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Preoperative albumin-bilirubin score and liver resection percentage determine postoperative liver regeneration after partial hepatectomy

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World Journal of Gastroenterology 2024年第14期30卷 2006-2017页

作者： Kazuhiro Takahashi Masahiko Gosho Yoshihiro Miyazaki Hiromitsu Nakahashi Osamu Shimomura Kinji Furuya Manami Doi Yohei Owada Koichi Ogawa Yusuke Ohara Yoshimasa Akashi Tsuyoshi Enomoto Shinji Hashimoto tatsuya oda Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery University of TsukubaTsukuba 3058-575IbarakiJapan Department of Biostatistics University of TsukubaTsukuba 3058-575IbarakiJapan

BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are scarce.Additionally,there is limited knowledge about the preoperative factors that influence postoperative regeneration.AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regenera-tion.METHODS A total of 268 patients who received partial hepatectomy were enrolled.Patients were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)groups.The regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,respectively.The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months postsurgery.RESULTS The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,respectively.The RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri group.According to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed regeneration.Furthermore,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.0 up]and liver resection percentage[OR=1.02(1.00

关键词： Liver regeneration Albumin-bilirubin score Liver resection percentage Partial hepatectomy Human Regeneration index

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Dualistic role of platelets in living donor liver transplantation: Are they harmful?

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World Journal of Gastroenterology 2022年第9期28卷 897-908页

作者： Chen Liang Kazuhiro Takahashi Kinji Furuya Nobuhiro Ohkohchi tatsuya oda Gastrointestinal and Hepatobiliary-Pancreatic Surgery University of TsukubaTsukuba 3058575IbarakiJapan

Platelets are anucleate fragments mainly involved in hemostasis and thrombosis,and there is emerging evidence that platelets have other nonhemostatic potentials in inflammation,angiogenesis,regeneration and ischemia/reperfusion injury(I/R injury),which are involved in the physiological and pathological processes during living donor liver transplantation(LDLT).LDLT is sometimes associated with impaired regeneration and severe I/R injury,leading to postoperative complications and decreased patient survival.Recent studies have suggested that perioperative thrombocytopenia is associated with poor graft regeneration and postoperative morbidity in the short and long term after LDLT.Although it is not fully understood whether thrombocytopenia is the cause or result,increasing platelet counts are frequently suggested to improve posttransplant outcomes in clinical studies.Based on rodent experiments,previous studies have identified that platelets stimulate liver regeneration after partial hepatectomy.However,the role of platelets in LDLT is controversial,as platelets are supposed to aggravate I/R injury in the liver.Recently,a rat model of partial liver transplantation(LT)was used to demonstrate that thrombopoietin-induced thrombocytosis prior to surgery accelerated graft regeneration and improved the survival rate after transplantation.It was clarified that platelet-derived liver regeneration outweighed the associated risk of I/R injury after partial LT.Clinical strategies to increase perioperative platelet counts,such as thrombopoietin,thrombopoietin receptor agonist and platelet transfusion,may improve graft regeneration and survival after LDLT.

关键词： Platelet Liver transplantation Regeneration Ischemia/reperfusion injury Kupffer cell Oxidative stress

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Recurrent renal cell carcinoma leading to a misdiagnosis of polycystic liver disease: A case report

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World Journal of Gastroenterology 2019年第18期25卷 2264-2270页

作者： Chen Liang Kazuhiro Takahashi Masanao Kurata Shingo Sakashita tatsuya oda Nobuhiro Ohkohchi Department of Surgery University of Tsukuba Department of Diagnostic Pathology University of Tsukuba

BACKGROUND Polycystic liver disease(PCLD) with a large cystic volume deteriorates the quality of life of patients through substantial effects on the adjacent organs,recurrent cyst infections, cyst rupture, and hemorrhage. Surgical or radiological intervention is usually needed to alleviate these symptoms. We report a rare case of the cystic metastasis of renal cell carcinoma(RCC), which was misdiagnosed as PCLD, as a result of the clinical and radiological similarity between these disorders.CASE SUMMARY A 74-year-old female who had undergone nephrectomy for papillary-type RCC(PRCC) was suffering from abdominal pain and the recurrent intracystic hemorrhage of multiple cysts in the liver. Imaging studies and aspiration cytology of the cysts showed no evidence of malignancy. With a diagnosis of autosomal dominant polycystic liver disease, the patient received hepatectomy for the purpose of mass reduction and infectious cyst removal. Surgery was performed without complications, and the patient was discharged on postoperative day 14. Postoperatively, the pathology revealed a diagnosis of recurrent PRCC with cystic formation.CONCLUSION This case demonstrates the importance of excluding the cystic metastasis of a cancer when liver cysts are observed.

