, Kenichi Taguchi, Rie Sugimoto, Yohei Mano, Terumasa Hisano, and Lingaku Lee

Subjects
Indocyanine Green, Vascular Endothelial Growth Factor A, 0301 basic medicine, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Urology, Case Report, Conversion surgery, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Surgical oncology, Internal medicine, medicine, Lenvatinib, Humans, business.industry, Phenylurea Compounds, Liver Neoplasms, Gastroenterology, General Medicine, Hepatology, medicine.disease, Vascular endothelial growth factor, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Quinolines, Indocyanine green retention test, Liver function, Liver cancer, business, Indocyanine green
Abstract

Use of lenvatinib, which has a high response rate in advanced hepatocellular carcinoma, sometimes results in tumor shrinkage and resectability of previously unresectable liver cancers. In Asia, including Japan, liver reserve, one of the determinants of resectability, is mainly determined by the indocyanine green (ICG) retention rate. Three patients with advanced liver cancer treated at our institution had very poor ICG retention rates during treatment with lenvatinib. Lenvatinib may reduce blood flow in both cancerous and non-cancerous regions by inhibiting vascular endothelial growth factor. Therefore, accurate determination of liver function likely requires withdrawal of this treatment several days before ICG retention testing.

Published
2021
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16. Adenomyomatous hyperplasia of the extrahepatic bile duct: a systematic review of a rare lesion mimicking bile duct carcinoma

Author

Tomohiro Iguchi, Rie Sugimoto, Yasushi Toh, Terumasa Hisano, Masaru Morita, Yohei Mano, Kenichi Taguchi, Keishi Sugimachi, and Yoshihiro Matsumoto

Subjects
medicine.medical_specialty, Pathology, Bile Duct Carcinoma, Malignant transformation, Lesion, 03 medical and health sciences, 0302 clinical medicine, Bile Ducts, Extrahepatic, Surgical oncology, Internal medicine, medicine, Humans, Hyperplasia, Bile duct, business.industry, Gallbladder, Carcinoma, Gastroenterology, General Medicine, Hepatology, medicine.anatomical_structure, Bile Duct Neoplasms, 030220 oncology & carcinogenesis, Etiology, Gallbladder Neoplasms, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract

Adenomyomatous hyperplasia (AH) is a tumor-like inflammatory hyperplastic lesion. In the biliary system, AH commonly arises in the gallbladder, but AH of the extrahepatic bile duct is extremely rare. AH usually develops and is found with symptoms related to biliary stenosis or obstruction, but there are few disease-specific manifestations. It is difficult to make a definitive diagnosis by imaging or cytopathological examination; thus, surgical resections were performed in all past reported cases. The pathophysiological etiology of AH is unknown, but it is considered to be associated with chronic inflammation. According to the epidemiological findings of cases reported to date, the possibility of malignant transformation is considered to be negative. However, the symptoms and imaging findings of AH are difficult to distinguish from those of early-stage bile duct carcinoma. In the current review, we discuss the epidemiology, pathophysiology, diagnosis, and management of AH of the bile duct.

Published
2021
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17. Risk factors for de novo hepatitis B during solid cancer treatment

Author

Takeshi Senju, Masami Miki, Lingaku Lee, Hiroki Inada, Terumasa Hisano, Masayuki Furukawa, Yoshihusa Aratake, Yuji Maruyama, Yuki Tanaka, Risa Hashimoto, Tatsuya Noguchi, Mototsugu Shimokawa, and Rie Sugimoto

Subjects
Hepatitis B core antibody titer, medicine.medical_specialty, HBsAg, Hepatitis C virus, Hepatitis B surface antibody, medicine.disease_cause, Gastroenterology, Virus, 03 medical and health sciences, 0302 clinical medicine, Retrospective Study, Internal medicine, medicine, Hepatitis B virus, Digestion and absorption organ, biology, business.industry, Cancer, Solid cancer treatment, General Medicine, Hepatitis B, medicine.disease, Reactivation, Titer, 030220 oncology & carcinogenesis, biology.protein, 030211 gastroenterology & hepatology, Antibody, business
Abstract

Background Reactivation of hepatitis B virus (HBV) during anticancer treatment is a critical issue. When treating patients with solid tumors, it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive patients, so-called de novo hepatitis B patients. The risk of de novo hepatitis B may vary based on different background factors. Aim To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment. Methods This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies (HBsAbs). The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements. Patient characteristics and disease and treatment information were investigated. HBV DNA measurements were performed using TaqMan polymerase chain reaction (PCR). To identify the risk factors associated with HBV DNA expression, the age, sex, original disease, pathology, treatment method, presence or absence of hepatitis C virus (HCV), and HBsAb and/or HBcAb titers of all subjects were investigated. In patients with HBV DNA, the time of appearance, presence of HBsAgs and HBsAbs at the time of appearance, and course of the subsequent fluctuations in virus levels were also investigated. Results Among the 1040 patients, 938 were HBcAb positive, and 102 were HBcAb negative and HBsAb positive. HBV DNA expression was observed before the onset of treatment in nine patients (0.9%) and after treatment in 35 patients (3.7%), all of whom were HBcAb positive. The HBV reactivation group showed significantly higher median HBcAb values [9.00 (8.12-9.89) vs 7.22 (7.02-7.43), P = 0.0001] and significantly lower HBsAb values (14 vs 46, P = 0.0342) than the group without reactivation. Notably, the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption (79.0% vs 58.7%, P = 0.0051). A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation (multivariate analysis, P = 0.0002 and P = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 vs day 193), and the frequency of reactivation within 6 mo was significantly higher in this group (P = 0.0459) than in the other group. Conclusion A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.

