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2. A case of pancreatic adenosquamous carcinoma with direct invasion to the gastrointestinal tract through the retention cyst wall: A rare case report

Author

Takuro Hamada, Atsushi Yamaguchi, Naohiro Kato, Syuhei Sugata, Nao Furuya, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Hiroshi Kohno, Takeshi Sudo, Kazuya Kuraoka, and Shiro Oka

Subjects
adenosquamous carcinoma, pancreatic cancer, pancreatic cyst, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract A 62‐year‐old man presented with a 7‐cm cystic lesion with irregularly thickened cyst wall in contact with the pancreatic tail. The pancreatic tail was described as hypoechoic on endoscopic ultrasonography. The cyst subsequently increased rapidly to 13 cm, and surgery was performed. This revealed adenosquamous carcinoma in the pancreatic tail to have invaded the stomach and transverse colon along the cyst wall. The cyst was diagnosed as a retention cyst due to pancreatic tail tumor. Invasion of nearby organs by a pancreatic cancer via the retention cyst wall is very rare, but it is necessary to keep the potential for such progress in mind.

Published
2023
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3. Clinical features and images of malignant lymphoma localized in the pancreatic head to differentiate from pancreatic ductal adenocarcinoma: a case series study

Author

Naohiro Kato, Atsushi Yamaguchi, Syuhei Sugata, Takuro Hamada, Nao Furuya, Takeshi Mizumoto, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Sho Tazuma, Takeshi Sudo, Miki Kido, Takuo Ito, Kazuya Kuraoka, and Hiroshi Kohno

Subjects
Malignant lymphoma, Pancreatic lymphoma, Pancreatic ductal adenocarcinoma, Pancreatic head, Adenocarcinoma, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Pathological examination by endoscopic ultrasonography–guided fine-needle aspiration (EUS-FNA) has been reported to be useful in diagnosing pancreatic malignant lymphoma (ML), but some ML cases are difficult to be differentiated from pancreatic ductal adenocarcinoma (PDAC). Methods This retrospective study included 8 patients diagnosed with ML that had a pancreatic-head lesion at initial diagnosis and 46 patients with resected PDAC in the pancreatic head between April 2006 and October 2021 at our institute. ML and PDAC were compared in terms of patients’ clinical features and imaging examinations. Results The median tumor size was larger in ML than in PDAC (45.8 [24–64] vs. 23.9 [8–44] mm), but the median diameter of the caudal main pancreatic duct (MPD) was larger in PDAC (2.5 [1.0–3.5] vs. 7.1 [2.5–11.8] mm), both showing significant differences between these malignancies (both, P

Published
2023
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4. Long-standing diabetes mellitus increases concomitant pancreatic cancer risk in patients with intraductal papillary mucinous neoplasms

Author

Atsushi Yamaguchi, Susumu Tazuma, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Naoyuki Toyota, Takeshi Sudo, Kazuya Kuraoka, and Hiroshi Kohno

Subjects
Intraductal papillary mucinous neoplasm (IPMN), Pancreatic cyst, Pancreatic ductal adenocarcinoma (PDAC), Diabetes mellitus, Surveillance, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background When monitoring patients with an intraductal papillary mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed the risk factors for concomitant PDAC in IPMN. Methods In total, 547 patients with pancreatic cysts, including IPMNs inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance by imaging examination once or twice a year. Results Five IPMNs with high-grade dysplasia and one IPMN associated with invasive carcinoma were encountered. In comparison, 14 concomitant PDACs were encountered. The prognosis was very poor for concomitant PDACs. All 14 PDAC patients had IPMNs. In patients with IPMNs, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analyses (P < 0.001 and P < 0.01, respectively). Furthermore, patients with IPMNs and diabetes mellitus had a high frequency of concomitant PDACs (9.5%, 9/95) in a median 48-month surveillance period. Conclusions When monitoring IPMNs, the development of not only IPMN-derived carcinomas but also concomitant PDACs should be considered. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

Published
2022
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6. A case of intraductal tubulopapillary neoplasm of the pancreas in a branch duct: a rare case report and literature review

Author

Atsushi Yamaguchi, Takuro Hamada, Kaoru Wada, Riho Moriuchi, Kanae Tao, Hirona Konishi, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Kohei Ishiyama, Naoto Hadano, Takeshi Sudo, Naoyuki Toyota, Junichi Zaitsu, Kazuya Kuraoka, and Hiroshi Kohno

Subjects
Intraductal tubulopapillary neoplasm (ITPN), Branch of pancreatic duct, Main pancreatic duct, Case report, Pancreatic cancer, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD). Case presentation We encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence. Conclusion ITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.

Published
2021
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7. Integrated GWAS and mRNA Microarray Analysis Identified IFNG and CD40L as the Central Upstream Regulators in Primary Biliary Cholangitis

Author

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

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

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

Published
2020
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8. Hematogenous metastasis to colon from gallbladder cancer

Author

Daiki Murata, Atsushi Yamaguchi, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Akira Ishikawa, Kazuya Kuraoka, and Hiroshi Kohno

Subjects
caudal‐type homeobox2, colon metastasis, cytokeratin 7, gallbladder cancer, hematogenous metastasis, Diseases of the digestive system. Gastroenterology, RC799-869
Published
2021
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9. Effectiveness of Abdominal Ultrasonography for Improving the Prognosis of Pancreatic Cancer during Medical Checkup: A Single Center Retrospective Analysis

Author

Atsushi Yamaguchi, Naohiro Kato, Shuhei Sugata, Takuro Hamada, Nao Furuya, Takeshi Mizumoto, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Naoyuki Toyota, Takeshi Sudo, Kazuya Kuraoka, and Hiroshi Kohno

Subjects
pancreatic cancer (PC), abdominal ultrasonography (US), surveillance, prognosis, medical checkup, 5-year survival, Medicine (General), R5-920
Abstract

Recent advancements in surgical and anti-cancer therapies have provided significant hope of long survival in patients with pancreatic cancer (PC). To realize this hope, routine medical checkups of asymptomatic people should be performed to identify operable PCs. In this study, we evaluated the efficacy of medical checkups using abdominal ultrasonography (US). We retrospectively analyzed 374 patients with PC at our institute between 2010 and 2021. We divided these patients into several groups according to the diagnostic approach and compared their background and prognosis. These groups comprised PCs diagnosed through (a) symptoms, 242 cases; (b) US during medical checkup for asymptomatic individuals, 17; and other means. Of the 374 patients, 192 were men (51.3%), and the median age was 74 years (34–105). Tumors were located in the pancreatic tail in 67 patients (17.9%). Excision ratio and 5-year survival rate were significantly better in group (b) than in (a) (58.8% vs. 23.1%, p < 0.01 and 42.2% vs. 9.4%, p < 0.001, respectively). The prognosis of patients diagnosed using US during medical checkup was better than that of patients identified through symptomatic presentation of PC. US for asymptomatic individuals with PC might be one of the useful modalities for promoting better prognosis of PCs.