关键词： Polycystic liver disease Polycystic kidney disease Cystic metastasis Renal cell carcinoma Case report

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Hepatitis B virus infection modeling using multi-cellular organoids derived from human induced pluripotent stem cells

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World Journal of Gastroenterology 2021年第29期27卷 4784-4801页

作者： Di Cao Jian-Yun Ge Yun Wang tatsuya oda Yun-Wen Zheng Institute of Regenerative Medicine and Affiliated Hospital of Jiangsu University Jiangsu UniversityZhenjiang 212001Jiangsu ProvinceChina Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery Faculty of MedicineUniversity of TsukubaTsukuba 305-8575IbarakiJapan Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine and School of Biotechnology and Heath SciencesWuyi UniversityJiangmen 529020Guangdong ProvinceChina School of Medicine Yokohama City UniversityYokohama 234-0006KanagawaJapan

Chronic infection with hepatitis B virus(HBV)remains a global health concern despite the availability of vaccines.To date,the development of effective treatments has been severely hampered by the lack of reliable,reproducible,and scalable in vitro modeling systems that precisely recapitulate the virus life cycle and represent virus-host interactions.With the progressive understanding of liver organogenesis mechanisms,the development of human induced pluripotent stem cell(iPSC)-derived hepatic sources and stromal cellular compositions provides novel strategies for personalized modeling and treatment of liver disease.Further,advancements in three-dimensional culture of self-organized liver-like organoids considerably promote in vitro modeling of intact human liver tissue,in terms of both hepatic function and other physiological characteristics.Combined with our experiences in the investigation of HBV infections using liver organoids,we have summarized the advances in modeling reported thus far and discussed the limitations and ongoing challenges in the application of liver organoids,particularly those with multi-cellular components derived from human iPSCs.This review provides general guidelines for establishing clinical-grade iPSC-derived multi-cellular organoids in modeling personalized hepatitis virus infection and other liver diseases,as well as drug testing and transplantation therapy.

关键词： Hepatitis B virus Induced pluripotent stem cells Liver organoid Multicellular organoid Modeling Transplantable

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Impelling force and current challenges by chemicals in somatic cell reprogramming and expansion beyond hepatocytes

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World Journal of Stem Cells 2019年第9期11卷 650-665页

作者： Jian-Yun Ge Yun-Wen Zheng Li-Ping Liu Hiroko Isoda tatsuya oda Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery Faculty of MedicineUniversity of TsukubaTsukubaIbaraki 305-8575Japan Institute of Regenerative Medicine and Affiliated Hospital Jiangsu UniversityZhenjiang 212001Jiangsu ProvinceChina Department of Regenerative Medicine School of MedicineYokohama City UniversityYokohama 236-0004Japan Faculty of Life and Environmental Sciences University of TsukubaTsukubaIbaraki 305-8572Japan

In the field of regenerative medicine,generating numerous transplantable functional cells in the laboratory setting on a large scale is a major challenge.However,the in vitro maintenance and expansion of terminally differentiated cells are challenging because of the lack of specific environmental and intercellular signal stimulations,markedly hindering their therapeutic application.Remarkably,the generation of stem/progenitor cells or functional cells with effective proliferative potential is markedly in demand for disease modeling,cell-based transplantation,and drug discovery.Despite the potent genetic manipulation of transcription factors,integration-free chemically defined approaches for the conversion of somatic cell fate have garnered considerable attention in recent years.This review aims to summarize the progress thus far and discuss the advantages,limitations,and challenges of the impact of full chemicals on the stepwise reprogramming of pluripotency,direct lineage conversion,and direct lineage expansion on somatic cells.Owing to the current chemical-mediated induction,reprogrammed pluripotent stem cells with reproducibility difficulties,and direct lineage converted cells with marked functional deficiency,it is imperative to generate the desired cell types directly by chemically inducing their potent proliferation ability through a lineagecommitted progenitor state,while upholding the maturation and engraftment capacity posttransplantation in vivo.Together with the comprehensive understanding of the mechanism of chemical drives,as well as the elucidation of specificity and commonalities,the precise manipulation of the expansion for diverse functional cell types could broaden the available cell sources and enhance the cellular function for clinical application in future.

