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Transcutaneous perianal sonography:A sensitive method for the detection of perianal inflammatory lesions in Crohn's disease

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World Journal of Gastroenterology 2004年第19期10卷 2859-2863页

作者： Jochen Wedemeyer Timm Kirchhoff Gernot Sellge Oliver Bachmann Joachim Lotz michael Galanski michael p.manns michael J.Gebel Jrg S.Bleck Department of Gastroenterology Hepatology and EndocrinologyMedical School of HannoverCarl Neuberg Str.130623 HannoverGermany M.D. Department of Diagnostic Radiology Medical School of HannoverCarl Neuberg Str.130623 HannoverGermany Department of Gastroenterology Hepatology and EndocrinologyMedical School of HannoverCarl Neuberg Str.130623 HannoverGermany

AIM: pelvic magnetic resonance imaging (MRI) and endoanalultrasound which are established imaging methods forperianal inflammatory lesions in patients with Crohn'sdisease require expensive specialized equipments andexpertise. We investigated the feasibility and sensitivity oftranscutaneous perianal ultrasound (pAUS) using regularultrasound probes in the imaging of perianal inflammatorylesions. The sonographic findings were correlated to pelvicMRI-scans.METHODS: We performed pAUS in 25 patients with Crohn'sdisease and clinical signs of perianal inflammatory disease.VCChin a median of 10 d (range 0-75) these patients underwentMRI of the pelvis. Regular convex and linear high resolutionprobes were used for pAUS. The sonographic findings werecorrelated to the MRI findings by blinded investigators.RESULTS: The sonographic investigations were welltolerated by all patients. Fistulae typically presented ashypoechoic tracks. Twenty-nine fistulae were detected in22 patients. Abscesses were detected in 7 patients andpresented as hypo- or anechoic formations. Twenty-six of29 fistulae and 6 of 7 abscesses could be confirmed byMRI. Kappa statistics showed an excellent agreement(kappa>0.83) between the two imaging methods.CONCLUSION: pAUS is a simple, painless, feasible, real-time method that can be performed without specific patientpreparation which is comparable in its sensitivity to pelvicMRI in the detection of perianal fistulae and/or abscesses.pAUS can especially be recommended as a screening toolin acute perianal disorders such as perianal abscess andfor follow-up studies of perianal inflammatory disease.

关键词：经皮肛周超声诊断法敏感法肛周损害节段性回肠炎临床作用

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

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World Journal of Gastroenterology 2005年第8期11卷 1091-1095页

作者： Timm Kirchhoff Lars Zender Sonja Merkesdal Bernd Frericks Nisar Malek Joerg Bleck Stefan Kubicka Stefan Baus Ajay Chavan michael p.manns michael Galanski Department of Diagnostic Radiology Department of Gastroenterology Division of Rheumatology Department of Radiology and Nuclear Medicine

AIM: In nonresectable cholangiocellular carcinoma (CCC)therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%.Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver.METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity.RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered.Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases,stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo.CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect

关键词：化学疗法胆管细胞癌肝脏全身联合治疗

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丙型肝炎:许多老病的新病毒

德国医学 1994年第4期11卷 227-229页

作者： michael p.manns 郝连杰 Department of Gastroenterology and Hepatology Zentrum Innere Medizin und DermatologieKonstanty Gutsehow Str.8D-30625 HannoverGermany 同济医科大学附属同济医院

自从1989年确定丙型肝炎病毒之后,关于丙型肝炎病毒分子结构和生物学的识识已有了其显著的提高。最令人激动的领域是 HCV 与免疫系统的相互作用,HCV 感染引起组织损伤的机理,特别是病毒本身的致细胞病变的程度如何?细胞对病毒惑染的免... 详细信息

自从1989年确定丙型肝炎病毒之后,关于丙型肝炎病毒分子结构和生物学的识识已有了其显著的提高。最令人激动的领域是 HCV 与免疫系统的相互作用,HCV 感染引起组织损伤的机理,特别是病毒本身的致细胞病变的程度如何?细胞对病毒惑染的免疫反应可致何种程度肝细胞损伤?