Published
2022
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11. Clinical features and images of malignant lymphoma localized in the pancreatic head to differentiate from pancreatic ductal adenocarcinoma

Author

Naohiro Kato, Atsushi Yamaguchi, Syuhei Sugata, Takuro Hamada, Nao Furuya, Takeshi Mizumoto, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Sho Tazuma, Takeshi Sudo, Miki Kido, Takuo Ito, Kazuya Kuraoka, and Hiroshi Kohno

Abstract

Background Pathological examination by endoscopic ultrasonography–guided fine-needle aspiration (EUS-FNA) has been reported to be useful in diagnosing pancreatic malignant lymphoma (ML), but some ML cases are difficult to be differentiated from pancreatic ductal adenocarcinoma (PDAC). Methods This retrospective study included 8 patients diagnosed with ML that had a pancreatic-head lesion at initial diagnosis and 46 patients with resected PDAC in the pancreatic head between April 2006 and October 2021 at our institute. ML and PDAC were compared in terms of patients’ clinical features and imaging examinations. Results The median tumor size was larger in ML than in PDAC (45.8 [24–64] vs. 23.9 [8–44] mm), but the median diameter of the caudal main pancreatic duct (MPD) was larger in PDAC (2.5 [1.0–3.5] vs. 7.1 [2.5–11.8] mm), both showing significant differences between these malignancies (both, P P

Published
2023
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13. A case of intraductal tubulopapillary neoplasm of the pancreas in a branch duct: a rare case report and literature review

Author

Takuro Hamada, Toshio Kuwai, Yuzuru Tamaru, Naoto Hadano, Riho Moriuchi, Hirona Konishi, Naoyuki Toyota, Junichi Zaitsu, Kaoru Wada, Ryusaku Kusunoki, Kazuya Kuraoka, Atsushi Yamaguchi, Kanae Tao, Kohei Ishiyama, Hiroshi Kohno, Hirotaka Kouno, and Takeshi Sudo

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, RC799-869, Branch of pancreatic duct, Branch Duct, 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Intraductal tubulopapillary neoplasm (ITPN), Case report, medicine, Humans, Cyst, Pancreas, Aged, 80 and over, Pancreatic duct, Intraductal papillary mucinous neoplasm, business.industry, Gastroenterology, General Medicine, Diseases of the digestive system. Gastroenterology, medicine.disease, Pancreaticoduodenectomy, Carcinoma, Papillary, Pancreatic Neoplasms, Major duodenal papilla, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Main pancreatic duct, 030211 gastroenterology & hepatology, Radiology, Neoplasm Recurrence, Local, business, Carcinoma, Pancreatic Ductal
Abstract

Background Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD). Case presentation We encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence. Conclusion ITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.

Published
2021

14. Advanced gallbladder cancer accompanied with cancer-associated dermatomyositis: A case report and literature review

Author

Haruka Kuroda, Atsushi Yamaguchi, Shuhei Sugata, Takuro Hamada, Riho Moriuchi, Kaoru Wada, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Takashi Kurashige, Tsuyoshi Torii, Akihisa Saito, Kazuya Kuraoka, and Hiroshi Kohno

Subjects
Muscle Weakness, Prednisolone, Humans, Female, Gallbladder Neoplasms, General Medicine, Deglutition Disorders, Dermatomyositis, Aged
Abstract

Muscle weakness due to cancer-associated dermatomyositis (CADM) can be misdiagnosed as cancer cachexia and disuse atrophy.A 75-year-old female was admitted to our institute with muscle weakness, dysphagia, and suspected gallbladder cancer. Computed tomography and cytopathological examinations of the liver biopsy and fine-needle aspiration from swollen lymph nodes using endoscopic ultrasonography revealed cancer in the gallbladder body and metastasis to the lymph nodes around the abdominal aorta. We avoided the administration of anticancer drugs due to her poor general condition.Subsequently, we diagnosed her with muscle weakness and dysphagia as a result of CADM using species from muscle and skin biopsy.Prednisolone therapy and anticancer agents partially improved the patient symptoms.CADM is reported to be associated with a high incidence of dysphagia, which may aid in the diagnosis of this disease.

Published
2022

15. Comparison of the Clinical Outcome of Ramucirumab for Unresectable Hepatocellular Carcinoma with That of Prior Tyrosine Kinase Inhibitor Therapy

Author

Masami Yamauchi, Shintaro Takaki, Keiji Tsuji, Yuwa Ando, Y. Ogawa, Masataka Tsuge, Hiroshi Aikata, Michio Imamura, Takayuki Fukuhara, Yoji Honda, Kei Amioka, Kensuke Naruto, Hirotaka Kouno, Yuki Yoshikawa, Hiroshi Kohno, Keiichi Masaki, Chihiro Kikukawa, Kei Morio, Hatsue Fujino, Shinsuke Uchikawa, Takashi Nakahara, Akira Hiramatsu, Kazuaki Chayama, Tomokazu Kawaoka, Eisuke Murakami, Nami Mori, and Yumi Kosaka

Subjects
Male, Oncology, Cancer Research, Treatment response, medicine.medical_specialty, Carcinoma, Hepatocellular, Pyridines, medicine.drug_class, Antibodies, Monoclonal, Humanized, Tyrosine-kinase inhibitor, Ramucirumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Overall survival, Humans, Medicine, Adverse effect, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Phenylurea Compounds, Liver Neoplasms, General Medicine, Middle Aged, Sorafenib, Prognosis, medicine.disease, Disease control, Survival Rate, Hepatocellular carcinoma, Quinolines, Female, business, Follow-Up Studies, Cohort study
Abstract

Introduction: The clinical outcome of ramucirumab in multi-molecular targeted agent (MTA) sequential therapy for unresectable hepatocellular carcinoma (u-HCC) was assessed in comparison with that of prior tyrosine kinase inhibitor (TKI) therapy. Methods: Sixteen patients who received ramucirumab as part of multi-MTA sequential therapy for u-HCC were enrolled in a retrospective, cohort study. Ramucirumab was started as 2nd line in 7 patients, 3rd line in 5 patients, and 4th line in 4 patients. Results: The overall response rate was 6.3%, the disease control rate (DCR) was 50.0%, median progression-free survival was 2.0 months (evaluated by mRECIST), median overall survival (OS) with ramucirumab was 7.9 months, and the median OS from 1st-line therapy was 28.1 months. One month after the start of ramucirumab, α-fetoprotein (AFP) decreased in 6 of 12 cases (50.0%), and the DCR in AFP-decreased cases was 83.3%. The DCR of ramucirumab was 66.7% in cases in which disease control was obtained by prior TKI therapy, whereas it was 0.0% in the cases in which disease control was not obtained by prior TKI therapy. Examining the adverse events, no new safety concerns were confirmed. Conclusion: The AFP response to ramucirumab and the treatment response to prior TKI therapy are associated with treatment response to ramucirumab.

