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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 mich.el Gebel Mathias J Bahr mich.el 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 ***: 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： Ultrasound Color Doppler Liver transplantation Monitoring

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 mich.el 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

AIM： To analyze the phenotype and function of dendritic cells （DC） from patients with hepatocellular carcinoma （HCC） in order to understand their role in this disease. METHODS： Myeloid dendritic cells were enumerated in peripheral blood of HCC patients. CD80, CD83, CD86 and HLA-DR expression on naive and stimulated myeloid dendritic cells from peripheral blood were analyzed. Myeloid dendritic cells were isolated from peripheral blood and their function was tested. phagocytosis was analyzed using FITC-dextran beads, peptide specific stimulation, the capacity to stimulate allogeneic T cells and secretion of cytokines upon poly dZ：dC was tested. RESULTS： Myeloid dendritic cells were reduced in patients with HCC. No differences in CD80, CD83, CD86 and HLA-DR expression were found on naive and stimulated myeloid dendritic cells from HCC patients and healthy controls. Normal phagocytosis or stimulation of peptide specific T cells was observed in contrast to an impaired allo-stimulatory capacity and a reduced IL-12 secretion. CONCLUSION： Impaired IL-12 production of mDCs in patients could lead to an impaired stimulatory capacity of naive T cells suggesting that IL-12 directed therapies may enhance tumor specific immune responses in HCC patients.

关键词： Myeloid DC Hepatocellular carcinoma CD80 CD83 CD86

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 mich.el p.manns mich.el 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 ***: 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 ***: 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 *** 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 ***: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizati

关键词： Cholangiocellular carcinoma Gemcitabine Intraarterial chemoembolization

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 mich.el Galanski mich.el p.manns mich.el 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 endoanal ultrasound which are established imaging methods for perianal inflammatory lesions in patients with Crohn's disease require expensive specialized equipments and *** investigated the feasibility and sensitivity of transcutaneous perianal ultrasound(pAUS)using regular ultrasound probes in the imaging of perianal inflammatory *** sonographic findings were correlated to pelvic MR]-scans. METHODS:We performed pAUS in 25 patients with Crohn's disease and clinical signs of perianal inflammatory disease. Wibhin a median of 10 d(range 0-75)these patients underwent MRI of the *** convex and linear high resolution probes were used for *** sonographic findings were correlated to the MRI findings by blinded investigators. RESULTS:The sonographic investigations were well tolerated by all *** typically presented as hypoechoic ***-nine fistulae were detected in 22 *** were detected in 7 patients and presented as hypo-or anechoic ***-six of 29 fistulae and 6 of 7 abscesses could be confirmed by *** 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 patient preparation which is comparable in its sensitivity to pelvic MRI in the detection of perianal fistulae and/or abscesses. pAUS can especially be recommended as a screening tool in acute perianal disorders such as perianal abscess and for follow-up studies of perianal inflammatory disease.

关键词： Anal Canal histology Anus Diseases Crohn Disease Humans Inflammation Ultrasonography, Doppler, Color

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 mich.el Gebel Lars Zender Nisar p Malek Bernhard panning Ajay Chavan Herbert Rosenthal Stefan Kubicka Susanne Krusche Sonja Merkesdal mich.el Galanski mich.el 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

AIM： To evaluate the treatment effect of percutaneous ethanol injection （pEI） for patients with advanced, non-resectable HCC compared with combination of transarterial chemoembolisation （TACE） and repeated single-session pEI, repeated single-session pEI alone, repeated TACE alone, or best supportive care. METHODS： All patients who received pEI treatment during the study period were included and stratified to one of the following treatment modalities according to physical status and tumor extent： combination of TACE and repeated single-session pEI, repeated single-session pEI alone, repeated TACE alone, or best supportive care. prognostic value of clinical parameters including Okuda-classification, presence of portal vein thrombosis, presence of ascites, number of tumors, maximum tumor diameter, and serum cholinesterase （CHE）, as well as Child-pugh stage, α-fetoprotein （AFp）, fever, incidence of complications were assessed and compared between the groups. Survival was determined using Kaplan-Meier and multivariate regression analyses.

关键词： HCC Single-session pEI TACE Survival prediction

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 mich.el p manns mich.el 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

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

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 mich.el p manns Ulrich Baumann Amar Deep Sharma mich.el 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 *** 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 ***) 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 ***). 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 *** 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 *** 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

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

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 mich.el p manns Guido Gerken Isabelle Colle mich.el 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)***:patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)***～TM(FS)was assessed at baseline and at week-12 post-treatment *** biopsy for METAVIR was assessed by a single ***～ transient elastogra-phy(TE)was performed during treatment in a patient ***: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 *** 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 eline FS(0.38 vs 0.51,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 ***: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： Albinterferon alfa-2b FibroScan FibroSURE Hepatitis C virus Interferon Sustained virological response -Transient elastography

自身免疫性肝炎的分类和自身抗体对发病机制及诊断的意义

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德国医学 1999年第3期16卷 144-150页

作者： mich.els p.manns 郝连杰 Meclical school of Hannover HannoverGermany 同济医科大学附属同济医院

自身免疫性肝炎是一原因不明症状群,病毒、细菌、化学物质和药物是遗传敏感个体诱发自身-参与炎症性疾病过程的潜在病因。自身免疫性肝炎的诊断根据许多临床和实验室指标,自身抗体是重要的诊断指标,常规实验室的检测方法是间接免疫荧光... 详细信息

自身免疫性肝炎是一原因不明症状群,病毒、细菌、化学物质和药物是遗传敏感个体诱发自身-参与炎症性疾病过程的潜在病因。自身免疫性肝炎的诊断根据许多临床和实验室指标,自身抗体是重要的诊断指标,常规实验室的检测方法是间接免疫荧光法。然而,间接免疫荧光法并不能区分个别抗体抗原系统,过去数年应用分子生物学技术。

关键词：肝炎自身免疫性肝炎自身抗体发病机制诊断