Published
2020

18. Factors for improving the performance of the separation membranes prepared by the blending of polyvinyl alcohol and a water absorbing agent

Author

Misato Mori, Rie Sugimoto, Yuriko Nishiyama, Hidetaka Yamada, and Fuminori Ito

Subjects
chemistry.chemical_compound, Membrane, Materials science, integumentary system, Polymers and Plastics, chemistry, Chemical engineering, General Chemical Engineering, technology, industry, and agriculture, Materials Chemistry, Polyvinyl alcohol
Abstract

This study investigated different factors to improve the separation performance of membranes composed of polyvinyl alcohol (PVA) and a water absorbing agent. The effects of the compositional differ...

Published
2020
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19. Development of Hepatocellular Carcinoma in Patients Aged 75–84 Years With Chronic Hepatitis C Treated With Direct-Acting Antivirals

Author

Eiji Kajiwara, Takeaki Satoh, Makoto Nakamuta, Kazuhiro Takahashi, Koichi Azuma, Toshimasa Koyanagi, Masami Kuniyoshi, Jun Hayashi, Kazufumi Dohmen, Aritsune Ooho, Chie Morita, Norihiro Furusyo, Hideyuki Nomura, Kimihiko Yanagita, Akira Kawano, Eiichi Ogawa, Shinji Shimoda, Hiromasa Amagase, Yasunori Ichiki, Rie Sugimoto, and Masaki Kato

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, Sustained Virologic Response, Hepatitis C virus, Hepacivirus, medicine.disease_cause, DIRECT ACTING ANTIVIRALS, Antiviral Agents, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Chronic hepatitis, Internal medicine, medicine, Humans, Immunology and Allergy, Aged, Retrospective Studies, business.industry, Incidence (epidemiology), Liver Neoplasms, Hazard ratio, Middle Aged, Hepatitis C, Chronic, medicine.disease, Hepatitis C, Infectious Diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, 030211 gastroenterology & hepatology, business, Cohort study
Abstract

Background Direct-acting antiviral (DAA) treatment has revolutionized hepatitis C virus (HCV) care. We aimed to evaluate the risk for the development of hepatocellular carcinoma (HCC) in patients aged 75–84 years with chronic hepatitis C after HCV elimination. Methods This multicenter cohort study included 2405 consecutive patients with chronic hepatitis C without a history of HCC who achieved HCV elimination by DAAs. Patients in whom HCC developed within 1 year of DAA initiation were excluded. Propensity score matching analysis was used to evaluate differences in HCC risk between patients aged 75–84 versus 60–74 years. Results The median observational period was 3.5 years. Among patients aged 75–84 years with a high Fibrosis-4 (FIB-4) index (≥3.25 at baseline), there was no significant difference in the annual incidence of HCCs between groups with an FIB-4 index ≥3.25 (2.75 per 100 person-years [PY]) versus Conclusions Older patients aged 75–84 years remained at high risk for the development of HCC, even after HCV elimination and the improvement of the FIB-4 index to

Published
2020
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21. Loss of adipose tissue or skeletal muscle during first‐line gemcitabine/nab‐paclitaxel therapy is associated with worse survival after second‐line therapy of advanced pancreatic cancer

Author

Masayuki Furukawa, Rie Sugimoto, Masami Miki, Lingaku Lee, and Terumasa Hisano

Subjects
medicine.medical_specialty, Cachexia, Paclitaxel, FOLFIRINOX, medicine.medical_treatment, Adipose tissue, Deoxycytidine, Gastroenterology, Albumins, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Muscle, Skeletal, Chemotherapy, Performance status, business.industry, Skeletal muscle, General Medicine, medicine.disease, Gemcitabine, Pancreatic Neoplasms, C-Reactive Protein, medicine.anatomical_structure, Adipose Tissue, Oncology, business, medicine.drug
Abstract

AIM Progression of cachexia indicated by decreased body weight and composition is associated with poor survival of advanced pancreatic cancer (APC). There are limited data concerning the prognostic effect of cachexia on second-line chemotherapy (L2). We aimed to assess the impact of cachexia progression during first-line therapy (L1) on survival after L2. METHODS We reviewed patients with gemcitabine/nab-paclitaxel (GEM/nabPTX)-refractory APC who underwent L2 with modified FOLFIRINOX or S-1 between 2015 and 2019 in our institution. We determined clinicopathological data including body composition parameters: subcutaneous fat area (SFA), visceral fat area (VFA), and skeletal muscle index (SMI). Correlations of changes in these parameters, as well as their effect on overall survival after L2 (OS2), were examined. RESULTS Median rates of change in SMI, SFA, and VFA were 0.19%, -4.17%, and -18.39%, respectively, in 59 patients during L1. Although there was moderate correlation in rate of change between SFA and VFA, there was no correlation between SMI and other parameters. We defined loss of SFA, VFA, and SMI as decreases greater than 8.5%, 34.1%, and 8.7%, respectively. Median OS2 of patients with loss in any of these parameters was significantly shorter than in patients without loss (3.83 vs. 8.73 months). Multivariate analysis revealed that loss in any parameters, performance status, and C-reactive protein/albumin ratio were independent negative prognostic factors. CONCLUSION Loss of adipose tissue or skeletal muscle during L1 had a considerable impact on OS2 in APC refractory to GEM/nabPTX.