Published
2021
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16. Newly developed self-expandable Niti-S MD colonic metal stent for malignant colonic obstruction

Author

Yuki Miyasako, Kazutaka Kuroki, Atsushi Yamaguchi, Yuzuru Tamaru, Hirona Konishi, Kanae Tao, Hirotaka Kouno, Sauid Ishaq, Toshio Kuwai, Ryoichi Miura, Ryusaku Kusunoki, Yuki Sumida, and Hiroshi Kohno

Subjects
medicine.medical_specialty, Self expandable, business.industry, medicine.medical_treatment, Stent, equipment and supplies, digestive system diseases, Surgery, Colonic obstruction, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Retrospective Cohort Study, 030211 gastroenterology & hepatology, business
Abstract

BACKGROUND: Colonic stents are increasingly used to treat acute malignant colonic obstructions. The WallFlex and Niti-S D type stents are the commonly used self-expandable metallic stents available in Japan since 2012. WallFlex stent has a risk of stent-related perforation because of its axial force, while the Niti-S D type stent has a risk of obstructive colitis because of its weaker radial force. Niti-S MD type stents not only overcome these limitations but also permit delivery through highly flexible-tipped smaller-caliber colonoscopes. AIM: To compare the efficacy and safety of the newly developed Niti-S MD type colonic stents. METHODS: This single-center retrospective observational study included 110 patients with endoscopic self-expandable metallic stents placed between November 2011 and December 2018: WallFlex (Group W, n = 37), Niti-S D type (Group N, n = 53), and Niti-S MD type (Group MD, n = 20). The primary outcome was clinical success, defined as a resolution of obstructive colonic symptoms, confirmed by clinical and radiological assessment within 48 h. The secondary outcome was technical success, defined as accurate stent placement with adequate stricture coverage on the first attempt without complications. RESULTS: The technical success rate was 100% in Groups W, N, and MD, and the overall clinical success rate was 89.2% (33/37), 96.2% (51/53), and 100% (20/20) in Groups W, N, and MD, respectively. Early adverse events included pain (3/37, 8.1%), poor expansion (1/37, 2.7%), and fever (1/37, 2.6%) in Group W and perforation due to obstructive colitis (2/53, 3.8%) in Group N (likely due to poor expansion). Late adverse events (after 7 d) included stent-related perforations (4/36, 11.1%) and stent occlusion (1/36, 2.8%) in Group W and stent occlusion (2/51, 3.9%) in Group N. The stent-related perforation rate in Group W was significantly higher than that in Group N (P < 0.05). No adverse event was observed in Group MD. CONCLUSION: In our early and limited experience, the newly developed Niti-S MD type colonic stent was effective and safe for treating acute malignant colonic obstruction.

Published
2020
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17. Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in Intraductal Papillary Mucinous Neoplasms

Author

Atsushi Yamaguchi, Susumu Tazuma, Yuzuru Tamaru, Ryusaku Kusunoki, Toshio Kuwai, Hirotaka Kouno, Naoyuki Toyota, Takeshi Sudo, Kazuya Kuraoka, and Hiroshi Kohno

Abstract

Background: When monitoring patients with an intraductal mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed risk factors for concomitant PDAC in IPMN.Methods: In total, 547 patients with pancreatic cysts, including IPMN inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance via imaging examination once or twice a year. Results: There were five intraductal papillary mucinous adenocarcinoma encountered. In comparison, there were 14 concomitant PDAC encountered. The prognosis was very poor in concomitant PDAC. All 14 PDAC patients had IPMN. In patients with IPMN, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analysis ( P < 0.001 and P < 0.01, respectively). Further, patients with IPMN and diabetes mellitus had high frequency of concomitant PDAC (9.5%, 9/95) in a median 48-month surveillance period.Conclusions: When monitoring IPMN, concomitant PDAC should be considered, rather than IPMN-derived carcinoma. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

Published
2022
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18. Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma

Author

Kei Amioka, Tomokazu Kawaoka, Masanari Kosaka, Yusuke Johira, Yuki Shirane, Ryoichi Miura, Serami Murakami, Shigeki Yano, Kensuke Naruto, Yuwa Ando, Yumi Kosaka, Yasutoshi Fujii, Kenichiro Kodama, Shinsuke Uchikawa, Hatsue Fujino, Atsushi Ono, Takashi Nakahara, Eisuke Murakami, Wataru Okamoto, Masami Yamauchi, Michio Imamura, Nami Mori, Shintaro Takaki, Keiji Tsuji, Keiichi Masaki, Yoji Honda, Hirotaka Kouno, Hiroshi Kohno, Takashi Moriya, Noriaki Naeshiro, Michihiro Nonaka, Hideyuki Hyogo, Yasuyuki Aisaka, Takahiro Azakami, Akira Hiramatsu, and Hiroshi Aikata

Subjects
Cancer Research, sequential therapy, overall survival, modified Response Evaluation Criteria in Solid Tumors (mRECIST), radiological response, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hepatocellular carcinoma, lenvatinib, Article, molecular targeted agent, Response Evaluation Criteria in Solid Tumors (RECIST), Oncology, RC254-282
Abstract

Simple Summary With the recent increase in the number of drug therapy options for unresectable hepatocellular carcinoma (u-HCC), the key issue has become how to prolong overall survival (OS). The aim was to evaluate the association between radiological response and OS in patients treated with lenvatinib as a first-line systemic treatment for u-HCC. Radiological response using both Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) is a predictor of OS and achieving an objective response at the first evaluation is an independent prognostic factor for OS. In addition, if an objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if stable disease is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation. Abstract The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child–Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin–bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

Published
2022
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20. 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

21. Analysis of Lenvatinib’s Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma

Author

Kei Amioka, Tomokazu Kawaoka, Takahiro Kinami, Shintaro Yamasaki, Masanari Kosaka, Yusuke Johira, Shigeki Yano, Kensuke Naruto, Yuwa Ando, Yasutoshi Fujii, Shinsuke Uchikawa, Atsushi Ono, Masami Yamauchi, Michio Imamura, Yumi Kosaka, Kazuki Ohya, Nami Mori, Shintaro Takaki, Keiji Tsuji, Keiichi Masaki, Yoji Honda, Hirotaka Kouno, Hioshi Kohno, Kei Morio, Takashi Moriya, Noriaki Naeshiro, Michihiro Nonaka, Yasuyuki Aisaka, Takahiro Azakami, Akira Hiramatsu, Hiroshi Aikata, and Shiro Oka

Subjects
Cancer Research, Oncology, hepatocellular carcinoma, lenvatinib, intermediate stage, LEN-TACE sequential therapy, radiological response, overall survival, modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Abstract

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin–bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

Published
2022
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22. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

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

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

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

Published
2021

23. Carcinoma in situ of the pancreas with fibrosis area around the carcinoma: A case report

Author

Shin Nakahira, Hiroshi Kohno, Hirotaka Kouno, Noriaki Matsuura, Kazuya Kuraoka, Naoyuki Toyota, Takeshi Mori, Toshio Kuwai, and Atsushi Yamaguchi

Subjects
Male, medicine.medical_specialty, pancreatic intraepitherial neoplasia, medicine.medical_treatment, pancreatic cancer, Endosonography, Lesion, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Pancreatic cancer, medicine, Carcinoma, Humans, case report, 030212 general & internal medicine, Clinical Case Report, pancreas, Aged, medicine.diagnostic_test, business.industry, Carcinoma in situ, fibrosis, carcinoma in situ, Magnetic resonance imaging, computed tomography, General Medicine, medicine.disease, Pancreaticoduodenectomy, Magnetic Resonance Imaging, Pancreatic Neoplasms, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Radiology, medicine.symptom, business, Pancreas, Research Article
Abstract

