基本情報
- 所属
- 自治医科大学 附属病院移植・再生医療センター 教授
- 通称等の別名
- Yasunaru Sakuma
- 研究者番号
- 10296105
- J-GLOBAL ID
- 202001003024187832
- researchmap会員ID
- R000014289
論文
626-
Clinical pharmacology and therapeutics 2025年3月16日While endogenous cortisol secretion rises in the early morning, the number of lymphocytes in the blood is higher at night, thus exhibiting an antiphase pattern to cortisol secretion. Therefore, compared with the daytime, the infiltration of lymphocytes into immune-reactive tissues is enhanced at night. This study aimed to determine whether the administration of methylprednisolone (mPSL) in the evening is more effective against T cell-mediated rejection (TCMR) after liver transplantation compared with morning administration. This study used a randomized, open-label, parallel-group comparison design. Pediatric patients scheduled to undergo living-donor liver transplantation were randomly divided into morning (8:00 a.m.) and evening (8:00 p.m.) mPSL administration groups. The primary endpoint was the occurrence of TCMR within 14 days of surgery. Sixty-two patients were enrolled between 2014 and 2023, and six patients were excluded from the analysis as their dose of mPSL deviated from the protocol within 14 days after surgery. Of the 56 subjects analyzed, TCMR was detected in 10 of the morning group (n = 29) and three of the evening group (n = 27) within 14 days after surgery. Stratified analysis of patients who did not receive preoperative rituximab treatment showed that none of the evening group and 36.4% of the morning group developed TCMR within 14 days after surgery (P < 0.01, 95% confidence interval; 2.00-infinity). Safety evaluation results were comparable between the two groups. This study shows that the evening administration of mPSL is an effective approach for suppressing TCMR. This study is hypothesis generating, and replication in further studies is needed.
-
BMC infectious diseases 25(1) 97-97 2025年1月21日BACKGROUND: Cytomegalovirus (CMV) is a major infectious complication in solid-organ transplant recipients, particularly in the context of pediatric liver transplantation. CMV serostatus is a well-established risk factor for postoperative CMV infection, with CMV seronegative recipients who receive organs from seropositive donors (D+/R-) being at the highest risk. Our previous research indicated a higher incidence of CMV infection in recipients with inherited metabolic diseases (IMDs) compared with those with biliary atresia (BA). This study aimed to determine whether IMDs constitute an independent risk factor for postoperative CMV infection. METHODS: We retrospectively analyzed data from 45 IMD and 230 BA recipients. We collected information on the occurrence and timing of episodes of CMV infections, methylprednisolone (mPSL) pulse therapy, patient characteristics, and peri- and postoperative data. RESULTS: Multivariable analysis identified mPSL pulse therapy (Odds Ratio (OR): 4.43), CMV serostatus (D+/R-) (OR: 6.03), and underlying IMDs (OR: 3.28) as independent risk factors for CMV infection. Further stratified analysis, which considered the timing of CMV infection diagnosis relative to mPSL pulse therapy, confirmed that CMV serostatus with (D+/R-) (OR: 5.61) and underlying IMDs (OR: 2.83) remained independent predictors of CMV infection, even when excluding the influence of mPSL pulse therapy. CONCLUSIONS: This study demonstrates that IMDs are a potent independent risk factor for CMV infection following pediatric liver transplantation. CLINICAL TRIAL NUMBER: Not applicable.
-
Biomedicines 13(1) 2024年12月31日Background: Even though many metabolic liver diseases can now be diagnosed using blood tests and diagnostic imaging, early diagnosis remains difficult. Understanding mechanisms contributing to the progression from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcoholic Hepatitis (AH) to cirrhosis is critical to reduce the burden of end-stage liver disease. Monitoring individual bile acids has been proposed as a way to distinguish various liver disorders. Methods: This study explored bile acid profiles in patients with MASH and AH. Plasma samples from patients with MASH, AH, and a control group were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify bile acid concentrations. Targeted metabolomic analysis was performed to compare bile acid levels between the hepatitis and control groups. Results: Concentrations of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) were significantly elevated in the hepatitis group. Correlation analysis revealed strong positive relationships between the total and direct bilirubin levels and TUDCA and GCDCA. Aspartate aminotransferase (AST) showed strong positive correlations with TCDCA and GCDCA. Child-Pugh score, Fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score were positively correlated with GCA, whereas the aspartate aminotransferase-to-platelet ratio correlated with TCA, TCDCA, and GCA. The model for end-stage liver disease (MELD) score showed a strong positive correlation with GCDCA. Implications: GCDCA may serve as a predictive biomarker for liver damage, potentially enabling early diagnosis and targeted intervention in patients with MASH and AH.