关键词：丙型肝炎丙型肝炎病毒肝病自身免疫病

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

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Hepatobiliary & pancreatic Diseases International 2007年第3期6卷 259-266页

作者： Timm D Kirchhoff Joerg S Bleck Arne Dettmer Ajay Chavan Herbert Rosenthal Sonja Merkesdal Bernd Frericks Lars Zender Nisar p Malek Tim F Greten Stefan Kubicka michael p.manns michael Galanski Department of Diagnostic Radiology Hannover Medical School Germany Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School Germany Department of Diagnostic and Interventional Radiology Klinikum Oldenburg Germany Division of Rheumatology Hannover Medical School Germany Department of Radiology and Nuclear Medicine Campus B.F-Charité-University Medicine Berlin Germany

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (pD) 9%, stable disease (SD) 55%, partial remission (pR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for pR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (pR as best response to TACE (Odds ratio=6.7) were significantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications

关键词： carcinoma, hepatocellular transarterial chemoembolization degradable starch microspheres Lipiodol tumor response survival

Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第20期12卷 3275-3282页

作者： Lars A Ormandy Anatol Frber Tobias Cantz Susanne petrykowska Heiner Wedemeyer Monique Hrning Frank Lehner michael p.manns Firouzeh Korangy Tim F Greten Department of Gastroenterology Hepatology and Endocrinology Hannover Medical SchoolGermany Departments of Visceral and Transplantation Surgery Hannover Medical School Germany

瞄准：与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法：骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80， CD83， CD86 和 HLA... 详细信息

瞄准：与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法：骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80， CD83， CD86 和 HLA 医生表示被分析。骨髓的的树枝状的房间从外部血被孤立，他们的功能被测试。吞噬作用用 FITC 葡聚糖祷告被分析，肽特殊刺激，在多形核白细胞 dI:dC 之上刺激 allogeneic T 房间和 cytokines 的分泌物的能力被测试。结果：骨髓的的树枝状的房间与 HCC 在病人被减少。在 CD80， CD83， CD86 和 HLA 医生表示的差别都没从 HCC 病人和健康控制在天真、刺激的骨髓的的树枝状的房间上被发现。肽 specific T 房间的正常吞噬作用或刺激与一个损害 allo-stimulatory 能力和减少的 IL-12 分泌物相对照被观察。结论：在病人的 mDCs 的损害 IL-12 生产能导致建议指导治疗可以提高的那 IL-12 的天真的 T 房间的一个损害 stimulatory 能力在 HCC 病人的肿瘤 specific 免疫者回答。

关键词：树状细胞肝细胞癌骨髓细胞外周血

Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model

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World Journal of Hepatology 2018年第2期10卷 277-286页

作者： Norman Junge Qinggong Yuan Thu Huong Vu Simon Krooss Christien Bednarski Asha Balakrishnan Toni Cathomen michael p.manns Ulrich Baumann Amar Deep Sharma michael Ott Department of pediatric Gastroenterology and Hepatology Hannover Medical School Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School TWINCORE Centre for Experimental and Clinical Infection Research Medical Center University of Freiburg Institute for Cell and Gene Therapy Research Group Micro RNA in Liver Regeneration Cluster of Excellence REBIRTH Hannover Medical School

AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-) mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human Fah c DNA including the TTR promoter from a lentivirus plasmid as described. The Fah expression cassette was flanked by homologous arms(620 bp and 749 bp long) of the Rosa26 gene locus. Mice were injected with 2.1 × 108 Vp of this vector(r AAV8-ROSA26.HAL-TTR.FahROSA26.HAR) via the tail vein. Mice in the control group were injected with 2.1 × 108 Vp of a similar vector but missing the homologous arms(r AAV8-TTR.Fah). primary hepatocytes from Fah-/-recipient mice, treated with our vectors, were isolated and 1 × 106 hepatocytes were transplanted into secondary Fah-/-recipient mice by injection into the spleen. Upon either vector application or hepatocyte transplantation NTBC treatment was stopped in recipient mice. RESULTS Here, we report successful HR-mediated genome editing by integration of a Fah gene expression cassette into the "safe harbour locus" Rosa26 by recombinant AAV8. Both groups of mice showed long-term survival, weight gain and FAH positive clusters as determined by immunohistochemistry analysis of liver sections in the absence of NTBC treatment. In the group of C57 BL/6 Fah?exon5 mice, which have been transplanted with hepatocytes from a mouse injected with r AAV8-ROSA26.HAL-TTR.Fah-ROSA26.HAR 156 d before, 6 out of 6 mice showed long-term survival, weight gain and FAH positive clusters without need for NTBC treatment. In contrast only 1 out 5 mice, who received hepatocytes from r AAV8-TTR.Fah treated mice, survived and showed few and smaller FAH positive clusters. These results demonstrate that homologous recombinationmediated Fah gene transfer corrects the phenotype in a mouse model of human tyrosinaemia type 1(Fah-/-mice) and is long lasting in a proliferating state of the

关键词： Gene therapy AAV8 Liver based metabolic disease Targeted integration ROSA26 paediatric liver disease

Changes of duplex parameters and splenic size in liver transplant recipients during a long period of observation

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World Journal of Gastroenterology 2005年第43期11卷 6787-6791页

作者： Bita Boozari michael Gebel Mathias J Bahr michael p.manns Christian p Strassburg Joerg S Bleck J Klempnauer Bjoern Nashan Department of Gastroenterology Department of Visceral and Transplant Surgery Department of Transplant Surgery

AIM: To assess the changes of portal and arterial velocities, resistance index, spleen and liver size during a long observation period (13.7 years) after orthotopic liver transplantation (OLT).METHODS: Two hundred and sixty patients were recruited retrospectively for this study and divided into groups with defined time intervals after OLT. The cross-sectional changes of portal and arterial velocities,resistance index, spleen and liver size between the defined time intervals were studied. The complications detected by ultrasound were compared to gold standard methods.RESULTS: The mean values for liver size were all within the normal range. The splenic size decreased between the time intervals 100 and 1 000 d after OLT (t;p＜0.01).While portal and arterial flow velocities decreased up to 5.5 years (t; portal velocity p＜0.01, maximal systolic velocity p=0.05, maximal end diastolic velocity p＜0.01),RI increased during this interval (t:p＜0.01). Higher RIvalues were found in older patients (r = 0.24, p＜0.001).CONCLUSION: The arterial and portal velocities show adaptation processes continuing over the course of many years after OLT and are reported for the first time. The vascular complications detected by ultrasound occur mostly up to 100 d after OLT.

关键词：肝移植脾疾病病理机制治疗

FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

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World Journal of Gastroenterology 2011年第41期17卷 4581-4589页

作者： Keyur patel Mireen Friedrich-Rust Yoav Lurie Mircea Grigorescu Carol Stanciu Chuan-Mo Lee Eugene R Schiff Dieter Hussinger michael p.manns Guido Gerken Isabelle Colle michael Torbenson Erik pulkstenis G Mani Subramanian John G McHutchison Stefan Zeuzem Department of Gastroenterology and Hepatology Duke Clinical Research Institute Department of Gastroenterology and Hepatology J.W.Goethe University Hospital Department of Gastroenterology and Hepatology Tel Aviv Sourasky Medical Center Department of Clinical Infectious Disease Spitalul Clinic de Urgenta Department of Gastroenterology and Hepatology Institutul de Gastroenterologie si Hepatologie Department of Gastroenterology Chang Gung Memorial Hospital-Kaohsiung Medical CenterChang Gung University College of Medicine Departments of Gastroenterology and Internal Medicine University of Miami Department of Gastroenterology and Hepatology Universittsklinik Department of Gastroenterology and Hepatology Department of Gastroenterology and Hepatology Ghent University Hospital Department of pathology Johns Hopkins University School of Medicine Department of Biostatistics Human Genome Sciences Department of Clinical Research Human Genome Sciences