关键词： Chemical induction Pluripotent reprogramming Direct lineage conversion Direct lineage expansion Hepatocyte expansion Cell fate specificity Transcriptional memory In vivo induction

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Novel alternative transplantation therapy for orthotopic liver transplantation in liver failure:A systematic review

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World Journal of Transplantation 2020年第3期10卷 64-78页

作者： Tomoaki Furuta Kinji Furuya Yun-Wen Zheng tatsuya oda Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery Faculty of MedicineUniversity of TsukubaTsukuba-shi 305-8575IbarakiJapan Institute of Regenerative Medicine and Affiliated Hospital of Jiangsu University Zhenjiang 212001Jiangsu ProvinceChina Department of Regenerative Medicine School of MedicineYokohama City UniversityYokohama 236-0004Japan Center for Stem Cell Biology and Regenerative Medicine The Institute of Medical ScienceThe University of TokyoTokyo 108-8639Japan

BACKGROUND Orthotopic liver transplantation(OLT)is the only treatment for end-stage liver failure;however,graft shortage impedes its applicability.Therefore,studies investigating alternative therapies are plenty.Nevertheless,no study has comprehensively analyzed these therapies from different perspectives.AIM To summarize the current status of alternative transplantation therapies for OLT and to support future research.METHODS A systematic literature search was performed using PubMed,Cochrane Library and EMBASE for articles published between January 2010 and 2018,using the following MeSH terms:[(liver transplantation)AND cell]OR[(liver transplantation)AND differentiation]OR[(liver transplantation)AND organoid]OR[(liver transplantation)AND xenotransplantation].Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation.Among them,we selected articles including in vivo transplantation.RESULTS A total of 89 studies were selected.There are three principle forms of treatment for liver failure:Xeno-organ transplantation,scaffold-based transplantation,and cell transplantation.Xeno-organ transplantation was covered in 14 articles,scaffold-based transplantation was discussed in 22 articles,and cell transplantation was discussed in 53 articles.Various types of alternative therapies were discussed:Organ liver,25 articles;adult hepatocytes,31 articles;fetal hepatocytes,three articles;mesenchymal stem cells(MSCs),25 articles;embryonic stem cells,one article;and induced pluripotent stem cells,three articles and other sources.Clinical applications were discussed in 12 studies:Cell transplantation using hepatocytes in four studies,five studies using umbilical cord-derived MSCs,three studies using bone marrow-derived MSCs,and two studies using hematopoietic stem cells.CONCLUSION The clinical applications are present only for cell transplantation.Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations,which warrants future research to find relev

关键词： Cell transplantation Liver transplantation Organ transplantation Xenotransplantation Tissue engineering Scaffold

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Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis

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World Journal of Gastroenterology 2016年第38期22卷 8596-8604页

作者： Yusuke Ohara tatsuya oda Shinji Hashimoto Yoshimasa Akashi Ryoichi Miyamoto Tsuyoshi Enomoto Kaishi Satomi Yukio Morishita Nobuhiro Ohkohchi Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery Faculty of MedicineUniversity of Tsukuba Department of Diagnostic Pathology Faculty of MedicineUniversity of Tsukuba Diagnostic Pathology Division Tokyo Medical University Ibaraki Medical Center

AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor(NET) from solid-pseudopapillary neoplasm(SPN), focusing primarily on immunohistochemical analysis.METHODS We reviewed 30 pancreatic surgical specimens of NET(24 cases) and SPN(6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pancytokeratin, E-cadherin, progesterone receptor,vimentin, α-1-antitrypsin, CD10, and β-catenin.RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles.CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

关键词： Neuroendocrine tumor Pancreas Solidpseudopapillary neoplasm Immunohistochemistry Diagnosis

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Neuroendocrine carcinoma of the extrahepatic bile duct: A case report

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World Journal of Gastroenterology 2016年第30期22卷 6960-6964页

作者： Yukio Oshiro Ryozo Gen Shinji Hashimoto tatsuya oda Taiki Sato Nobuhiro Ohkohchi Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery Faculty of Medicine University of Tsukuba Department of Pathology Faculty of MedicineUniversity of Tsukuba

Neuroendocrine carcinoma(NEC) originating from the gastrointestinal hepatobiliary-pancreas is a rare, invasive, and progressive disease, for which the prognosis is extremely poor. The patient was a 72-year-old man referred with complaints of jaundice. He was diagnosed with middle extrahepatic cholangiocarcinoma(cT 4N1M0, c Stage Ⅳ). He underwent a right hepatectomy combined with extrahepatic bile duct and portal vein resection after percutaneous transhepatic portal vein embolization. Microscopic examination showed a large-cell neuroendocrine carcinoma according to the WHO criteria for the clinicopathologic classification of gastroenteropancreatic neuroendocrine tumors. Currently, the patient is receiving combination chemotherapy with cisplatin and etoposide for postoperative multiple liver metastases. Although NEC is difficult to diagnose preoperatively, it should be considered an uncommon alternative diagnosis.