-
Clinical journal of gastroenterology 17(6) 1080-1086 2024年12月Portal cavernoma cholangiopathy (PCC) is a complex condition associated with portal hypertension, particularly in patients with extrahepatic portal vein obstruction (EHPVO). Herein, we present a case of liver failure with PCC in a 55-year-old male successfully treated with living-donor liver transplantation (LDLT). The patient had a history of gastrointestinal bleeding and recurrence of cholangitis. Imaging studies confirmed cavernous transformation and pericholedochal varices. Preoperative angiography verified hepatopetal flow in the pericholedochal varix, which facilitated successful anastomosis with the donor's portal vein during LDLT. Histological examination of the explanted liver confirmed vanishing bile duct syndrome (VBDS) and secondary bile stasis was considered to have caused liver failure. No postoperative complications were observed within 13 months of LDLT. We report the first case of VBDS in the PCC resulting from EHPVO that was successfully managed with LDLT. Careful management of similar cases should involve angiography and long-term postoperative monitoring of portal vein complications.
-
Stem cell research & therapy 15(1) 395-395 2024年11月4日BACKGROUND: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis. METHODS: Male Lewis rats were fed with a methionine and choline-deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV). RESULTS: The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division. CONCLUSIONS: MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx.
MISC
134-
生体医工学 57 S200_1-S200_1 2019年<p>昨今の内視鏡外科手術の普及に伴い、シミュレーション教育や手術トレーニング環境の整備が進んだ。特に内視鏡外科手術では、外科医は体腔内臓器をモニタ画像情報で判断し、手術を行う。特に執刀医、助手すべてが同じ術野を共有することから、オンサイトでのトレーニングが可能である。手術映像を記録可能なことから、繰り返し再生によるオフサイトトレーニングも広く行われている。実際の手術を想定したオフサイトでのタスクトレーニングは、最善の手術を完遂する上で重要である。開腹手術に比較し多様な機材を使用する内視鏡外科手術では、高忠実度(Hi-Fi)臓器モデルによる手術トレーニングも行われている。Hi-Fiモデルでは、より実践に近い感覚でトレーニングを行うことが可能と考えられる。このような臓器モデルはシリコン樹脂やPVAなどの石油原料由来の臓器モデルが主である。ところがトレーニングモデルにおいても廃棄物の問題は重要であり、マンナンなどの植物由来原料を用いたタスクトレーニングモデルも開発されている。継続してトレーニングが必要な手術教育においては、コストを含めた持続可能なトレーニング環境の整備が必須である。</p>
-
日本臨床外科学会雑誌 79(増刊) 424-424 2018年10月
-
日本癌学会総会記事 77回 2174-2174 2018年9月
-
小切開・鏡視外科学会雑誌 9(1) 47-51 2018年6月症例1は30歳男性で、発熱と左腹部痛で来院した。CTで感染性Walled-off necrosis(WON)と診断し、保存的治療を行ったが、症状ならびに炎症所見の改善を認めず、インターベンション治療目的に当院転院となった。造影CT所見から壊死物質を主成分とした感染性WONと診断し、小切開Videoscope補助下に後腹膜経路でネクロセクトミーを行った。1回のネクロセクトミーで炎症所見とCT所見は速やかに改善し、追加の処置は不要となった。左後腹膜のドレーンは留置したまま入院40日目に退院した。症例2は34歳男性で、急性膵炎の診断で保存的治療が開始され、退院約2週間後に間歇的腹痛と発熱で来院し、炎症反応高値、CTで感染性WONと診断され再入院した。造影CT所見から膵体尾部の壊死物質を主成分とする左側感染性WONと診断し、腹腔経路で小切開Videoscope補助下にネクロセクトミーを行った。その後、右側WON増大による閉塞性黄疸が出現し、開腹ネクロセクトミーと胆道ドレナージが必要となった。症状出現から7ヵ月後、ERCPで左右肝管にERBD tubeを留置し退院した。
書籍等出版物
2共同研究・競争的資金等の研究課題
11-
日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
-
日本学術振興会 科学研究費助成事業 2023年6月 - 2025年3月
-
日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
-
日本学術振興会 科学研究費助成事業 基盤研究(B) 2021年4月 - 2024年3月