Published
2021
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22. 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

25. Initial experience with the combination of atezolizumab and bevacizumab in patients with unresectable hepatocellular carcinoma progressing after tyrosine kinase inhibitor therapy: A multicenter prospective observational study

Author

Takeshi Senju, Koutarou Uchimura, Tomoyuki Kurashige, Kenta Motomura, Yuki Tanaka, Seiya Tada, Rie Sugimoto, Yoshifusa Aratake, Aritsune Ooho, Tsukasa Nakamura, Masami Kuniyoshi, Motoyuki Kohjima, Toshimasa Koyanagi, Shinsaku Yamashita, Masatake Tanaka, Akihiro Ueda, Takeaki Satoh, and Nobito Higuchi

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, business.industry, medicine.drug_class, medicine.disease, Tyrosine-kinase inhibitor, Text mining, Atezolizumab, Hepatocellular carcinoma, Internal medicine, medicine, In patient, Observational study, business, medicine.drug
Abstract

Background There is no evidence for the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma previously treated with tyrosine kinase inhibitors (TKIs). Methods Twelve patients treated with atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma (HCC) and previously treated with TKIs were enrolled in the study. Results The treatment lines ranged from second line to sixth line. HCC staging was Barcelona Clinic Liver Cancer (BCLC) stage B in four cases and BCLC stage C in eight cases. The overall response rate and disease control rate according to the response evaluation criteria in solid tumors (RECIST) were 18.1% and 54.4%, respectively. Progression-free survival was 2.7 months, indicating that early response to treatment may differ depending on the type of previous therapy. The side effects profile also differed from that observed in IMbrave150, a phase 3 trial of atezolizumab plus bevacizumab, with many adverse events related to liver reserve. Conclusions The therapeutic effects and side effects differed from those previously reported during the treatment course of atezolizumab plus bevacizumab as first-line therapy.

Published
2021
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26. [A case of obstructive jaundice and duodenal stenosis caused by vaginal cancer and retroperitoneal metastasis]

Author

Tatsuya, Noguchi, Rie, Sugimoto, Sho, Yasumori, Risa, Hashimoto, Takeshi, Senju, Yoshifusa, Aratake, Terumasa, Hisano, Masayuki, Furukawa, and Kenichi, Taguchi

Subjects
Jaundice, Obstructive, Vaginal Neoplasms, Intestinal Atresia, Humans, Female, Duodenal Obstruction, Retroperitoneal Neoplasms, Aged
Abstract

A 76-year-old woman with a history of radiation therapy for vaginal cancer was referred to our hospital because of fever and hepatobiliary dysfunction. Computed tomography showed stenosis of the lower bile duct and edema-like changes in the duodenum from the descending to transverse parts. Endoscopic biliary stenting was performed according to the rendezvous method. Squamous cell carcinoma, similar to vaginal cancer, was found on pathological examination of the duodenum. We accordingly diagnosed obstructive jaundice and duodenal stenosis caused by vaginal cancer and retroperitoneal metastasis. To the best of our knowledge, other such cases have not been reported.

Published
2021

27. Sequential HBV Treatment With Tenofovir Alafenamide for Patients With Chronic Hepatitis B: Week 96 Results From a Real-world, Multicenter Cohort Study

Author

Kazuhiro Takahashi, Naoki Yamashita, Eiichi Ogawa, Chie Morita, Nobuyuki Yamashita, Shinji Shimoda, Akira Kawano, Aritsune Ooho, Eiji Kajiwara, Masami Kuniyoshi, Hideyuki Nomura, Kazufumi Dohmen, Hiromasa Amagase, Koichi Azuma, Toshimasa Koyanagi, Takeaki Satoh, Makoto Nakamuta, Jun Hayashi, Rie Sugimoto, Yasunori Ichiki, and Norihiro Furusyo

Subjects
medicine.medical_specialty, Chronic hepatitis, business.industry, Internal medicine, medicine, business, Tenofovir alafenamide, Cohort study
Abstract

Background and AimsOutcome data of sequential hepatitis B virus treatment with tenofovir alafenamide (TAF) are limited. We aimed to assess the effectiveness and renal safety of TAF in chronic hepatitis B (CHB) patients who were previously treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or nucleos(t)ide analog (NA) combination. MethodsThis multicenter, retrospective, cohort study included 458 consecutive CHB patients who switched to TAF monotherapy after at least two years of treatment with another NA. The longitudinal virological/laboratory responses were evaluated up to 96 weeks after switchover. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR)2. ResultsThe proportions of HBV DNA suppression (HBV DNAPP

