研究者詳細 - 河上　洋

Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C virus infection aged 75 years or older 査読あり

Komaki Y., Ozono Y., Nakamura K., Iwakiri H., Hasuike S., Sueta M., Miike T., Yamamoto S., Uto H., Kusumoto K., Ochiai T., Kato J., Komada N., Kuroki K., Eto T., Shigehira M., Hirono S., Nagata K., Kawakami H.

BMC Gastroenterology 22 ( 1 ) 210 2022年12月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：BMC Gastroenterology

Background: It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years. Methods: This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group. Results: In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups. Conclusions: Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.

DOI： 10.1186/s12876-022-02284-z

Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: Nationwide survey in Japan 査読あり

Kitano M., Yoshida M., Ashida R., Kita E., Katanuma A., Itoi T., Mikata R., Nishikawa K., Matsubayashi H., Takayama Y., Kato H., Takenaka M., Ueki T., Kawashima Y., Nakai Y., Hashimoto S., Shigekawa M., Nebiki H., Tsumura H., Okabe Y., Ryozawa S., Harada Y., Mitoro A., Sasaki T., Yasuda H., Miura N., Ikemoto T., Ozawa E., Shioji K., Yamaguchi A., Okuzono T., Moriyama I., Hisai H., Fujita K., Goto T., Shirahata N., Iwata Y., Okabe Y., Hara K., Hashimoto Y., Kuwatani M., Isayama H., Fujimori N., Masamune A., Hatamaru K., Shimokawa T., Okazaki K., Takeyama Y., Yamaue H., Abue M., Aiura K., Akashi T., Akiyama T., Aoyagi H., Araki M., Arizumi T., Aruga Y., Asada M., Asai S., Baba T., Ban S., Chinen K., Doi S., Eguchi T., Endo M., Endo S., Ezaki T., Fujii K., Fujii M., Fujimori M., Fujimoto Y., Fujita Y., Fujita Y., Fukasawa M., Fukuba N., Fukuchi S., Fukuda K., Furukawa M., Furumatsu K., Hakamada K., Hanada K., Harada K., Harano M., Hashigo S., Hashiguchi K., Hayashi K., Hayashi N., Hayatsu S., Hijioka S., Hirano A., Hirao M., Hirooka Y., Hirota M., Horino K., Hotta Y., Ijima M., Ikuta Y., Imakiire K., Imamura T., Inatomi O.

Digestive Endoscopy 34 ( 7 ) 1442 - 1455 2022年11月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Digestive Endoscopy

Objectives: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. Methods: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. Results: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P = 0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P = 0.037). Conclusions: Needle tract seeding appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

DOI： 10.1111/den.14346

Fully covered metal stents vs plastic stents for preoperative biliary drainage in patients with resectable pancreatic cancer without neoadjuvant chemotherapy: A multicenter, prospective, randomized controlled trial 査読あり

Mandai K., Tsuchiya T., Kawakami H., Ryozawa S., Saitou M., Iwai T., Ogawa T., Tamura T., Doi S., Okabe Y., Chiba Y., Itoi T.

Journal of Hepato-Biliary-Pancreatic Sciences 29 ( 11 ) 1185 - 1194 2022年11月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Hepato-Biliary-Pancreatic Sciences

Background/Purpose: Whether a fully covered self-expanding metal stent (FCSEMS) or plastic stent (PS) is preferable for preoperative biliary drainage in patients with resectable pancreatic cancer (RPC) is controversial. This study aimed to evaluate the safety and efficacy of drainage with FCSEMS for obstructive jaundice caused by RPC without neoadjuvant chemotherapy. Methods: Seventy patients with RPC who required preoperative biliary drainage were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was endoscopic re-intervention rate during the waiting period for surgery. Secondary endpoints were drainage procedure time, drainage-related adverse events (AE), waiting period for surgery, operative time, intraoperative blood loss, surgery-related AE, and postoperative hospital stay. Results: Thirty-nine patients underwent surgery. None required re-intervention in the FCSEMS group, whereas five PS patients underwent re-intervention (P =.023). The FCSEMS group had significantly more intraoperative blood loss (P =.0068) and AE (P =.011) than the PS group. Postoperative hospital stay was significantly longer in the FCSEMS group (P =.016). Conclusions: Fully covered self-expanding metal stent had a lower rate of endoscopic re-intervention during the waiting period for surgery than PS, but showed more intraoperative blood loss, higher incidence of surgery-related AE, and longer postoperative hospital stays.