关键词： Neuroendocrine carcinoma Extrahepatic bile duct Neuroendocrine tumor

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Enhanced hepatic differentiation in the subpopulation of human amniotic stem cells under 3D multicellular microenvironment

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World Journal of Stem Cells 2019年第9期11卷 705-721页

作者： Kinji Furuya Yun-Wen Zheng Daisuke Sako Kenichi Iwasaki Dong-Xu Zheng Jian-Yun Ge Li-Ping Liu Tomoaki Furuta Kazunori Akimoto Hiroya Yagi Hiromi Hamada Hiroko Isoda tatsuya oda Nobuhiro Ohkohchi Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery Faculty of MedicineUniversity of TsukubaTsukubaIbaraki 305-8575Japan Institute of Regenerative Medicine and Affiliated Hospital Jiangsu UniversityZhenjiang 212001Jiangsu ProvinceChina Department of Regenerative Medicine School of MedicineYokohama City UniversityYokohama 236-0004Japan Department of Medicinal and Life Sciences Faculty of Pharmaceutical SciencesTokyo University of ScienceNoda 278-8510Japan Department of Obstetrics and Gynecology Faculty of MedicineUniversity of TsukubaTsukuba 305-8575Japan Faculty of Life and Environmental Sciences University of TsukubaTsukuba 305-8572Japan

BACKGROUND To solve the problem of liver transplantation donor insufficiency,an alternative cell transplantation therapy was investigated.We focused on amniotic epithelial cells(AECs)as a cell source because,unlike induced pluripotent stem cells,they are cost-effective and non-tumorigenic.The utilization of AECs in regenerative medicine,however,is in its infancy.A general profile for AECs has not been comprehensively analyzed.Moreover,no hepatic differentiation protocol for AECs has yet been established.To this end,we independently compiled human AEC libraries,purified amniotic stem cells(ASCs),and co-cultured them with mesenchymal stem cells(MSCs)and human umbilical vein endothelial cell(HUVECs)in a 3D system which induces functional hepatic organoids.AIM To characterize AECs and generate functional hepatic organoids from ASCs and other somatic stem cells METHODS AECs,MSCs,and HUVECs were isolated from the placentae and umbilical cords of cesarean section patients.Amnion and primary AEC stemness characteristics and heterogeneity were analyzed by immunocytochemistry,Alkaline phosphatase(AP)staining,and flow cytometry.An adherent AEC subpopulation was selected and evaluated for ASC purification quality by a colony formation assay.AEC transcriptomes were compared with those for other hepatocytes cell sources by bioinformatics.The 2D and 3D culture were compared by relative gene expression using several differentiation protocols.ASCs,MSCs,and HUVECs were combined in a 3D co-culture system to generate hepatic organoids whose structure was compared with a 3D AEC sphere and whose function was elucidated by immunofluorescence imaging,periodic acid Schiff,and an indocyanine green(ICG)test.RESULTS AECs have certain stemness markers such as EPCAM,SSEA4,and E-cadherin.One AEC subpopulation was also either positive for AP staining or expressed the TRA-1-60 and TRA-1-81 stemness markers.Moreover,it could form colonies and its frequency was enhanced ten-fold in the adherent subpopulation after selective primary passage.Bioinfo

关键词： 3D micropattern Amniotic epithelial cells Amniotic stem cells Hepatic differentiation Heterogeneity Human placental tissue Human umbilical vein endothelial cells Mesenchymal stem cells Multicellular microenvironment Organoid

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Three-dimensional imaging identified the accessory bile duct in a patient with cholangiocarcinoma

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World Journal of Gastroenterology 2014年第32期20卷 11451-11455页

作者： Ryoichi Miyamoto Yukio Oshiro Shinji Hashimoto Keisuke Kohno Kiyoshi Fukunaga tatsuya oda Nobuhiro Ohkohchi Division of Gastroenterological and Hepatobiliary Surgery and Organ Transplantation Department of Surgery University of Tsukuba Ibaraki 305-8575 Japan

The development of diagnostic imaging technology, such as multidetector computed tomography(MDCT) and magnetic resonance cholangiopancreatography(MRCP), has made it possible to obtain detailed images of the bile duct. Recent reports have indicated that a 3-dimensional(3D) reconstructed imaging system would be useful for understanding the liver anatomy before surgery. We have investigated a novel method that fuses MDCT and MRCP images. This novel system easily made it possible to detect the anatomical relationship between the vessels and bile duct in the portal hepatis. In this report, we describe a very rare case of extrahepatic cholangiocarcinoma associated with an accessory bile duct from the caudate lobe connecting with the intrapancreatic bile duct. We were unable to preoperatively detect this accessory bile duct using MDCT and MRCP. However, prior to the second operation, we were able to clearly visualise the injured accessory bile duct using our novel 3D imaging modality. In thisreport, we suggest that this imaging technique can be considered a novel and useful modality for understanding the anatomy of the portal hepatis, including the hilar bile duct.

关键词： 3-dimensional imaging Hepatobiliary and pancreatic

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