Published
2021
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28. Sequential HBV treatment with tenofovir alafenamide for patients with chronic hepatitis B: week 96 results from a real-world, multicenter cohort study

Author

Eiichi, Ogawa, Makoto, Nakamuta, Toshimasa, Koyanagi, Aritsune, Ooho, Norihiro, Furusyo, Eiji, Kajiwara, Kazufumi, Dohmen, Akira, Kawano, Takeaki, Satoh, Kazuhiro, Takahashi, Koichi, Azuma, Nobuyuki, Yamashita, Naoki, Yamashita, Rie, Sugimoto, Hiromasa, Amagase, Masami, Kuniyoshi, Yasunori, Ichiki, Chie, Morita, Masaki, Kato, Shinji, Shimoda, Hideyuki, Nomura, and Jun, Hayashi

Subjects
Male, Hepatitis B virus, Alanine, Hepatitis B Surface Antigens, Adenine, Antiviral Agents, Cohort Studies, Hepatitis B, Chronic, Treatment Outcome, DNA, Viral, Humans, Female, Renal Insufficiency, Chronic, Tenofovir, Retrospective Studies
Abstract

Outcome data of sequential hepatitis B virus treatment with tenofovir alafenamide (TAF) are limited. We aimed to assess the effectiveness and renal safety of TAF in chronic hepatitis B (CHB) patients who were previously treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or a nucleos(t)ide analogue (NA) combination.This multicenter, retrospective, cohort study included 458 consecutive CHB patients who switched to TAF monotherapy after at least 2 years of treatment with another NA. The longitudinal virological/laboratory responses were evaluated up to 96 weeks after switchover. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 mThe proportions of complete viral suppression (CVS) (HBV DNA 20 IU/mL) at week 96 were 99.0%, 98.5%, and 98.4% in the prior ETV (n = 198), TDF (n = 137), and NA combination (n = 123) groups, respectively. Almost all patients with HBV DNA of 20-2000 IU/mL at baseline achieved CVS at week 96. On multivariable generalized estimated equation analysis, a low quantitative hepatitis surface antigen (qHBsAg) level at baseline was associated with a lower follow-up qHBsAg level (coefficient 0.81, p 0.001). The eGFR showed greater improvement in patients with CKD compared to those without (coefficient 21.7, p 0.001). However, the increase of eGFR reached a peak between weeks 24 and 48.Based on this longitudinal data analysis up to 96 weeks, sequential NA therapy with a switch to TAF is a good option to achieve high viral suppression and renal safety.

Published
2021

29. Survival Benefit of Hepatic Arterial Infusion Chemotherapy over Sorafenib in the Treatment of Locally Progressed Hepatocellular Carcinoma

Author

Hideki, Iwamoto, Takashi, Niizeki, Hiroaki, Nagamatsu, Kazuomi, Ueshima, Takako, Nomura, Teiji, Kuzuya, Kazuhiro, Kasai, Yohei, Kooka, Atsushi, Hiraoka, Rie, Sugimoto, Takehiro, Yonezawa, Akio, Ishihara, Akihiro, Deguchi, Hirotaka, Arai, Shigeo, Shimose, Tomotake, Shirono, Masahito, Nakano, Shusuke, Okamura, Yu, Noda, Naoki, Kamachi, Miwa, Sakai, Hiroyuki, Suzuki, Hajime, Aino, Norito, Matsukuma, Satoru, Matsugaki, Kei, Ogata, Yoichi, Yano, Takato, Ueno, Masahiko, Kajiwara, Satoshi, Itano, Kunitaka, Fukuizumi, Hiroshi, Kawano, Kazunori, Noguchi, Masatoshi, Tanaka, Taizo, Yamaguchi, Ryoko, Kuromatsu, Atsushi, Kawaguchi, Hironori, Koga, Takuji, Torimura, New Fp Study Group, and Kurume Liver Cancer Study Group Of Japan

Subjects
Oncology, Sorafenib, Cancer Research, medicine.medical_specialty, molecular targeted therapy, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Hepatic arterial infusion chemotherapy, medicine, Overall survival, intra-arterial infusions, neoplasms, Cisplatin, business.industry, hepatocellular carcinoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, digestive system diseases, Regimen, Survival benefit, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, 030211 gastroenterology & hepatology, sorafenib, business, medicine.drug
Abstract

BACKROUND: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. METHODS: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib, 1624 (New-FP, n = 644, sorafenib n = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed (n = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment. RESULTS: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months, sorafenib, 7.9 months, p &lt, 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2. CONCLUSIONS: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS.