DOI： 10.1002/jhbp.1090

特集胃疾患アトラス改訂版各論 Ⅲ. 陥凹を呈する病変 1. 上皮性･非腫瘍性陥凹病変胃Dieulafoy潰瘍

山本章二朗, 三池忠, 河上洋

消化器内視鏡 34 ( 13 ) 194 - 195 2022年10月

掲載種別：研究論文（学術雑誌）出版者・発行元：東京医学社

DOI： 10.24479/endo.0000000413

Liver abscess in advanced hepatocellular carcinoma after atezolizumab plus bevacizumab treatment: A case report 査読あり

Uchida K., Ozono Y., Uchiyama N., Hatada H., Nakamura K., Komaki Y., Iwakiri H., Hasuike S., Nagata K., Sato Y., Kawakami H.

Medicine (United States) 101 ( 35 ) e30486 2022年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Medicine (United States)

Rationale: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally. Since 2020, combination treatment with atezolizumab and bevacizumab were approved in patients with unresectable HCC in Japan, and atezolizumab plus bevacizumab is the first-line treatment for unresectable HCC. Patient concerns: A 73-year-old Japanese man diagnosed with a large HCC was treated with atezolizumab plus bevacizumab. After 2 cycles, he had fever and fatigue and was admitted to the hospital. Diagnosis: Abdominal contrast-enhanced computed tomography revealed tumor necrosis in HCC with gas formation in the necrotic area. Laboratory examination revealed a white blood cell (WBC) count of 16,340/μL and C-reactive protein (CRP) level of 33.0 mg/dL. Based on the above findings, he was diagnosed with a liver abscess. Interventions: Percutaneous transhepatic liver abscess drainage and broad-spectrum antibiotics treatment were performed. Outcomes: Despite liver abscess drainage, persistent fever and no improvement in the WBC count or CRP level was observed. The patient's respiratory condition and renal function gradually worsened; The patient's general condition did not improve despite the ventilator support and continuous hemodiafiltration, and he died on day 37. Lessons: We report the first case of liver abscess after atezolizumab plus bevacizumab treatment for unresectable HCC.

DOI： 10.1097/MD.0000000000030486

特集胆道ドレナージのすべて-適応･方法 2.各論(7)経皮的胆囊ドレナージ

河上洋, 畑田紘志, 内山尚美, 小川宗一郎, 田村穂高, 大園芳範

臨床消化器内科 37 ( 10 ) 1342 - 1349 2022年8月

掲載種別：研究論文（学術雑誌）出版者・発行元：日本メディカルセンター

DOI： 10.19020/cg.0000002361

特集肝門部領域胆管ドレナージを極める [各論] 肝門部領域胆管狭窄に対するENBD

河上洋, 畑田紘志, 内山尚美, 小川宗一郎, 内田圭祐, 田村穂高, 吉田直樹, 市成直樹, 大園芳範

消化器内視鏡 34 ( 6 ) 1079 - 1083 2022年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：東京医学社

DOI： 10.24479/endo.0000000230

Risk of Pancreatitis Following Biliary Stenting With/Without Endoscopic Sphincterotomy: A Randomized Controlled Trial 査読あり

Kato S., Kuwatani M., Onodera M., Kudo T., Sano I., Katanuma A., Uebayashi M., Eto K., Fukasawa M., Hashigo S., Iwashita T., Yoshida M., Taya Y., Kawakami H., Kato H., Nakai Y., Kobashigawa K., Kawahata S., Shinoura S., Ito K., Kubo K., Yamato H., Hara K., Maetani I., Mukai T., Shibukawa G., Itoi T.