Rationale: Pancreatic cancer (PC) has the worst prognosis among all carcinomas. However, patients with carcinoma in situ (CIS) of the pancreas, usually, have a good prognosis. Many previous reports have mentioned the high frequency of fibrosis around CIS. In some cases, the fibrosis is detected on endoscopic ultrasonography (EUS), but there are few past reports of fibrosis detected on computed tomography (CT). Patient concerns: We encountered a case of fibrosis around CIS detected by CT. A 74-year-old man was being followed for chronic hepatitis C. On a contrast-enhanced CT (CE-CT), a space-occupied lesion (7 mm in size) in the pancreatic head was identified in the delayed phase. Diagnosis: It was shown to be a hypo echoic lesion in EUS, and EUS-fine-needle aspiration was performed. Cytological examination revealed abnormal cells suspicious for a neuroendocrine tumor. Interventions: Consequently, a pancreaticoduodenectomy was performed. Histopathological examination showed CIS in the branch duct with 10 mm of fibrosis around CIS. The fibrotic area corresponded to the mass detected by preoperative CE-CT. Outcomes: He had no relapse of PC but died 2 years later from another cause. Lessons: This case highlights the importance of identifying the enhanced area in the delayed phase on CE-CT, as this can be fibrosis around CIS.

Published
2020

24. [A case of Salmonella bacteremia in an otherwise healthy young man]

Author

Yoshikazu, Hirose, Toshio, Kuwai, Yuzuru, Tamaru, Ryouichi, Miura, Yuki, Sumida, Yuki, Miyasako, Kazutaka, Kuroki, Atsushi, Yamaguchi, Hirotaka, Kouno, and Hiroshi, Kouno

Subjects
Adult, Diarrhea, Male, Young Adult, Salmonella, Salmonella Infections, Humans, Bacteremia, Anti-Bacterial Agents
Abstract

A 19-year-old man was admitted to our hospital because of persistent fever of38°C for 6 days and diarrhea for 4 days. Initially, he was treated for infectious enteritis, but on his second day in the hospital, the two sets of blood cultures came back positive. Cultures from the blood and stool yielded Salmonella sp. (Group O4). The patient's symptoms improved after treatment with fluoroquinolone-based antimicrobial agents for 14 days. Cases of nontyphoidal Salmonella bacteremia are rare;therefore, we reported this case with bibliographic consideration of the risk factors for Salmonella bacteremia.

Published
2020

25. Gastric and enteric anisakiasis successfully treated with Gastrografin therapy: A case report

Author

Sumio Iio, Ryoichi Miura, Toshiki Yamaguchi, Hiroki Fujikawa, Hiroshi Kohno, Toshio Kuwai, Yuki Sumida, Yuki Miyasako, Takeshi Takasago, Hiroki Imagawa, Hirotaka Kouno, Tomoyuki Nishimura, and Atsushi Yamaguchi

Subjects
medicine.medical_specialty, Ileus, Gastrografin, Anisakis larvae, 030231 tropical medicine, Case Report, Gastroenterology, Anisakis, Epigastric pain, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ascites, Gastric mucosa, medicine, biology, medicine.diagnostic_test, business.industry, Enteric anisakiasis, medicine.disease, biology.organism_classification, Endoscopy, Endoscopic extraction, medicine.anatomical_structure, Epigastrium, Vomiting, medicine.symptom, business
Abstract

We report a case of a 59-year-old woman who was diagnosed with gastric and small intestinal anisakiasis, which was successfully treated with endoscopic extraction and Gastrografin therapy. She was admitted to our hospital with epigastric pain and vomiting one day after eating raw fish. She exhibited tenderness in the epigastrium without obvious rebound tenderness or guarding. Computed tomography (CT) demonstrated segmental edema of the intestinal wall with proximal dilatation and a small number of ascites. Because enteric anisakiasis was suspected based on the patient’s history of recent raw fish consumption and abdominal CT, we performed gastroscopy and confirmed that nine Anisakis larvae were attached to the gastric mucosa. All of the Anisakis larvae were extracted via endoscopy, and the patient was diagnosed with gastric and enteric anisakiasis. Additionally, in the hospital, we performed ileography twice using Gastrografin, which led to shortened hospital stay. Based on the clinical results of this case, we suggest that Gastrografin therapy is a safe, convenient, and useful method to extract enteric Anisakis larvae.

Published
2018
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26. Mo1428 THE NEUTROPHIL PROPORTION AMONG WHITE BLOOD CELLS IS A USEFUL MARKER FOR PREDICTING BACTEREMIA AND SEVERITY IN ACUTE CHOLANGITIS PATIENTS

Author

Kaoru Wada, Yuzuru Tamaru, Atsushi Yamaguchi, Hirona Konishi, Ryoichi Miura, Riho Moriuchi, Toshio Kuwai, Hirotaka Kouno, Hiroshi Kohno, Kanae Tsutsui, and Ryusaku Kusunoki

Subjects
medicine.medical_specialty, White (horse), Hepatology, business.industry, Bacteremia, Internal medicine, Gastroenterology, Medicine, business, medicine.disease
Published
2020
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27. Mo1345 DIABETES MELLITUS IS A RISK FACTOR FOR PANCREATIC CANCER IN PATIENTS WITH PANCREATIC CYST

Author

Yuzuru Tamaru, Kaoru Wada, Kanae Tsutsui, Hirona Konishi, Riho Moriuchi, Hiroshi Kohno, Atsushi Yamaguchi, Toshio Kuwai, Ryusaku Kusunoki, Hirotaka Kouno, and Ryoichi Miura

Subjects
medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, medicine.disease, Pancreatic cancer, Internal medicine, Diabetes mellitus, Pancreatic cyst, medicine, In patient, Risk factor, business
Published
2020
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28. [Surgical Resection of Hepatic Portal Lymph Node Metastasis after Repeated Treatment for Hepatocellular Carcinoma Recurrence]

Author

Kohei, Ishiyama, Takashi, Onoe, Haruna, Kubota, Masato, Kojima, Naoto, Hadano, Hirofumi, Tazawa, Wataru, Shimizu, Takahisa, Suzuki, Takeshi, Sudo, Yosuke, Shimizu, Takao, Hinoi, Kazuya, Kuraoka, Hirotaka, Kouno, Hiroshi, Kohno, and Hirotaka, Tashiro

Subjects
Male, Carcinoma, Hepatocellular, Lymphatic Metastasis, Liver Neoplasms, Catheter Ablation, Humans, Lymph Nodes, Chemoembolization, Therapeutic, Aged
Abstract

We encountered a case of hepatic portal lymph node metastasis after repeated treatment for hepatocellular carcinoma (HCC)recurrence. A 73-year-old male patient underwent partial gastrectomy following rupture of a gastrointestinal stromal tumor 8 years ago. A 70mm tumor was simultaneously revealed in the posterior segment of the liver, and imatinib treatment was initiated based on the diagnosis of a metastatic liver tumor. Due to the absence of an increasing tendency in the tumor, extended posterior segmentectomy was performed, and the pathological diagnosis was moderately differentiated HCC. During observation, transcatheter arterial chemoembolization(TACE)plus radiofrequency ablation(RFA)therapy was performed twice, and partial resection of the liver was performed once again for HCC recurrence. Recently, PIVKA-Ⅱ showed a high value of 1,720mAU/mL, and follow-up computed tomography showed HCC recurrence in S4/8 and hepatic portal lymph node metastasis. TACE was administered for recurrent lesions in S4/8, and surgical resection of the hepatic portal lymph node was performed together. The pathological diagnosis revealed extensive liver tissue necrosis and moderately-topoorly differentiated HCC in the excised lymph nodes. Lymph node metastasis of HCC is rare, and in this case, a change in lymph flow caused by repeated treatment for HCC recurrence was considered a factor influencing the course.