Published
2021

30. 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. 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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

31. Diagnostic benefit of cytological and histopathological examinations for recurrent vaginal cancer metastasizing to the duodenum: A case report

Author

Toshiaki Saito, Kenzo Sonoda, Masao Okadome, Rie Sugimoto, Kenichi Taguchi, and Takahiro Fujimoto

Subjects
metastatic neoplasm, Medicine (General), Pathology, medicine.medical_specialty, recurrence, cytological diagnosis, Vaginal neoplasm, Case Report, Case Reports, 030204 cardiovascular system & hematology, Vaginal squamous cell carcinoma, Metastatic neoplasm, 03 medical and health sciences, Duodenal metastasis, R5-920, 0302 clinical medicine, medicine, Duodenal Neoplasm, business.industry, General Medicine, duodenal neoplasm, medicine.anatomical_structure, 030220 oncology & carcinogenesis, immunohistochemistry, Duodenum, vaginal neoplasm, Medicine, Immunohistochemistry, Recurrent Vaginal Cancer, business
Abstract

This is the first case report of a vaginal squamous cell carcinoma that metastasized to the duodenum. Cytological and histopathological examinations are useful for the diagnosis of a duodenal metastasis.

Published
2020

33. A multicenter Phase II study of sorafenib in Japanese patients with advanced hepatocellular carcinoma and Child Pugh A and B class

Author

Ayumu Hosokawa, Kohichiroh Yasui, Takuji Okusaka, Keiji Sano, Rie Sugimoto, Akinori Asagi, Kensei Yamaguchi, Hiroshi Ishii, Takeshi Aramaki, Eiichiro Suzuki, Tosiya Sato, Shuichi Kaneko, Naoya Kato, Masafumi Ikeda, and Junji Furuse

Subjects
Male, Niacinamide, Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Time Factors, Phases of clinical research, macromolecular substances, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Asian People, Internal medicine, otorhinolaryngologic diseases, Carcinoma, Clinical endpoint, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Survival analysis, Aged, Neoplasm Staging, business.industry, Phenylurea Compounds, Liver Neoplasms, General Medicine, Middle Aged, medicine.disease, Survival Analysis, digestive system diseases, carbohydrates (lipids), stomatognathic diseases, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Disease Progression, Child-Pugh Class B, Female, 030211 gastroenterology & hepatology, Liver function, business, medicine.drug
Abstract

Objective To evaluate prospectively the efficacy and safety of sorafenib, which has been the first-line treatment for advanced hepatocellular carcinoma (HCC), in Japanese HCC patients (pts) with not only Child-Pugh (C-P) A class but also C-P B class. Methods Sorafenib was administered orally at the dose of 400 mg twice daily for pts with HCC and liver function of C-P score of 5-8. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint was time to progression (TTP), and toxicity and the secondary endpoints included objective response, overall survival (OS). Results Forty C-P A pts and 12 C-P B pts were enrolled. The median TTP in the C-P A pts and C-P B pts was 3.3 months and 3.2 months, respectively. Among the pts with C-P A, complete response, partial response, and stable disease were achieved for 2.5%, 7.5% and 47.5%. Among the pts with C-P B, there were no treatment responses, 66.7% of pts had stable disease. The median OS in the C-P A pts and C-P B pts was 13.4 months and 7.4 months, respectively. With regard to toxicities, fewer C-P A pts experienced Grade 3/4 toxicities than C-P B pts (77.5% vs. 91.6%). There were no treatment-related deaths in either group of patients. Conclusions This study shows sorafenib has similar effectiveness in the recent post-approval studies and is well-tolerated in Japanese pts with HCC and Child Pugh A class. Sorafenib should be used with great care for Child Pugh class B pts.

Published
2018
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34. Development of hepatocellular carcinoma by patients aged 75 years or over after HCVelimination by all-oral DAA therapy: results from a large-scale, multicenter cohort study

Author

Eiichi Ogawa, Nomura Hideyuki, Makoto Nakamuta, Norihiro Furusyo, Eiji Kajiwara, Kazufumi Dohmen, Akira Kawano, Aritsune Ooho, Koichi Azuma, Kazuhiro Takahashi, Takeaki Satoh, Toshimasa Koyanagi, Yasunori Ichiki, Masami Kuniyoshi, Kimihiko Yanagita, Hiromasa Amagase, Chie Morita, Rie Sugimoto, Masaki Kato, Shinji Shimoda, and Jun Hayashi

Subjects
Hepatology
Published
2020
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37. Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment

Author

Shuichi Mitsunaga, Taiga Otsuka, Rie Sugimoto, Arsene-Bienvenu Loembe, Kei Muro, Masafumi Ikeda, Yusuke Tadayasu, Kohei Inoue, Isao Saito, Takuji Okusaka, and Hideki Ueno

Subjects
Male, Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Indoles, Hepatocellular carcinoma, Nausea, Antineoplastic Agents, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Liver Function Tests, Pharmacokinetics, Clinical Research, Internal medicine, nintedanib, Biomarkers, Tumor, medicine, Humans, Adverse effect, Aged, Neoplasm Staging, Aged, 80 and over, maximum tolerated dose, business.industry, Liver Neoplasms, Original Articles, General Medicine, phase I, Middle Aged, medicine.disease, Confidence interval, Treatment Outcome, Oncology, chemistry, 030220 oncology & carcinogenesis, Japanese, Vomiting, Original Article, Female, 030211 gastroenterology & hepatology, Nintedanib, Drug Monitoring, medicine.symptom, business, medicine.drug
Abstract

