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Mapping of liver-enriched transcription factors in the human intestine

World Journal of Gastroenterology 2010年第31期16卷 3919-3927页

作者： Frank Lehner Ulf Kulik juergen klempnauer juergen Borlak Department of General Visceral and Transplantation SurgeryHanover Medical School Molecular Medicine and Medical Biotechnol-ogy Fraunhofer Institute of Toxicology and Experimental Medi-cine Center of Pharmacology and Toxicology Hanover Medical School

AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at

关键词： Liver-enriched transcription factors Human intestine Caco-2 Gene expression

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Surgical experience in splitting donor liver into left lateral and right extended lobes

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World Journal of Gastroenterology 2005年第27期11卷 4220-4224页

作者： Ji-Qi Yan Thomas Becker Michael Neipp Cheng-Hong Peng Rainer Lueck Frank Lehner Hong-Wei Li juergen klempnauer Department of Surgery Ruijin Hospital Affiliated to Shanghai Second Medical University Shanghai 200025 China Department of Abdominal and Transplant Surgery Medical School of Hannover Carl-NeubergStr. 1 Hannover 30625 Germany

AIM： To outline the surgical experience with donor liver splitting in split liver ***： From March 1 to September 1 in 2004, 10 donor livers were split ex situ into a left lateral lobe （segments Ⅱ and Ⅲ） and a right extended lobe （segments Ⅰ, Ⅳ-Ⅷ） in Medical School of Hannover, and thereafter split liver transplantation was performed successfully in 29 cases. The average age, weight and ICU slaying period of the donors were 32.7 years （25-52 years）, 64.5 kg（45-75 kg） and 2.4 d （2-8 d） ***： The average weight of the whole graft and the left lateral lobe was 2 322.6 g （956-2 665 g） and 282.8 g （298-373 g） respectively, and the average ratio of left lateral lobe to the whole graft was 0.225 （0.278-0.274）.The average graft to recipient weight ratio （GRWR） of the left lateral lobe and the right extended lobe reached 2.44% （2.22-5.42%） and 2.73% （2.32-2.30%） *** average it took approximately 205 min （85-235 rain）to split the donor liver. Five donor organs showed anatomic variation including the left hepatic vein variation in two cases, the left hepatic artery variation in two cases and the bile duct variation in one ***： Split liver transplantation has become a mature surgical technique to expand the donor pool with promising results. In the process of graft splitting, close attention needs to be paid to potential anatomic variations,especially to variations of the left hepatic vein, the left hepatic artery, and the bile duct.

关键词： Split Donor liver Anatomic variation

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劈离式肝移植——解决供肝短缺的有效方法

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外科理论与实践 2004年第6期9卷 528-530页

作者：严佶祺 Thomas Becker 彭承宏李宏为 juergen klempnauer 上海第二医科大学附属瑞金医院外科上海200025 德国汉诺威医学院腹部和器官移植外科

在过去十数年间,肝移植数量呈几何级增长,美国和欧洲面临着供受体需求数量的巨大差别,越来越多的待移植受体却在等待过程中发生死亡,文献统计认为受体等待死亡率即便是10%～15%也还是被低估的[1].而随着国内肝移植开展的不断深入和发展... 详细信息

在过去十数年间,肝移植数量呈几何级增长,美国和欧洲面临着供受体需求数量的巨大差别,越来越多的待移植受体却在等待过程中发生死亡,文献统计认为受体等待死亡率即便是10%～15%也还是被低估的[1].而随着国内肝移植开展的不断深入和发展,许多移植中心也面临着同样痛楚的现实.

关键词：劈离式肝移植方法介绍

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劈离式肝移植中供肝分离的手术经验

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中华肝胆外科杂志 2005年第11期11卷 738-741页

作者：严佶祺 Thomas Becker 彭承宏李宏为 juergen klempnauer 上海第二医科大学附属瑞金医院外科上海市200025 德国汉诺威医学院腹部和器官移植外科

目的探讨劈离式肝移植中供肝分离的手术经验.方法自2004年3月1日至9月1日,共计施行了10例体外供肝的劈离,将其分为左肝外侧叶(Ⅱ、Ⅲ段)和扩大右半肝(Ⅰ、Ⅳ～Ⅷ段)两部分,并为19位病人施行了劈离式肝移植.供体的平均年龄为32.7岁(15～5... 详细信息