Published
2019

29. 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

30. Mo1696 PRELIMINARY CLINICAL STUDY ON A NEWLY DEVELOPED SELF-EXPANDABLE METALIC STENT, NITI-S MD COLONIC STENT, FOR MALIGNANT COLONIC OBSTRUCTION

Author

Yuki Miyasako, Kanae Tao, Yuki Sumida, Hirona Konishi, Yuzuru Tamaru, Kazutaka Kuroki, Atsushi Yamaguchi, Ryoichi Miura, Hiroshi Kohno, Toshio Kuwai, and Hirotaka Kouno

Subjects
Clinical study, Colonic obstruction, medicine.medical_specialty, business.industry, Self expandable, medicine.medical_treatment, Gastroenterology, medicine, Stent, Radiology, Nuclear Medicine and imaging, business, Colonic stent, Surgery
Published
2019
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31. Endoscopic submucosal dissection for early esophageal neoplasms using the stag beetle knife

Author

Hiroki Imagawa, Yuki Sumida, Sumio Iio, Hirotaka Kouno, Tomoyuki Nishimura, Takeshi Takasago, Hiroshi Kohno, Toshio Kuwai, Atsushi Yamaguchi, Ryoichi Miura, Toshiki Yamaguchi, Sauid Ishaq, and Yuki Miyasako

Subjects
Adult, Male, medicine.medical_specialty, Endoscopic Mucosal Resection, Esophageal Neoplasms, Stag beetle, education, Operative Time, Outcome measures, 03 medical and health sciences, 0302 clinical medicine, Esophagus, Postoperative Complications, Japan, Retrospective Study, Neoplasms, Medicine, Humans, Esophageal, Aged, Retrospective Studies, Aged, 80 and over, biology, business.industry, Gastroenterology, Neoplasms, Second Primary, General Medicine, Endoscopic submucosal dissection, Middle Aged, biology.organism_classification, Surgery, Survival Rate, stomatognathic diseases, surgical procedures, operative, Treatment Outcome, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Feasibility Studies, 030211 gastroenterology & hepatology, Female, Stag beetle knife, sense organs, Esophagoscopy, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

AIM To determine short- and long-term outcomes of endoscopic submucosal dissection (ESD) using the stag beetle (SB) knife, a scissor-shaped device. METHODS Seventy consecutive patients with 96 early esophageal neoplasms, who underwent ESD using a SB knife at Kure Medical Center and Chugoku Cancer Center, Japan, between April 2010 and August 2016, were retrospectively evaluated. Clinicopathological characteristics of lesions and procedural adverse events were assessed. Therapeutic success was evaluated on the basis of en bloc, histologically complete, and curative or non-curative resection rates. Overall and tumor-specific survival, local or distant recurrence, and 3- and 5-year cumulative overall metachronous cancer rates were also assessed. RESULTS Eligible patients had dysplasia/intraepithelial neoplasia (22%) or early cancers (squamous cell carcinoma, 78%). The median procedural time was 60 min and on average, the lesions measured 24 mm in diameter, yielding 33-mm tissue defects. The en bloc resection rate was 100%, with 95% and 81% of dissections deemed histologically complete and curative, respectively. All procedures were completed without accidental incisions/perforations or delayed bleeding. During follow-up (mean, 35 ± 23 mo), no local recurrences or metastases were observed. The 3- and 5-year survival rates were 83% and 70%, respectively, with corresponding rates of 85% and 75% for curative resections and 74% and 49% for non-curative resections. The 3- and 5-year cumulative rates of metachronous cancer in the patients with curative resections were 14% and 26%, respectively. CONCLUSION ESD procedures using the SB knife are feasible, safe, and effective for treating early esophageal neoplasms, yielding favorable short- and long-term outcomes.

Published
2018

32. Endoscopic submucosal dissection of early colorectal neoplasms with a monopolar scissor-type knife: short- to long-term outcomes

Author

Yuki Miyasako, Toshiki Yamaguchi, Sauid Ishaq, Hiroki Imagawa, Sumio Iio, Yuki Sumida, Tomoyuki Nishimura, Hirotaka Kouno, Hiroshi Kohno, Toshio Kuwai, Atsushi Yamaguchi, and Takeshi Takasago

Subjects
Male, medicine.medical_specialty, Time Factors, Endoscopic Mucosal Resection, Operative Time, Endoscopic mucosal resection, Postoperative Hemorrhage, Complete resection, 03 medical and health sciences, 0302 clinical medicine, medicine, Long term outcomes, Humans, Large intestine, Neoplasm Metastasis, Survival rate, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Gastroenterology, Cancer, Retrospective cohort study, Endoscopic submucosal dissection, Middle Aged, medicine.disease, Surgery, Tumor Burden, Survival Rate, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Neoplasm Recurrence, Local, business, Colorectal Neoplasms
Abstract

Background and study aims Endoscopic submucosal dissection (ESD) for colorectal neoplasms remains challenging because of technical issues imposed by the complex anatomical features of the large intestine. We evaluated the feasibility, and the short- and long-term clinical outcomes of ESD for early colorectal neoplasms performed using the Stag-beetle Knife Jr. (SB Knife Jr.) Patients and methods We retrospectively assessed 228 patients who underwent ESD for 247 colorectal lesions with the SB Knife Jr. Clinicopathological characteristics of the neoplasms, complications, and various short- and long-term outcomes were evaluated. Results Mean tumor size was 34.3 mm and median procedure time was 76 minutes. The SB Knife Jr. achieved 98.4 % en bloc resection, 93.9 % complete resection, and 85.4 % curative resection. No perforations occurred during the procedure, and a delayed bleeding rate of 2.4 % was observed. Long-term outcomes were favorable with no distant recurrence, 1.1 % local recurrence, a 5-year overall survival rate of 94.1 % and 5-year tumor-specific survival rate of 98.6 % in patients with cancer. Conclusions ESD using the SB Knife Jr. is technically efficient and safe in treating early colorectal neoplasms and is associated with favorable short- and long-term outcomes.

Published
2017

33. A case of ileus due to radiation enteritis 19 years after radiotherapy

Author

Tomoyo, Okumoto, Toshio, Kuwai, Toshiki, Yamaguchi, Sumio, Iio, Hiroki, Imagawa, Atsushi, Yamaguchi, Hirotaka, Kouno, and Hiroshi, Kohno

Subjects
Double-Balloon Enteroscopy, Ileus, Time Factors, Radiotherapy, Humans, Female, Tomography, X-Ray Computed, Enteritis, Aged
Abstract

A 73-year-old female visited our hospital complaining of nausea and epigastric pain because of ileus. She had a history of two laparotomy procedures in her youth, interferon treatment for chronic hepatitis C, and radiation therapy for uterine cervical cancer 19 years ago. Transanal double-balloon enteroscopy demonstrated annular stenosis with ulceration of the anal side of the dilated small intestine. Therefore, surgical resection was performed, and late radiation enteritis was diagnosed on histopathological examination. We report a case of ileus due to radiation enteritis 19 years after radiotherapy.