This phase I, dose‐escalation study evaluated the safety, preliminary efficacy and pharmacokinetics of nintedanib, a triple angiokinase inhibitor, in Japanese patients with advanced hepatocellular carcinoma and mild/moderate liver impairment. Thirty patients with unresectable hepatocellular carcinoma were enrolled to groups, depending on whether liver impairment was mild (group I, aspartate aminotransferase and alanine aminotransferase ≤2× upper limit of normal and Child–Pugh score 5 [n = 14] or 6 [n = 2]) or moderate (group II, Child–Pugh score 5–6 and aspartate aminotransferase or alanine aminotransferase >2× to ≤5× upper limit of normal [n = 7] or Child–Pugh score 7 [n = 7]); 22 patients had prior sorafenib treatment. Nintedanib was given twice daily in 28‐day cycles until disease progression or unacceptable adverse events, starting at 150 mg (group I) or 100 mg (group II) and escalating to 200 mg. The primary objective was to define the maximum tolerated dose based on occurrence of dose‐limiting toxicities during cycle 1 (grade ≥3 non‐hematological and grade 4 hematological adverse events). No dose‐limiting toxicities were reported during cycle 1 and the maximum tolerated dose for both groups was 200 mg twice daily. The most frequent adverse events were gastrointestinal (diarrhea, nausea, vomiting, and decreased appetite). No patients discontinued nintedanib due to adverse events; 31% of group I and 21% of group II had dose reductions. Median time to progression was 2.8 months (95% confidence interval, 1.05–5.52) for group I and 3.2 months (95% confidence interval, 0.95–6.70) for group II. Nintedanib showed a manageable safety profile and efficacy signals, including in patients previously treated with sorafenib. Clinical trial registration NCT01594125; 1199.120 (ClinicalTrials.gov).

Published
2016
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38. The prognostic role of lactate dehydrogenase serum levels in patients with hepatocellular carcinoma who are treated with sorafenib: the influence of liver fibrosis

Author

Shinichiro Takao, Naoki Yamashita, Kenta Motomura, Nobuhiko Higashi, Shinsaku Yamashita, Kazuhiro Kotoh, Masayuki Miyazaki, Shusuke Morizono, Motoyuki Kohjima, Masayoshi Yada, Yoshifusa Aratake, Rie Sugimoto, Masami Kuniyoshi, Takeaki Satoh, Makoto Nakamuta, and Akihide Masumoto

Subjects
Sorafenib, medicine.medical_specialty, Pathology, Liver fibrosis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, In patient, Platelet, neoplasms, business.industry, Hypoxia (medical), medicine.disease, digestive system diseases, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Original Article, 030211 gastroenterology & hepatology, medicine.symptom, business, Progressive disease, medicine.drug
Abstract

Background: Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis. Methods: Eighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment. Results: Overall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH. Conclusions: We demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy.

Published
2016
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39. <scp> CO 2 ‐facilitated </scp> transport membranes prepared by blending polyvinyl alcohol and various <scp>water‐absorbing</scp> agents

Author

Yuriko Nishiyama, Fuminori Ito, Hidetaka Yamada, Misato Mori, and Rie Sugimoto

Subjects
chemistry.chemical_compound, Membrane, Materials science, Polymers and Plastics, chemistry, Chemical engineering, Facilitated diffusion, Materials Chemistry, General Chemistry, Polyvinyl alcohol, Surfaces, Coatings and Films
Published
2020
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40. Incidence of Hepatocellular Carcinoma after Treatment with Sofosbuvir-Based or Sofosbuvir-Free Regimens in Patients with Chronic Hepatitis C

Author

Hideyuki Nomura, Koichi Azuma, Toshimasa Koyanagi, Chie Morita, Akira Kawano, Aritsune Ooho, Hiromasa Amagase, Masaki Kato, Kazufumi Dohmen, Yasunori Ichiki, Eiichi Ogawa, Norihiro Furusyo, Jun Hayashi, Rie Sugimoto, Kazuhiro Takahashi, Kimihiko Yanagita, Shinji Shimoda, Masami Kuniyoshi, Takeaki Satoh, Makoto Nakamuta, and Eiji Kajiwara

Subjects
hepatitis C virus, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Cirrhosis, Sofosbuvir, Hepatitis C virus, medicine.disease_cause, lcsh:RC254-282, sofosbuvir, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, direct-acting antiviral, business.industry, Incidence (epidemiology), Hazard ratio, hepatocellular carcinoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, digestive system diseases, Regimen, 030104 developmental biology, Oncology, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, business, Cohort study, medicine.drug
Abstract

Advanced fibrosis/cirrhosis and related biomarkers have been recognized as useful predictors of the development of hepatocellular carcinoma (HCC) by patients with chronic hepatitis C (CHC) following hepatitis C virus (HCV) cure by direct-acting antivirals (DAAs). However, it remains unclear if DAAs themselves have an influence on or facilitate the development of HCC. This multicenter cohort study included CHC patients without a history of HCC who achieved HCV elimination by DAAs. Cohorts of 835 patients treated with a sofosbuvir (SOF)-based regimen and 835 treated with a SOF-free regimen were matched 1:1 by propensity scoring with nine variables to evaluate differences in HCC incidence. The median observation period was 3.5 years. Sixty-nine cases of HCC were found during 5483.9 person-years (PY) over the entire follow-up period. The annual incidence was similar for both groups (SOF-based 1.25 and SOF-free 1.27 per 100 PY, respectively: adjusted hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.75&ndash, 2.12, p = 0.39). However, the annual incidence within the first two years was higher for patients treated with SOF than for those without, but did not reach significance (1.50 and 0.97 per 100 PY incidence rates, respectively: adjusted HR 2.05, 95% CI 0.98&ndash, 4.25, p = 0.06). In summary, DAA treatment with SOF was not associated with an increase in the development of de novo HCC.