Clinical Gastroenterology and Hepatology 20 ( 6 ) 1394 - 1403.e1 2022年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Clinical Gastroenterology and Hepatology

Background & Aims: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP. Methods: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement. Results: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%–23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups. Conclusion: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm

DOI： 10.1016/j.cgh.2021.08.016

Hematochezia Due to Panitumumab-induced Colitis with Vitamin K Deficiency. 査読あり

Tamura H, Nakashima K, Uchiyama N, Ogawa S, Hatada H, Yoshida N, Uchida K, Ozono Y, Tanaka H, Yamamto K, Kawakami H

Internal medicine (Tokyo, Japan) 61 ( 10 ) 1503 - 1509 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本内科学会

Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be useful in treating either advanced or recurrent <i>KRAS/NRAS/BRAF</i> wild-type colorectal cancer. We herein report the case of a 60-year-old man with short bowel syndrome who developed hematochezia due to panitumumab-induced colitis with vitamin K deficiency during third-line chemotherapy. The cause of vitamin K deficiency was the lack of intravenous vitamin K supplementation following a change from central venous nutrition to peripheral venous nutrition. We advise clinicians to carefully check for colitis and manage the infusions of chemotherapy patients with short bowel syndrome.

DOI： 10.2169/internalmedicine.8254-21

EUS-GUIDED BILIARY AND JEJUNAL DRAINAGE FOR RECURRENT GALLBLADDER CANCER: A CASE REPORT

Uchiyama N., Kawakami H., Kubota Y., Hatada H., Ogawa S., Tamura H., Yoshida N.

Gastroenterological Endoscopy 64 ( 3 ) 270 - 276 2022年3月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Gastroenterological Endoscopy

A 65-year-old man with small bowel obstruction (SBO) and obstructive jaundice due to recurrence of cystic duct cancer was admitted to our division. He had history of gallbladder bed and extrahepatic bile duct resection (partial liver resection) with Roux-en-Y reconstruction. We performed EUS-guided hepaticogastrostomy (EUS-HGS) for biliary drainage and EUS-guided transluminal drainage of dilated jejunal limb. Obstructive jaundice and abdominal pain were resolved, thereby improving the patient's QOL. We searched PubMed for articles published between October 2000 and October 2021 using the terms "EUS-guided transluminal drainage, gastrojejunostomy, or gastroenterostomy" and "small bowel obstruction". On the basis of search results, this is the first report on EUS-guided transmural drainage for SBO and jaundice due to recurrence of cystic duct cancer. It is difficult to improve prognosis and QOL of patients with SBO caused by recurrent cancer with surgical treatment. Thus, endoscopic internal drainage is desirable. In the future, the development of dedicated devices and elaborate indications for currently available devices are required.

DOI： 10.11280/gee.64.270

Usefulness of intraoperative contrast-enhanced ultrasonography in laparoscopic enucleation of small pancreatic metastases from renal cell carcinoma: A case report

Kai K., Imamura N., Hiyoshi M., Hamada T., Uchise Y., Hatada H., Kawakami H., Mukai S., Kamoto T., Nanashima A.

Asian journal of endoscopic surgery 15 ( 1 ) 211 - 215 2022年1月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Asian journal of endoscopic surgery

Pancreatic metastasis from renal cell carcinoma (RCC) is relatively rare. Surgical resection of the lesion is recommended if no residual tumor remains. Although there is no clear standard for surgical procedures, enucleation can be considered for small lesions. Lesion identification is important for enucleation, and contrast-enhanced ultrasound which takes advantage of the characteristics of hypervascular lesions was useful in a 68-year-old woman who underwent a left nephrectomy for RCC 11 years ago that was pathologically diagnosed as clear cell carcinoma. Recent computed tomography checkup showed a hypervascular tumor of 6 mm in the uncinated process and 10 mm in the pancreatic tail. Endoscopic ultrasonography-guided fine-needle aspiration was performed for the tail lesion, a diagnosis of clear cell carcinoma was made, and laparoscopic enucleation of the pancreatic tumors was performed aided by intraoperative contrast-enhanced ultrasound. The postoperative course was uneventful, and no pancreatic fistula occurred.

DOI： 10.1111/ases.12974

膵インスリノーマに対するEUSガイド下ラジオ波焼灼術：三次医療センター２施設の経験

河上洋

日本消化器内視鏡学会雑誌 64 ( 8 ) 1519 - 1519 2022年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本消化器内視鏡学会