Published
2017

34. Sa1942 A HIGH-FREQUENCY GENERATOR FOR ENDOSCOPIC SUBMUCOSAL DISSECTION USING A SCISSORS-TYPE KNIFE FOR EARLY COLORECTAL NEOPLASMS

Author

Tomoyuki Nishimura, Yuki Miyasako, Sauid Ishaq, Yuki Sumida, Toshiki Yamaguchi, Hiroki Imagawa, Ryoichi Miura, Takeshi Takasago, Atsushi Yamaguchi, Toshio Kuwai, Hirotaka Kouno, and Hiroshi Kohno

Subjects
medicine.medical_specialty, business.industry, Gastroenterology, medicine, Radiology, Nuclear Medicine and imaging, Radiology, Endoscopic submucosal dissection, business
Published
2018
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35. Su1365 RISK FACTORS FOR RE-BLEEDING EVENTS IN OBSCURE GASTROINTESTINAL BLEEDING(OGIB)

Author

Hiroshi Kohno, Toshio Kuwai, Yuzuru Tamaru, Kazutaka Kuroki, Atsushi Yamaguchi, Hirona Konishi, Yuki Sumida, Ryoichi Miura, Hirotaka Kouno, Kanae Tao, and Yuki Miyasako

Subjects
medicine.medical_specialty, Re bleeding, business.industry, General surgery, Gastroenterology, Medicine, Radiology, Nuclear Medicine and imaging, business, Obscure gastrointestinal bleeding
Published
2019
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39. Impact of Dose Reduction on the Efficacy of Triple Therapy for Patients Infected with Genotype 1b and High Viral Loads

Author

Hiroshi Kohno, Hirotaka Kouno, Toshiki Yamaguchi, Atsushi Yamaguchi, and Toshio Kuwai

Abstract

To examine the impact of dose reduction on the efficacy of pegylated interferon (PEG-IFN) plus ribavirin (RBV) plus telaprevir (TVR) triple therapy for patients infected with genotype 1b and high viral loads. A total of 51 patients were recruited for this study. Patients were divided into groups receiving either 2,250 mg of TVR for 12 weeks and 600 – 1,200 mg of RBV for 24 weeks according to body weight (Group 1, N = 39) or 1,500 mg of TVR for 12 weeks and 400 mg of RBV for 24 weeks (Group 2, N = 13) plus 1.5 μg/Kg (range: 1.3 - 2.0 μg/Kg) of peg-IFN alpha-2b for 24 weeks. Patients of Group 1 were less than 65 years old or IL28 non T/T and over 65 to less than 70 years old. Patients of Group 2 were IL28B T/T and over 65 to less than 70 years old or over 70 years old. Rapid virological response (RVR) rates were 66.7% in Group 1 and 84.2% in Group 2 (NS). Early virological response (RVR) rates were 79.5% in Group 1 and 91.7% in Group 2 (NS). End of treatment response (ETR) rates were 71.8% in Group 1 and 69.2% in Group 2 (NS). Sustained virological response (SVR) rates were 60.5% in Group 1 and 69.2% in Group 2 (NS). In multivariate analysis, significant contribution factors for SVR were IL28B (genotype TT; OR 1.83, P = 0.0032) and platelet counts (< 120,000; OR 2.14, P = 0.0140). It was concluded that the treatment strategy of dose reduction based on patient background (age and IL28B SNP polymorphism) was proper in Japanese patients.

Published
2017
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40. Characteristics of Acute Cholangitis and Endoscopic Management of Elderly Patients at Our Institute

Author

Atsushi Yamaguchi, Toshiki Yamaguchi, Toshio Kuwai, Hirotaka Kouno, and Hiroshi Kohno

Abstract

The clinical presentation of acute cholangitis, etiology and complications from endoscopic early biliary drainage in elderly patients was evaluated. 205 patients with acute cholangitis treated at the Kure Medical Center and Chugoku Cancer Center were enrolled. Of these, 108 patients were 75 years old or older (elderly) and 97 patients were younger than 75 years old. Patients’ clinical characteristics, etiology and severity of cholangitis, and complications of endoscopic early biliary drainage were compared between the elderly and younger cohorts. There was a significant difference in severe cholangitis between elderly and younger patients, at 17.6% and 0%, respectively. There was no significant difference in complications between elderly and younger patients, and between patients with and without early biliary drainage. One 91-year old woman with early biliary drainage had post-ERCP (endoscopic retrograde cholangiopancreatography) aspiration pneumonia and died. Acute cholangitis in elderly patients may become severe in degree with a high incidence. Early ERCP for elderly persons is relatively safe, but it should be done carefully, not induce a consequent death due to complications such as aspiration pneumonia.

Published
2017
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41. Efficacy and Safety of Endoscopic Submucosal Dissection Using A Scissors-Type Knife for Early Colorectal Neoplasms

Author

Toshio Kuwai, Toshiki Yamaguchi, Atsushi Yamaguchi, Hirotaka Kouno, and Hiroshi Kohno

Abstract

To reduce the risk of adverse events related to colorectal endoscopic submucosal dissection (ESD) using a conventional knife, we used a scissors-type knife (SB Knife Jr.) that allowed us to prevented unexpected muscular-layer injury. The aims of our study were to evaluate the efficacy and safety of ESD using a SB Knife Jr. for early colorectal neoplasms. 121 lesions in 115 patients (M: F=63: 52; median age=68) were resected with ESD using a SB Knife Jr. from October 2010 to March 2014. We evaluated en bloc resection rate, complete resection rate, size of tumor, adverse events and local recurrence rate. The sites of the neoplasms included the following: 39 lesions were located in the right colon; 38 in the left colon; and 44 in the rectum. By histological examination, 57 lesions were intramucosal cancers, 14 slightly submucosal cancers (1,000 μm), and 35 tubular adenomas. All lesions were treated safely without unexpected incision. The en bloc resection rate was 96.7% (117/121), and the complete resection rate was 95.0% (115/121). The mean size of the resected tumors was 32.1 mm (range, 7-120 mm), respectively. With regard to adverse events, there were no perforations, and postoperative bleeding occurred in 5 cases (4.1%). All cases were controlled by endoscopic hemostasis. During a median follow-up duration of 15.5 months, local recurrence rate was 0% (0/121). ESD using a SB Knife Jr. can be adequately adopted as a technically efficient method for resecting early colorectal neoplasms.