Published
2020
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41. 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

42. Hepatic resection of hepatocellular carcinoma after proton beam therapy: A case report

Author

Eiji Tsujita, Hiroyuki Kawano, Shohei Yamaguchi, Manabu Yamamoto, Shinichiro Maehara, Yasuharu Ikeda, Rie Sugimoto, Yasushi Toh, Akinori Egashira, Nao Kinjo, Masaru Morita, Kenichi Taguchi, Kazuhito Minami, and Takeshi Okamura

Subjects
medicine.medical_specialty, Hepatology, business.industry, medicine.medical_treatment, Therapeutic effect, medicine.disease, Sacrum, 030218 nuclear medicine & medical imaging, Radiation therapy, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Toxicity, medicine, Carcinoma, Radiology, Liver function, Hepatectomy, business
Abstract

Despite the widespread use of proton beam therapy (PBT) as locoregional therapy, there is currently a lack of histological evidence about the therapeutic effect of PBT for hepatocellular carcinoma (HCC). We present a case of hepatectomy and histological examination of HCC initially treated by PBT. A 76-year-old man with chronic hepatitis C underwent routine ultrasound surveillance, which revealed a 22-mm HCC in segment 4 of the liver. His hepatic reserve was adequate for surgical resection of the tumor; however, he chose to undergo PBT because of his cardiac disease. The patient received 66 Gy in 10 fractions with no toxicity exceeding grade 1. Six months after completion of PBT, contrast computed tomography showed that the tumor had increased in size to 27 mm, and the marginal part of the tumor, but not the central region, was enhanced. Additionally, two new hypervascular nodules were present in segments 5 and 6. The patient underwent surgical treatment 7 months after PBT. The operation and postoperative clinical course were uneventful. Nine months later, however, computed tomography demonstrated new, small, enhanced nodules in the remnant liver (segments 3, 5 and 6) and sacrum. In conclusion, PBT is a valuable treatment for HCC; however, it is difficult to evaluate therapeutic effect of HCC during the early post-irradiation period and provide an alternative treatment if PBT is not effective, especially in HCC cases with good liver function.

Published
2015
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43. Acoustic Effects of Liner Damage on Zero-Splice Turbofan Intake Liners: Computational Study

Author

Andrew Kempton, Rie Sugimoto, Prateek Mustafi, and R. Jeremy Astley

Subjects
musculoskeletal diseases, Engineering, business.industry, Nacelle, Numerical analysis, technology, industry, and agriculture, Aerospace Engineering, Structural engineering, equipment and supplies, Turbofan, Acoustic effect, Acoustic propagation, splice, Overall performance, business, Sound pressure
Abstract

Traditional installations of turbofan intake liners include acoustically “hard” axial splices between liner segments for ease of fabrication and assembly. The splices scatter energy from strong rotor-locked tones into adjacent azimuthal orders for which the liner is less effective, thereby degrading the liner performance. The significance of this “splice effect” has led to the adoption of “zero-splice” liners in recent turbofan nacelles. However, damage can occur to such liners in service, and the extent to which local liner repairs reduce the effectiveness of the zero-splice design then becomes an issue. In the current paper, the acoustic effect of damage and repair in a zero-splice liner is simulated numerically. The effects of the extent and the location of a hard patch, representing the liner damage and repair, on the overall performance of the liner are predicted. A close agreement is demonstrated with results from an asymptotic analytical model valid for small patch widths. An approximate method is ...

Published
2015
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44. A pivotal role of team medicine for recurrent ovarian cancer patient affected by Clostrioides difficile enterocolitis

Author

Toshiaki Saito, Yoriko Ando, Rie Sugimoto, Toyomi Ninomiya, Shoko Kitade, Seiko Miyamoto, Kiyoshi Aiko, Yuko Hashimoto, Shoji Maenohara, Masao Okadome, Kazuya Ariyoshi, Yui Tomita, Kenzo Sonoda, Aya Matsukura, and Rina Nagayama

Subjects
medicine.medical_specialty, Toxic megacolon, Bevacizumab, Diet therapy, business.industry, medicine.medical_treatment, Cancer, Hematology, bacterial infections and mycoses, medicine.disease, Debulking, Radiation therapy, Breast cancer, Oncology, Internal medicine, medicine, Ovarian cancer, business, medicine.drug
Abstract