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;p p pa vs 11.9 kpa,p = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

关键词：丙型肝炎病毒治疗慢性 TM 评估基准亚洲人工作曲线 TE

Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第23期12卷 3707-3715页

作者： Arne Dettmer Timm D Kirchhoff michael Gebel Lars Zender Nisar p Malek Bernhard panning Ajay Chavan Herbert Rosenthal Stefan Kubicka Susanne Krusche Sonja Merkesdal michael Galanski michael p.manns Joerg S Bleck Department of Gastroenterology Hepatology and EndocrinologyHannover Medical SchoolGermany Department of Diagnostic Radiology Hannover Medical SchoolGermany Department of Anaesthesiology Hannover Medical SchoolGermany Department of Diagnostic and Interventional Radiology Klinikum OldenburgGermany S Bleck Department of GastroenterologyHepatology and EndocrinologyHannover Medical SchoolGermany Division of Rheumatology Hannover Medical SchoolGermany

瞄准：为病人评估经皮的乙醇注射(pEI ) 的治疗效果与先进， non-resectable HCC 与 transarterial chemoembolisation 的联合相比(不作声) 并且重复单个会议的 pEI，独自重复了单个会议的 pEI，重复不作声独自一个，或最好的支持的照... 详细信息

瞄准：为病人评估经皮的乙醇注射(pEI ) 的治疗效果与先进， non-resectable HCC 与 transarterial chemoembolisation 的联合相比(不作声) 并且重复单个会议的 pEI，独自重复了单个会议的 pEI，重复不作声独自一个，或最好的支持的照顾。方法：在学习时期期间接受了 pEI 治疗的所有病人根据物理地位和肿瘤程度被包括并且成层到下列治疗形式之一：联合不作声并且重复单个会议的 pEI，独自重复了单个会议的 pEI，重复不作声独自一个，或最好的支持的照顾。包括Okuda分类，门静脉血栓的存在，腹水的存在，肿瘤的数字，最大的肿瘤直径，和假胆硷酯酶( CHE )的临床的参数的预示的价值，以及孩子呸上演， alpha-fetoprotein (法新社)，发烧，复杂并发症的发生在这些组之间被估计并且比较。幸存用 Kaplan-Meier 被决定，多，变量回归分析。结果：所有病人的 1 年、 3 年的幸存是 73% 和 47% 。在亚群分析，联合不作声， pEI (1 ) 与更长的幸存被联系(1- ， 3- ， 5 年的幸存：90% ， 52% ，和 43%) 与 pEI 治疗相比独自一个(2 )(1- ， 3- ， 5 年的幸存：65% ， 50% ，和 37%) 。(3 ) 在起始的层化以后的第二等的 pEI 产出可比较的结果不作声(1- ， 3- ， 5 年的幸存：91% ， 40% ，和 30%) 当在到最好的支持的照顾(4 ) 的层化以后的 pEI 与减少的幸存被联系时(1- ， 3- ， 5 年的幸存：50% ， 23% ， 12%) 。除了选择治疗形式，为更好的幸存的预言者是肿瘤数字(n pEI 前的没有腹水，和在 pEI 以后的稳定的假胆硷酯酶(p pEI 以后的 2 wk 以内的死亡是 2.8%(n = 3 ) 。有 24 (8.9%) 主修在包括部分肝梗塞，焦点的肝坏死，和肝脓肿的 pEI 以后的复杂并发症。所有复杂并发症能非通过手术被管理。结论：重复单个会议的 pEI 在有以可接受、可管理的复杂并发症率的先进 HCC 的病人是有效的。病人们成层到联合不作声， pEI 能比那些独自成层到重复 pEI 期望更长的幸存。而且，有在好临床的地位的大或多重的肿瘤的病人可以也从联合获利不作声并且为第二等的 pEI 的再考虑。

关键词：经皮注射乙醇肝细胞癌疾病预防