Published
2017
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42. Endoscopic full-thickness resection for inverted Meckel's diverticulum using double-balloon enteroscopy

Author

Hiroki Imagawa, Toshiki Yamaguchi, Kazutoshi Konomatsu, Atsushi Yamaguchi, Hirotaka Kouno, Hiroshi Kohno, and Toshio Kuwai

Subjects
Double-Balloon Enteroscopy, Male, medicine.medical_specialty, Meckel's diverticulum, medicine.diagnostic_test, business.industry, Gastroenterology, medicine.disease, Capsule Endoscopy, law.invention, Meckel Diverticulum, 03 medical and health sciences, 0302 clinical medicine, Capsule endoscopy, law, 030220 oncology & carcinogenesis, Double-balloon enteroscopy, Medicine, Humans, 030211 gastroenterology & hepatology, Radiology, Full thickness resection, business, Aged
Published
2017

43. BEN3/BIG2 ARF GEF is involved in brefeldin a-sensitive trafficking at the trans-golgi network/early endosome in arabidopsis thaliana

Author

Hirokazu Tanaka, Yuki Matsuura, Christian S. Hardtke, Tatsuo Kakimoto, Maciek Adamowski, Hirotaka Kouno, Luca Santuari, Saeko Kitakura, Jiří Friml, and Kohei Arima

Subjects
0301 basic medicine, Auxin efflux, ADP ribosylation factor, Physiology, Endosome, Green Fluorescent Proteins, Endocytic cycle, Arabidopsis, Plant Developmental Biology, Endosomes, Plant Science, ARF GEF, Biology, environment and public health, 03 medical and health sciences, symbols.namesake, chemistry.chemical_compound, PIN-FORMED1, Guanine Nucleotide Exchange Factors, Auxin, Cloning, Molecular, Alleles, Brefeldin A, ADP-Ribosylation Factors, Arabidopsis Proteins, Cell Membrane, Cell Biology, General Medicine, Golgi apparatus, Cell Compartmentation, Cell biology, Protein Transport, Phenotype, 030104 developmental biology, Trans-Golgi network, Membrane protein, chemistry, Codon, Nonsense, Seedlings, symbols, Guanine nucleotide exchange factor, EPS, trans-Golgi Network
Abstract

Membrane traffic at the trans-Golgi network (TGN) is crucial for correctly distributing various membrane proteins to their destination. Polarly localized auxin efflux proteins, including PIN-FORMED1 (PIN1), are dynamically transported between the endosomes and the plasma membrane (PM) in the plant cells. The intracellular trafficking of PIN1 protein is sensitive to the fungal toxin brefeldin A (BFA), which is known to inhibit guanine nucleotide exchange factors for ADP ribosylation factors (ARF GEFs) such as GNOM. However, the molecular details of the BFA-sensitive trafficking pathway have not been fully revealed. In a previous study, we identified an Arabidopsis mutant BFA-visualized endocytic trafficking defective 3 (ben3) which exhibited reduced sensitivity to BFA in terms of BFA-induced intracellular PIN1 agglomeration. Here, we show that BEN3 encodes a member of BIG family ARF GEFs, BIG2. BEN3/BIG2 tagged with fluorescent proteins co-localized with markers for the TGN/early endosome (EE). Inspection of conditionally induced de novo synthesized PIN1 confirmed that its secretion to the PM is BFA sensitive, and established BEN3/BIG2 as a crucial component of this BFA action at the level of the TGN/EE. Furthermore, ben3 mutation alleviated BFA-induced agglomeration of another TGN-localized ARF GEF, BEN1/MIN7. Taken together, our results suggest that BEN3/BIG2 is an ARF GEF component, which confers BFA sensitivity to the TGN/EE in Arabidopsis.

Published
2017

44. Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population

Author

Kazuaki Chayama, Masao Honda, Yoshiyuki Ueno, Masaru Harada, Norihiro Kokudo, Hajime Ota, Yoshihiro Aiba, Shinji Shimoda, Atsushi Naganuma, Kenichi Harada, Shotaro Sakisaka, Katsushi Tokunaga, Satoshi Yamagiwa, Toyokichi Muro, Fujio Makita, Kazuhiko Yamauchi, Masao Nagasaki, Tatsuji Komatsu, Hideo Nishimura, Yuki Hitomi, Nao Nishida, Hidetaka Shibata, Kazuhide Yamamoto, Hiromi Ishibashi, Takafumi Ichida, Tsutomu Yamashita, Keisuke Ario, Kazuhiko Nakao, Masanori Abe, Hirotaka Kouno, Kiyoshi Furuta, Makoto Nakamuta, Yasuhiro Miyake, Hiroto Egawa, Yosuke Kawai, Seigo Abiru, Michio Senju, Makiko Taniai, Yukio Ohara, Yoshihiko Maehara, Atsushi Tanaka, Hiroshi Yatsuhashi, Masahiro Kikuchi, Noboru Hirashima, Kazuhiro Sugi, Kaname Kojima, Shintaro Yagi, Hitomi Nakamura, Nobuyoshi Fukushima, Masashi Mizokami, Kiyoshi Migita, Hirotoshi Ebinuma, Kaname Yoshizawa, Kazumoto Murata, Takashi Himoto, Eiichi Takesaki, Naohiro Takahashi, Hiroshi Kouno, Toshiki Nikami, Atsumasa Komori, Tomohiro Tanaka, Shinji Uemoto, Yoko Nakamura, Kouki Matsushita, Hajime Takikawa, Akira Mori, Masahiro Ito, Toshiki Komeda, Hiromasa Ohira, S. Tamura, Etsuko Hashimoto, Naohiko Masaki, Osamu Yokosuka, Ken Shirabe, Shinya Nagaoka, Michio Yasunami, Takeji Umemura, Masaaki Shimada, Masataka Seike, Mikio Zeniya, Shuichi Kaneko, Haruhiro Yamashita, Minae Kawashima, Motoyuki Kohjima, Hiroshi Mano, Minoru Nakamura, Satoru Joshita, and Tatsuo Kanda

Subjects
0301 basic medicine, Male, Genotype, General Population Cohort, Genome-wide association study, Locus (genetics), Disease, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Asian People, Japan, Protein Kinase C beta, Genetics, Genetic predisposition, Humans, Genetic Predisposition to Disease, Molecular Biology, Genetics (clinical), Liver Cirrhosis, Biliary, General Medicine, Odds ratio, Japanese population, digestive system diseases, 030104 developmental biology, Female, Genome-Wide Association Study
Abstract

A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.

Published
2016

45. Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population

Author

Yoshihiko Maehara, Nobuyoshi Fukushima, Makoto Nakamuta, Kuniaki Arai, Noboru Hirashima, Hajime Takikawa, Kentaro Kikuchi, Yasuhiko Sugawara, Hiromasa Ohira, Shintaro Yagi, Yoshihiro Aiba, Akinobu Taketomi, Masakazu Kobayashi, Toshiki Komeda, Kazuhiro Sugi, Hirotoshi Ebinuma, Ken Shirabe, Jinya Ishida, Tatsuki Ichikawa, Minoru Nakamura, Katsuji Hirano, Hiromi Ishibashi, Kyoko Monoe, Eiichi Takesaki, Tatsuji Komatsu, Koichi Honda, Yasuni Nakanuma, Makiko Taniai, Masao Honda, Yasuhiro Miyake, Satoshi Yamagiwa, Kiyoshi Migita, Michiyasu Yagura, Toyokichi Muro, Yasuaki Takeyama, Kenichi Harada, Kazuhide Yamamoto, Atsushi Tanaka, Masanori Abe, Michiaki Koga, Yukio Watanabe, Masaaki Shimada, Morikazu Onji, Noriyo Yamashiki, Teru Kumagi, Masahiro Ito, Michio Yasunami, S. Tamura, Masataka Seike, Shuichi Kaneko, Takeji Umemura, Mikio Zeniya, Etsuko Hashimoto, Atsumasai Komori, Keisuke Ario, Naohiko Masaki, Nao Nishida, Norihiro Kokudo, Hiroki Takahashi, Kaname Yoshizawa, Hiroshi Yatsuhashi, Akira Mori, Takafumi Ichida, Kazuhiko Nakao, Hirohito Tsubouchi, Masashi Mizokami, Katsushi Tokunaga, Shinji Uemoto, Yoko Nakamura, Minae Kawashima, Hitomi Nakamura, Takeo Saoshiro, Keiichi Hirata, Satoru Joshita, Shinji Shimoda, Shotaro Sakisaka, Hirotaka Kouno, Hirotsugu Kouno, Hajime Ota, and Yoshiyuki Ueno