Introduction Clostrioides difficile enterocolitis (CDAD) varies from asymptomatic soft feces to severe cases that cause intestinal perforation and toxic megacolon. We experienced a case of CDAD ovarian cancer that developed after multidisciplinary therapies without prior antibiotics administration. We here report a pivotal role of team medicine for CDAD. Case A 66-year-old woman had medical history of gastric cancer (endoscopic resection) at 60 years old. Her family history was as follows: father: prostate cancer; mother: breast cancer; maternal grandfather: gastric cancer; and maternal grandmother: rectal cancer. We conducted interval debulking surgery after 4 courses of paclitaxel and carboplatin (TC) therapy as the initial treatment in diagnosis of ovarian cancer stage IIIC (ypT3CpN0pM0, serous carcinoma). Six courses of TC therapy were postoperatively performed, but intraperitoneal recurrence was diagnosed 1 year and 10 months after the initial treatment. Then, 7 courses of TC and bevacizumab (Bev) therapy were performed followed by 9 courses of Bev maintenance treatment. A second recurrence (para-aortic lymph node) was confirmed 1 year and 2 months after the end of chemotherapy, and 3 courses of TC/Bev treatment and intensity-modulated radiation therapy (IMRT) were performed. On the 7th day after IMRT, she complained of fever, abdominal pain and bloody mucous stools. Although antibiotics were administered with a diagnosis of CDAD, CDAD relapsed during the treatment. In this case, we worked on patient mental support and infection spread prevention with nutritional management mainly based on oral intake. Conclusion In treatment of CDAD, multi-professional team medicine is essential. In gynecologic cancers where multidisciplinary therapies are performed, CDAD has been reported to be not rare. Both prompt diagnose and adequate multi-professional team medicines are considered to be important for CDAD.

Published
2019
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45. SAT-254-Incidence of hepatocellular carcinoma and mortality after HCV elimination by all-oral DAA therapy: Results from a large-scale, multicenter cohort study

Author

Rie Sugimoto, Masami Kuniyoshi, Takeaki Satoh, Makoto Nakamuta, Eiichi Ogawa, Chie Morita, Aritsune Ooho, Kimihiko Yanagita, Eiji Kajiwara, Akira Kawano, Koichi Azuma, Toshimasa Koyanagi, Kazuhiro Takahashi, Hiromasa Amagase, Kazufumi Dohmen, Masaki Kato, Jun Hayashi, Shinji Shimoda, Yasunori Ichiki, Nomura Hideyuki, and Norihiro Furusyo

Subjects
Oncology, medicine.medical_specialty, Hepatology, Scale (ratio), business.industry, Internal medicine, Incidence (epidemiology), Hepatocellular carcinoma, Medicine, business, medicine.disease, Hcv elimination, Cohort study
Published
2019
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46. A study on the effectiveness of additional chemotherapy in patients with advanced pancreatic cancer that have become resistant to the treatment of both S-1 and gemcitabine

Author

Takashi Fujiyama, Rie Sugimoto, Yukihiko Okumura, Terumasa Hisano, and Masayuki Furukawa

Subjects
Oncology, Unresectable Pancreatic Cancer, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, medicine.disease, Gemcitabine, Internal medicine, Pancreatic cancer, medicine, Overall survival, In patient, business, medicine.drug
Published
2013
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48. Computational aero-acoustics for fan duct propagation and radiation. Current status and application to turbofan liner optimisation

Author

R.J. Astley, Rie Sugimoto, and Prateek Mustafi

Subjects
Engineering, Acoustics and Ultrasonics, Mechanics of Materials, Nacelle, business.industry, Mechanical Engineering, Acoustics, Acoustic propagation, Critical assessment, Duct (flow), Condensed Matter Physics, business, Turbofan
Abstract

Novel techniques are presented to reduce noise from turbofan aircraft engines by optimising the acoustic treatment in engine ducts. The application of Computational Aero-Acoustics (CAA) to predict acoustic propagation and absorption in turbofan ducts is reviewed and a critical assessment of performance indicates that validated and accurate techniques are now available for realistic engine predictions. A procedure for integrating CAA methods with state of the art optimisation techniques is proposed in the remainder of the article. This is achieved by embedding advanced computational methods for noise prediction within automated and semi-automated optimisation schemes. Two different strategies are described and applied to realistic nacelle geometries and fan sources to demonstrate the feasibility of this approach for industry scale problems.

Published
2011
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50. Reprint of: A review of CAA for fan duct propagation and radiation, with application to liner optimisation

Author

I.M. Achunche, E.P. Deane, Matthew Kewin, R.J. Astley, Prateek Mustafi, and Rie Sugimoto

Subjects
Engineering, Computational Aero-acoustics, noise reduction, business.industry, Nacelle, optimisation, Acoustics, turbofan ducts, Sound field, General Medicine, Turbofan, Acoustic propagation, Duct (flow), acoustic liners, business
Abstract

This article reviews the application of Computational Aero-Acoustics (CAA) to the prediction of acoustic propagation in turbofan ducts. The challenge of resolving the radiated sound field for realistic nacelle geometries is discussed and evidence is presented to indicate that current CAA is able to represent the effect of in-duct liners on far-field measured rig and engine data. Two approaches are presented for incorporating CAA predictions within liner optimisation schemes for a turbofan intake.

Published
2010
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