【背景と目的】インスリノーマは膵神経内分泌腫瘍の中でもっとも頻度が高く，温存手術が適応となる．EUSガイド下ラジオ波焼灼術（EUS-guided radiofrequency ablation：EUS-RFA）は限局性腫瘍に対する新たな治療法である．本研究は20mm未満の膵インスリノーマに対するEUS-RFAの安全性と有効性に関するプレリミナリーな臨床研究である．【方法】三次医療センター２施設で膵インスリノーマに対してEUS-RFAを施行した臨床経過を解析した．【結果】2017年11月～2020年12月の期間中，７例（男：女＝１：６，年齢中央値：66歳）が登録された．EUS-RFA １回の焼灼により全例で速やかに低血糖が改善し，画像診断では７例中６例が完全寛解に至り，無症候を維持していた（観察期間中央値：21カ月（範囲：３～38カ月））．３例で軽症合併症がみられた．高齢者の１例では15日目に胃後部に液体貯留を生じ，１カ月後に死亡した．【結論】２cm未満の膵インスリノーマに対するEUS-RFAは有効で，安全性は許容範囲と考えられる．長期予後や再発に関してはさらなるエビデンスの蓄積が必要である．

DOI： 10.11280/gee.64.1519

メインデバイスとしてのHookKnifeJの効果的な手技とコツ

三池忠, 河上洋, 小山恒男

日本消化器内視鏡学会雑誌 64 ( 10 ) 2295 - 2307 2022年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本消化器内視鏡学会

HookKnifeは2003年に小山らにより開発されたESDのデバイスである．シンプルなデザインにもかかわらず，咽頭，食道，胃，十二指腸，大腸等のあらゆる臓器に有用である．先端部のHook partでの細かい操作のみならず，根本部のArm partでの大胆な操作が特徴的であり，また他のナイフの苦手な垂直病変へのアプローチや瘢痕合併症例で剝離に対しての繊細な操作も可能である．2015年には送水機能を完備し，HookKnifeJ（オリンパス社）と生まれ変わり，その有用性はさらに進化した．難易度の高いESDの際には使用することが多いデバイスであり，是非，普段からメインデバイスとして手技を熟練し習得しておくべきであり，その手技を解説する．

DOI： 10.11280/gee.64.2295

Precut―最近の動向と手技のコツ（動画付き）招待あり

河上洋

日本消化器内視鏡学会雑誌 64 ( 11 ) 2391 - 2411 2022年

担当区分：筆頭著者,　責任著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本消化器内視鏡学会

Precutは本邦では選択的胆管挿管困難例に対して施行されることが多く，エキスパートのみが行うサルベージ手技として位置づけられている．近年，エキスパートの術者が行うearly precutの有用性が欧米から報告され，最近ではdirectすなわちprimary precutの有用性がアジア（韓国，インド）から報告された．トレイニーが習得するにはハードルが高い手技の１つであるが，今後はその有用性からエキスパートのみではなく，エキスパートの監督下であればトレイニーも行うべき手技の１つとなる大きな転換期を迎える可能性がある．しかし，precutは用語を始め，手技に至るまでその詳細は確立していない．そこで，本稿ではprecutの用語の整理，現時点での動向などを解説する．また，precut施行時の観察ポイントや処置具の選択，具体的な手技の解説を行う．

DOI： 10.11280/gee.64.2391

Biliary drainage for malignant perihilar biliary obstruction

Kawakami H.

Journal of Japanese Society of Gastroenterology 119 ( 4 ) 310 - 320 2022年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Japanese Society of Gastroenterology

悪性肝門部領域胆管閉塞に対する胆道ドレナージは，切除の可否にかかわらず経乳頭的が第一選択である．切除例であれば術前に内視鏡的経鼻胆道ドレナージ（endoscopic nasobiliary drainage；ENBD）を予定残肝側の片葉へ留置する．一方，切除不能例であればプラスチックステントあるいはアンカバードタイプの金属ステントを留置する．片葉あるいは両葉留置の優越性については結論が出ていない．最近，筆者は肝門部領域胆管閉塞用にENBDと胆管内留置用のinsideステントを一体化した2 in 1ステントを開発した．切除あるいは切除不能例や急性胆管炎例に対する新たな方法として注目されつつある．本稿では，悪性肝門部領域胆管閉塞に対する胆道ドレナージの実際について解説する．

DOI： 10.11405/nisshoshi.119.310

Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C virus infection aged 75years or older

大園芳範, 中村憲一, 岩切久芳, 蓮池悟, 末田光恵, 三池忠, 山本章二朗, 永田賢治, 河上洋

BMC Gastroenterology 22 ( 1 ) 210 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Nature

Background
It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years.

Methods
This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group.

Results
In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups.

Conclusions
Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.