Subjects
Adult, Male, Tumor Necrosis Factor Ligand Superfamily Member 15, Genome-wide association study, Human leukocyte antigen, Biology, White People, Young Adult, Primary biliary cirrhosis, Asian People, HLA Antigens, Report, Genetics, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Genetics(clinical), STAT4, Genetics (clinical), Aged, Aged, 80 and over, B-Lymphocytes, Polymorphism, Genetic, Liver Cirrhosis, Biliary, Tumor Necrosis Factor-alpha, Case-control study, NF-kappa B p50 Subunit, Cell Differentiation, Odds ratio, Middle Aged, STAT4 Transcription Factor, medicine.disease, IKZF3, Genetic Loci, Case-Control Studies, Immunology, Trans-Activators, Female, Genome-Wide Association Study
Abstract

For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

Published
2012
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46. Impact of ribavirin dose reduction on the efficacy of pegylated interferon plus ribavirin combination therapy for elderly patients infected with genotype 1b and high viral loads

Author

Shiomi Aimitsu, Mikiya Kitamoto, Kazuaki Chayama, Hiroiku Kawakami, Yasuyuki Aisaka, Hiroshi Kohno, and Hirotaka Kouno

Subjects
medicine.medical_specialty, Hepatology, Combination therapy, business.industry, viruses, Ribavirin, virus diseases, Virology, Gastroenterology, digestive system diseases, Virological response, chemistry.chemical_compound, Infectious Diseases, chemistry, Genotype 1b, Pegylated interferon, Internal medicine, PEG ratio, medicine, Dose reduction, business, Viral load, medicine.drug
Abstract

Aim: To examine the impact of ribavirin dose reduction on the efficacy of pegylated interferon (PEG IFN) plus ribavirin combination therapy for elderly patients infected with genotype 1b and high viral loads. Methods: A total of 72 patients, over 65 years old, were recruited for this study. Patients were divided into groups receiving either 600–800 mg of ribavirin according to bodyweight (Group 1, n = 36) or 400 mg of ribavirin (Group 2, n = 36) plus 1.5 µg/kg (range: 1.3–2.0 µg/kg) of PEG IFN-α-2b for 48 weeks. Results: Total ribavirin doses were administrated at 9.80 ± 2.39 mg/kg per day (3.29 ± 0.80 g/kg) for Group 1 and 5.87 ± 1.82 mg/kg per day (1.97 ± 0.61 g/kg) for Group 2 (P

Published
2011
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47. Sa1259 HIGH BLOOD UREA NITROGEN LEVEL CAN BE A PREDICTIVE CLINICAL FACTOR FOR EARLY DEATH AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY

Author

Toshiki Yamaguchi, Yuki Miyasako, Yuki Sumida, Atsushi Yamaguchi, Tomoyuki Nishimura, Toshio Kuwai, Hiroshi Kohno, Hirotaka Kouno, Ryoichi Miura, Takeshi Takasago, and Hiroki Imagawa

Subjects
medicine.medical_specialty, business.industry, Percutaneous endoscopic gastrostomy, medicine.medical_treatment, Gastroenterology, medicine, Radiology, Nuclear Medicine and imaging, Early death, business, Blood urea nitrogen, Surgery
Published
2018
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48. An Improvement of an Ileus in the Jejunal Pouch by Aspiration with the Overtube of a Balloon Endoscopy: A Case Report

Author

Takeshi Mizumoto, Akiyoshi Tsuboi, Toshiki Yamaguchi, Kazuki Boda, Hirotaka Kouno, Yuichi Hiyama, Kiyomi Taniyama, Hiroshi Kohno, Takahiro Amano, Ken Yamashita, Toshio Kuwai, and Atsushi Yamaguchi

Subjects
medicine.medical_specialty, Ileus, medicine.diagnostic_test, business.industry, medicine.medical_treatment, digestive, oral, and skin physiology, Anastomosis, medicine.disease, Surgery, Endoscopy, Jejunum, medicine.anatomical_structure, Medicine, Abdomen, Gastrectomy, Esophagus, Pouch, business
Abstract

We report a case of an 86-year-old Japanese woman diagnosed with a food-induced ileus whose condition improved by aspiration with the overtube of a balloon endoscopy. She had undergone a total gastrectomy for gastric cancer and reconstruction by Roux-en Y anastomosis and jejunum pouch 17 years earlier. She complained of constipation and loss of appetite lasting more than 1 wk before admission. Her left abdomen showed gradual fullness, and tenderness was also found at the same site. Contrast computed tomography (CT) of the abdomen showed that the jejunal pouch lumenwas markedly expanded by food residue and was pressed into the intestinal tract of the small intestine. Gastrointestinal endoscopy revealed that the food residue was fluid and flowed back up into the esophagus, and the jejunum pouch was filled with food residue. As the patient was elderly, we attempted to aspirate the food residue with the overtube of a balloon endoscopy device. Food-induced ileus has been improved by surgery in the past; however, in determining treatment for ileus it is always necessary to consider the individual patients’ conditions, including the gastrointestinal contents.

Published
2015
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49. Mo1106 Efficacy and Prognostic Effect of Endoscopic Submucosal Dissection for Early Gastric Neoplasms in Patients Aged 80 Years or Older

Author

Tomoyuki Nishimura, Toshio Kuwai, Atsushi Yamaguchi, Toshiki Yamaguchi, Yuki Sumida, Sumio Iio, Yuki Miyasako, Hirotaka Kouno, Hiroki Imagawa, Takeshi Takasago, and Hiroshi Kohno

Subjects
medicine.medical_specialty, business.industry, Gastroenterology, medicine, Radiology, Nuclear Medicine and imaging, In patient, Endoscopic submucosal dissection, business, Gastric Neoplasm, Surgery
Published
2017
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50. Tu1230 Short- and Long-Term Outcomes of Endoscopic Submucosal Dissection Using a Scissors-Type Knife for Early Esophageal Neoplasms

Author

Yuki Miyasako, Sumio Iio, Hirotaka Kouno, Toshiki Yamaguchi, Hiroki Imagawa, Toshio Kuwai, Tomoyuki Nishimura, Takeshi Takasago, Atsushi Yamaguchi, Hiroshi Kohno, and Yuki Sumida

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Gastroenterology, medicine, Long term outcomes, Radiology, Nuclear Medicine and imaging, Endoscopic submucosal dissection, business, Surgery
Published
2017
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