目的探讨劈离式肝移植中供肝分离的手术经验.方法自2004年3月1日至9月1日,共计施行了10例体外供肝的劈离,将其分为左肝外侧叶(Ⅱ、Ⅲ段)和扩大右半肝(Ⅰ、Ⅳ～Ⅷ段)两部分,并为19位病人施行了劈离式肝移植.供体的平均年龄为32.7岁(15～51岁),平均体重64.5kg(45～75kg),ICU平均救治时间为2.4 d(1～8 d).结果劈离前整体供肝和劈离后左肝外侧叶的平均重量分别为1322.6 g(956～1665 g)和281.8 g(198～373 g),后者与前者的平均比值为0.215(0.178～0.274).左肝外侧叶部分的移植物与受体重量比(GRWR)的平均值为2.44%(1.22%～5.41%),而扩大右半肝部分GRWR的平均值为1.73%(1.31%～2.30%).供肝劈离平均花费的时间为105 min(85～135 min).共出现5例解剖变异,包括左肝静脉变异2例、肝动脉变异2例、胆管变异1例.结论劈离式肝移植已经成为扩大供肝来源的一种成熟的外科技术,且效果满意.在供肝劈离中需要正确应对各种可能的解剖变异,尤其是左肝静脉、左肝动脉和胆管的变异.

关键词：肝移植供肝解剖变异

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老年供体肝移植的临床经验

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外科理论与实践 2006年第4期11卷 295-298页

作者：严佶祺 Thomas Becker 彭承宏李宏为 juergen klempnauer 上海交通大学医学院附属瑞金医院外科瑞金器官移植中心上海200025 德国汉诺威医学院腹部和器官移植外科

目的:供肝来源的短缺日益成为肝移植的突出问题,本文旨意在探讨老年供体肝移植的疗效。方法:收集2004年3月至9月德国汉诺威医学院施行的69例肝移植的临床资料。供体年龄>60岁的肝移植有11例,占同期肝移植总数的15.9%,其中包括急诊肝移植... 详细信息

目的:供肝来源的短缺日益成为肝移植的突出问题,本文旨意在探讨老年供体肝移植的疗效。方法:收集2004年3月至9月德国汉诺威医学院施行的69例肝移植的临床资料。供体年龄>60岁的肝移植有11例,占同期肝移植总数的15.9%,其中包括急诊肝移植2例,再移植1例,供体的平均年龄为66.7岁,年龄最大者为75岁。而供体年龄≤60岁的肝移植共58例,供体平均年龄为36.3岁,年龄最小者为10岁。结果:老年供体组病人肝移植的总体效果令人满意,两组病人的1年生存率分别为81.8%(9/11)和87.9%(51/58),移植肝1年存活率为72.7%(8/11)和82.7%(48/58),两组间无显著差异。结论:在审慎的选择下,老年供体的肝脏是能够安全运用的,供体年龄并非是影响肝移植预后的因素。

关键词：供体老年人肝移植

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Split liver transplantation: a reliable approach to expand donor pool

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Hepatobiliary & Pancreatic Diseases International 2005年第3期4卷 339-344页

作者： Ji-Qi Yan, Thomas Becker, Cheng-Hong Peng, Hong-Wei Li and juergen klempnauer Department of Surgery, Ruijin Hospital Affiliated to Shanghai Second Medical University, Shanghai 200025, China ( Yan JQ, Peng CH and Li HW) Department of Abdominal and Transplant Surgery, Medical School of Hannover, Carl-Neuberg-Str. 1 , 30625 Hannover, Germany Department of Surgery Ruijin Hospital Affiliated to Shanghai Second Medical University Shanghai 200025 China. jiqiyan@***

Orthotopic liver transplantation as a successful treatment of end-stage liver disease is hampered by a persistent lack of cadaveric organs. Split liver transplantation, which was first successfully performed by Medical School of Hannover in 1988, has become a mature surgical technique to expand the donor pool. Between 1993 and 1999, split liver transplantation activities have increased in Europe from 1. 2% to 10. 4% in all performed liver transplantations. Current data have strongly supported that the survival rate of patients after split liver transplantation is not significantly different from that of patients after whole-size orthotopic liver transplantation. The most important step of donor graft selection is surgeon' s observation judged by the experience of individual transplant center. The paper aims to provide the guideline of donor selection, hepatic graft splitting, and recipient management as well. DATA SOURCES: Medical School of Hannover has accumulated plentiful experience of split liver transplantation for more than 10 cases ever since 1998. Besides that, we also reviewed a variety of literatures from other famous European and American centers specialized in this field for many years. RESULTS:According to our experience combined with the view points of others, the donor should meet the following criteria as well: (1) age less than 50 years; (2) hemodynamics stable; (3) ICU less than 5 days; (4) Na less than 170 mmol/L or better if less than 150 mmol/L. In 1996 and 1997, the Hamburg group and the UCLA group separately introduced a breakthrough technique performing split liver transplantation in situ. Evidently, the in situ technique has been limited by prolonged time of donor organ procurement , coordination with other organ procurement teams, and even extra burden on donor hospital. Some groups, therefore, have restored the ex situ or bench splitting technique , and fortunately the transplant outcomes of the ex situ technique are equivalent to those of

关键词： donor liver split transplantation

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